insights - IMS Health

Volume 2, Issue 4 • May 2012 

AccessPoint 

News, views and insights from leading experts in HEOR 

Accounting for direct evidence gaps 

New lifecycle 

demands for RWE 

Early planning is essential 

Emerging markets in Asia Pacific 

move to formalize HTA 

Jon Resnick 

Chris Blanchette 

Núria Lara Surinach, 

presents a lifecycle 

measures drug 

Xavier Badia and 

plan for real-world 

Page OUTCOMES 1 - Issue 1 

evidence 

treatment exposure 

Núria Perulero 

IMS HEALTH ECONOMICS AND OUTCOMES RESEARCH Page 1 

in asthma 

consider the growing 

Page 10 

Page 21 

importance of PROs 

Page 16 

THE MAGAZINE OF IMS HEALTH ECONOMICS & OUTCOMES RESEARCH

Volume 2, Issue 4 • May 2012 

AccessPoint 

News, views and insights from leading experts in HEOR 

providers 

Preparing for a lifecycle of real-world evidence 

Increasing demand brings a need for new capabilities, data 

considerations, and effective planning for RWE across the 

entire product lifecycle. 

page 10 


with indirect treatment comparisons 

Network meta-analysis offers growing potential. 

page 26 

Who drives the lion’s share of costs? 

Understanding healthcare spending in the 

commercially-insured US population under age 65. 

page 32 

Pharmacogenomics comes of age 

Continued evolution of pharmacogenomics brings 

new considerations for RWE. 

page 44 

IMS HEALTH ECONOMICS & OUTCOMES RESEARCH

“2012 is shaping a future that will be 

transformed by real-world evidence” 

WELCOME 

Welcome to the fourth issue of AccessPoint, a twice-yearly 

highlight of news, views and insights from the international 

HEOR team at IMS Health – casting an expert eye on the 

evolving dynamics that are changing the basis for healthcare 

decision making with potential for improved efficiency through 

real-world evidence (RWE) generation. 

RWE is not a new concept - HEOR researchers have been 

generating evidence for years - but growing demand is driving 

new opportunities to expand, enhance and do more. As we move 

through 2012, we see a year that is shaping a future where 

healthcare is transformed by RWE: the emerging markets of Asia 

Pacific (page 40) have joined a growing body of countries 

globally that depend on RWE to inform HTA; significant, too, is 

an important shift in the timeframe over which value is 

determined, extending the use of RWE far into the product 

lifecycle (page 10); at the same time, the science of personalized 

medicine (page 44) brings further potential for the expanded 

application of RWE; and underpinning these trends, the bar is 

being raised for real-world studies, setting new standards for their 

design and validation (page 16). 

Today, regulators, HTA bodies, payers, practitioners, patients and 

manufacturers are united in the goal of improving treatment 

based on the best available evidence. IMS is committed to 

advancing the use of RWE to enable improved efficiency in 

healthcare and enrich the dialog across the healthcare setting. Our 

recent lead in a national debate on RWE studies in France (page 

6) has already paved the way for a smoother process based on a 

new collaborative spirit, and in our joint initiative with 

AstraZeneca in Europe (Page 7) we look forward to leveraging a 

shared perspective on the transformative power of RWE in 

informing the delivery of effective and cost-efficient healthcare. 

Fulfilling the potential of RWE requires new capabilities in 

managing, analyzing and leveraging real-world information. In 

responding to the demand for more compelling, credible evidence, 

companies will need to reconsider the way they collect and interact 

with real-world data. 

IMS has a global team of more than 200 experts in outcomes 

research, economic modeling, RWE and market access. Our 

research calls for creative thinking to connect and integrate 

fragmented information and build the tools, interfaces and technical 

platforms that will enable faster, more robust RWE generation. 

We continue to invest in research programs to ensure the strongest 

foundation for identifying, interpreting and communicating realworld 

outcomes. Our recent validations of the IMS CORE 

Diabetes Model (page 8) and integration of our global patient-level 

assets, including IMS LifeLink PharMetrics PLUS (page 2), confirm our 

ongoing efforts in this area. 

I hope you find this issue of AccessPoint timely, informative and 

stimulating in a year that is defining a clearer path to stronger, 

evidence-based decision making. 

Jon Resnick 

VICE PRESIDENT, REAL-WORLD EVIDENCE SOLUTIONS, IMS HEALTH 

Jresnick@uk.imshealth.com 

CONTENTS 

NEWS SECTION 

2 IMS announces LifeLink PharMetricsPLUS 4 Oncology leads IMS research agenda 

6 IMS drives French debate on RWE 

7 Landmark RWE partnership with AstraZeneca 

8 IMS CORE Diabetes Model maintains 

leadership position 

INSIGHTS 

10 REAL-WORLD EVIDENCE 

Developing a lifecycle plan 

16 PATIENT-REPORTED OUTCOMES 

Increasing relevance adds to expectations 

21 DRUG EXPOSURE MEASUREMENT 

Standardization key to meaningful results 

26 INDIRECT TREATMENT COMPARISONS 


32 US PRIVATE HEALTHCARE SPENDING 


40 IMPLEMENTING HTA IN ASIA PACIFIC 

Critical success factors in emerging markets 

44 PHARMACOGENOMICS 

New imperatives for RWE strategy 

PROJECT FOCUS 

50 IMS CORE BUDGET IMPACT MODEL 

Payer-relevant pharmacy analyses 

52 DATA LINKAGE IN ONCOLOGY 

EMR oncology data platform 

54 METASTATIC COLORECTAL CANCER 

Informing optimal treatment strategies 

IMS HEOR OVERVIEW 

56 ENABLING YOUR REAL-WORLD SUCCESS 

Locations, expertise, IMS LifeLink AccessPoint is published twice yearly by the Health 

Economics & Outcomes Research team of IMS Health. 

VOLUME 2 ISSUE 4. PUBLISHED MAY 2012. 

IMS HEALTH 210 Pentonville Road, London N1 9JY, UK 

Tel: +44 (0) 20 3075 4800 • HEORinfo@uk.imshealth.com 

www.imshealth.com/heor 

© 2012 IMS Health Incorporated and its affiliates. All rights reserved. 

Trademarks are registered in the United States and in various 

other countries. 

ACCESSPOINT • VOLUME 2 ISSUE 4 PAGE 1

NEWS | IMS LIFELINK PHARMETRICS PLUS 

Major investment extends the leverage of IMS linked patient-level data bringing new 

possibilities for health economics and outcomes research. 

IMS announces LifeLink PharMetrics PLUS 

- the most comprehensive integrated 

database available in the US market 

Marking a strong commitment to advance the use 

of real-world evidence (RWE) for assessing the way 

in which a drug or medical device performs in 

actual clinical practice, IMS continues to make 

significant investments to enhance and better 

leverage its existing patient-level datasets. 

IMS is already widely recognized as a leading provider of the 

IMS LifeLink Health Plan Claims database. Formerly known as 

PharMetrics, this is the largest independent claims data source 

in the US, covering more than 73 million unique patients. With 

the acquisition of SDI in Q4 2011 came a range of 

complementary LifeLink Information Assets, providing insights 

into the total patient experience in the US - as patients receive 

care from providers, pharmacies, hospitals, labs and other 

facilities – and the way in which this care is influenced by other 

factors, such as patient characteristics and behaviors, past 

treatments, managed care coverage, and further key attributes. 

IMS LIFELINK PHARMETRICSPLUS The SDI legacy further included established and published 

expertise in data linkage and integration which has now been 

leveraged to develop a new, integrated dataset, known as 

IMS LifeLink PharMetricsPLUS . 

LifeLink PharMetricsPLUS brings IMS Health Plan Claims data 

integrated with: 

• Hospital Charge Data Master: Collected from general 

medical-surgical and specialty hospital's in-patient and 

out-patient records. Includes detailed diagnoses, procedures, 

drugs, devices, applied charges, sites of service, as well as 

patient demographics and admission/discharge characteristics. 

• Oncology EMR data: Collected in the out-patient office 

setting from medium and large community-based oncology 

urology, dialysis, radiation, cancer registry, hospital, and 

general/ambulatory practices. Provides detailed clinical 

data, including diagnoses, treatments, oral and injectable 

medications, in-office procedures, lab results, vitals, 

patient demographics, cancer staging, tumor morphology, 

and metastatic identifier. 

• Ambulatory EMR: Collected from GP/IM practices and 

clinics. Out-patient, clinical, patient-level charts in an 

electronic format with representative coverage of most 

regions. Provides detailed clinical and patient attributes, 

including diagnoses, written prescriptions, procedures, 

test results, and clinical variables (eg, BMI, BP). 

• Lab data: Collected from a leading national lab provider, 

laboratory data including demographics, diagnosis, test 

date, test description, result, reference results ranges, and 

ordering provider's geographic location. 

• Consumer attributes: Collected from a respected global 

leader in compiling unique consumer data including 

financial, demographic, race/ethnicity, mortality, and 

psychographic profiles. 

• Retail purchasing OTC/CPG: Collected from a respected 

source of loyalty card purchasing data. Contains retail 

purchasing information which allows classification of 

consumers based on buying behavior. 

IMS LIFELINK PHARMETRICS PLUS INTEGRATED DATASETS 

Pharmacy 

prescription 

Hospital 

Retail 

purchasing 

OTC/CPG 

Ambulatory 

EMR 

Health Plan 

Claims 

Consumer 

attributes 

Oncology 

EMR 

PAGE 2 IMS HEALTH ECONOMICS & OUTCOMES RESEARCH 

Medical 

claims

IMS DE-IDENTIFICATION ENGINE 

IMS LIFELINK PHARMETRICS PLUS | NEWS 

Retail & LTC Rx Customer data 

Medical claims 

Hospital charge 

detail master 

Healthcare provider 

attributes 

Labs 

Electronic medical 

Records 

Consumer 

demographics 

& psychographics 

• Medical claims: Pre-adjudicated claims (switch source) 

collected from office-based physicians and specialists. 

Expands the demographics of the database to include 

populations and claims that might be under-represented 

in health plan claims data, including Medicare and 

Medicaid. The data include patient demographics, 

physician demographics, diagnoses, procedures, and 

in-office administered drugs. 

• Pharmacy prescription data: Collected from retail, mailorder, 

long-term care and specialty pharmacy records. 

Includes claims submitted for payment and other 

prescriptions directly from key pharmacy locations. 

In addition to commercial and government payers, cash 

transactions are recorded. 

NEW ANALYTICAL POTENTIAL 

Directly linked via unique patient identifiers, using a unique 

and proprietary algorithm for de-identification of patients, 

ensuring HIPAA compliance, these data open up new 

analytical possibilities, overcoming the limitations in 

scope or clinical detail of current databases. Analyses types 

enabled include: 

• Monitoring post-discharge outcomes of detailed in-patient 

clinical pathways 

• Adding health status variables (eg, biomarkers and vitals) 

to comparative effectiveness and cost-of-care analyses 

Source 

IMS 

de-identi�cation 

engine 

De-identi�ed data 

IMS uses a unique 

and proprietary 

algorithm for 

de-identi�cation of 

patients, ensuring 

compliance with 

HIPAA regulations 

Data 

warehouse 

• Enhancing drug exposure measures impacted by 

administrative data loss 

• Expanding the availability of clinical endpoints such as 

mortality and progression in database analyses 

EARLY ACCESS 

As this exciting development progresses, work on establishing 

linkage for the various datasets continues, reflecting the 

significant level of investment involved in incorporating 

information provided by multiple health plans and other 

data sources. In advance of full commercialization, IMS is 

providing clients with early access to the new integrated 

dataset, LifeLink PharMetrics PLUS which is now ready for 

research. As from June 2012, the information available in the 

database can be used for client projects leveraging the 

analytical expertise and data knowledge of the IMS HEOR 

team. While the initial linked dataset is based on selected 

health plans, IMS anticipates significant growth in the size 

of the database over the course of the coming months, 

allowing even more research questions to be answered • 

If you would like to learn more about IMS LifeLink 

PharMetrics PLUS , the most comprehensive integrated database 

available in the US market, please email Michael Nelson at 

Mnelson@us.imshealth.com 


NEWS | IMS ONCOLOGY EXPERTISE 

The IMS HEOR Bibliography captures more than 2200 research publications with a history 

of 25 years across all key therapy areas. Oncology is one of our leading fields of research. 

Oncology is a key research area for IMS HEOR 

The oncology market is experiencing spectacular 

growth and unprecedented innovation. 

It is predicted to become the largest single therapy 

sector in value terms by 2015 – worth US$75 billion. 

New molecular targeted therapies, diagnostics, 

genomics and proteomics are changing the face of 

cancer treatment, spurring exciting opportunities 

- and also new challenges - for this healthcare 

sector worldwide. 

The IMS HEOR global team has completed projects 

on 20 different tumor types, spanning all aspects 

of health economics and outcomes research, with 

particular emphasis on health economic modeling 

and retrospective outcomes research. 

The top ten cancers we have covered are: 

1. Breast 

2. Lung [NSCLC/SCLC] 

3. Colorectal 

4. Lymphoma 

5. Melanoma/BCC 

6. Prostate 

7. Multiple myeloma 

8. Leukemias [CLL/CML] 

9. Mesothelioma 

10. Cervical 

IMS HEOR ONCOLOGY PROJECTS SPAN ALL ASPECTS OF HEOR 

43% 

ONCOLOGY IS A LEADING AREA OF IMS HEOR EXPERTISE 

116 107 


150 

233 

259 

330 

Diabetes Oncology Cardiovascular 

Mental health 

HE modeling 

Prospective 

outcomes research 

Neurological 

disorders 

14% 

30% 

13% 

Retrospective 

outcomes research 

Value 

communications 

Respiratory 

diseases

IMS HEOR Bibliography 

Health economics review of 

bowel cancer in Australia 

NSW Cancer Institute, 2008, 

Sydney, Australia (Review) 

Bishop J, Glass P, Tracey E, 

Hardy M, Warner K, Makino K, 

Gordois A, Wilson J, 

Guarnieri C, Feng J, 

Sartori L 

Economic model of granulocyte 

-colony stimulating factor (G-CSF) 

in primary (PP) and secondary 

prophylaxis (SP) of febrile 

neutropenia (FN) in Non-Hodgkin's 

Lymphoma (NHL) patients 

undergoing chemotherapy in France 

ISPOR 14th Annual European 

Congress, Madrid, Spain, 

5-8 November, 2011 

Perrier L, Sebban C, 

Leon N, Maurel F, 

Cohen-Nizard S, 

De Liège F 

IMS ONCOLOGY EXPERTISE | NEWS 

Our research expertise and therapy area knowledge are captured in more than 

200 publications each year, spanning virtually all therapy areas and 50+ 

countries worldwide. Contact IMS (details on back cover) for a copy of the 

latest IMS HEOR Bibliography of published papers (2008-2012) or visit 

www.imsheorbibliography.com to explore our database online. 

The IMS HEOR bibliography in oncology spans all key areas of health economics and outcomes 

research, including retrospective and observational analyses, budget impact, cost-effectiveness and 

cost utility modeling, model adaptations, epidemiology and burden of disease studies, indirect 

comparisons, and meta-analyses, bringing important new findings across all key tumor types and 

countries around the world. 

Breast cancer diagnostic 

process: Management and cost 

evaluation in Italy 


Congress, Paris, France, 24-27 

October, 2009 

Pantaleoni M, 

Marchese E 

Second-line therapy for 

non-small cell lung cancer 

(NSCLC): A retrospective cost 

analysis 

Tumordiagn u Ther, 2008; 

29:211-217 

Gatzemeier U, Pirk O, 

Gabriel A, 

Kotowa W, 

Heigener D 

Development of a 

co-morbidity scale in patients 

with chronic lymphocytic 

leukemia 


Congress, Prague, Czech 

Republic, 6-9 November, 2010 

Carbonell F, De La Serna J, 

Giraldo P, Lopez A, Rios E, 

Perulero N, 

Castro-Gomez AJ 

Cost-effectiveness of cetuximab, 

bevacizumab, and panitumumab 

in first-line treatment of 

metastatic colorectal cancer 

(mCRC) for patients with KRAS 

wild-type (wt) tumors in the UK 

Journal of Clinical Oncology, 

2011;29(Suppl):A16571 

Samyshkin Y, Hertel N, 

Griebsch I 

Five-year routine cervical 

cancer screening rates and 

intervals in a United States 

health plan 

Current Medical Research and 

Opinion, 2008; 24(9):2429- 

2435 

Schabert VF, Ye X, Insinga RP, 

Singhal PK, Riedel AA 

Cost-utility analysis of dasatinib 

as a second-line treatment in 

the chronic phase of chronic 

myeloid leukaemia in Russia 


Congress, Prague, Czech 

Republic, 6-9 November, 2010 

Kuznetzov SV, Mungapen L, 

Samyshkin Y, Jakouloff D, 

Sbarigia U, 

van Baardewijk M 

Economic evaluation in the 

treatment of advanced and/or 

metastatic gastric cancer from 

the perspective of the public 

health system in Mexico 

ISPOR 17th Annual 

International Meeting, 

Washington, DC, USA, 

2-6 June, 2012 

Lechuga D, Alva M, 

Salinas GE, Leyva V 

Epidemiologic study to assess 

patient involvement in choice 

of adjuvant chemotherapy in 

breast cancer (PROSA study) 

Clinical and Translational 

Oncology, 2009; 11(4):221-7 

Tusquets I, Espinosa Arranz E, 

Méndez M, Gil JM, 

Guallar JL, 

Perulero N 

A retrospective analysis 

illustrating the substantial 

clinical and economic burden 

of prostate cancer 

Prostate Cancer and Prostatic 

Diseases, 2010; 13(2):162-167 

Crawford ED, Black L, 

Eaddy M, Kruep EJ 

Risk of treatment failure after 

first-line sunitinib therapy in 

patients with metastatic renal 

cell carcinoma 

Journal of Clinical Oncology, 

2012; 30 (Suppl 5): Abstract 

438 

Chen CC, Hess GP, Liu Z, 

Gesme DH, Agarwala SS, 

Hill JW, Guo MA 


NEWS | REAL-WORLD EVIDENCE IN FRANCE 

Senior French healthcare stakeholders respond to IMS lead for tackling process 

bottlenecks hindering real-world evidence development. 

IMS HEOR drives national debate on 

RWE studies in France 

IMS HEOR has taken a leadership role in France to 

address problems that are hindering the 

development of real-world evidence (RWE) studies 

required for market access regulation. By creating 

a platform for stakeholder discussion at the highest 

level, the IMS HEOR team in France, led by 

Principal, Dana Morlet-Vigier, has paved the way 

for alignment and solutions. 

In France, every drug must pass through a value assessment 

by the High Authority for Health (HAS) and negotiation with 

the pricing committee (CEPS) to achieve reimbursement. Both 

government agencies are placing greater emphasis on RWE to 

determine how a new technology performs in actual clinical 

practice. Manufacturers can face significant financial sanctions 

if studies are not provided in a reasonable timeframe. However, 

the process for initiating RWE studies in France is currently 

slow and complex, involving multiple stakeholders. CEPS 

president, Gilles Johanet, has himself acknowledged the 

imperative for a more dynamic evaluative approach. 

PROPOSAL FOR ACTION 

With the entire economic life of a drug dependent on 

compulsory post-listing, post-reimbursement studies, IMS 

recognized the need to kick-start change and approached 

CEPS direct with a proposal: as a “neutral” expert in RWE 

studies, the IMS HEOR team would organize and facilitate a 

workshop with all relevant stakeholders, as well as a 

specialist in process industrialization, to identify and analyze 

critical bottlenecks in the system. 

DRIVING ALIGNMENT 

The offer was accepted and in late 2011, 75 top decision 

makers in France came together at the invitation of IMS for 

a day of structured presentations and debate. Participants 

included pharma Directors/VPs of market access and HEOR, 

doctors/clinical investigators, and senior representatives 

from HAS, CEPS and other public policy stakeholders. The 

discussions, framed by IMS, focused on the need for RWE, its 

impact on the pharmaceutical industry, the process and subprocesses 

of RWE studies in France, database studies and 

ad-hoc observational trials. 

The workshop proved transformational, achieving consensus 

on issues compromising the timeliness and quality of RWE 

studies. It was so successful in reaching this point that IMS 

was invited to set up and moderate a second, follow-on 

session early in 2012, where specific recommendations for 

the scope and management of RWE studies were identified. 

SMOOTHER PROCESS 

By coordinating brainstorming and communication between 

major public decision makers and pharma, this initiative has 

paved the way for a smoother process and helped to shape 

the future development of RWE in France. It also reaffirms 

the potential of alignment and collaboration in fostering 

positive change and advancing efforts to improve healthcare 

efficiency, ensure safety and demonstrate value for money. • 

75 top decision makers in France came together at the invitation 

of IMS for a day of structured presentations and debate on RWE. 

Above: Gilles Johanet (left) and Dana Morlet-Vigier 

Below: Workshop sessions during the event 

PAGE 6 IMS HEALTH ECONOMICS & OUTCOMES RESEARCH

REAL-WORLD EVIDENCE COLLABORATION | NEWS 

Groundbreaking partnership heralds potential for improving healthcare efficiency by 

advancing the use of real-world evidence (RWE) in Europe 

IMS enters collaboration with AstraZeneca 

to expand real-world evidence 

Early in 2012, AstraZeneca announced a three-year agreement with IMS to advance the use of 

real-world evidence (RWE) - and establish standards for RWE generation - based on observational and 

retrospective studies throughout Europe, to inform the delivery of effective and cost-efficient healthcare. 

The partnership with IMS Health will give AstraZeneca access 

to pre-existing anonymized electronic health records, which 

include clinical outcome, economic and treatment pattern 

data. In addition, the companies will jointly develop a 

customized research and data analysis platform. The 

information will provide a deeper insight into how medicines 

that are already on the market are working in real-world 

settings across Europe, painting a picture of unmet needs in 

the current standard of care and treatment patterns across a 

number of therapeutic areas, with an emphasis on chronic 

illnesses. The data will also be used to inform AstraZeneca’s 

discovery and clinical development programs. 

The collaboration reflects the interest among healthcare 

decision makers in examining the cost and effectiveness of 

new and existing medicines and health technologies to help 

allocate their increasingly limited resources more efficiently. 

Unlike controlled clinical trials, RWE studies use observational 

data such as electronic medical records, claims information, 

patient registries and patient surveys. By evaluating the data 

associated with the delivery of care, ‘real-world’ analyses can 

demonstrate treatment impact on measurable outcomes such 

as hospital length of stay, readmissions, overall health status 

and total cost of care. 

This is how senior leaders from AstraZenca and IMS see the 

partnership: 

“Our collaboration with IMS is a key milestone in our 

commitment to understand the impact of our medicines in the 

real world, beyond what we see in controlled clinical trials. 

This insight will help us and healthcare decision makers to 

improve the treatment of disease and ensure effective use of 

medicines to minimize the burden on individuals and 

healthcare budgets.” 

Martin Mackay, President of Research and Development, 

AstraZeneca 

“This joint initiative reflects a shared perspective on the 

transformative power of real-world evidence on global health 

systems. Our unique information assets, coupled with our 

services and technology capabilities, make IMS a leading 

partner for healthcare organizations in the identification, 

integration and interpretation of real-world outcomes. 

We are extremely pleased to be working with AstraZeneca on 

this collaboration.” 

Jon Resnick, Vice President of Real-World Evidence Solutions, 

IMS Health 

The press release has since received wide media coverage and 

has featured in more than 30 articles, including reports in the 

Wall Street Journal, The Pink Sheet and Pharma Times online. 

In an interview on February 22 with PharmaExec, Jon Resnick, 

when asked how others could benefit from this partnership, 

confirmed that there will be active efforts to involve payers 

and other providers in “an honest set of conversations" about 

how to work with the information, both during and beyond 

the collaboration. 

“For this to work, you need the buy-in,” says Jon. “You can’t 

create real information in a vacuum; you can’t work with a set 

of databases that are closed to the universe and then hand 

the information to a payer and say you want to charge 20 

percent more.” Whichever data will eventually be made publicly 

available depends on the type of study it relates to, but Jon 

emphasizes that the IMS/AZ research is not just between the 

two companies. “Opening it up to academics and broader 

audiences is healthy if we want to maintain credibility. A 

broader set of participants will be needed to ratify 

the information.” • 

The full text of the press release can be found here: 

www.astrazeneca.com/Media/Pressreleases/Article/ 

20120111--astrazeneca-and-ims-health 

For further information about IMS capabilities, 

please email Jon Resnick at Jresnick@imshealth.com 


NEWS | IMS CORE DIABETES MODEL 

Strong research-focused investment maintains IMS CORE Diabetes Model at the 

forefront of decision support for diabetes. 

New validations enhance credibility of 

IMS CORE Diabetes Model 

Since 2011, IMS HEOR has undertaken extensive 

work on the validation and practical applications 

of its market leading IMS CORE Diabetes Model 

(CDM). Marking a continued commitment to 

ensuring robust, contemporary decision support in 

diabetes, the work has focused on enhancing the 

model's credibility and providing users with insight 

into the range of potential applications for the 

CDM. The results will ensure that evaluations of 

new technologies in diabetes are supported by a 

model that is at the forefront of health economic 

research in this area. 

Research abstracts have been submitted to several 

prestigious international conferences, including the ADA 

Scientific Sessions in Philadelphia and 1st Middle East 

Congress in Dubai; the EASD Meeting in Berlin; ISPOR in 

Washington, Berlin and Taipei; and the 2012 Mount Hood 

challenge in Baltimore – a particularly relevant platform for 

demonstrating the robustness of the CDM across a range of 

challenging validation exercises versus diabetes models from 

other research groups. 

Fully exploiting important new features of the CDM, such as 

modeling patient-level data, this latest IMS research also 

develops diabetes modeling methodology. Some of the key 

studies covering validation, applications, methodologies and 

cost are summarized below: 

MODEL VALIDATION 

• Type 1 and Type 2 long-term diabetes outcomes trials: 

Driven by extensive use of the CDM to estimate long-term 

clinical outcomes in diabetes, the goal of this study was 

to validate the model to trial data over a 20-30 year 

horizon against long-term observations of the DCCT (EDIC) 

and UKPDS, and to compare those to short- or 

intermediate time validations over 5 (Type 1) and 10 (Type 

2) years. In Type 1 diabetes, simulations produced R 2 

values of 0.9 and 0.67 against 5-year and 30-year followup 

studies respectively. In Type 2 diabetes, R2 values of 

0.89 and 0.86 were produced for intensive and 

conventional treatment in both short- and long-term 

observations. The study supports the CDM as a credible 

policy support tool for extrapolating health outcomes in 

DCCT and UKPDS like populations. 1 

• Risk-to-benefit ratio of glucose-lowering therapies in 

high cardiovascular risk Type 2 diabetes: In this study, 

the CDM was populated with characteristics consistent 

with the ACCORD trial to compare predicted 5-year relative 

risks of cardiovascular morbidity and all cause mortality 

to random effects meta-analysis of ACCORD, ADVANCE and 

VADT. Results were extrapolated over a lifetime to derive 

overall expected benefit. The CDM 5-year relative risk 

reductions associated with intensive glucose control in 

high-risk Type 2 diabetes patients were consistent with 

meta-analysis results and fell within the 95% confidence 

intervals. Long-term projections suggest intensive therapy 

contributes to both increased life and quality adjusted life 

expectancy. 2 

PRACTICAL APPLICATIONS OF 

CONTEMPORARY ISSUES 

• Relationship between effect of glycemic control and 

avoided symptomatic hypoglycemia on QoL in Type 2 

diabetes: Achieving optimal glycemic control (GC) while 

avoiding hypoglycemia is the basis of diabetes 

management. Tight GC, while reducing macro and 

microvascular complications also promotes hypoglycemia 

thus representing a barrier to low HbA1c values and 

directly impacting costs and health utility. Using the CDM, 

this equilibrium analysis showed that an HbA1c reduction 

of 0.54% is needed to achieve the same QoL benefit as 

achieved by avoiding one event of non-severe 

symptomatic hypoglycemia (NSHE) per year. The analysis 

is noteworthy in demonstrating the significant 

contribution to QALE by avoiding NSHE; particularly in 

comparison with levels of HbA1c change typically 

associated with current anti-hyperglycemic agents. The 

avoidance of NSHE is at least as powerful a driver of QALE 

as lowering HbA1c. 

continued opposite 


• Significance of HbA1c durability in costeffectiveness 

analysis of second-line oral therapies 

in Type 2 diabetes: Patients with Type 2 diabetes 

generally require dose escalation and/or combination 

therapies to maintain acceptable glycemic control (GC). 

Time to escalation is a function of initial treatment 

effect and durability of GC. Durability can be assumed 

to be a key driver of cost-effectiveness especially when 

rescue therapies are expensive. The influence of 

different durability assumptions was explored in the 

CDM which evaluated scenarios to compare 

sulphonylurea vs DPP-4s as second-line therapies added 

to metformin, followed by insulin rescue therapy. CDM 

projections demonstrated that the annual rate of 

increase in HbA1c exerts considerable influence over 

predicted cost-effectiveness and is therefore an 

important variable in assessing value for money of new 

interventions for Type 2 diabetes. 

METHODOLOGICAL ASPECTS OF 

DIABETES MODELING 

• Correlating cost-effectiveness output with patientlevel 

data input: The CDM was used to ascertain if 

particular patient-level data (PLD) input profiles were 

predictive of cost-effectiveness sub-groups in Type 2 

diabetes subjects treated with second-line oral 

therapies. A series of patient characteristics were 

identified as being associated with greater potential for 

health gain. The study showed that the analysis of PLD, 

alongside simulation model output, provides an 

additional mechanism for informing healthcare 

decision making. 3 

• Reducing Monte Carlo error in stochastic 

simulations: This study sought to quantify the 

minimum run-time requirements for reducing Monte 

Carlo error to acceptable levels in probabilistic 

sensitivity analysis (PSA). Conducted with the CDM, it 

showed how Monte Carlo error can be quantified and 

put into context versus expected parameter uncertainty 

and further demonstrated that the degree of input 

parameter variability has an influence on the run-time 

requirements to reduce Monte Carlo error. 4 

IMS CORE DIABETES MODEL | NEWS 

COST QUANTIFICATION 

• Direct medical costs of diabetes mellitus in China: 

This research used the CDM to estimate annual cost of 

illness for all patients and lifetime diabetes costs for 

diagnosed patients in China. The 2011 cost of diabetes 

was estimated as CNY 13,326 per diagnosed patient and 

CNY 4,727 per undiagnosed patient, with the difference 

attributable to diabetes treatment and management costs. 

Based on a total population approaching 1.4 billion and 

previously reported disease prevalence rates, the national 

cost of diabetes in 2011 was estimated as CNY 1,214 

billion. In diagnosed patients the lifetime cost of diabetes 

was estimated as CNY 301,716 per patient (or CNY 18,253 

billion nationally); diabetes complications comprised 53% 

of the lifetime cost burden. 5 • 

For further information on recent research with the IMS 

CORE Diabetes Model, please email David Grant, Senior 

Principal HEOR, IMS Health at Dgrant@uk.imshealth.com 

The IMS CDM allows comparison and correlation of input profile 

vs. output from patient-level data for each included patient – 

thereby offering the possibility of sub-group analysis. The graph 

below shows, for example, that patients with higher A1c level at 

baseline had a higher chance of being cost-effective vs. patients 

with lower levels. 

1 Validation of the CORE Diabetes Model to type 1 and type 2 long-term diabetes outcomes trials. Accepted as poster presentation at ADA, Philadelphia, June 2012 

2 Validation and evaluation of the risk-to-benefit ratio of glucose lowering therapies in high cardiovascular risk type 2 diabetes patients; Modeled projections 

using the CORE diabetes model. Accepted as oral presentation at ADA, Philadelphia, June 2012 

3 Correlating cost effectiveness output with patient level data input via the IMS Core Diabetes Model (CDM). Accepted at Mount Hood 2012 Challenge, Baltimore. 

4 Minimum run-time requirements to reduce Monte Carlo error in stochastic simulations. Accepted at Mount Hood 2012 Challenge, Baltimore 

5 Direct medical costs of diabetes mellitus in China: Annual cost of illness and long-term projections using a validated diabetes model. Accepted at ISPOR 

5th Asia Pacific Conference, Taipei, Sept 2012 


INSIGHTS | REAL-WORLD EVIDENCE 

The increasing demand for real-world evidence by a 

growing body of decision makers is creating a need for 

new capabilities, data considerations, and 

effective planning for RWE generation across the entire 

product lifecycle. 

The authors 

Jon Resnick, MBA 

is Vice President Real-World Evidence Solutions, IMS Health 

Jresnick@uk.imshealth.com 

Jacco Keja, PHD 

is Regional Principal HEOR, IMS Health 

Jkeja@nl.imshealth.com 


A global plan for success 

REAL-WORLD EVIDENCE | INSIGHTS 

Preparing for a lifecycle of 

real-world evidence 

The concept of real-world evidence (RWE) is not a new one: researchers have been 

generating RWE to support product use among physicians and payers for nearly 20 years. 

However, recent growth in the demand for RWE to inform market access decisions has 

shifted the timeframe over which value is determined far into the post-launch lifecycle 

with significant implications for manufacturers. 

Traditionally, much of the work already completed for market access at the time of launch was 

based on evidence from randomized clinical trials (RCTs). While these remain the gold 

standard for demonstrating product safety and efficacy, the inherent limitations of their data – 

small sample size, controlled environment and focus on short-term outcomes – meant 

negotiations were primarily focused on qualitative documentation of value. Quantification was 

mainly extrapolated using health economic modeling. 

Increased payer interest in RWE reflects a shift toward more quantitative measurements of 

value and acceptance of data sources and endpoints that are not explicitly derived from RCTs. 

This comes with growing acknowledgment that while RWE may have limitations in data 

quality relative to RCTs, its findings are more relevant to the payer perspective. Regulators, 

too, recognize the value of RWE on safety, relative to that offered by RCTs. 

Other trends are also broadening the use of RWE. In recent years, payers have been 

experimenting with approaches that shift the risk to manufacturers, such as value-based 

contracting and conditional reimbursement or access, as well as to other stakeholders through 

pay-for-performance and consumer-directed plans. Disease management pilots with riskshifting 

consequences are also underway in several European countries. These developments 

converge with another important trend - the deferral of risk to healthcare practitioners, who 

need to understand in detail the right patient for a product and the way in which treatment 

algorithms can be optimized in the real world. If these models form the basis of future practice 

in healthcare delivery, RWE perspectives and endpoints will need to start resonating with the 

broader range of stakeholders, including providers and patients, who have been delegated more 

decision-making power. 

The future for RWE is one of certain challenge for all key stakeholders as scientific advancements 

and external dynamics place increasing demands on decision making. However, it is also one of 

tremendous potential for the expanded role of RWE. 



EVOLVING PATTERNS OF USE 

Currently, there is no global or regional model for the practical application of RWE: requests 

vary in the intended use of findings, the timing during the product lifecycle when 

manufacturers are expected to product RWE, and the endpoints or analyses that are prioritized 

when making RWE-supported decisions. In key markets, these mainly concern the permitted 

use of a product, although in some cases, market access or pricing is becoming conditional on 

the results of RWE studies (Figure 1). There is also localized interest in using RWE for labeling 

modifications, further entrenching product positioning based on post-launch evaluations. Over 

time, both the number of countries requiring RWE and the scope of its application will 

continue to expand, further increasing the heterogeneity of the market access landscape. 

FIGURE 1: EXAMPLES OF NATIONAL VARIATION IN THE APPLICATION OF RWE 

Application 

Country Context Label Price Market 

access 

Use 

Germany AMNOG ruling specifies that prices are to be 

re-asssessed post-launch 

France Drug utilization studies specified as a condition 

of market access, pharmacovigilance 

Sweden Observational data used in post-launch 

decision making 

Spain Phase IV studies potentially influencing regional 

payer decisions 

UK Value-based pricing will potentially re-assess 

price post-launch 

US Private payer attention to Patient-Centered 

Outcomes Research Institute, private comparative 

effectiveness research, Food and Drug 

Administration Modernization Act Section 114 

DEVELOPING A LIFECYCLE RWE PLAN 

No application Limited application Application 

The complexity of logistics involved in fulfilling each country's RWE requirements calls for a 

heterogeneous approach, and fundamentally, early planning, to ensure the quality of responses, 

rational RWE spend throughout the lifecycle, and pro-activity to differentiation and 

positioning. This will be dependent on: 

1. Careful and routinely updated analysis of current and future comparators, drilling down to 

actual/perceived differentiation on specific claims, to enable tactical planning of individual 

studies to address those differentiation claims. 

2. A long-term view of supporting a product's claims with analyses of specific data sources, 

based on early inventory/vetting of databases that could support RWE studies of individual 

claims, and specific plans to address gaps by creating data sources where they are unavailable. 



3. A tactical evidence-generation plan enabling prioritization of data acquisition and 

analyses, both to anticipate external demands and to maximize the execution of a 

differentiation strategy. 

Ideally, the lifecycle plan should be initiated no later than Phase II; some subsequent data 

development activities may require a head start several years before launch. It may be 

appropriate to start these plans at therapy area or indication level when pipelines include 

multiple similar candidates, to mitigate the risks of early investment in RWE planning. 

1. Comparators 

• Pre-launch: RWE should focus here on documenting the real-world performance of 

existing comparators and the standard of care, particularly relative to the claims/endpoints 

that are central to the Target Product Profile (TPP). Patient segmentation and market sizing 

should also be completed pre-launch. 

• Post-launch: RWE emphasis after launch should shift towards not only replicating RCT 

efficacy and safety findings in real-world settings, but also seeking explicit head-to-head 

differentiation from comparators in the real world. In addition to safety and efficacy claims, 

this should consider product usage characteristics, such as dose adjustments, adherence, 

appropriate use, and cost-consequences of treatment, which can influence its costeffectiveness 

or value equation. 

• Established products: A range of RWE studies can be valuable for established products 

facing new market entrants or the generic conversion of comparators. By this stage in its 

lifecycle, the large body of RWE evidence supporting a product’s safety, effectiveness and 

use can be viewed as a competitive advantage – while competitive intelligence on the 

expected profile of new entrants can inspire RWE studies that cement differentiation claims 

before they can launch. RWE can also enhance generic defense strategies, highlighting the 

magnitude of a product's differentiation to prevent discussions coming down to price 

reductions alone. 

2. Supporting claims 

Manufacturers are familiar with developing new evidence during R&D to secure approval of 

particular endpoints, such as patient-reported outcomes (PROs), as part of their 

labeling/promotional claims. However, this investment rarely extends to planning for these 

endpoints in RWE and manufacturers may be caught out by the fact that they are not easily 

accessible in commercialized datasets. 

A good example is patient adherence to medication which continues to present a major 

problem for treatment effectiveness. In the US, poor medication adherence is reported to be 

responsible for between 33 and 69 percent of all medication-related hospital admissions, 

resulting in a cost of approximately $100 billion a year. 1 The difficulty in understanding poor 

adherence is that many of its predictors are patient-related factors, such as cognition, 

motivation, and relationships with doctors – all issues which claims data cannot enlighten. 

Classic retrospective approaches also have many confounders and sources of bias to overcome, 

including frequent under-reporting of diagnoses as well errors in diagnosis. The rate of 

inconsistencies is particularly high in pain, psychiatric and behavioral disorders. Primary care 

providers have been found to detect major depressive disorder in only one-third to half of 

patients with this condition. 2 

continued on next page 



Additionally, the scope of the data is often very limited. With the primary focus on health 

insurance claims, pharmacy records, hospital discharge data, GP electronic patient records, etc, 

many aspects are simply not documented. Consequently, while prescription data, hospital data, 

diagnostic codes, tests and procedures are often captured, the elements that provide deep 

insight into patient status and motivation, such as quality of life, severity of symptoms, and 

treatment satisfaction, are not. 

Given the increasing evaluation of these endpoints by payers for post-launch price and market 

access reviews, it is critical to plan for data development to maximize timely access to RWE 

for TTP claims. 

Broader perspectives 

By giving consideration to the stakeholders who may use RWE, manufacturers can expand 

their thinking about data sources and endpoints that will be available and relevant for RWEsupported 

claims. 

• Payers: As payers have embraced RWE, their mindset has been shaped by the availability of 

their own billing and reimbursement claims data. This has allowed them to consider effects 

over longer time horizons, and costs from more sites of care and more diverse populations, 

than have typically been available in RCTs. Today, a growing number of patient-level health 

data initiatives, particularly in the US, are being built around claims data assets for outcomes 

research. However, payer data sources typically exclude key information on patient health 

status that drives medical decision making meaning that an even broader range of 

perspectives is required. 

• Providers and patients: As the importance of providers and patients grows in considering 

RWE, value determinations will be based more on the perspectives of disease management 

than market access. The alternatives considered by physicians will be driven by the types of 

health status information they typically record in their charts, practice management systems, 

and electronic records. RWE findings must be responsive to this and stratify patient 

populations appropriately. Patient choice is dominated by very practical considerations of 

ease of use and perceptions of anticipated benefits: RWE will be more likely to persuade 

them if it clarifies the behavioral costs and consequences of particular treatments. 

Approaches that go beyond claims data are thus important to consider. Potential ways forward 

include patient charts, dedicated registries and observational methodologies. A high degree of 

sophistication will be essential to ensure the right level of granularity, as will the ability to 

couple different data sources to accommodate the sheer size of data assets required to reach a 

better understanding of patients and patient segmentation. This is a skill set that requires 

significant development, implying investment in enabling technologies and in turn, 

partnerships, transparency and trust. 


3.Tactical planning 

VALUE OF COLLABORATION 

BENEFITS OF RWE PLANNING 


The final step in the planning process is to outline the specific tactical studies and activities 

required to execute an effective RWE strategy. This involves integrating the list of internal 

desires and external demands for RWE insights, mapping out the geographies where requests 

are relevant, and sequencing them for efficient budget and staffing allocation. 

Companies may judge that certain claims do not require support in specific countries, based 

on an assessment of the RWE environment. It is better to actively decide against RWE tactics 

in certain regions based on the perceived gains than be forced into inaction because it is too 

late to identify appropriate data sources or execute quality analyses. 

Developing an inventory of RWE activities further enables companies to optimize spending 

when new data sources are required to support specific RWE claims, as well as facilitate 

communication between global headquarters and affiliates. It can further become a platform 

for headquarters to communicate product strategy early to affiliates, who can in turn validate 

assumptions regarding the fulfillment of local demands for RWE to the satisfaction of local 

HTA bodies. 

To effectively execute an RWE plan, companies will need to consider and collaborate with 

internal and external stakeholders who are not always part of the standard operating model for 

market access teams, including R&D. Much of the investment in R&D goes beyond just 

demonstrating an outcome; they are also required to understand the drivers of outcomes and 

the mechanisms that make treatments work. These perspectives will be invaluable as lifecycle 

plans incorporate endpoints on product use factors such as dosing and adherence. R&D 

perspectives are also more closely aligned with those of the providers who may ultimately 

consider RWE findings as they take on added risk for patient care. 

The future for RWE is one of certain challenge for all key stakeholders as scientific 

advancements and external dynamics place increasing demands on decision making. However, 

it is also one of tremendous potential for the expanded role of RWE. For manufacturers, the 

adoption of a global, coordinated, lifecycle plan for RWE needs will bring four key benefits: 

1. Enable efficiency gains to be realized by anticipating environmental and competitive 

developments and investing in timely analyses with minimal duplication of effort 

2. Ensure that the existing patchwork of data sources is effectively utilized to provide 

information for addressing internal and external needs 

3. Increase the chance that staff and budgets will be available to produce high quality responses 

4. Allow companies to effectively transition from passive or reactive players in evidence-based 

access to successful competitors and industry leaders 

Overall, these gains will translate into greater returns in markets with RWE opportunities and 

more rational investment to achieve those gains. RWE will be useful for all parties: for physicians 

to optimize care by finding exactly the right patient; for regulators to continuously monitor 

benefit/risk; for decision makers to devise policy on usage (including HTA agencies that assess 

cost-effectiveness); and for business-to-business negotiations between industry and payers. • 

1 Osterberg, L, Blaschke, T N. Adherence to medication. N Engl J Med, 2005; 353:487–497 

2 Institute for Clinical Systems Improvement. Major Depression in Adults in Primary Care, May 2011. http://www.icsi.org 


INSIGHTS | PATIENT-REPORTED OUTCOMES 

Patient-reported outcomes (PROs) are an increasingly 

relevant decision-making tool for a growing audience of 

stakeholders, capturing first-hand the disease and 

treatment experience from a real-world, patient perspective. 

But alongside their growing significance are increasing 

expectations of their design and validity – meriting careful 

review of the attributes that must be considered. 

The authors 

Núria Lara Surinach, MD, MSC 

is Principal HEOR, IMS Health 

Nlara@es.imshealth.com 

Xavier Badia, MD, PHD, MPH 

is Senior Principal HEOR, IMS Health 

Xbadia@es.imshealth.com 

Núria Perulero, BSC 

is Director HEOR, IMS Health 

Nperulero@es.imshealth.com 


PATIENT-REPORTED OUTCOMES | INSIGHTS 

Getting the measure of PROs 

A review of key considerations 

The importance of understanding a patient’s perception of their disease and the impact 

of treatment has become increasingly recognized in recent years. Today, a patient 

perspective, captured in patient-reported outcomes (PROs), is a key consideration in 

everyday practice as well as in clinical development (Figure 1). 

FIGURE 1: PROs ARE A MAJOR FOCUS FOR ALL KEY HEALTHCARE STAKEHOLDERS 

PRO GUIDELINES 

Sponsor 

• Ensure product provides 

benefits from a patient 

as well as clinical 

perspective 

Decision makers 

• Provide important 

information for product 

approval, pricing and 

reimbursement 

PROs 

Prescribers 

• Support optimal 

treatment decisions 

based on patient 

perception 

Patients 

• Enable greater patient 

involvement in clinical 

and therapeutic 

management 

The increasing use of PROs to support manufacturer claims for medical products has given rise 

to the publication of specific guidance by the US Food and Drug Administration (FDA) and 

the European Medicines Agency (EMA) on the development and application of these measures. 

The FDA, in guidelines on the use of PROs in labeling claims issued in 2009, defines a PRO 

as “any report of the status of a patient’s health condition that comes directly from the patient, without 

interpretation of the patient’s response by a clinician or anyone else. (…) In clinical trials, a PRO 

instrument can be used to measure the effect of a medical intervention on one or more concepts (…)”. 1 

According to the EMA, in a reflection paper on regulatory guidance for the use of healthrelated 

quality of life (HRQoL) measures in evaluating medicinal products, “any outcome 

evaluated directly by the patient himself and based on patient’s perception of a disease and its treatment(s) 

is called patient-reported outcome (PRO)”. 2 

The overarching term of “PROs” embraces all elements of patient-reported data, including 

treatment preference, satisfaction, and adherence as well as burden of symptoms and HRQoL 

(Figure 2 overleaf). 

Although recommendations for PRO development are not mandatory, the bar is now set very 

high, particularly for outcomes that are complex and multi-domain, such as HRQoL. Broad 

claims invariably give rise to concern at the FDA. Simple, single items and single-domain 

instruments require less documentation, assuming adequate validation. Careful examination and 

analysis of PRO instruments can provide useful insights for improving the chances of success. 


ACCESSPOINT - ISSUE 4 PAGE 17


FIGURE 2: PROs COVER ALL PATIENT-REPORTED HEALTH DATA 

Preference 

to treatment 

Treatment or 

health service 

satisfaction 

KEY CONSIDERATIONS 

According to the FDA guidance, the use of a PRO instrument to support claims in medical 

product labeling includes consideration of: 

• Population enrolled in the clinical trial 

• Clinical trial objectives and design 

The attributes of PRO instruments reviewed by the FDA include: 

• Concepts being measured 

• Number of items 

• Conceptual framework of the instrument 

• Medical condition for intended use 

• Population for intended use 

• Data collection method of administration 

• Response options 

Adherence 

to treatment 

Burden of 

symptoms 

HRQoL 

• PRO instrument’s conceptual framework 

• PRO instrument’s measurement properties 

• Recall period 

• Scoring 

• Weighting of items or domains 

• Format 

• Respondent burden 

• Translation or cultural adaptation availability 

PSYCHOMETRIC PROPERTIES 

The principal measurement properties for PROs are validity, reliability and ability to 

detect change. 

1. Validity: The relevance of a PRO is evaluated in terms of both its content and 

construct validity. 

• Content validity: Requires evidence that the instrument in question measures the 

concept of interest. This includes evidence from qualitative studies that the items and 

domains of an instrument are appropriate and comprehensive relative to its intended 

measurement concept, population and use. Testing other measurement properties will not 

replace or rectify problems with content validity. 

• Construct validity: Requires evidence that relationships among items, domains and 

concepts conform to an a priori hypothesis concerning logical relationships that should 

exist with measures of related concepts or scores produced in similar or diverse patient 

groups. 


PATIENT-REPORTED OUTCOMES | INSIGHTS 

2. Reliability: The reliability of a PRO is assessed on several levels. 

• Test/re-test or intra-interviewer reliability: Stability of scores over time when no 

change is expected in the concept of interest 

• Internal consistency as determined by: 

• Extent to which items comprising a scale measure the same concept 

• Inter-correlation of items that contribute to a score 

• Internal consistency 

• Inter-interviewer reliability (for interviewer-administered PROs only): Agreement 

among responses when the PRO is administered by two or more different interviewers 

3. Ability to detect change: This requires evidence that a PRO instrument can identify 

differences in scores over time in individuals or groups (similar to those in the clinical trials) 

who have changed with respect to the measurement concept. 

VALIDATION PROCESS 

The validation process follows the structure shown in Figure 3. This involves evaluating the 

ability of the PRO to detect change (Group A), ensuring sufficient time between visits to 

allow for a treatment effect; assessing test/re-test reliability (Group B), with time between visits 

appropriate to ensure patient stability; and thirdly, determining construct validity in the general 

population as a control (Group C). 

FIGURE 3: PRO VALIDATION PROCESS 

Group A: To evaluate ability 

to detect change 

Patients diagnosed who need clinical 

and/or therapeutic intervention 

Visit 1 Visit 1 Visit 1 

Visit 2 

Time between visits must be 

sufficient to allow for treatment 

effect 

Group B: To evaluate 

test/re-test reliability 

Patients diagnosed who are stable 

according to clinical criteria 

Visit 2 

Time between visits must be 

sufficient to ensure patient 

stability 

Group C (control): To evaluate 

construct validity 

General population 

Once the appropriate questionnaire has been chosen, the frequency of assessments needs to be 

defined. This should correspond with the length of recall asked by the instrument’s response 

options, the natural history of the disease condition, the nature of treatment, the measurement 

properties and the specific research questions being addressed. Some diseases, conditions, or 

clinical trial designs may necessitate more than one baseline assessment and several PRO 

assessments during treatment. 

DEMONSTRATING QoL BENEFITS WITH A PRO QUESTIONNAIRE 

IMS HEOR has many years experience in developing and validating disease-specific 

questionnaires incorporating relevant patient-reported outcomes - an example 

is presented overleaf... 




Case in practice: Demonstrating QoL benefits with a PRO questionnaire 

One recent case study involved a large international pharmaceutical company that wished to explore 

the impact of a particular disease on quality of life (QoL) and show that as well as being more 

effective, their new product also significantly improved QoL relative to its competitors. The 

involvement of key opinion leaders and a high number of physicians would be key to providing new 

arguments for increasing market access and demonstrating superior outcomes. These would be supported 

by a strong value communication plan to disseminate the results in national and international 

journals and congress communications and to underscore the company’s core scientific orientation. 

PRO questionnaire: IMS proposed the development and validation of a specific QoL questionnaire 

for patients with the disease in question. The two-stage process involved first the design of the 

questionnaire, leveraging input from an expert focus group, in-depth patient interviews, a consensus 

group of experts and a patient pilot to assess the questionnaire’s measurement properties; and 

secondly, comprehensive validation using an observational, naturalistic and prospective study with a 

sample of more than 200 patients (Figure 4). 

FIGURE 4: TWO-STAGE PROCESS TO STUDY DESIGN 

Phase 1: Questionnaire development 

Phase 2: Questionnaire validation 

(observational, naturalistic and prospective 

study with sample of more than 200 patients) 

Baseline visit 

Visit 1: certain period of time after baseline visit 

Visit 2: certain period of time after baseline visit 

Focus group with experts 

Interviews with patients 

Consensus group of experts 

Pilot study with patients 

Objective: to assess QoL before and after 

therapeutic intervention 

Relevant, reliable tool: The resulting questionnaire was short and its scoring system easy to 

administer in routine clinical practice. The questionnaire was shown to be a relevant tool under realworld 

conditions in terms of reliability, validity and sensitivity to change. In addition to QoL, other 

patient-based variables, such as treatment satisfaction and therapeutic compliance, were assessed 

with very positive results for the company’s product. 

Robust scientific validation of benefits: With patient-reported evidence demonstrating the disease 

impact on QoL, the company was able to position the product accordingly and communicate its benefits on 

the basis of proven clinical effectiveness and improved QoL. The involvement of multiple disease specialists 

significantly strengthened messaging to the scientific community. • 

1 Guidance for industry. Patient-reported outcome measures: Use in medical product development to support labeling claims. Accessed May 11, 2012 at: 

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM193282 

2 Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medicinal products. 

Accessed May 11, 2012 at: http://www.emea.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003637.pdf 


DRUG EXPOSURE MEASUREMENT | INSIGHTS 

Standardizing the measurement 

of drug exposure 

The ability to determine drug exposure in real-world clinical 

practice enables important insights for the optimal use of 

medicines and healthcare resources. With significant 

potential for treatment complexities to confound the 

measurement process, finding valid approaches to 

standardization can be key to meaningful results. 

Here we consider a recent case study in asthma. 

The author 

Christopher Blanchette, PHD, MS, MA 


Cblanchette@us.imshealth.com 


INSIGHTS | DRUG EXPOSURE MEASUREMENT 

Standardizing the measurement 

of drug exposure 

A case study in asthma 

The measurement of drug treatment exposure can be complex, based on the underlying 

assumptions that drive the product’s use. These are most easily encountered with the 

classic 30-day prescription fills of oral medications. However, in cases where medications 

are prescribed as needed, where various routes of administration apply, or where dosing 

is inconsistent across diverse generics manufacturers, the accurate measurement of drug 

exposure becomes significantly more involved. 

STUDY DESIGN 

CAPTURING DATA 

All three of these issues were encountered in a series of studies assessing short-acting beta 

agonists (SABA) exposure as a predictor of subsequent asthma-related exacerbations, most 

notably dealing with as-needed prescribing of SABA in either a metered dose inhaler (MDI) 

or in a nebulized inhalant form. 1,2,3,4,5 

This retrospective analysis included both prevalent and incident asthmatics, to assess patients 

with various levels of severity during the available observation period (Figure 1). For all 

analyses, evaluations were performed for three groups: all subjects (ages 6-56 years), pediatrics 

(ages 6-17 years) and adults (ages 18-56 years). 

Data were obtained on subjects enrolled in a health plan that participated in the PharMetrics 

Patient-Centric Database between July 1, 2003 and June 30, 2007. The database comprises 

information from enrollment files as well as facility, professional service and out-patient 

pharmacy claims, from a variety of private healthcare benefit plans. Its coverage extends to 

more than 40 million patients enrolled in over 70 health plans across the US, with health plans 

providing data on a continuous basis. The number of plans contributing to the PharMetrics 

FIGURE 1: RETROSPECTIVE STUDY DESIGN 

Baseline and medical 

characteristics assessed 

Q1 SABA use 

Q2 

exacerbation 

risk 

Q2 SABA use 

1 year pre-index period Index 

date 

1 year post-index period 

Q3 

exacerbation 

risk Q4 

Q3 SABA use exacerbation 

risk 

Q1 Q2 Q3 Q4 



dataset has increased over time. Demographic information (excluding race and ethnicity) is 

available for all patients. Most plans also provide information on dates of eligibility for medical 

and out-patient pharmacy benefits. 

Data available for each out-patient pharmacy claim (“prescription”) included the drug 

dispensed (in National Drug Code [NDC] format) and the dispensing date. Most plans also 

provided information on the quantity and number of therapy days dispensed. Data available for 

each facility or professional service claim (“medical claim”) include dates of service and 

International Classification of Diseases 9th Edition, Clinical Modification (ICD-9-CM) 

diagnosis codes and ICD-9-CM procedure codes (facility claims) or Current Procedural 

Terminology, Version 4 (CPT-4) procedure codes (professional service claims). All plans 

provided information on payments. Most plans also provided information on billed charges. 

Payments were imputed for claims with missing payment information (due to capitation 

arrangements). All claims for any given person could be linked using a unique encrypted identifier. 

The dataset is fully de-identified and HIPAA compliant. 

The criteria applied for the study population were as follows: 

Inclusion 

• Patients aged 6–56 years on the index date 

• Continuous enrollment in a health plan in the database for 2 years 

• Claim with asthma diagnosis (ICD-9 code 493.XX) 

• Claim for either a SABA or any asthma controller medication in each of the pre-index and 

post-index periods 

Exclusion 

• Any diagnosis of COPD, emphysema, chronic bronchitis, or bronchiectasis 

• Subjects with diagnoses requiring frequent oral corticosteroid (OCS) use 

• Subjects with a diagnosis of respiratory tract cancer 

DRUG EXPOSURE EVALUATION APPROACH 

Since pharmacy use can only be identified in the PharMetrics dataset using National Drug 

Codes (NDC), the first step was to compile an exhaustive list of NDCs for each drug of 

interest. The starting point for this was to link the list of identified brand and proprietary drug 

names to the in-house, composite drug dictionary. 

SABA dosing exposure standardization was determined through prior studies. These included 

the 2002 evaluation by Glauber and Fuhlbrigge which provided a compelling argument for 

using a canister-equivalent measure, comprised by inhaled and nebulized SABA, instead of just 

simple counts of medication. 6 

They introduced a scheme for standardizing doses of inhaled and nebulized SABA equivalent 

to two inhalations of albuterol, dispensed from a metered dose inhaler (MDI) as the standard 

for comparison. 

Using a high threshold level of >8 SABA canisters (counts method) or >8 canister-equivalents, 

the canister-equivalent method increased the population identified as having high SABA use 

by 39% (16.6% vs. 11.9%) relative to the simple-count method. 



INSIGHTS | DRUG EXPOSURE MEASUREMENT 

Hospitalization 

ED/UC Visit 

OCS claim 

Any of the above 

Thus, in studies that do not recognize the use of nebulized SABA there is likely to be 

substantial misclassification of patient risk based on high SABA utilization. 

The present study utilized the method described by Chan, et al, 7 being inclusive of almost all 

MDI and nebulized SABA types identified in the dataset. Canister equivalents were 

determined for each claim represented. A standard SABA canister size was defined to be one 

containing 200 metered actuations, which encompassed more than 97% of MDI SABA claims. 

More than 96% of total SABA MDI claims were for albuterol; 2.2% were for pirbuterol; and 

1.6% were for levalbuterol. In the case of pirbuterol, whose standard dispensing contains 400 

actuations, claims were set to two canisters. Levalbuterol was considered to be equivalent in 

potency to albuterol. In cases where insufficient information was available to make the 

determination, canister size was imputed using days supply of medication. Thirty days supply or 

less was determined to be equivalent to one canister, 31 to 60 days supply as two canisters, etc. 

FIGURE 2: SABA CANISTER FILLS 2ND QUARTER (POST-INDEX YEAR) 

N=93,444 

0 Canisters 

1 ⁄2-3 Canisters 

> 3 Canisters 

0 5 10 15 20 

0 Canisters (n=59,653) Percentage of Patients 

1 ⁄2-3 Canisters (n= 26,525) 

> 3 Canisters (n= 4,266) 

32% 

5% 

64% 

FIGURE 3: Q3 EXACERBATION INCIDENCE BY Q2 SABA USE STRATA 

ED = Emergency department 

UC = Urgent care 

OCS = Oral corticosteroid 

Nebulized SABA canister claims comprised 

12% of all SABA claims. Based on the Chan 

study method, canister-equivalents were 

derived for each nebulized SABA claim. 

The vast majority of these claims were for 

albuterol or levalbuterol (considered 

equivalent in potency to albuterol), in which 

case one 3ml ampule was equivalent to 0.02 

canister-equivalents, making fifty ampules of 

3ml of medication equivalent to one canister. 

The quantity of medicine is typically given in 

ml in the dataset. Each ampule typically 

contains 3ml of medicine and is most often 

dispensed in boxes of 24, 25 or 30, each of 

which was equated to a half canister of SABA. 

It was determined that the most accurate 

method to represent these medication 

quantities was to round to the nearest halfcanister 

because most boxes contained 24, 25 

or 30 ampules and most claims were in 

multiples of these. Less than 1% of claims 

observed were clear outliers (eg, >180 

ampules). For these, the maximum dose was 

capped at three canister equivalents per claim. 

Due to the heterogeneity of asthma 

controller medications, it was elected to use 

annual days supply during the pre-index and 

post-index years, and days supply per quarter 

for the quarterly analysis regardless of the 

medication being inhaled (eg, ICS) or oral 

(eg, leukotriene modifiers). Controller 

medications prescribed concomitantly and 

measured as covariates were assessed as the 

sum of days supply provided on the claims, 

a proxy for days of exposure. A similar 

method was used to describe use of nasal 

steroid sprays and antibiotics. 


CONCLUSIONS 


FIGURE 4: RISK OF EXACERBATIONS BY Q2 SABA STRATA (REFERENCE=0 CANISTERS) 

Hospitalization 

1/2 -3 

>3 

ED/UC Visit 

1/2 -3 

>3 

OCS claim 

1/2 -3 

>3 

Any of the above 

1/2 -3 

>3 

1 2 3 

ED = Emergency department 

UC = Urgent care 

OCS = Oral corticosteroid 

4 

Odds Ratio (95% CI) 

5 6 

All oral corticosteroid (OCS) claims, regardless of days supplied, were counted as one claim. 

Ninety percent of prescription dispensing for OCS was found to be for 21 days or less. In the 

analysis, OCS were evaluated as a binary variable for the presence of one or more claims, and 

as a count of claims during the specified time period. Injectable corticosteroids were not 

captured, since these are typically administered in a physician’s office and are rarely registered 

as NDC-based claims. 

The study found that a quarterly assessment of SABA utilization can be used to identify 

patients at risk for asthma-related exacerbations. The incidence of an asthma exacerbation was 

associated with greater SABA use in the previous quarter (Figures 2,3,4).Variability in SABA 

exposure measurement and standardization between nebulized and MDI routes may have 

provided biased estimates on associated cost and asthma-related exacerbations. 

Notwithstanding this caveat, however, these findings provided critical insights for optimizing 

the treatment and management of asthma patients. • 

1 Blanchette CM, Silver H, Petersen H, Kamble S, Meddis D, Gutierrez B. Quarterly assessment of short-acting ß-agonist use as a predictor of subsequent 

healthcare services use for asthmatics in the US. ISPOR 14th Annual International Meeting, Orlando, FL; May 16-20, 2009. 

2 Blanchette CM, Silver H, Petersen H, Kamble S, Meddis D, Gutierrez B. Identification of a threshold for high utilization of short-acting ß2-agonists in a 

commercially insured adult asthmatic population in the United States. American Academy for Asthma, Allergy, and Immunology 2009 Annual Meeting, 

Washington, DC; March 13-17, 2009. 

3 Silver H, Blanchette CM, Petersen H, Kamble S, Meddis D, Gutierrez B. Short-acting beta agonist utilization and risk of asthma exacerbation among a 

commercially insured pediatric population in the United States. American Academy for Asthma, Allergy, and Immunology 2009 Annual Meeting; 

Washington, DC; March 13-17, 2009. 

4 Silver HS, Blanchette CM, Kamble S, Petersen H, Letter M, Meddis D, Gutierrez B. Relationship between short-acting ß2-adrenergic agonist use and 

healthcare costs. American Journal of Managed Care. 2011 Jan; 17(1):19-27. 

5 Silver HS, Blanchette CM, Kamble S, Petersen H, Letter M, Meddis D, Gutierrez B. Quarterly assessment of short-acting ß2-adrenergic agonist use as a 

predictor of subsequent health care use for asthmatic patients in the United States. Journal of Asthma. 2010 Aug; 47(6):660-6. 

6 Glauber JH, Fuhlbrigge AL. Stratifying asthma populations by medication use: How you count counts. Ann Allergy Asthma Immunol. 2002; 88:451-456. 

7 Chan J, Hui RL, Spence MM. Effects on resource utilization of adding salmeterol in combination or separately to inhaled corticosteroids. J Manag Care 

Pharm. Jan-Feb 2007; 13(1):21-27. 


INSIGHTS | INDIRECT TREATMENT COMPARISONS 

Direct evidence from randomized trials remains the ultimate 

gauge of relative value when comparing competing technologies. 

In its absence, the need for indirect methods is becoming 

increasingly accepted. Here, we consider the growing role of 

network meta-analysis and its evolving capabilities as a key 

enabler of indirect treatment comparisons. 

The authors 

Mark Lamotte, MD 


Mlamotte@be.imshealth.com 

Karen Moeremans, MD 


Kmoeremans@be.imshealth.com 

Tiago Fonseca, MSC 

is Consultant HEOR, IMS Health 

Tfonseca@uk.imshealth.com 

Stijn Vandekerckhove, MSC 

is Analyst HEOR, IMS Health 

Svandekerckhove@be.imshealth.com 


INDIRECT TREATMENT COMPARISONS | INSIGHTS 


with indirect treatment comparisons 

Growing potential of network meta-analysis 

Direct, head-to-head comparisons via robustly designed randomized controlled clinical 

trials (RCTs) are still considered the gold standard for assessing the relative efficacy and 

safety of competing treatments. Where there are multiple trials of two interventions, 

pair-wise meta-analyses may be performed to obtain a pooled estimate and respective 

confidence interval for the relative efficacy of the target treatments, taking account of 

all available direct evidence. However, direct evidence is often lacking. 

Several factors can contribute to critical gaps in the necessary head-to-head RCT evidence base: 

• RCTs supporting drug licensing approval only, often compare the new intervention with 

placebo; industry perceptions of excessive risk negate the commercial incentive to compare 

with an active control. 

• Even if an active comparator is included in the RCT, it may not be relevant in all settings 

• As new evidence continues to be generated, available treatments change/increase over time. 

This is particularly true for hematologic diseases and oncology. A recent IMS research 

project identified 115 Phase III trials, including more than 80 alternative therapy regimens, 

for the management of advanced non-small cell lung cancer over the last decade alone. 

Thus, for some indications, it is unfeasible to incorporate all the competing interventions in 

a single clinical trial. Furthermore, the most relevant comparator at the time of assessment 

may well differ from the standard at the time of trial design. 

These shortfalls in direct evidence impose challenges for the assessment of treatment pathways, 

leaving clinicians, patients, and health policy makers with an incomplete picture in 

determining which treatments are the most effective (and cost-effective). 

TAKING THE INDIRECT ROUTE 

In cases where direct evidence is insufficient or non-existent, indirect comparisons and mixed 

treatment comparisons, also known as network meta-analyses (NMAs), can provide the 

opportunity to compare what may not otherwise have been compared. NMAs represent 

extensions of the pair-wise meta-analysis1 : rather than pooling information on trials 

comparing treatments A and B, as in pair-wise meta-analysis, NMA combines data from 

different randomized comparisons: A vs B; A vs C; A vs D; and so on (Figure 1 overleaf). 

Additional advantages of NMAs include the increase in sample size derived from the 

combination of studies, and the systematic and quantitative nature of the synthesis, enabling a 

full assessment of uncertainty about the relative results. Furthermore, NMAs allow 

quantification of relative treatment effects (eg, odds ratio, relative risk, or difference in change 

from baseline) of different therapeutic classes (eg, Glucagon-like peptide-1 (GLP-1) receptor 

agonists and insulins), different drugs within the same class (eg, exenatide and liraglutide), and 

different doses of the same drug (eg, exenatide BID or QW vs liraglutide 1.2mg or 1.8mg). 




FIGURE 1: META-ANALYSIS AND NETWORK META-ANALYSIS 

A B A A 

Direct comparison 

Direct evidence 

TRIAL SELECTION KEY TO QUALITY 

To ensure that all relevant trials are considered for inclusion, ideally the potentially eligible 

studies should be identified via a systematic review. 

In order to obtain an internally consistent set of estimates, while respecting the randomization 

in the evidence, the underlying assumption is that the trials included are sufficiently 

homogeneous to be quantitatively combined, via a common comparator. This assumption 

requires not only similarity of trial populations (in- and exclusion criteria, patient 

characteristics, etc) but also methodological similarity (eg, trial quality, definition of outcomes, 

randomization method, etc). An example of consistency is that the treatment effect estimated 

by the BC trials would be the same as the treatment effect estimated by the AC and AB trials if 

they had included B and C arms. 

Trial quality should be sufficient for consideration. It is important to bear in mind that a set of 

badly conducted studies does not lead to a good analysis; hence, the importance of defining a 

coherent set of inclusion and exclusion criteria at an initial stage – usually when systematically 

reviewing the literature. 


B 

C C 

Indirect comparison Mixed treatment comparison 

Meta-analysis Network meta-analysis 

D 

Indirect evidence 

NMAs enable the evaluation of competing treatment options that may not otherwise have been 

directly compared. Although the level of evidence they generate may be perceived to be inferior to 

that of gold standard RCTs, they nevertheless have important strengths. 

B


FIGURE 2: EMBASE SEARCH RESULTS REVEAL MARKED RISE IN NMA, INDIRECT OR MIXED TREATMENT COMPARISONS 

Number 

of hits 

700 

600 

500 

400 

300 

200 

100 

Hits 

INCREASINGLY ACCEPTED ALTERNATIVE 

0 1992-1997 1997-2002 

2002-2007 2007-2012 

(week 15) 

Today, the use of NMA methods is becoming more widespread and, possibly as a consequence, 

more widely accepted in informing healthcare stakeholders. An ad hoc search in EMBASE, 

using "network meta-analysis”, “indirect comparison” and “mixed treatment comparison” as 

search terms, identified more than 640 publications between 2007 and 2012 with any of these 

words in the title, abstract or as key word fields. Between 1992 and 1997 this number was only 

12 (Figure 2). Experience at IMS confirms this trend, with an increase in client requests for 

these types of studies, primarily in support of market access submissions as well as to 

demonstrate (and communicate) product value. 

ACKNOWLEDGED NEED 

Globally, more payers and HTA bodies are acknowledging the need for and acceptability of 

indirect comparisons to accommodate the lack of direct comparative evidence from RCTs. 

Some have published statements relating to the admissibility of methodologies within the 

indirect and mixed treatment comparisons area (Table 1). 

The European Medicines Agency (EMA) notes that comparisons to active control will usually 

need to be ‘direct’ (ie, within the same trial) in order to estimate relative efficacy and safety, 

but acknowledges that there are some circumstances where an indirect comparison might be 

considered sufficiently reliable. 8 In the US, the FDA has not as yet published guidelines on 

indirect comparisons (based on keyword searches April, 2012). 

An Australian Indirect Comparison Working Group (IWCG) has written an extensive report 

on this topic for the Australian Pharmaceutical Benefits Advisory Committee (PBAC). This 

illustrates that the value of indirect comparisons largely depends on the underlying 

assumptions of the individual RCTs being compared. 




TABLE 1: PAYER/HTA PERSPECTIVE ON INDIRECT COMPARISONS IN KEY MARKETS 

COUNTRY PAYER/HTA PERSPECTIVE ON INDIRECT COMPARISONS 

Belgium KCE 

Canada CADTH 

France HAS 

Germany IQWiG 

Netherlands CVZ 

Scotland SMC 

Sweden TLV 

UK NICE 

KEY 

CADTH: Canadian Agency for Drugs and Technologies in Health 

CVZ: College Voor Zorgverzekeringen 

HAS: Haute Autorité de Santé 

IQWiG: Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen 

Indirect comparisons are only allowed under specific conditions: the 

choice of an indirect instead of direct head-to-head comparison 

between study treatment and comparator should be explained, and 

limitations of the indirect comparison described. 2 

No formal guidance but best practices outlined by ISPOR and NICE 

should be considered for submissions. 

Methodological guide, Oct 2011, states:”If direct comparative data 

are not available or are insufficient, it may be necessary to perform 

indirect comparisons according to validated methodologies”. Offers 

two techniques: simple adjusted indirect comparison (straightforward 

and transparent); and network Bayesian methodology (provides best 

solution to determine hierarchy of treatment pathways). 3 

Recognizes methods supported by NICE. Stares that indirect 

comparisons can be considered useful, necessary and inevitable in 

some cases. However, also claims that results based on indirect 

comparisons are associated with more uncertainty than 

direct comparisons. 4 

Allows use of indirect comparisons while recognizing that this type 

of evidence is less valuable than direct comparisons. 5 

Guidance notes (2012) stipulate requirement for indirect comparisons 

if head-to-head evidence is not available. 6 

No published statement on indirect comparisons but in evaluations of 

reimbursement dossiers, TLV has been pragmatic, evaluating on a 

case-by-case basis. The use of MTC and indirect comparisons has been 

accepted when well supported and scientifically robust. 

NICE guidance states: 

“Data from head-to-head RCTs should be presented in the referencecase 

analysis, if available. When head-to-head RCTs exist, evidence 

from mixed treatment comparison analyses may be presented if it is 

considered to add information that is not available from the head-tohead 

comparison.” “If data from head-to-head RCTs are not available, 

indirect treatment comparison methods should be used.” “There may 

be circumstances in which data from head-to-head RCTs are less than 

ideal (for example, the sample size may be small or there may be 

concerns about the external validity). In such cases additional 

evidence from mixed treatment comparisons can be considered.” 7 

KCE: Federaal Kenniscentrum voor de Gezondheidszorg 

NICE: National Institute for Health and Clinical Excellence 

TLV: Tand-och Lakemedelsformansverket 



The authors conclude that indirect comparisons are not randomized and so the associated 

uncertainty should be recognized in the submission. Nevertheless, suggestions are provided on 

producing a more convincing indirect comparison. 9 

An ISPOR task force published two reports in 2011 to help guide decision bodies on 

generating and interpreting evidence that involves indirect comparisons. 10 

METHODOLOGICAL POSSIBILITIES 

When the indirect results are inconsistent with the direct evidence, it is important to 

investigate possible causes of discrepancy such as chance or heterogeneity across trials. For 

example, the synthesized evidence may be influenced by differences in the baseline 

characteristics of the patients across the included trials. In this case, statistical methods exist to 

produce a valid and coherent analysis. 

The recent development of computational power allows the use of the Bayesian framework in 

NMAs. The results produced within this framework can be interpreted in terms of 

probabilities – an advantage over the classical approach in allowing treatments to be rank 

ordered and the best ones to be determined. Furthermore, with RCTs still considered the 

gold standard for assessing relative efficacy and safety, the inclusion of other types of studies 

(eg, observational) would be seen as a weakness of the analysis. However, RCTs are 

experiments conducted in extremely controlled environments which may limit the 

applicability of their findings to the real world. The Bayesian approach allows the combination 

of real-world evidence with that observed in the controlled environments of RCTs, thus 

increasing the external validity of the analysis, ie, the extent to which the results can provide a 

correct basis for generalization to other circumstances. 

EVOLVING POTENTIAL 

NMAs enable the evaluation of competing treatment options that may not otherwise have 

been directly compared. Although the level of evidence they generate may be perceived to be 

inferior to that of gold standard RCTs, they nevertheless have important strengths. This topic 

continues to evolve; Bayesian methods are a good example of this evolution, allowing the 

expression of relative hierarchy of treatment efficacy and potentially increasing the 

generalizability of results to broader settings by combining RCT data with other sources, such 

as observational data. These methods are increasingly being used and accepted by authorities as 

solutions to address the absence of randomized direct comparative data. • 

1 Pair-wise meta analytic methods are typically restricted to comparisons of two interventions, using direct, head-to-head evidence alone. 

2 Cleemput I, Van Wilder P, Vrijens F, Huybrechts M, Ramaekers D. Richtlijnen voor farmacoeconomische evaluaties in België. Health Technology 

Assessment (HTA). Brussel: Federaal Kenniscentrum voor de Gezondheidszorg (KCE); 2008. KCE Reports 78A (D/2008/10.273/23). 

3 Guide méthodologique, choix méthodologiques pour l’évaluation économique à la HAS,Haute Autorité de santé, Octobre 2011. 

Available from www.has-sante.fr 

4 Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG). Stellenwert von Ergebnissen aus indirekten Vergleichen. Köln: IQWiG 2012. 

5 College voor zorgverzekeringen (CVZ). CFH-criteria voor beoordeling therapeutische waarde. Diemen: CVZ 2010. Available from www.cvz.nl 

6 Scottish Medicines Consortium. Guidance to Manufacturers for Completion of New Product Assessment Form (NPAF). November, 2011. 

7 National Institute for Health and Clinical Excellence (NICE). Guide to the Methods of Technology Appraisal. London: NICE, 2008. 

8 Reflection paper on the need for active control in therapeutic areas where use of placebo is deemed ethical and one or more established medicines are 

available. EMA/759784/2010. EMA, November 2010. Available from www.ema.europa.eu. Accessed 12/05/2012. 

9 Indirect Comparisons Working Group (ICWG) (30/01/2012). Report of the Indirect Comparisons Working Group to the Pharmaceutical Benefits 

Advisory Committee: Assessing indirect comparisons. Available from www.health.gov.au Accessed 10/04/2012. 

10 Jansen JP, Fleurence R, Devine B, Itzler R, Barrett A, Hawkins N, Lee K, Boersma C, Annemans L, Cappelleri JC. Interpreting indirect treatment 

comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good 

Research Practices: Part 1. Value Health. 2011 Jun;14(4):417-28. 


INSIGHTS | US PRIVATE HEALTHCARE SPENDING 

The US Affordable Care Act is expected to extend health 

insurance coverage to an additional 44 million Americans 

through 2020. New research from the IMS Institute 

suggests that a deeper understanding of spending patterns 

among private plan enrollees – especially for the smaller 

number who significantly impact overall costs – will be 

essential to ensuring effective strategies for the future. 

The author 

Murray Aitken, MBA 

is Executive Director, IMS Institute for Healthcare Informatics 

Maitken@theimsinstitute.org 

This article is summarized from “Healthcare Spending Among 

Privately Insured Individuals Under Age 65” published by the 

IMS Institute for Healthcare Informatics in February, 2012. 


US PRIVATE HEALTHCARE SPENDING | INSIGHTS 


Understanding healthcare spending in the commercially-insured 

US population under age 65 

Healthcare spending and utilization patterns among the privately insured population in 

the US are not widely understood – or widely available – yet are critical to addressing 

trends in cost growth and ensuring appropriate planning for this evolving population. 

THE SCOPE OF THE STUDY 

With limited access to information on the private sector, health services researchers have 

traditionally relied on analyses of publicly available data (principally Medicare) to advance 

policy recommendations. This analysis uses comprehensive, proprietary data for more than 

10 million privately insured members under age 65 to examine their patterns of outpatient, 

inpatient and pharmacy healthcare spending and consider the potential implications. The 

analysis also highlights distinctions between IMS aggregated healthcare use and spending 

patterns and those commonly cited among health services researchers, including the Agency 

for Healthcare Research and Quality (AHRQ) and Centers for Medicare and Medicaid 

Services (CMS). 

The findings are derived from an analytic subset of the LifeLink Health Plan Claims 

Database, which comprises 6.7 billion medical and pharmacy claims, 79 health plans, and 79.4 

million members from 2001 to the present. The time period covered was from January 1, 2009 

through December 31, 2010. Only privately insured health plan members under age 65 with 

continuous enrollment and medical and pharmacy benefit coverage were included. 

Cost and usage patterns across 17 chronic conditions, 12 cancers, and 10 auto-immune and 

other specialty conditions were evaluated in the study population. Costs reported reflect the 

plan-allowed amount (ie, plan paid amount plus member contribution) for a given service. 

Members were identified by condition based on Year 1 experience, and their cost and 

utilization is reported based on Year 2. 

More than 50% of the total cost was accounted for by just 5% of all health plan members. 

More than 25% of total spending was for just 1% of all members. Conversely, only 3% of total 

cost was incurred by the 50% of members with the least annual spending. 




TOTAL HEALTHCARE SPENDING 

All payers 

In 2010, 184 million Americans, representing 63% of the insured population, were enrolled in 

a private health insurance plan (Figure 1). Collectively, they were responsible for $822 billion 

in healthcare expenditures. Medicare and Medicaid expenditures were $525 billion and 

$400.7 billion respectively. 

By 2020, enrollment in private health insurance is expected to be 198 million with 

expenditures reaching $1.4 trillion. Private health insurance enrollees are projected to remain 

the largest segment (57%) of the overall covered population and their expenditures the largest 

share of insurance spending (41%), even as the impact of implementing the Affordable Care 

Act transforms the healthcare landscape. Medicare and Medicaid will represent 27.7% and 

26.7% of total healthcare spending on insurance respectively. 

FIGURE 1: US ENROLLMENT IN PRIVATE HEALTH INSURANCE REACHES 197.8 MN BY 2020 

48.5 

21.1 

162.8 

5.9 

53.7 

183.9Mn 

individuals, 

63% of 

insured 

population 

46.8 55.4 62.3 


25.8 

18.8 

7.3 

168.9 

5.2 

80.6 

195Mn 

individuals, 

58% of 

insured 

population 

25.9 

24.8 

5.2 

167.8 

1.4 

83.5 

2010 2016 2020 

Uninsured Exchanges Other Private Employer 

CHIP Medicaid Medicare 

Source: Centers for Medicare & Medicaid Services, Office of the Actuary, 

National Health Statistics Group 1 , Dec 2010 

197.8Mn 

individuals, 

57% of 

insured 

population 

Understanding at a more granular level the profile, behavior and usage patterns of the privately 

insured under age 65 health plan members who will have the greatest overall impact on 

healthcare costs, is key to the design and implementation of more effective, efficient care 

management programs.


PRIVATELY INSURED 

Highly concentrated 

For the total sample of more than 10.6 million privately insured health plan members, average 

healthcare spending in 2010 was $3,840, or $320 per member per month. However, more than 

50% of the total cost was accounted for by just 5% of all health plan members. More than 25% 

of total spending was for just 1% of all members. Conversely, only 3% of total cost was 

incurred by the 50% of members with the least annual spending (Figure 2). Understanding the 

profile, behavior and interventions that can be optimally applied to the relatively small number 

of members who have a substantial impact on overall healthcare costs is thus critical. 

Age-related increase 

Health plan members between the ages of 45 and 64 expended, on average, nearly twice the 

amount on health services annually as their counterparts between the ages of 20 and 44, and 

four times that of members in the youngest group of 0 to 9 years of age. Analysis of Medicare 

enrollees also shows increased spending with age, with average annual spending per enrollee 

higher than for the IMS privately-insured study population. 

FIGURE 2: DISTRIBUTION OF SPENDING IN THE US PRIVATELY INSURED 

25.6% 

50.6% 

Top 1% Top 5% 

65.2% 

Outpatient driven 

The largest share of all spending of the privately insured under age 65 population was for 

outpatient services, which represented 59% of total spending. Expenditures for retail pharmacy 

and inpatient services accounted for the remaining 21% and 20% of spending respectively. 

ACCESSPOINT • VOLUME 2 ISSUE 4 PAGE 35 

74.3% 

80.7% 

85.4% 

96.9% 

3.1% 

Top 10% Top 15% Top 20% Top 25% Top 50% Bottom 

50% 

(>=$44,957) (>=$14,947) (>=$8,582) (>=$5,773) (>=$4,169) (>=$3,130) (>=$874) (


This distribution of costs differs significantly from that reported by the Medical Expenditure 

Panel Survey (MEPS) for all payers and for the Medicare 65 and over population2 . 

In particular, Medicare 65 and over population spending on inpatient services represented 43% 

of total spending, while outpatient and pharmacy services were 39% and 18%, respectively 

(Figure 3). 

The differences in spending distribution between the privately insured under age 65 

population and the Medicare 65 and over population are substantial and highlight the need for 

correspondingly differentiated analysis, understanding, and actions aimed at bending the overall 

US healthcare cost curve. 

FIGURE 3: SIGNIFICANT DIFFERENCES IN DISTRIBUTION OF SPENDING BY PAYER TYPE 

21% 22% 

59% 

20% 

IMS Privately Insured 

Under Age 65 

Inpatient 

Disproportionate for certain conditions 

Among health plan members, there were noteworthy differences in treatment patterns across 

diseases, which were outpatient driven among those with chronic or oncology conditions, and 

pharmacy driven for members with auto-immune or other specialty conditions. 

Members with chronic conditions like diabetes, congestive heart failure, chronic renal failure 

or back pain, were responsible for a disproportionate share of spending. When the prevalence 

of the 17 chronic conditions evaluated was compared to total spending for members affected 

by these conditions, their impact was immediately evident and dramatic: more than one third 

of members had at least one chronic condition and accounted for more than two-thirds of 

total spending for all members. 

Members with cancers, auto-immune or other conditions treated with specialty medications 

also accounted for larger shares of spending. Those with cancers accounted for only 1.5% of all 

health plan members and almost 8% of total spending, while members with auto-immune or 

other specialty conditions represented 1.7% of all members, and were responsible for 7% of 

total spending. 


47% 

31% 

18% 

39% 

43% 

MEPS All Payers MEPS Medicare 

65 and Over 

Outpatient 

Source: IMS LifeLink Health Plan Claims Database, Dec 2010; 

Medical Expenditure Panel Survey 2 , 2009 

Pharmacy


OUTPATIENT SPENDING 

INPATIENT SPENDING 

PHARMACY SPENDING 

TOP 1% SPENDING COHORT 

Outpatient services represented the largest share of total spending, averaging $2,251 per 

member per year, or $188 per member per month. Professional and facility visits accounted for 

74% of overall outpatient spending, with emergency room visits a further 10%. 

Outpatient medical drug therapy, including office, facility and home-based injections and 

infusions, represented 5% of all outpatient spending, or $9 per member per month on average. 

However, outpatient drug therapy for oncology, auto-immune and other specialty condition 

populations studied were significantly higher, amounting to 19% and 18%, respectively. 

Facility-based costs represented 84% of the total inpatient spending, with the balance being 

professional service costs. Spending per inpatient admission was $14,248 on average, and 

represented 20% of overall spending per member. 

Members with chronic conditions accounted for the largest share of all hospital admissions at 

63%, equating to 29 admissions per 1,000 members. They also had the largest share of 

professional visits, at 219 per 1,000 members. Average spending per admit was $15,566, with 

an average 4.5 days of stay. 

Members with oncology conditions had the highest average cost per admission at $20,074 but 

admissions only totaled 2.8 per 1,000 members. Oncology patients also had a longer average 

length of stay compared to the overall member population and members with chronic 

conditions, making cancer admissions the most expensive. 

Inpatient services were only 16% of all spending among members with auto-immune or other 

specialty conditions. 

Average pharmacy spending – including outpatient drug claims for both specialty and nonspecialty 

medicines – amounted to 21% of total healthcare spending for the privately insured 

under age 65 population. For every 1,000 members, 11,950 prescriptions were filled in 2010, 

of which 78% were for members with chronic illnesses. Those with oncology and those with 

auto-immune or other specialty conditions filled only 4% and 5% of the total number of 

prescriptions, respectively. 

Specialty drugs represented about 1% of total pharmacy prescriptions but 17% of total 

pharmacy spending. Relative to total healthcare spending – including inpatient costs, 

outpatient medical costs and non-specialty pharmacy costs – specialty drug therapy and 

outpatient medical drug therapy were particularly high for members with auto-immune or 

other specialty conditions, representing 33% of their total healthcare spending. This reflects the 

growing availability of treatment options for members with auto-immune or other specialty 

conditions, where medications can be administered outside of the hospital setting. 

By comparison, these drugs accounted for 17% of spending for oncology patients, and just 6% 

for those members with chronic conditions. 

Consistent with patterns across the healthcare system, privately insured under age 65 health 

plan members who are among the top 1% in annual spending were found to be vastly 

disproportionate users of healthcare resources, averaging almost $100,000 in annual spending 

per member. 




POTENTIAL IMPLICATIONS 

Within the top 1% cohort, our analysis shows that 77% of the members had at least one 

chronic condition, 16% had one or more cancers, and 13% suffered from auto-immune or 

other specialty conditions (some members had conditions in more than one of these 

groupings). Oncology patients had the highest average spending, of $118,000 per year. 

The distribution of spending in the 1% cohort is similar to that of the Medicare 65 and over 

population, with 45% of spending being for inpatient, 45% for outpatient, and 10% for 

pharmacy services. 

Average spending for the top 1% of members with specific chronic conditions was up to 

ten-fold the average spending for all members with the same conditions. For example, 

members with diabetes averaged $11,858 in annual spending while those in the top 1% cohort 

suffering from diabetes averaged $102,465 in annual spending. Similarly, those with chronic 

renal failure on average spent $33,801 per year, but those within the top 1% cohort spent over 

$150,000 annually. 

What is clear from these findings is that health plan management strategies for privately 

insured, under age 65 members cannot simply be an extension of Medicare strategies, given 

their lower share of expenditure for inpatient service spending, and higher shares for 

outpatient and retail pharmacy spending. Out-patient service pricing, use and management are 

important to the ability of private payers to manage costs across their membership, particularly 

as health exchanges result in large numbers of new entrants to the privately insured 

population. 

Effective benefits packages will need to fully consider services used by the three high-cost 

member segments – those with chronic conditions, cancer, and those with auto-immune or 

other specialty diseases. 

1. Chronic conditions 

Members with chronic conditions are responsible for the majority of healthcare expenditure 

in the overall as well as the top 1% spending cohort populations studied. These members and 

their plans would benefit from: 

• Employer-led wellness efforts 

• Prospective outpatient service management and outreach to reduce co-morbidity and 

complication risks 

• Healthcare payment and delivery model innovations that reward primary care physicians for 

coordinating specialty care for chronic care patients and align incentives to facilitate care 

coordination across providers 

• Care management programs targeting reductions in re-admission rates among members 

with conditions such as MI, stroke, diabetes or chronic renal failure, which could lead to 

system cost savings and improved member quality of life 

Managing health status among health plan members with chronic conditions may result in 

cost savings for Medicare into the future, if investment in these individuals reduces or delays 

complications. 


SUMMARY 


2. Cancer 

Members with cancers remain a small proportion of all members but have high per patient 

spending and higher proportions of outpatient spending, including medical drug therapy. 

• These patients could benefit from treatment pathway and setting management initiatives 

that align incentives among providers for care coordination 

• Where possible, providing coverage for self-administered therapies through retail pharmacy 

outlets may lead to greater efficiency and better quality of life for members with cancers 

• Emerging guidelines around cancer screening and treatment may improve treatment 

effectiveness, lower cost, and improve quality of life for patients with different cancers 

3. Specialty 

In certain disease populations, the increased use of specialty retail drug therapy may lead to 

decreased overall member spend. 

• Specialty medications dispensed through the traditional or specialty retail pharmacy setting 

are a key cost driver and need contracting and utilization management 

• At the same time, patients with autoimmune and other specialty conditions had lower 

spending and use rates for inpatient services than members with cancers or for chronic 

conditions without specialty drugs 

• Additionally, members with auto-immune and other specialty conditions in the top 1% 

cohort, including MS and RA, had lower overall per member spending, despite higher 

shares of retail pharmacy spending 

Medicare and private payers face similar challenges managing spending and utilization for drug 

therapy administered in an outpatient facility, office or home setting and paid under the 

medical benefit. These include: 

• Coordinating the management of outpatient medical and retail pharmacy drug use, 

spending, and appropriateness 

• Evaluating effects of offering specialty medications through the retail or home health 

setting, in addition to or instead of in the outpatient facility or office setting, when clinically 

possible 

Efforts to address healthcare spending levels and ensure optimal care for patients require 

detailed understanding from timely and robust information. This analysis is intended to focus 

attention on the patient segments, care settings, and treatment options that can best bring 

improved health outcomes at lowest cost to those in need. Understanding at a more granular 

level the profile, behavior and usage patterns of the privately insured under age 65 health plan 

members who will have the greatest overall impact on healthcare costs, is key to the design 

and implementation of more effective, efficient care management programs. Addressing the 

health needs of this evolving population efficiently will bring significant benefits to the entire 

healthcare system. • 

1 National Health Expenditure Projections 2010-2020. Centers for Medicare & Medicaid Services, Office of the Actuary, National 

Health Statistics Group. 2010. https://www.cms.gov/nationalhealthexpenddata/downloads/proj2010.pdf 

2 Medical Expenditure Panel Survey: Tables of Expenditures by Health Care Services. Agency for Healthcare Research and Quality, 2009. 

http://www.meps.ahrq.gov/mepsweb/data_stats/quick_tables_results.jsp 


INSIGHTS | IMPLEMENTING HTA IN ASIA PACIFIC 

In their efforts to optimize healthcare resources while 

improving access to new innovations, more emerging 

markets in Asia Pacific are signaling the move to a formal 

process for assessing healthcare technologies. 

While opportunities beckon for industry to help shape the 

landscape, challenges remain for successful implementation 

of HTA in the region. 

The author 

Joe Caputo, BSC 


Jcaputo@sg.imshealth.com 


IMPLEMENTING HTA IN ASIA PACIFIC | INSIGHTS 

Implementing HTA processes in the 

emerging markets of Asia Pacific 

Critical factors for success 

Across the emerging markets of Asia Pacific, government health ministers continue to 

emphasize their desire to develop and implement formal pharmacoeconomic guidelines 

in their respective countries. 

The political desire of many of the region’s authorities to provide broader access to healthcare 

for its populations, along with the growing prevalence of non-communicable diseases (NCDs) 

such as cancer and diabetes, are placing a strain not only on government budgets but also on the 

healthcare infrastructure across Asia Pacific. As in the West, increasing life expectancy is giving 

rise to the greater burden associated with ageing populations, while governments struggle to 

balance growing costs with a need to expand healthcare provision to all. 

APPROACHES TO COST CONTAINMENT 

At the heart of any cost-containment strategy is a set of tools, ranging from complex 

risk-sharing schemes and health technology assessment (HTA) through to more simplistic 

mechanisms, such as prescribing controls and mandatory price cuts. Analysis of 

cost-management trends across Asia Pacific, relative to Europe and North America, 

suggests a leaning towards less complex approaches (Figure 1 overleaf). 

One postulated reason for this is that before being able to even contemplate more sophisticated 

initiatives, governments must first address basic infrastructure needs. These include having 

sufficient doctors and clinics to diagnose and treat patients or, even more fundamentally, 

ensuring the provision of clean water and sanitation – as is the case in Indonesia. 

At the same time, there is growing appreciation that cost containment can only be effective 

when implemented in a systematic manner. Hence, the use of more complex tools is gaining 

in popularity across the region. South Korea and Taiwan already have formal guidelines in 

place and are now considered ‘mature’ markets in terms of HTA adoption. However, with 

Japan and China, amongst other Asian countries, announcing their intention to develop and 

implement pharmacoeconomic assessments, there is an opportunity for industry to engage 

with payers and governments to help shape the HTA environment and become a valued 

stakeholder in the healthcare process. 

CHALLENGING PATH TO IMPLEMENTATION 

The caveat, here, is that declaring a wish to establish an HTA process and effectively 

implementing that process are two very different things. Success – or otherwise – will be 

contingent on a number of factors, including technical expertise, availability of local data, 

stakeholder education and last, but not least, transparency of decision making. 

• Technical expertise: Lack of technical expertise among the regional and national health 

authorities is a key challenge for moving the agenda forward. Many of the region’s 

authorities are looking to countries with established approaches and organizations such as 



INSIGHTS | IMPLEMENTING HTA IN ASIA PACIFIC 

FIGURE 1: COST CONTAINMENT IN ASIA PACIFIC HAS FOCUSED ON LOW-COMPLEX MEASURES 

DECREASING COMPLEXITY OF TOOL 

Cost containment 

tools FR DE IT ES UK AUS CH IN JP KR TW ID MY PH SG TH VT 

VBP/Risk-sharing 

agreements 

HTA/cost-effectiveness 

assessments 

Quality/innovation/ 

therapeutic value rating 

Generics promotion 

International price 

referencing 

Spending caps 

Patient contributions 

Prescribing controls 

Mandatory price cuts 

EU APAC ASEAN 

Most cost-containment tools used are at the relatively low complexity end of the scale 

Only recently implemented/limited application FR: France, DE: Germany, IT: Italy, ES: Spain, UK: United Kingdom, AUS: Australia, 

CH: China, IN: India, JP: Japan, KR: South Korea, TW: Taiwan, ID: Indonesia, 

MY: Malaysia, PH: Philippines, SG: Singapore, TH: Thailand, VT: Vietnam 

NICE (National Institute for Health and Clinical Excellence) in the UK, for guidance on 

the design and implementation of their HTA processes. Even with the relevant expertise in 

place, the issue of which therapy areas to prioritize remains a critical question. 

• Data availability and real-world evidence: The effective working of an HTA process 

relies heavily on local data, be they clinical data in the local population (particularly 

important in populations where genetic differences may result in different levels of efficacy), 

or healthcare resource use and cost data which will be used to evaluate the costeffectiveness 

of different treatment options relative to the current standard of care. Hence, 

the growing demand for real-world evidence (RWE) to support HTA submissions. 

For the emerging Asian markets, the need for RWE in itself brings another set of challenges. 

Local databases are scarce; even when they exist they tend not to be readily available. They 

are invariably limited in scope, restricted to a particular locality or condition, or provide 

only a sub set of relevant information (eg, diagnosis but no test results). Traditionally not 

collected for research purposes, data are neither gathered nor coded in a consistent manner, 

meaning that databases cannot necessarily be combined to give an accurate bigger picture. 

This reality reflects the relatively early stage of HTA programs across the region; however, it 

will have to change in the future, with greater investment in databases and generation of 

RWE evidence fast becoming a priority. 


IMPLEMENTING HTA IN ASIA PACIFIC | INSIGHTS 

THE TIME IS NOW 

• Stakeholder education and understanding: Stakeholder awareness will also be critical 

to the success of any HTA process. Experience from Europe has taught us that the role of 

HTA differs from country to country. Factor in the complex and diverse nature of Asian 

markets and this is also likely to be the case across Asia Pacific. 

Stakeholder understanding of the role of HTA for each country will be a key factor, 

although this also represents an opportunity for Asia Pacific to learn from Europe’s 

experience and fast forward through the learning process. 

• Transparency: Finally, any HTA process that is implemented will need to be transparent in 

its decision making and influence. One of the criticisms leveled at authorities by industry 

currently is that even in cases where manufacturers are invited or permitted to submit 

pharmacoeconomic data there is a lack of transparency as to how this data is actually used. 

When the sweeping price cuts announced on a regular basis by health ministers are added 

into the mix, the industry could be forgiven for weighing up the benefits and risks of 

complying with the process. 

Despite the obvious challenges, some would argue that the time for HTA has arrived in 

Asia Pacific. Implemented correctly, it can play a role in the future of the region, not only as a 

key component of cost containment but also as a pivotal enabler for the efficient use of 

resources, as governments look to provide broader access to affordable healthcare for all. 

In this regard, Asian markets can learn from the experience of countries in Europe, whilst 

industry can also take the opportunity to help shape their healthcare strategy and become a 

key stakeholder in that process. Should they choose to ignore the lessons from addressing 

growth in costs and demand for healthcare in Europe, Asia Pacific may well face a decade of 

potentially painful development. • 

For the emerging Asian markets, the need for RWE in itself brings another set of challenges. 

Data are neither gathered nor coded in a consistent manner, meaning that databases cannot 

necessarily be combined to give an accurate bigger picture. It will have to change in the future, 

with greater investment in databases and generation of RWE evidence fast becoming a priority. 


INSIGHTS | PHARMACOGENOMICS 

The full potential of pharmacogenomics may still be to come 

but as its role in healthcare continues to evolve, there are 

new priorities to consider and address – including a deeper 

understanding of the impact and implications for real-world 

evidence generation. 

The authors 




Maartje Smulders, MSC, MPH 


Msmulders@nl.imshealth.com 


PHARMACOGENOMICS | INSIGHTS 

Pharmacogenomics comes of age 

Imperatives for a real-world evidence strategy 

On completion of the Human Genome Project in the early 2000s, pharmacogenomics (PGx) 

was hailed as the research area that would transform the pharmaceutical landscape; 

knowledge about the effects of DNA variation in man would revolutionize research and 

development (R&D) and approaches to diagnosing, treating and even preventing diseases. 

Now, ten years on, it seems those expectations may have been too high. 

In other words, PGx has not so far delivered the revolutionary outcomes that were promised. 

With hindsight, this is perhaps not surprising given the complexity of general health, drug 

response and toxicity and the way in which they vary by not only genotype presentation and 

manifestation, but also environmental factors. 

INCREASING VISIBILITY 

Notwithstanding the slower than anticipated progress to date, there is no doubt that in the 

coming decade, PGx will be more visible in research and clinical applications. It has the 

potential to accelerate drug discovery and development by identifying better drug targets, and 

to establish preferred segmented patient populations, thereby improving safety, efficacy and 

effectiveness profiles in clinical practice. Accordingly, the number of useful biomarkers for 

predicting drug response is expected to increase rapidly both in quantity and quality. 1,2 In fact, 

some currently available biomarkers are already integrated into drug label inserts by the US 

FDA and European Medicines Agency (eg, HercepTest, TPMT test) and are required for 

reimbursement. Overall, PGx is now a reality of doing business. Clear progress is being made, 

especially in the field of cancer. 

A number of factors have been influential in the development of PGxs. These have been well 

elaborated by Garrison, et al, including public policy issues and the challenges in linking 

pharmacogenomics-based diagnostics and drugs for personalized medicine. 3,4,5 This article 

focuses on two critical success factors for PGx: coping with the (perhaps negatively-perceived) 

impact of associated increased market segmentation; and the consequent increased need for 

more detailed and complex patient-centric data. 

DOES PHARMACOGENOMICS LEAD TO DECREASED MARKET POTENTIAL? 

The prevailing view in the pharmaceutical industry has been that many executives, marketing 

and sales people held back on PGx – a resistance that was possibly driven by concerns about 

PGx reducing market size and cases where it had negatively affected commercial success. 

Consider, for example, the many drug withdrawals that may have been a direct result of 

pharmacogenomic differences among small patient sub-populations (eg, Seldane ® , Baycol ® , 

Redux ® , Rezulin ® ), and the potential of poor responders to negatively impact overall safety 

and efficacy in product development. 




However, perceptions have been evolving since then, amid growing recognition that PGx has 

the potential to impact product market size in a number of ways – both good and bad (Figure 

1). As Bernard has observed in analyzing the myths of PGx, the introduction of PGx testing 

may yield loss of market share (A, B, C). On the other hand, it may drive an increase in share 

as a result, for example, of: earlier market approvals enabled by faster identification of drug 

targets and responsive patients during R&D (D); recruitment of patients from less effective 

competing products (E); identification of patients who refused treatment due to efficacy/safety 

concerns (F); and potential for higher pricing or reimbursement advantage for drugs that, with 

the test, can identify the patients who will respond favorably (J) 6 . 

FIGURE 1: MARKETING A GENERIC TEST WITH A PRODUCT CAN PRODUCE BOTH SHARE LOSS AND GAIN, POTENTIALLY 

RESULTING IN A MARKET SHARE INCREASE 

Product X’s Market 

Share without 

Pharmacogenomics 

Y 

Market Share = Y 

Share Loss 

Share Gain 

Earlier market 

introduction with 

faster approvals 

Recruitment of 

patients from less 

effective drugs 

D 

Adverse event risk 

E 

Non responders 

Product X’s Market 

Share with 

Pharmacogenomics 

Increased use in 

diagnosed but 

untreated patients 

Potential for higher 

pricing reimbursement 

for best-in-class drug 

Expansion of 

treatment to new 

subgroup/diseases 

Earlier/ 

preventive 

use 

Enhanced 

patient 

compliance 

Thus, by monitoring PGx development and thoroughly analyzing the potential impact of PGx 

early, an appropriate assessment of commercial impact can be made. It is imperative that this 

type of evaluation is undertaken prior to Phase II development. One key question to address is 

the potential for higher pricing and improved reimbursement to be enabled by a PGx 

approach. It is here that health economics and outcomes research plays a quintessential role. 


A 

B 

Low responders 

C 

F 

Y 

Market Share = Y - (A+B+C+) + (D+E+F+G+H+I+J) 

Source: Bernard S., The 5 myths of pharmacogenomics. Pharmaceutical Executive, 2003; October 1: 70-78 

J 

G 

I 

H


DO WE NEED DATA? 

PGx has the potential to establish preferred segmented patient populations, thereby improving 

safety, efficacy and effectiveness profiles in clinical practice. Here, the need for real-world 

evidence (RWE) is implicit. 

In the EU and US, changing safety regulations, risk management procedures and 

reimbursement requirements already require RWE and hence access to patient-centric 

longitudinal data. These data enable follow-up of patients over time to understand disease 

progression, (drug) treatment and associated outcomes, as well as safety. With advancements in 

PGx, the need for more detailed and complex patient-centric data will grow even further. 

Manufacturers should look to establishing RWE plans early in drug development and 

anticipate on co-development of RWE programs to collect, or enable a certain level of access 

to, the complex patient-centric data that are needed. 

The challenge is that access to real-life patient-centric data in general is limited for industry, 

due to privacy regulations, security systems, laws and public opinion. This is even more the 

case for genotypic information. Additionally, acceptance of and requirements for data use vary 

among countries, due to differing systems infrastructure, regulations and stakeholder trust. 

Furthermore, the fragmentation of data sources necessitates linkage of multiple data assets 

– calling for bespoke and well-governed approaches. Consider the example of oncology. 

PGx IN ONCOLOGY 

Data content considerations in oncology are challenging; for robust observational 

pharmacoepidemiology and pharmacovigilance research to support payer and regulatory 

requirements successfully, there are multiple data issues to address: 

• Longitudinal and patient-centric 

• Sufficiently large 

• Covering all population ages (not just >65) 

• Tumor staging, grading and patient wellbeing 

• Biomarkers 

• Exposure (drug treatment, including chemotherapy, radiotherapy, surgery) 

• Outcomes as mortality and hospitalizations 




Taking the aforementioned considerations into account, much of the relevant data is actually 

already routinely collected in practice. However, the sources are fragmented. Consequently, 

often de novo data collection projects are being developed which provide the full and 

complete information that is needed. However, these are expensive and time consuming. 

An alternative is the linkage of several routine databases (+/- ad hoc data collection). In this 

case, linking pathology and/or (pharmaco-) genomics databases, cancer registries and 

administrative healthcare or claims databases would provide an ultimately comprehensive RWE 

platform allowing for robust pharmacoepidemiology and pharmacovigilance research in 

oncology (Figure 2). In Europe, pathology and laboratory databases and cancer registries 

provide more details on diagnosis (eg, staging, histological classification, receptor status, etc); 

administrative healthcare databases (EMR) and to a certain extent claims data, generally 

provide insights into treatment and (co-) morbidities; pathology databases provide more 

information on, for example, biomarkers to the extent that they are used in real-world 

practice. 

In terms of the patient population segmentation driven by PGx, sample size is an important 

consideration and often limiting factor in pharmacoepidemiology and pharmacovigilance. To 

increase sample size, multiple national databases would need to be harmonized and integrated. 

The importance of managing the heterogeneity of underlying healthcare systems, coding and 

treatment pathways, and technical aspects (hardware limits) must be taken into account, 

particularly in relation to biobanks and PGx databases given their extensive size. 

FIGURE 2: LINKING FRAGMENTED DATA SOURCES COVERING CANCER CARE 

Pathology 

Cancer 

register 

Genotypic 

data 

PATIENT CORE 

Rx (community 

& in-patient) 

Microbiology Hospitalizations 

Mortality Clinical Lab 


GP


INITIATIVES AND TRENDS 

The good news is that many different initiatives are ongoing at national and international 

level. Specifically in PGx, biobanks and PGx databases are being developed and becoming 

more open to research by third parties, in some cases providing industry with a seat at the 

table. A good example of such collaborative effort is the Biotech Cluster Rhine-Neckar 

(http://www.biorn.org/biorn-start/). 

There are multiple ongoing national and international biobank harmonization and linking 

initiatives in the EU and US. Several multi-country consortia exist, whose overall aim is 

(stimulating) pooling of data, including the development of harmonized measures and 

standardized computing infrastructures to enable the effective pooling of the data. 

Examples include BioSHaRE (http://www.bioshare.eu/), BBMRI (http://www.bbmri.eu) 

and PharmGKB. 7 Further, in response to recent calls for the development of common 

principles applying to data access and use, several networks are working on an international 

data-sharing Code of Conduct, for example, the global Public Population Project in Genomics 

(P³G; http://www.p3gobservatory.org), the European Network for Genetic and Genomic 

Epidemiology (ENGAGE) and the Centre for Health, Law and Emerging Technologies 

(HeLEX) in the EU. 8 

PLAN FOR ACTION 

It is clear that these advancements in PGx impact early drug and commercial strategy 

development. This calls for an early and thorough analysis of potential PGx implications even 

before Phase II development, and the development of appropriate plans for RWE generation. 

These plans need to incorporate the co-development of RWE programs to collect, or enable a 

certain level of access to the complex patient-centric data required. This early anticipation is 

already implicit for “normal” product development, but takes on even greater significance 

with the introduction of PGx given the even greater complexity of the data requirements and 

the need for co-development of diagnostics and treatment interventions. 

It goes without saying that industry must take partnered control of RWE to improve its access 

to and understanding of valuable information, even more so in PGx. Positive advancements 

have seen various different initiatives established in which the industry has a role to play. To a 

growing extent, data sharing is regarded as an ethical and scientific imperative that advances 

knowledge and thereby respects the contributions of the participants. Increased public trust, 

which is increasingly translated through broad consents and efforts in harmonization of data 

privacy are also positive trends. Perhaps the downside is that biobank and pharmacogenomic 

data access (and if feasible, linkages) will take much time investment in building relationships 

and establishing well-managed governance and access models which ensure platform quality 

and integrity and are in-line with data standards. Now is the time to start investing in 

these partnerships. • 

This article partially draws on a recent MSc. Thesis “Is the pharmaceutical industry ready to make its choice for PGx?” by Jorien van Luling, Erasmus University, 2012, working 

under Dr Keja’s supervision. 

1 Sim SC, Ingelman-Sundberg M. Pharmacogenomic biomarkers: New tools in current and future drug therapy. Trends Pharmacol Sci. 2011, Feb; 32(2): 72-81. 

2 Sim SC, Altman R B, Ingelman-Sundberg M. Databases in the area of pharmacogenetics. Human Mutation. 2011, May; 32(5): 526-31. Epub 5 April 2011. 

3 Garrison LP Jr, Finley Austin MJ. Linking pharmacogenetics-based diagnostics and drugs for personalized medicine. Health Affairs, 2006; 25(5): 1281-90. 

4 Garrison LP Jr, et al. A review of public policy issues in promoting the development and commercialization of pharmacogenomic applications: Challenges 

and implications. Drug Metabolism Reviews, 2008; 40(2): 377-401. 

5 Garrison LP. Will pharmacogenomics disrupt the U.S. Health Care System? No. Public Health Genomics, 2009; 12(3): 185-90. 

6 Bernard S. The 5 Myths of Pharmacogenomics, Pharmaceutical Executive, 2003; Oct 1: 70-78. 

7 McDonagh EM, Whirl-Carrillo M, Garten Y, Altman RB, Klein TE. From pharmacogenomic knowledge acquisition to clinical applications: The 

PharmGKB as a clinical pharmacogenomic biomarker resource.” Biomarkers in Medicine, 2011, Dec; 5(6): 795-806. 

8 Knoppers BM, et al. Towards a data sharing Code of Conduct for international genomic research. Genome Medicine, 2011; 3: 46. 


PROJECT FOCUS | IMS CORE BUDGET IMPACT MODEL 

Sophisticated, 

user-centric modeling 

solutions are bringing 

new possibilities for 

uniformly analyzing 

the budget impact of 

technologies across 

multiple stakeholder 

settings 

The authors 

Julie Munakata, MS 


Jmunakata@us.imshealth.com 

Cheryl Prasad Ferrufino, MS 

is Senior Consultant HEOR, IMS Health 

Cferrufino@us.imshealth.com 

Developing payer-relevant 

pharmacy budget impact 

analyses in OAB 

Budget impact analyses (BIA) are increasingly required by national 

regulatory agencies and managed care organizations to estimate the 

financial consequences of adopting and diffusing a new healthcare 

intervention within a particular setting of care. They may be planneutral 

(eg, nationally representative data in the US for an Academy 

of Managed Care Pharmacy dossier) or customized, based on a 

particular plan’s characteristics (eg, state-level commercial data 

for field-based discussions). By enabling critical insights into the 

impact of a drug or technology on a healthcare budget over time, 

they are a source of key information for healthcare decision makers. 

Recent advancements in health economic modeling are now 

broadening the scope of these analyses to provide a consolidated 

solution for multiple stakeholders. 

REQUIREMENT FOR STAND ALONE TOOL 

A leading pharmaceutical manufacturer based in the US, was 

interested in developing a stand-alone tool that would enable it to 

determine and communicate the pharmacy budget impact of adding 

and/or increasing the uptake of a previously launched treatment for 

overactive bladder (OAB) within a health plan’s formulary. OAB, a 

chronic and embarrassing condition characterized by urinary urgency 

with or without urge incontinence, is a considerable health concern 

with an estimated prevalence of 16%-17% among adults in the US. 1 

It is often under diagnosed and under treated – despite the 

availability of pharmacotherapy – and can significantly impact 

quality of life, making strategies to improve its management and 

outcomes important. 

The proposed tool was primarily intended for use by the company’s 

field-based account managers and internal health outcomes 

specialists. It was further being considered as a possible leavebehind 

for clients. In order to be fit for purpose, it would need to 

fulfill several key criteria: 

• A streamlined, “uncluttered” user interface 

• Transparent and logical presentation of data inputs and calculations 

• Populated with data sourced from syndicated databases to 

promote company-wide consistency and familiarity in modeling 

approach, and create efficiencies for model updates and training 

• Functionality to allow custom input overrides and scenario analyses 

• Clear within-model documentation of methods, assumptions 

and references 


IMS CORE BUDGET IMPACT MODEL | PROJECT FOCUS 

FIGURE 1: IMS CORE BUDGET IMPACT MODEL: LANDING AND RESULTS SCREENS 

• IMS benchmark 

• Medi-Span 

• First DataBank 

ADVANCED MODELING SOLUTION 

In approaching IMS HEOR for help, the company found an 

expert team with proven capabilities in evidence-based and 

user-centric, advanced design modeling solutions. These were 

backed by in-depth market knowledge, insights from worldclass 

data assets and relevant stakeholder networks, and 

access to the IMS CORE Budget Impact Model. 

Developed in MS Excel and in accordance with local and national 

guidelines for BIAs, the IMS CORE Budget Impact Model is an 

interactive, flexible, multi-use and standardized framework 

enabling pharmacy budget impact analyses (Figure 1). 

The model is designed to be an efficient turnkey modeling 

solution – packaged and delivered pre-populated with userspecified 

default values, such as therapy area and products 

of interest, geographic coverage, method of payment, etc. 

All model screens are presented in a logical fashion and 

include informational, user-input (population, market share, 

drug prices and contracting), results and sensitivity analyses 

screens. Users are able to select default data sources and 

assumptions and override all inputs to perform exploratory 

scenario analyses. 

User Requirements 

• Therapy area 

• Products of interest 

1 DATA EXTRACTION 

2 CONFIGURATION 

• IMS Core BIM 

• Custom features 

• Geographic coverage 

• Method of payment 

• Etc… 

STAKEHOLDER-RELEVANT ANALYSES 

IMS benchmark data permit a view of retail pharmacy 

utilization and cost trends at national, state, or local 

(Metropolitan Statistical Area) level based on the IMS 

National Prescription Audit, the industry-standard source 

of national prescription activity in the US. In addition, drug 

and cost inputs for the model may be sourced from First 

DataBank and/or Medi-Span. Key metrics may be shown by 

method of payment (commercial, Medicare, Medicaid) in 

addition to geography, and include total prescriptions, 

average price per prescription and quantity, and patient copay 

averages. Such granularity offers the user an opportunity 

to configure targeted analyses for clients with similar 

underlying policy or demographic characteristics. 

BRIDGING A CRITICAL GAP 

DELIVERY 

• Targeted analyzer 

• Stakeholder bridge 

Co-developed by IMS HEOR and the Payer Solutions unit of 

IMS Health, the IMS CORE Budget Impact Model has been 

specifically designed to be used by manufacturers and payers 

alike and is the first of its kind to bridge the critical gap 

between payers and manufacturers. Through their work with 

IMS, the client gained a simple, easy-to-use tool that could 

be custom-configured by geographic region and payment 

methods, enabling up-to-date, relevant and impactful 

analytics and insight to inform OAB therapy options within 

their targeted health plans. • 

1 Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL. Prevalence and burden of overactive bladder in the United States. 

World J Urol, 2003;20(6):327-336. 


3

PROJECT FOCUS | DATA LINKAGE IN ONCOLOGY 

Advanced techniques 

linking multiple 

patient-level data sets 

allow insights across 

the spectrum of care 

for robust, 

comprehensive 

real-world evidence 

The author 

Jerrold Hill, PHD, MS 


Jhill@us.imshealth.com 

Enabling rigorous outcomes 

research with an EMR 

oncology data platform 

The growing requirement for pharmaceutical manufacturers to 

demonstrate the value and safety of pharmaceutical and other medical 

technologies is increasing the need for research based on real-world 

evidence (RWE). The use of large, anonymized patient-level databases, 

based on electronic medical records (EMR), health plan and other 

medical claims data, has been rising significantly as a consequence. 

While these datasets allow important and unique insights into drug 

effectiveness and utilization patterns, they are typically not linked 

across service provision in a way that captures the total patient 

experience. This is particularly relevant in fast-evolving areas like 

oncology where complex pathways and changing treatment 

preferences can confound a true understanding of real-world practice. 

Innovative approaches that are able to integrate existing data 

sources through sophisticated linkage methodologies are key to 

overcoming these limitations. For one US biotechnology corporation, 

this technique proved pivotal to providing RWE for demonstrating 

product value within the broader context of current care in oncology. 

CAPTURING REAL-WORLD OUTCOMES 

The company, a market leader in developing innovative new cancer 

therapies, faced increased demands for RWE across its oncology 

product portfolio. However, the disparate and clinically sparse nature 

of patient EMR data in oncology across the US was challenging its 

ability to capture real-world outcomes or track utilization patterns 

in this field. Keen to find a practical solution, it approached IMS 

HEOR for help in developing and building a comprehensive data 

acquisition, integration, warehousing, and analytics platform to 

explore treatment patterns, drug usage and clinical outcomes in the 

real-world setting – without compromising patient confidentiality. 

UNIQUE, COMPREHENSIVE RESOURCE 

The development of the EMR oncology data platform took IMS 

through a lengthy and rigorous process of firstly pinpointing data 

gaps within existing data resources, next identifying and evaluating 

new data resources, and ultimately curating and linking external 

claims and registry data to existing data sources. The resulting data 

warehouse and research platform incorporated and linked EMR, 

insurance claims, tumor registry, death, biospecimen, and more. 

Today, the EMR oncology data platform contains more than 540,000 

patient records, with a history from 2004. Data are sourced from 65 

oncology/hematology clinics across more than 30 States in America, 

encompassing about 550 treating providers. Approximately 60,000 

patients are observed in the database every month. 

The clinical data available are extensive, spanning: cancer staging; 

TNM values; patient demographics; lab results; injectables and oral 


DATA LINKAGE IN ONCOLOGY | PROJECT FOCUS 

FIGURE 1: EMR ONCOLOGY PLATFORM FIVE-YEAR PROGRAM OF DEVELOPMENT 

2006 

• Client identifies 

need to build an 

oncologyspecific 

EMR data 

repository 

2007 

• Request for 

proposals 

• Contract for 

platform building 

awarded 

to IMS 

• Project initiated 

by IMS at end 

of year 

2008 

• Aggregate EMR 

data feeds 

• Privacy & advisory 

boards held 

• Design & 

delivery of 

standard reports 

• Analysis & 

publications to 

support FDA & 

CMS negotiations 

• Evaluation of 

data gaps 

• Plans for filling 

gaps 

medications (including chemo-therapeutic and hormonal 

drugs); dosing; treatment intervals; disease progression; 

vitals; drug regimens; and radiation treatments, including 

sites radiated. Linked to patient-level medical claims, 

prescription drug claims and hospital data they provide 

information on the full spectrum of patient care. 

FULLY-INTEGRATED SOLUTION 

In the five years since its inception, the EMR oncology data 

platform has served as a fully-integrated data solution, 

allowing the company to quickly, easily and comprehensively 

address ad-hoc real-world clinical and economic questions from 

payers and regulators as well as internal customers (Figure 1). 

WIDE-RANGING APPLICATIONS 

Outputs leveraging the EMR oncology platform data have formed 

the basis of various custom research studies and standard 

tracking reports developed by IMS to support the company’s 

oncology portfolio, particularly in the use of erythropoiesisstimulating 

agents (ESAs) for chemotherapy-induced anemia 

(CIA) – a common complication of cancer treatment. 

Typically, data afforded by the platform data have not been 

available in other sources, such as health insurance claims data 

sets, enabling unique real-world evidence for negotiations on 

product labeling at the FDA Oncologic Drugs Advisory 

Committee (ODAC) and on reimbursement decisions at CMS. 

Analyses include cost-effectiveness, comparative effectiveness, 

trends in practice patterns, physician adherence to product 

label instructions, impacts of FDA and Centers for Medicare and 

Medicaid Services (CMS) policies on product use, and patient 

risks (eg, transfusion risk in chemotherapy patients). 

The use of patient hemoglobin data, for example, has 

provided important insights into the real-life costs and 

effects of treatment for CIA as well as enabling the company 

2009 

• Gap projects 

initiated 

• Evaluation of 

new data 

• Licensing of new 

data 

• Design & delivery 

of more reports 

• Launch of 

multiple research 

projects 

2010 

• Gap projects 

complete 

• Licensing of 6 

new linkable data 

feeds 

• Projection of 

platform to US 

treated 

population 

• Platform linked 

to death records 

& claims data 

provider tumor 

registry 

22 Poster/Podium presentations and 13 peer-reviewed papers 

2011 

• Transition of 

platform to 

client 

• Evaluation and 

analysis of 

patient 

subpopulation 

data 

• Launch of 

platform-based 

research projects 

• 88 reports 

designed & 

delivered to 

clients 

to demonstrate significant benefits for its ESA, including: 

• Lower cost compared to the alternative ESA therapy 

• Fewer associated healthcare visits as a result of a less 

frequent dosing schedule 

• Increased likelihood of enabling chemotherapy and ESA 

therapy on the same visit 

A further study showing that physicians administered the 

product at hemoglobin levels consistent with label 

instructions also found that following FDA restrictions on 

indications for the product, and CMS restrictions on 

reimbursement, red blood transfusion rates increased in 

patients receiving chemotherapy – with significant 

implications for cost, outcomes and quality of life. 

Research findings from these and other studies using data 

from the EMR oncology platform have been communicated in 

peer-reviewed journals and disseminated in more than 20 

poster or podium presentations at professional conferences 

such as ISPOR, American Society of Clinical Oncology (ASCO), 

Hematology/Oncology Pharmacy Association (HOPA), 

Multinational Association of Supportive Care in Cancer 

(MASCC) and Association of Schools of Public Health (ASPH). 

KEY DECISION SUPPORT 

Collaborating with IMS on the development of the EMR 

oncology data platform has provided the company with the 

means to generate fast, accurate answers to key clinical 

research, health economic and commercialization questions, 

as well as improving standardization of processes and 

reducing costs internally. In enabling the development of 

robust RWE in oncology through the associated research 

program it has been instrumental in providing value messages 

for payers and physicians and informing the broader medical 

community on key issues in cancer care. • 

ACCESSPOINT - ISSUE 4 PAGE 53

PROJECT FOCUS | METASTATIC COLORECTAL CANCER 

Retrospective cohort 

analyses of physiciansurvey 

data can 

enable value 

messages based on 

real-world evidence of 

current patterns of 

practice 

The author 

Elise Pelletier, MS 


Epelletier@us.imshealth.com 

Informing optimal treatment 

strategies in advanced 

colorectal cancer in Europe 

Pharmaceutical manufacturers face a growing need to generate, 

analyze and apply real-world evidence (RWE) to support value 

demonstrations for their products and ensure optimal use in 

treatment protocols. This is particularly valid in crowded therapy 

areas like oncology, where scientific breakthroughs are expanding 

treatment options and the range of indications they can address, 

but where new agents must compete for inclusion in complex 

regimens, often involving multiple modalities, including surgery. 

The ability to determine and demonstrate added value within the 

context of current and emerging practice patterns is key to ensuring 

optimal outcomes – and successful product differentiation. 

Anonymized patient-level databases, which track the treatment 

experience of large patient cohorts over time, afford unique 

glimpses into the real-world use of medicines and, importantly, the 

implications of attributes associated with different interventions. 

When one leading biopharmaceutical manufacturer needed help in 

generating RWE in Europe for its new monoclonal antibody (mAB) 

for metastatic colorectal cancer (mCRC), the retrospective analysis 

of physician-survey patient-level data in IMS LifeLink Oncology 

Analyzer proved pivotal to identifying value differentiators based 

on the relative safety profile of its competitors. 

UNDERSTANDING THE IMPACT OF ATTRIBUTES 

In Europe, CRC is the most common newly diagnosed cancer and the 

second leading cause of death from cancer. 1 Between 15-25% of 

newly identified CRC patients present with metastatic disease, and 

up to 50% of all CRC patients will eventually develop metastases. 2 

Consequently, high numbers of patients seek treatment for mCRC, 

where prolonged survival/prevention of tumor progression, 

reduction of associated symptoms, and/or maintenance of quality 

of life are the key goals. 3 After many years of limited therapeutic 

options for mCRC, recent advances in systemic approaches, including 

new combination chemotherapies and targeted treatment with mABs 

combined with chemotherapy, have significantly improved the 

ability to achieve these outcomes. 

The company, a key player in oncology, wanted to explore the value 

of its mAB, which was indicated for second-line treatment of mCRC, 

but lacked sufficient post-launch experience to study the drug’s 

performance in the real world. However, by understanding the use 

of other targeted agents and the distribution of chemotherapy 

backbones, it could better determine the potential patient segment 

for a first-line indication. One significant adverse effect of a 


METASTATIC COLORECTAL CANCER | PROJECT FOCUS 

FIGURE 1: SURGERY BY PURPOSE: PATIENTS WITH AT LEAST ONE SURGERY FOR ANY PURPOSE AND FOR DIAGNOSTIC, CURATIVE AND 

PALLIATIVE PURPOSE, BY COUNTRY 

45% 

40% 

35% 

30% 

25% 

20% 

15% 

10% 

5% 

0% 

36.3% 

12.8% 15.7% 

11.5% 

competing mAB was serious wound-healing complications, 

causing treatment discontinuation for a period of 5-8 weeks 

prior to surgery and 28 days after. Keen to understand the 

limitations this imposed and thereby better communicate the 

benefits of a product without this safety issue, the company 

approached IMS for help. Through the course of working with 

the HEOR team on several economic evaluations leveraging 

IMS LifeLink Oncology Analyzer, it had come to rely on the 

quality and rigor of the analyses and the power of the 

underlying data. 

EXPLORING THE EVIDENCE 

35.2% 

9.2% 

20.5% 

8.4% 

France 

Germany 

Total patients with at least 1 surgery for any purpose 

(curative, palliative, diagnostic) 

38.4% 

Source: Zhao A, Pelletier E, Barber B, Bhosle M, Wang S, Klingman D, Gao S Major surgery in patients with metastatic colorectal cancer in Western Europe. 

J Gastrointest Cancer, Epub 2011, Nov 29. 

Given the potential connection between surgical events and 

treatment for mCRC, and to better understand the 

implications of interruptions in therapy, the IMS team set 

out to establish the prevalence of major surgery following a 

diagnosis of mCRC. 

The retrospective cohort study used physician-survey data 

from the IMS LifeLink Oncology Analyzer database for mCRC 

patients in France, Germany, Italy, Spain and the UK. This 

includes information on patients with all types and stages of 

cancer treated by a panel of nearly 2,300 physicians at 

hospitals, private clinics and other cancer care centers across 

Europe, the US and Japan. Physicians provide case histories 

on a quarterly basis for the last 5-25 patients they have seen, 

without including the same patient’s details twice in any 12month 

period. The database records include full treatment 

history from diagnosis to current treatment, including all 

major surgical procedures (MSP), with patients segmented by 

13.4% 

Italy Spain UK 

Total patients with at least 1 surgery for curative purposes 

Total patients with at least 1 surgery for palliative purposes 

Total patients with at least 1 surgery for diagnostic purposes 

diagnosis, stage and line of therapy. Both physician 

recruitment and data collection meet exacting quality standards. 

All patients aged 21 years and over at the time of 

mCRC diagnosis were included, and MSPs were examined 

descriptively by the purpose and location of surgery. 

UNDERSTANDING THE IMPLICATIONS 

The study identified at least one MSP for any purpose 

in 30.5% (UK),35.2% (Germany), 35.6% (Spain), 36.3% (France), 

and 38.4% (Italy) of patients, indicating that major surgery 

is highly prevalent in the mCRC population, and thus has a 

significant role to play in meeting the goals of mCRC 

treatment (Figure 1). 

KEY VALUE DIFFERENTIATOR 

The results of the analysis 4 enabled the company to 

demonstrate, based on RWE, the importance of considering 

the role of pharmacological treatment options and their 

potential to interfere with both the use of surgery and 

surgical outcomes when evaluating treatment strategies for 

mCRC. With an additional study conducted by IMS indicating 

that nearly half of patients with mCRC in western Europe 

(with the exception of the UK) receive mAB therapy as part 

of their pharmacological treatment, 5 the company was able 

to further quantify the implications of the results. The 

findings have been disseminated to the broader medical 

community in several peer-reviewed publications and at 

leading conferences. • 

1 Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer, 2010:46(4):765-781. 

2 Kindler HL, Shulman KL. Metastatic colorectal cancer. Curr Treat Options Oncol, 2001;2:459-71. 

3 Van Cutsem E, Nordinger B, Cervantes A. Advanced colorectal cancer: ESMO clinical practice guidelines for treatment. Ann Oncol, 2010; 21 (Suppl 5):v93-7. 

4 Zhao Z, Pelletier E, Barber B, Bhosle M, Wang S, Klingman D, Gao S. Major surgery in patients with metastatic colorectal cancer in Western Europe. J 

Gastrointest Cancer, Epub 2011, Nov 29. 

5 Zhao Z, Pelletier E, Barber B, et al. Current chemotherapy and monoclonal antibody use patterns in metastatic colorectal cancer in Western Europe. 

35th EMSO Congress, Milan Italy, 8-12 October 2010. 


19.4% 

7.3% 

35.6% 

10.3% 

20.5% 

5.7% 

30.5% 

14.1% 

10.8% 

7.2%

IMS HEOR | OVERVIEW 

Enabling your real-world success 

IMS offers a spectrum of world-class expertise in Health Economics & Outcomes Research 

(HEOR) and real-world evidence (RWE) to deliver the local excellence you need. 

In a future where healthcare efficiency and quality are measured through the lens of ‘real-world’ 

insights, external validity demands a focus on the right data sources, best-in-class research and 

actionable communication. 

IMS is committed to helping you succeed: 

• Largest multi-disciplinary team of HEOR experts, based in 18 countries worldwide 

• Credible scientific voice and deep therapy area knowledge, captured in 200+ publications each year 

• Market leadership in developing and adapting robust economic models 

• Most advanced capabilities in RWE management and analysis leveraging relevant IMS proprietary 

and other key data assets 

• Proven expertise in generating and communicating RWE to advance stakeholder engagement at all levels 

IMS is a leading independent provider of outcomes research, economic modeling, 

RWE and market access solutions leveraging relevant IMS and other key data assets. 

Our unique, data-agnostic market position can help you develop and support the evidence 

required to engage global and local healthcare stakeholders, with deep insights into product 

safety, efficacy, cost, value for money and affordability. 

Outcomes Research 

• Evidence generation 

• Late-phase studies 

• Patient-Reported Outcomes (PROs) 

• Database studies 

• Epidemiology 

• Risk management 

Health Economic Modeling 

• Health economic evaluations 

• Core models & local adaptations 

• Budget impact 

• Meta-analyses 

• Indirect comparisons 

• IMS CORE Diabetes Model 

Market Access 

• Value development planning 

• Market access strategy 

• Core value dossiers & local adaptations 

• HTA readiness 

• Value communication 

• Reimbursement submissions 

Real-World Evidence Solutions 

• Data sourcing & validation 

• Data integration & linking 

• Data management & curation 

• Platform development 

• Customized analytics & reporting 

• Evidence planning 

Datasets 

Largest collection of scientifically validated, 

anonymized patient-level data assets: 

• Health plan claims 

• Longitudinal Rx 

• Electronic medical records 

• Hospital disease 

• Oncology 

• Diabetes 

Technology 

• Platform engines 

• Data warehouse/data marts 

• Encryption systems & linking technology 

• Meta-data repository 

• User interface & sophisticated 

analytics library 

• Electronic data capture 


Global scope, local expertise 

IMS HEOR experts are located in 18 countries worldwide and they have published on 

projects completed in more than 50 countries on all continents. 

YOUR PRIMARY CONTACTS: 

Dr. Xavier Badier 

Senior Principal HEOR 


Doctor Ferran 25-27 

08034 Barcelona 

Spain 

Tel: +34 93 749 63 00 

Xbadia@es.imshealth.com 

IMS HEOR office locations 

NORTH AMERICA 

REGIONAL HEADQUARTERS 

200 Campus Drive 

Collegeville, PA 19426 

USA 

Tel: +1 610 244 2000 

UNITED STATES 

1725 Duke Street 

Suite 510 

Alexandria, VA 22314 

USA 

Tel: +1 703 837 5150 

The Arsenal on the Charles 

311 Arsenal Street 

Watertown, MA 02472 

USA 

Tel: +1 800 783 6362 

CANADA 

303 Terry Fox Drive 

Suite 300 

Ottawa K2K 3J1, Ontario 

Canada 

Tel: +1 613 599 0711 

LATIN AMERICA 


Insurgentes Sur # 2375 

5th Floor, Col. Tizapan 

Mexico City D.F. - C.P. 01090 

Mexico 

Tel: + 52 (55) 50 62 52 00 

ext 5269 

Dr. Jacco Keja 



210 Pentonville Road 

London N1 9JY 

United Kingdom 

Tel: +31 (0) 631 693 939 


EUROPE 



London N1 9JY 


Tel: +44 (0)20 3075 4800 

BELGIUM 

Medialaan 38 

1800 Vilvoorde 

Belgium 

Tel: +32 2 627 3211 

FRANCE 

91 rue Jean Jaurès 

92807 Puteaux cedex 

France 

Tel: +33 1 41 35 1000 

GERMANY 

Erika-Mann-Str. 5 

80636 München 

Germany 

Tel: +49 89 457912 6400 

ITALY 

Viale Certosa 2 

20155 Milano 

Italy 

Tel: +39 02 69 78 6721 

Adam Lloyd 




London N1 9JY 


Tel: +44 (0)20 3075 4800 

Alloyd@uk.imshealth.com 

SPAIN 

Dr Ferran, 25-27 

08034 Barcelona 

Spain 

Tel: +34 93 749 63 00 

SWEDEN 

Sveavägen 155/Plan9 

11346 Stockholm 

Sweden 

Tel: +46 8 508 842 00 

SWITZERLAND 

Theaterstr. 4 

4051 Basle 

Switzerland 

Tel: +41 61 204 5071 

UNITED KINGDOM 


London N1 9JY 


Tel: +44 (0)20 3075 4800 

ASIA PACIFIC 


10 Hoe Chiang Road 

Keppel Towers #23-01/02 

Singapore 089315 

Tel: +65 6227 3006 

LOCATIONS | IMS 

Dr. Michael Nelson 



1725 Duke Street, Suite 510 


USA 

Tel: +1 703 837 5150 

Mnelson@us.imshealth.com 

AUSTRALIA 

Level 5, Charter Grove 

29 - 57 Christie Street 

St Leonards, NSW 2065 

Australia 

Telephone: +61 2 9805 6800 

CHINA 

7/F Central Tower 

China Overseas Plaza 

Jianguomenwai Avenue, 

Chaoyang District 

Beijing 100001 

China 

Tel: +86 10 8567 4255 

SOUTH KOREA 

9F Handok Building 

735 Yeoksam1-dong 

Kangnam-ku Seoul 

135-755 

S. Korea 

Tel: +82 2 3459 7307 

FOR FURTHER INFORMATION: email HEORinfo@uk.imshealth.com or visit www.imshealth.com/heor 

TAIWAN 

8th Floor 

No 2, Tun Hwa South Road 

Section 1 

Taipei 10506 

Taiwan 

ROC 

Tel: +886 2 2721 5337 


IMS | EXPERTISE 

Expertise in depth 

IMS has one of the largest global teams of experts in HEOR, RWE and market access of 

any organization in the world. 

Our senior team 

We apply unrivalled experience and specialist expertise to help our clients meet the demands of an 

increasingly complex global, regional and local pharmaceutical landscape. 

Our highly-qualified, multi-disciplinary consultants and researchers have proven skills and 

capabilities across all key therapy areas. Spanning industry, consulting, government and academia, 

their expertise reflects a global grasp, local experience and a unique, inside market perspective. 

The strength of our ability to support 

clients in healthcare decision making 

for health economics, outcomes research, 

RWE and market access, is built on 

the quality of our global team. 

Renée J. G. Arnold, PHARM D 

• Dr. Renée Arnold is Principal HEOR at IMS Health with particular expertise in the use of technology to 

collect and/or model real-world data to facilitate rational decision making by healthcare practitioners 

and policy makers. 

• Renée was previously President and CEO, Arnold Consultancy & Technology where she developed and 

oversaw outcomes research for the pharmaceutical, biotech and device industries as well as federal 

government programs. Her distinguished career in health economics and outcomes research includes 

roles as President and co-founder of Pharmacon International, Center for Health Outcomes Excellence 

and Senior VP and Medical Director at William J Bologna International. 

• Founding member and former Chair of the Education Committee of ISPOR, Renée has several adjunct 

appointments and is the author of numerous articles on pharmacoeconomics and cost-containment 

strategies. She holds a Doctor of Pharmacy degree from the University of Southern California in Los Angeles. 

Xavier Badia, MD, MPH, PHD 

• Dr. Xavier Badia is Senior Principal HEOR at IMS Health with extensive experience in all areas of 

outcomes research. 

• A founder of Health Outcomes Research Europe, Xavier has extensive experience in consulting and 

research outcomes, patient-reported outcomes, and effectiveness and cost-effectiveness 

evaluations. A respected scientific speaker and member of EuroQol since 1993, he serves on several 

international advisory and editorial boards and has published over 150 peer-reviewed papers. 

• Xavier holds an MD, a PhD in Medicine, and a Master’s in Public Health and Health Economics from 

the University of Barcelona. 


EXPERTISE | IMS 

Karin Berger, MBA 

• Karin Berger is Principal HEOR at IMS Health with a particular focus on outcomes research, patientreported 

outcomes, and cost-effectiveness evaluation analyses at a national and international level. 

• Formerly Managing Director of MERG (Medical Economics Research Group), an independent German 

organization providing health economics services to the pharmaceutical industry, university 

hospitals and European Commission, Karin has more than 14 years experience in the health 

economics arena. She lectures at several universities, has published extensively in peer-reviewed 

journals, and regularly presents at economic and medical conferences around the world. 

• Karin graduated as Diplom-Kaufmann (German MBA equivalent) from the Bayreuth University, 

Germany, with a special focus on health economics. 

Christopher M. Blanchette, PHD, MS, MA 

• Dr. Chris Blanchette is Principal HEOR at IMS Health, with extensive experience in retrospective database 

research and observational studies with particular emphasis on respiratory diseases. 

• Chris was previously Director of Clinical & Outcomes Research at the Lovelace Respiratory Research 

Institute, where he led a team of 50 people conducting clinical research, biostatistics, and 

outcomes research programs. He also spent time in market access and R&D health economics at 

GlaxoSmithKline, most recently as Director for Health Data Analytics, and was formerly a researcher 

at the Premier Hospital Alliance and Agency for Healthcare Research and Quality. 

• In addition to serving in leadership positions for ISPOR and several respiratory disease associations, 

Christopher is on the editorial board of the Journal of Medical Economics and advisory board of 

Current Medical Research and Opinion. He holds a PhD in Pharmaceutical Health Services Research 

and an MS in Epidemiology from the University of Maryland, and an MA in Medical Sociology from 

the University of North Carolina. 

Nevzeta Bosnic, BA 

• Nevzeta Bosnic is Principal at IMS Brogan, where she manages projects to meet the broad spectrum 

of client needs in the Canadian pharmaceutical market. 

• Formerly Director of Economic Consulting at Brogan Inc, Nev has led many strategic consulting, 

policy and data analyses for pharmaceutical clients, government bodies and academic institutions in 

Canada. She has extensive knowledge of public and private drug plans across the country and 

in-depth expertise and experience on the drug reimbursement process. 

• Nev holds a Bachelor’s degree in Business Economics from the School of Economics and Business at 

the University of Sarajevo, Bosnia-Herzegovina. 

Joe Caputo, BSC 

• Joe Caputo is Regional Principal HEOR at IMS Health leveraging more than 15 years experience in 

the pharmaceutical sector to help clients address the challenges of global reimbursement and 

market access throughout the drug development program. He has led numerous projects involving 

payer research, value dossiers, local market access models and HTA submissions. 

• With a background that spans industry roles in drug development, sales & marketing and UK & 

global health outcomes, and consulting in health economics, Joe has wide-ranging knowledge of 

the drug development process at both local and international level and a unique understanding of 

evidence gaps in light of reimbursement and market access requirements. 

• Joe holds a BSc in Applied Statistics and Operational Research from Sheffield Hallam University, UK. 

Frank-Ulrich Fricke, PHD, MSC 

• Dr. Frank-Ulrich Fricke is Principal HEOR at IMS Health and Professor for Health Economics, Georg- 

Simon-Ohm University of Applied Sciences, Nuremberg in Germany, with a focus on health economic 

evaluations, market access strategies and health policy. 

• Formerly a Managing Director of Fricke & Pirk GmbH, and previously Head of Health Economics at 

Novartis Pharmaceuticals, Frank-Ulrich has conducted health economic evaluations across a wide 

range of therapeutic areas, developing a wealth of experience in pricing, health affairs and health 

policy. As a co-founder of the NIG 21 association, he has forged strong relationships with health 

economists, physicians and related researchers working in the German healthcare system. 

• Frank-Ulrich holds a PhD in Economics from the Bayreuth University, and an MBA equivalent from 

the Christian-Albrechts-University, Kiel. 



David Grant, MBA 

• David Grant is Senior Principal HEOR at IMS Health, specializing in reimbursement and market 

access, environmental analysis, prospective and retrospective data collection and 

communications for product support. 

• A co-founder and former Director of Fourth Hurdle, David’s experience spans 10 years in health 

economics and outcomes research consulting, and 15 years in the pharmaceutical industry, 

including roles in clinical research, new product marketing and health economics in the U.K. 

and Japan. 

• David holds a degree in Microbiology and an MBA from the London Business School. 


• Dr. Jacco Keja is Senior Principal HEOR at IMS Health, drawing on deep expertise in global market 

access, operational and strategic pricing, and health economics and outcomes research. 

• Jacco’s background includes four years as global head of pricing, reimbursement, health outcomes 

and market access consulting services at a large clinical research organization and more than 

13 years experience in the pharmaceutical industry, including senior-level international and global 

roles in strategic marketing, pricing and reimbursement and health economics. 

• Jacco holds a PhD in Biology (Neurophysiology) from Vrije Universiteit in Amsterdam, a Masters in 

Medical Biology, and an undergraduate degree in Biology, both from Utrecht. He is also visiting 

Professor at the Institute of Health Policy & Management at Erasmus University, Rotterdam. 

Rob Kotchie, MCHEM, MSC 

• Rob Kotchie is Principal HEOR at IMS Health, with particular expertise in health economics, 

outcomes research, evidence-based medicine and real-world evidence. 

• Previously with ZS Associates, Rob specializes in the design and roll-out of global 

pharmacoeconomic models, the production of health technology assessment dossiers and the use of 

retrospective database analytics. He has a strong focus on the areas of cardiovascular medicine, 

oncology, respiratory and mental health, in addition to organizational design and market access 

capability assessments. 

• Rob holds a first class honors degree in Chemistry from the University of Oxford and an MSc in 

International Health Policy & Health Economics from the London School of Economics. 

Mark Lamotte, MD 

• Dr. Mark Lamotte is Principal HEOR at IMS Health with responsibility for the content and quality 

of all health economic evaluations conducted by his team. 

• A physician by training (cardiology), Mark spent a number of years in medical practice before 

joining Rhône-Poulenc Rorer as Cardiovascular Medical Advisor and later becoming Scientific 

Director at the Belgian research organization, HEDM. He has since worked on more than 150 

projects, involving expert interviews, patient record reviews, extensive modeling and report 

writing across a wide range of therapy areas, and authored many peer-reviewed publications. 

• Mark holds an MD from the Free University of Brussels (Vrije Univeristeit Brussel, Belgium) and 

is fluent in Dutch, French, English and Spanish. 

Won Chan Lee, PHD 

• Dr. Won Chan Lee is Principal HEOR at IMS Health, specializing in prospective and retrospective 

health economics research. 

• Over the course of his career, Won has completed numerous international economic evaluations 

employing a variety of analytical methods across a range of diseases and geographies. His expertise 

includes econometric database analysis, quality of life assessment and advanced economic modeling 

to establish the economic and humanistic value of new and existing therapeutic interventions. 

• Won holds a Master’s in Economics from the University of Grenoble II, and a PhD in Economics from 

the Graduate Center of the City University of New York. 

PAGE Page PAGE 60 60 IMS IMS HEALTH HEALTH ECONOMICS ECONOMICS & & OUTCOMES OUTCOMES RESEARCH 

RESEARCH


Claude Le Pen, PHD 

• Dr. Claude Le Pen is a member of the strategic committee of IMS Health and Professor of Health 

Economics at Paris-Dauphine University, providing expert economic advisory services to the 

consulting practice. 

• A renowned economist, leading academic, and respected public commentator, Claude has served 

as an appointed senior member of several state commissions in the French Ministry of Health and 

is an expert for a number of parliamentary bodies, bringing a unique perspective and unparalleled 

insights into the economic evaluation of pharmaceutical technologies at the highest level. 

• Claude studied Business Administration in HEC Business School in Paris and holds a PhD in 

Economics from Panthéon-Sorbonne University. 

Adam Lloyd, MPHIL, BA 

• Adam Lloyd is Senior Principal HEOR at IMS Health, with a particular focus on economic modeling 

and the global application of economic tools to support the needs of local markets. 

• A former founder and Director of Fourth Hurdle, and previously Senior Manager of Global Health 

Outcomes at GlaxoWellcome, Adam has extensive experience leading economic evaluations of prelaunched 

and marketed products, developing submissions to NICE and the SMC, decision-analytic 

and Markov modeling, and in the use of health economics in reimbursement and marketing in 

continental Europe. 

• Adam holds an MPhil in Economics, and a BA (Hons) in Philosophy, Politics and Economics from the 

University of Oxford. 

Charles Makin, MS, MBA, MM, BS 

• Charles Makin is Principal HEOR at IMS Health, focusing on naturalistic trials, adherence 

interventions, chart abstractions, patient-reported outcomes and other studies involving 

primary data collection. 

• During a career that includes senior roles at the UnitedHealth Group and Wellpoint, Charles has 

led numerous studies involving database analyses, economic modeling, multi-country patient 

registries, systematic literature reviews and survey-based research. 

• Charles holds a BS in Pharmacy from the University of Pune, India, an MS in Pharmacy 

Administration from Purdue University, Indiana, U.S. and an MBA in Marketing Management and 

a Master’s in Management, both from Goldey Beacom College, Delaware, U.S. 

Frédérique Maurel, MS, MPH 

• Frédérique Maurel is Principal HEOR at IMS Health, with a particular focus on observational research 

and health economics studies. 

• A skilled consultant and project manager, Frédérique has extensive experience in the economic 

evaluation of medical technologies gained in roles at ANDEM, Medicoeconomie, and AREMIS 

Consultants. 

• Frédérique holds a Masters degree in Economics – equivalent to an MS – and completed a postgraduate 

degree equivalent to an MPH with a specialization in Health Economics at the University 

of Paris-Dauphine (Paris IX) as well as a degree in Industrial Strategies at the Pantheon-Sorbonne 

University (Paris I). 

Joan McCormick, MBA 

• Joan McCormick is Principal at IMS Brogan, leading a team providing strategic advice to 

companies with new products coming to market and ongoing consultation on the rules for 

existing drugs post launch. 

• Formerly Head of Price Regulation Consulting at Brogan Inc, Joan has supported many major 

pharmaceutical companies with the preparation of pricing submissions to the Patented 

Medicine Prices Review Board (PMPRB), gaining extensive insights into the operation of the 

Canadian pharmaceutical market. 

• Joan holds a Bachelor’s degree in Life Sciences from Queen’s University in Kingston, Canada, 

and an MBA from the University of Ottawa, Canada. 

ACCESSPOINT AccessPoint ACCESSPOINT - • Issue VOLUME 3 2 ISSUE 4 PAGE Page 61 

61


Dana Morlet-Vigier, MD 

• Dr. Dana Morlet-Vigier is Principal HEOR at IMS Health, applying in-depth expertise and extensive 

experience in pharmaceutical pricing, reimbursement and market access to help clients meet the 

growing challenges of today’s increasingly complex product launch process. 

• A medical doctor and INSEAD executive, Dana’s background spans 15 years in pharmaceuticals and 

includes roles in R&D, commercial, market access, strategy and government affairs at 

GlaxoSmithKline, Organon and 3M Pharma. She has worked on numerous pricing and reimbursement 

negotiations and designed and implemented national and international Phase II, III and IV studies 

across a wide range of therapy areas. 

• Dana holds an MD from Bucharest Medical University, Romania and the Paris-Cochin Faculty, Paris, France. 

Julie Munakata, MS 

• Julie Munakata is Principal HEOR at IMS Health, with a particular focus on global economic 

modeling, value development planning, and survey data analysis. 

• An accomplished researcher and author of more than 25 original articles, Julie has extensive 

experience in managing clinical trials, health economic studies and decision analytic modeling work, 

gained in senior roles at ValueMedics Research LLC, the VA Health Economics Resource Center and 

Stanford Center for Primary Care & Outcomes Research, and Wyeth Pharmaceuticals. 

• Julie holds an MS in Health Policy and Management from the Harvard School of Public Health and a 

BS in Psychobiology from the University of California, Los Angeles. 

Michael Nelson, PHARM D 

• Dr. Michael Nelson is Senior Principal HEOR at IMS Health, with particular expertise in retrospective 

database research, prospective observational research, health program evaluation, and costeffectiveness 

analysis. 

• During a career that includes leadership roles in HEOR at PharmaNet, i3 Innovus, SmithKline 

Beecham, and DPS/UnitedHealth Group, Mike has gained extensive experience in health 

information-based product development, formulary design, drug use evaluation, and disease 

management program design and implementation. 

• A thought leader in health economics for more than 20 years, Mike holds a doctorate in Pharmacy 

and a Bachelor of Science degree, both from the University of Minnesota College of Pharmacy. He 

also served as an adjunct clinical faculty member at the University of Minnesota whilst in clinical 

pharmacy practice. 

Olaf Pirk, MD, PHD 

• Dr. Olaf Pirk is Senior Scientific Consultant to IMS Health and previously Principal HEOR at IMS 

Health, with a particular focus on health technology assessment, healthcare system research, 

health policy and health economic modeling across a range of countries and therapeutic areas. 

• Formerly a Managing Director of Fricke & Pirk GmbH, Olaf has considerable pharmaceutical 

industry experience gained in roles within health economics, pricing, health policy, marketing 

and clinical research. As a co-founder of the NIG 21 association, he has forged strong 

relationships with health economists, physicians and related researchers working in the German 

healthcare system. 

• Olaf holds an MD and PhD in Medicines from the Medical University of Lübeck. 

Jon Resnick, MBA 

• Jon Resnick is Vice President Real-World Evidence Solutions at IMS Health, leading the 

company’s global real-world evidence (RWE) business, including the development of RWE 

strategy, offerings, collaborations and foundational technologies to meet the RWE needs of 

healthcare stakeholders. 

• A former Legislative Research Assistant in Washington DC and member of the Professional 

Health and Social Security staff for the US Senate Committee on Finance, Jon has 10 years 

consulting experience at IMS. He was most recently responsible for leading the European 

management consulting team and global HEOR business teams of 300 colleagues, advising 

clients on a wide range of strategic, pricing and market access issues. 

• Jon holds an MBA from the Kellogg School of Management, Northwestern University, with a 

major in Management & Strategy, Finance, Health Industry Management and Biotechnology. 


RESEARCH


Vernon Schabert, PHD 

• Dr. Vernon Schabert is Senior Principal HEOR at IMS Health, with a particular focus on the 

assessment and validation of patient-reported outcomes (PRO) instruments, retrospective 

analyses of claims and survey databases, and primary data collection surveys. 

• A founder and former President of Integral Health Decisions, Inc, Vernon has extensive 

experience in conducting claims analyses, creating custom administrative databases, 

developing business intelligence software, and leading national quality research projects, 

gained in roles with Thomson Reuters, Strategic Healthcare Programs LLC, and CIGNA 

HealthCare. His expertise spans numerous disease areas and diverse topics including medication 

adherence, in-patient safety and outcomes in post-acute care. 

• Vernon holds a PhD in Personality and Social Psychology from Stanford University and a BA in 

Psychology from Princeton University. 

Núria Lara Surinach, MD, MSC 

• Dr. Núria Lara is Principal HEOR at IMS Health, with a particular focus on the design and coordination 

of local and international observational and patient-reported outcomes studies. 

• A former practicing GP and clinical researcher, Núria’s experience spans roles in outcomes research 

at the Institute of Public Health in Barcelona and in Catalan Health Authorities, and consulting 

positions within the pharmaceutical and medical device industries focusing on medical regulatory 

and pricing affairs, pharmacoeconomics and market access strategies. 

• Núria holds an MD (specializing in Family and Community Medicine in Barcelona), and a Master’s in 

Public Health from the London School of Hygiene and Tropical Medicine and London School of Economics. 

Christian Thielscher, MD, MBA, PHD 

• Dr. Christian Thielscher is Principal HEOR at IMS Health and Professor for Health Economics at 

the FOM University in Germany, with expertise in clinical medicine, health economics, strategic 

consulting, business administration and innovative service development. 

• Christian began his career in medical practice before moving into healthcare consulting at 

McKinsey, where he established one of the first disease management programs in Germany. He 

later founded GHX Europe where his work included developing the “health card” and the first 

German internet-based hospital guide. 

• Founding president of the DGFM eV and editor of ‘Medizinökonomie’, Christian’s current research 

interests include quality in medicine and healthcare business management and marketing. He 

holds an MD from Bonn University, an MBA, and a PhD in Economics from the University of 

Frankfurt am Main, Germany. 

Massoud Toussi, MD, MSC, PHD 

• Dr. Massoud Toussi is Medical Director HEOR at IMS Health with particular expertise in 

methodological and operational aspects of clinical research to assure the quality of interventional, 

observational and database studies. 

• Previously Head of Global Clinical Research Operations at Cegedim, Massoud has also worked at the 

French High Authority for Health and various CROs as Project Lead, Scientific Manager and 

Operations Director. His experience includes defining and elaborating a new service process in drug 

safety signal detection and transmission. 

• Massoud holds an MD from Mashad University in Iran, an MSc in Medical Informatics and 

Communication Technology from Paris IV, a PhD in Medical Informatics from Paris XIII University 

and a diploma in Transcultural Psychiatry from Paris Nord University. 

Arnaud Troubat, PHARM D, MBA, MHEM 

• Dr. Arnaud Troubat is Principal HEOR at IMS Health. He has extensive consulting experience and 

special expertise in the development of registration dossiers and market access strategies 

across a large number of therapeutic areas. 

• A pharmacist by training, Arnaud began his career at the French pharmaceutical industry 

association (LEEM), supporting members in understanding and interpreting the changing 

economical environment in France. He then spent a number of years in pharmaceutical affairs 

at ICI, leading regulatory work on registration submissions and reimbursement strategies, 

before subsequently moving into consulting. Most recently, he was Director at Carré-Castan 

Consultants, managing a team working for a wide range of pharmaceutical companies. 

• Arnaud holds a Doctor of Pharmacy degree and an MBA from IAE Paris and a Master’s in Health 

Economics and Management from Paris-Dauphine University. 


63

IMS | MEETINGS 

Conferences and events 

The global HEOR team at IMS Health play an active role in the HEOR community at 

events and conferences around the world and we look forward to meeting you and 

sharing our latest research at forthcoming meetings this year: 

Conference City Country Date 

ASCO Chicago US Jun 1-5 

ISPOR Washington US Jun 2-6 

Mount Hood 2012 Challenge Baltimore US Jun 7-8 

American Diabetes Association (ADA) Philadelphia US Jun 8-12 

HTAi Bilbao Spain Jun 23-27 

ISPE Barcelona Spain Aug 23-26 

ISPOR Taipei Taiwan Sept 2-4 

European Association for 

Study of Diabetes (EASD) 

Society of Medical 

Decision Making (SMDM) 

Berlin Germany Oct 1-5 

Phoenix US Oct 17-20 

ISPOR Berlin Germany Nov 3-7 

Visit us online 

IMS Health Economics & Outcomes Research web pages 

are at www.imshealth.com/heor 


RESEARCH

Powering a patient perspective 

LIFELINK | IMS 

Pharmaceutical companies worldwide rely on LifeLink to power patient-centered 

decisions – from the first exploratory questions that drive clinical development to 

tactical sales planning for mature brands. 

They are recognizing significant benefits, such as: 

• Better global decision making through consistent insights across all brands and across the 

product lifecycle 

• Improved internal alignment with consistent patient segments defined across Research & 

Development and Commercial functions 

• Enhanced communication with healthcare payers and other stakeholders through the use of a 

consistent patient view and common language 

• Faster and more accurate views across three key dimensions: patients, payers and prescribers 

• Confidence working with a partner who is committed to driving new metrics for new business models 

IMS has made extensive investments in anonymized patient-level data in markets around the world. 

Today, we capture information for more than 260 million patient lives - for unparalleled real-world 

treatment insights. 

Through the global IMS LifeLink program, we provide a powerful patient lens to drive focus and 

alignment across your business, deepening your understanding of critical patient, physician and 

payer dynamics. LifeLink allows you to identify the right patient segments early on, in order to gain 

competitive advantage in today’s complex environment. 

We make a patient-centered perspective easy – by integrating patient-level intelligence into our 

industry leading offerings and giving you expert consultants who apply it to your key issues. 

LifeLink provides the insights of primary research with the benefits of secondary: lower cost, 

repeatable, faster, larger sample size. 

IMS LifeLink has everything you need to succeed in a patient-centered universe. 

AN UNPARALLELED ARRAY OF ANONYMIZED PATIENT-LEVEL DATA WORLDWIDE 

CANADA 


• Drug Plan Claims 

(Oncology, hospital) 

UNITED STATES 


• Health Plan Claims 

• Oncology Analyzer 

• Electronic Medical Records 

(Oncology, ambulatory) 

• Medical Encounters 

• Hospital Charge Detail Master 

EUROPE 


(Belgium, France, Germany, Italy, 

Netherlands, Sweden, UK) 

• Electronic Medical Records 

(France, Germany, Italy, UK) 


(France, Germany, Italy, Netherlands, 

Spain, Turkey, UK) 

• Hospital Disease Database 

(Belgium) 

• Longitudinal Patient Database 

(Sweden) 

ASIA PACIFIC 


(China, Japan, South Korea, 

Taiwan) 


(Japan, South Korea) 

AUSTRALIA 



65

IMS HEALTH ECONOMICS & OUTCOMES RESEARCH 

is based in 18 countries worldwide with regional headquarters in: 

EUROPE & WORLDWIDE 


London N1 9JY 


Tel: +44 (0)20 3075 4800 

HEORinfo@uk.imshealth.com 

www.imshealth.com/heor 

ABOUT IMS 

THE AMERICAS 

1725 Duke Street 

Suite 510 


USA 

Tel: +1 (703) 837 5150 

IMS Health is the leading provider of information services for the healthcare industry around the world. The company 

draws on its global technology infrastructure and unique combination of in-depth, sophisticated analytics, on-shore and 

off-shore commercial services, and consulting platforms to help clients better understand the performance and value of 

medicines. With a presence in 100+ countries and more than 55 years of industry experience, IMS Health serves leading 

decision makers in healthcare, including pharmaceutical manufacturers and distributors, providers, payers, government 

agencies, policymakers, researchers and the financial community. Additional information is available at 

www.imshealth.com 

© 2012 IMS Health Incorporated and its affiliates. All rights reserved. 

Trademarks are registered in the United States and in various other countries. 

LATIN AMERICA 

Insurgentes Sur # 2375 

5th Floor 

Col. Tizapan 

México D.F. - C.P. 01090 

Tel: + 52 (55) 50 62 52 00 

ASIA PACIFIC 

10 Hoe Chiang Road 

Keppel Towers # 23-01/02 

Singapore 089315 

Tel: +65 6412 7365 

HEORAP0512

insights - IMS Health

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