How does ICES do it? - Research Data Centre

Introduction to the
Institute for Clinical Evaluative Sciences (ICES)
and ICES expansion site, ICES@Western
November 7, 2012
CPAH/RDC Statistics and Data Series at Western
Amit Garg, Director ICES@Western
Theresa Hands, Privacy Officer
Salimah Shariff, Lead Epidemiologist
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Outline
• Who are we?
• What does ICES do?
• What does ICES@Western offer?
• Where is ICES@Western located?
• When will ICES@Western be operational?
• How does ICES do it?
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Who are we?
ICES
• Independent, non-profit organization
• Conducts research that contributes to:
effectiveness, quality, equity and efficiency of
health care and health services in Ontario
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for Ontarians through research

Who are we?
Network of Health Services Research Centres
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Opened 2012
Enhancing the effectiveness of health care
for Ontarians through research

What does ICES do?
ICES goals
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• Carry out population-based health services research
that is relevant to clinical practice and health policy
development
• Document province-wide patterns and trends in
health care delivery
• Develop and share evidence to inform decisionmaking
by policy makers, managers, clinicians,
planners and consumers
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for Ontarians through research

What does ICES do?
ICES goals
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• Promote linkages among health services
researchers and decision-makers
• Train researchers and promote a wider
understanding of epidemiology and health services
research
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What does ICES do?
Examples of ICES studies
• Some of these you may have heard of….
Mortality among Patients Admitted to Hospitals on
Weekends as Compared with Weekdays (NEJM, 2001)
Cyclo-oxygenase-2 inhibitors versus non-selective nonsteroidal
anti-inflammatory drugs and congestive heart
failure outcomes in elderly patients: a population-based
cohort study (Lancet, 2004)
Unwalkable neighborhoods, poverty, and the risk of
diabetes among recent immigrants to Canada compared
with long-term residents (Diabetes Care, 2012)
Enhancing the effectiveness of health care
for Ontarians through research

ICES Ontario, Canada
linked database characteristics
Cost: if had to collect data same data prospectively or
through medical chart review very expensive.

Question
Do kidney
donors
compared to
non donor
controls of
similar health
have a higher risk of
major cardiovascular
events
when followed
for years after
donation?
Garg AX et al. BMJ 2012

We conducted a retrospective,
population-based, matched cohort
study that used large Ontario, Canada
population-based healthcare
databases

Ontario Residents
Restriction: Excluded any Ontario
resident with a medical condition before
their index date that could preclude
donation:
Randomly assigned an index date to entire Ontario i.e. population kidney disease, DM, HTN, Cancer,
(using same distribution of index dates in donors) CVD, pulmonary dx, liver dx, SLE,
chronic infections, HIV
This provided on average of 11 years of medical From records 9.6 million for baseline Ontarians assessment, this resulted in
with 99% of people having at least two years of exclusion baseline of data 85% for of review adults (15% remained)
Healthy Non-Donors
Living Kidney Donors
1992-2009
- Manual review of all charts
Date of nephrectomy
referred to as index date
(start time of follow-up)
Match each donor to 10 non-donors
Age Non-Donors (±2 years), Sex (controls)
Index of similar Date health (±6 months) as donors
Income and Residential Status

Some Baseline Characteristics
Living Kidney Donors
(N = 2028)
Non-Donors
(N = 20,280)
Age at Index Date, Years (IQR) 43 (34-50) 43 (34-50)
Age Last Follow-Up, Years (IQR) 50 (42-58) 50 (42-58)
Women 60% 60%
Follow-Up, years (range) 6.8 (0.5 to 18) 6.5 (0.1 to 18)
Follow-up, total-person years 15,176 147,332

Validated codes were used

Major cardiovascular event (death censored)
Good precision in the estimate
No difference between the groups
Donors: 1.3%; 1.7 events per 1000 person years
Non-donors: 1.4%; 2.0 events per 1000 person years
Hazard ratio 0.85, 95% CI 0.57 to 1.27

Population database strengths
• Large population-based assessment
• Databases allow for rigorous selection of non-donor controls
• F/u up to 18 years, minimal loss to follow-up. (

2) Hepatocytes
2%
Statin Metabolism
CYP3A4 Metabolized Statins
Atorvastatin, simvastatin, lovastatin
2% Systemic Availability
40%
1) Enterocytes - Small Intestine
100%
40%

Statin Metabolism + CYP3A4 inhibitor
2) Hepatocytes
80%
40%
CYP3A4 Metabolized Statins
Clarithromycin / erythromycin
inhibits CYP3A4
40% Systemic Availability
1) Enterocytes - Small Intestine
100%
+
Clarithromycin or Erythromycin
Azithromycin a macrolide
antibiotic used for similar
indications does not inhibit
CYP3A4
80%

Population Based Study of Older statin users
with new outpatient co-prescriptions
Can’t ethically randomize
Clarithro /
Erythro
(n ~ 75,000)
compared to
Azithro
(n ~ 68,000)
Question:
30 days
a patient to a potentially severe
adverse drug-drug interaction.
Hospitalization with
rhabdomyolysis
Hospitalization with AKI
Would be required to intervene
All cause mortality
at time knew about worrisome
prescription.
+ AKI based on serum
creatinine
(data in subpopulation)
Patel A et al. (under review) 2012

Baseline Characteristics by co-prescription
Clarithromycin
n=72,591
Erythromycin
n = 3,267
total n = 75,858
Azithromycin
n = 68,478
Demographics
Age, years 74 (SD 6) 74 (SD 6)
Women 40,130 (53%) 36,323 (53%)
Co-morbidities
Cerebrovascular disease 3,189 (4%) 2,765 (4%)
Peripheral vascular disease 2,101 (3%) 1,844 (3%)
Coronary artery disease 39,908 (53%) 36,950 (54%)
Congestive heart failure 12,652 (17%) 11,776 (17%)
Systemic malignancy 21,875 (29%) 19,955 (29%)

Clarithromycin
n=72,591
Erythromycin
n = 3,267
total n = 75,858
Azithromycin
n = 68,478
Statin Characteristics
Atorvastatin 55,027 (73%) 50,111 (73%)
Simvastatin 18,421 (24%) 16,369 (24%)
Lovastatin 2,410 (3%) 1,998 (3%)
High dose statin 30,296 (40%) 27,550 (40%)
Low dose statin 45,562 (60%) 40,928 (60%)
Medication use in preceding year
Oral hypoglycemic or insulin 20,367 (27%) 17,819 (26%)
Beta-blockers 29,318 (39%) 27,008 (39%)
Verapamil or diltiazem 7,941 (11%) 7,206 (11%)
Use of other calcium channel blockers 18,521 (24%) 16,982 (25%)
Potassium sparing diuretics 3,307 (4%) 2,992 (4%)
Non-potassium sparing diuretics 26,901 (36%) 24,720 (36%)
NSAIDs (excluding aspirin) 16,516 (22%) 14,797 (21%)
ACE inhibitor or ARB 49,017 (65%) 44,323 (65%)

Clarithromycin
n=2,334
Erythromycin
n = 93
total n = 2,427
Azithromycin
n = 1,488
Renal Function
serum creatinine, µmol/L 90 (76-108) 90 (76-108)
eGFR mL/min/1.73 m 2 66 (51-80) 65 (51-79)
eGFR category
≥ 90 mL/min/1.73m 2 170 (7%) 109 (7%)
60-89 mL/min/1.73m 2 1294 (53%) 782 (53%)
45-59 mL/min/1.73m 2 564 (23%) 331 (22%)
30-44 mL/min/1.73m 2 281 (11%) 199 (13%)
< 30 mL/min/1.73m 2 118 (5%) 67 (5%)

Results
Number of Events (%)
Clarithromycin/
Erythromycin
n=75,858
Azithromycin
n=68,478
Adjusted
Relative Risk
(95% CI)
Rhabdomyolysis 24 (0.03%) 10 (0.01%) 2.17 (1.03 to 4.52)
Acute kidney
injury
347 (0.46%) 176 (0.26%) 1.78 (1.52 to 2.19)
Mortality 529 (0.70%) 306 (0.45%) 1.56 (1.37 to 1.82)
Number needed to harm (death) 1 in 400

Subpopulation with Lab Values
Number of Events (%)
Clarithromycin/
Erythromycin
Azithromycin
Relative Risk
(95% CI)
n=2,427
n=1,488
Acute kidney injury
(AKIN stage 1)
47 (1.94%) 10 (0.67%) 2.92 (1.47 to 5.79)
Number needed to harm (AKI) 1 in 80
Patel A et al. (under review) 2012

Strengths
Limitations
‣ First population based study
looking at outcomes of this
drug-drug interaction.
‣ Consistent with
pharmacokinetic and case
report data.
‣ Large number of patients.
‣ Associations, therefore not
causal.
‣ Unable to analyze by specific
statin type.
‣ Analysis restricted to older
adults.
‣ Near identical baseline
characteristics table for both
groups.

How does ICES do it?
Key to ICES research
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• Ability to anonymously link population-based
health information on an individual patient basis
• Linked data allows researchers to obtain a more
comprehensive view of specific health care
issues
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Ms. Theresa Hands
Privacy Officer, ICES@Western
Enhancing the effectiveness of health care
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How does ICES do it?
How health data is generated
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• Patient enters hospital to receive care
• Person sees physician for a consult
• Elderly person lives in nursing home
CONSENT
• Given to the institution / caregiver only
• Can be explicit or implicit
• Use data for care, or for improving future care
Enhancing the effectiveness of health care
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How does ICES do it?
How health data is generated
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• Patient enters clinical study
• Person fills out survey
EXPLICIT CONSENT
• to use data for specified purpose
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How does ICES do it?
Ontario Privacy Law: PHIPA (2004)
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• Personal Health Information Protection Act
• No use of Personal Health Information
(PHI) without consent
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How does ICES do it?
So… how can we do our work?
EXCEPTION: “Prescribed Entities”
• 4 of these in Ontario
Pediatric Oncology Group of Ontario (POGO)
Cancer Care Ontario (CCO)
Canadian Institute for Health Information (CIHI)
Institute for Clinical Evaluative Sciences (ICES)
Enhancing the effectiveness of health care
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How does ICES do it?
Privacy
• ICES is a prescribed entity under PHIPA 2004 (s. 45[1]
and O. Reg 329/04 section 18[1] ): Disclosure for
planning and management of the health system
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• Health information custodians may disclose personal
health information (PHI) to ICES for the purposes of:
• Analysis and compiling statistical information related to
managing the health system
allocation of resources
evaluation and monitoring
planning for all or part of the health system
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How does ICES do it?
Prescribed Entities
• Have policies, practices and procedures in place to
protect the privacy interests of the individuals and
the capacity to make sure it is kept securely
• The Ontario Information and Privacy
Commissioner (IPC) has reviewed and approved
these policies, practices and procedures
• The review / approval is renewed every three years
• VERY big deal!
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Dr. Salimah Shariff
Lead Epidemiologist, ICES@Western
Enhancing the effectiveness of health care
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How does ICES do it?
Key to ICES research
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• Ability to anonymously link population-based
health information on an individual patient basis
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How does ICES do it?
Data sources – Patient-level data
• Health Services Databases
“transactions” of health care utilization
Ontario Health Insurance Plan Claims (OHIP)
Discharge Abstracts for Inpatient Hospitalizations
(CIHI DAD)
Same Day Surgery (CIHI SDS)
National Ambulatory Care Reporting System (NACRS)
Ontario Drug Benefit Claims (ODB)
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How does ICES do it?
Data sources – Patient-level data
• Disease Cohorts/Registry Databases
Received from partner organization
Ontario Cancer Registry (OCR)
Canadian Organ Replacement Register (CORR)
ICES Derived Databases
Ontario Diabetes Database (ODD)
Linkage of delivering mothers to their newborns
(MOMBABY)
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How does ICES do it?
Data sources – Patient-level data
• Externally Linked Data Sources
Chart reviews
Electronic medical records (ex. Cerner)
Surveys
• Statistics Canada
(Canadian Community Health Survey - CCHS)
• Interviews, questionnaires
Research datasets
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How does ICES do it?
Data sources – Patient-level data
• Patient-level data sources can be linked to
each other using unique patient identifiers
ICES Key Numbers (IKN)= Encrypted OHIP #
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How does ICES do it?
Data sources – Supporting data
• Population and Demographic Data
Registered Persons Database files (RPDB)
Population Estimates
Canadian Census Profiles
PCCF+ (StatsCan postal code conversion file)
Citizenship and Immigration Canada
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How does ICES do it?
Data sources – Supporting data
• Other Supporting Data Sources
Care providers (all physicians in Ontario)
Facilities and Institutions
Management Information System (MIS;
financial and statistical data for hospitals)
Geographic conversion tables (LHIN, Census
Subdivisions, Counties, Residence codes, etc)
Coding tables (ICD9, ICD10, CCP, CCI, OHIP)
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How does ICES do it?
Linking datasets
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• All data sources can be linked at various levels
IKN
RPDB
Health
care
facilities
Facility
Identifier
Patientlevel
Physician
Identifier
Care
providers
Postal Code, LHIN
Population
&
Geography
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for Ontarians through research

What does ICES@Western offer?
Process for intaking ICES studies
1. Develop a research question
Do we have the data you need?
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2. Identify ICES Scientist
Only ICES Scientists can access ICES data for
research
Principal investigator or co-principal investigator must
be an ICES scientist
Must participate fully in the research project
Responsible party within ICES
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What does ICES@Western offer?
Process for intaking ICES studies
3. Submit 1-page research proposal &
Privacy Impact Assessment (PIA)
Reviewed by a lead Scientist
PIA used to ensure privacy requirements at ICES
mandated by the “Personal Health Information
Protection Act” (PHIPA)
Ensures that project conforms to ICES policies and
procedures
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What does ICES@Western offer?
Process for intaking ICES studies
4. Submit Project Activation Worksheet (PAW)
Required in order to activate the project
Provide estimate of resources and time for project
(budget)
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5. Request REB approval from Western
Submit to Health Sciences REB, Delegated Review
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What does ICES@Western offer?
Process for intaking ICES studies
6. Develop Dataset Creation Plan (DCP)
Study design
Data sources and data elements
Time-frames
Inclusion/Exclusion criteria
Variable definitions
• Exposure
• Outcomes
• Other variables
Analytic plan
Output tables
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for Ontarians through research

What does ICES@Western offer?
Process for intaking ICES studies
7. Submit project for execution at ICES@Western
Reviewed by lead epidemiologist/analyst
Entered into the queue
Analyst assigned
• Only ICES staff and faculty have access to ICES data
holdings
• Analysts are trained and have expertise in conducting
health administrative database research
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What does ICES@Western offer?
Process for intaking ICES studies
8. Project commences
Continuous communication with analyst & study
team
May require modifications to DCP
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9. Results provided
Aggregate level
Results with fewer than 6 individuals are reported as
“

What does ICES@Western offer?
Things to consider
• Cost
Cost recovery
• Project must have grant (or other) money
• Staff time is billed to investigator
Grant support letter
• Must be submitted at least 4 weeks prior to grant
submission deadline
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• Time
Projects vary in time depending on scope and
resources required
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What does ICES@Western offer?
Services we can provide
• Epidemiological
Literature searches
Study design/methodology, DCP advice
• Biostatistical
Analytic design advice
• Administrative
Grant support letters
REB submission
New data linkages
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What does ICES@Western offer?
Services we can provide
• Support for Graduate Student Training
Work closely with an analyst
Have limited access to data
Can perform own analyses
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What does ICES@Western offer?
Services we can provide
• Faculty Scholars Program
www.iceswestern.ca
Open to all Western Faculty
Training, mentorship, epidemiologic and analytic
support to help Scholars develop and complete a
minimum of one ICES study
Guidance on grant writing and manuscript preparation
Applications accepted until February 2013 for
program commencement in September 2013
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When & Where
ICES@Western
• When will we be operational?
January, 2013
Process for new projects can start NOW
• Where are we located?
ELL-218 (within Pharmacy hallway)
Victoria Hospital, E-Tower, Lower Level
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Contact Us
ICES@Western
• Amit Garg, Director ICES@Western
amit.garg@lhsc.on.ca
519-685-8502
• Theresa Hands, Privacy Officer
theresa.hands@lhsc.on.ca
519-685-8500 x56045
• Salimah Shariff, Lead Epidemiologist
salimah.shariff@ices.on.ca
519-685-8500 x56555
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Questions?
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