Clinical Trials in the UK - Biotekforum
Clinical Trials in the UK - Biotekforum
Clinical Trials in the UK - Biotekforum
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<strong>Cl<strong>in</strong>ical</strong> Studies <strong>in</strong> <strong>the</strong><br />
United K<strong>in</strong>gdom<br />
Steven Knox<br />
Director, <strong>Cl<strong>in</strong>ical</strong> Research<br />
November 24, 2009<br />
SMERUD MEDICAL RESEARCH GROUP<br />
1
Summary<br />
• MHRA<br />
• Organisation<br />
• <strong>UK</strong> Regulatory Framework<br />
• Legislation, regulation and guidance<br />
• The CTA<br />
• The EC<br />
• Contract<strong>in</strong>g<br />
• <strong>Cl<strong>in</strong>ical</strong> Trial Insurance<br />
• Investigator Selection<br />
• Geographic Factors<br />
SMERUD MEDICAL RESEARCH GROUP<br />
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MHRA<br />
• The Medic<strong>in</strong>es and Healthcare products Regulatory<br />
Agency (MHRA) is <strong>the</strong> government agency<br />
responsible for drug and device approval/regulation<br />
• 10 Divisions<br />
Licens<strong>in</strong>g<br />
Vigilance<br />
Device Technology and Safety<br />
Devices, <strong>Cl<strong>in</strong>ical</strong><br />
Inspection, Enforcement & Standards<br />
Information Management<br />
Human Resources<br />
Operations and F<strong>in</strong>ance<br />
Policy<br />
Communications<br />
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MHRA: Executive Board<br />
Chief Executive<br />
Kent Woods<br />
Licens<strong>in</strong>g<br />
Ian Hudson<br />
Vigilance Risk<br />
Management of<br />
Medic<strong>in</strong>es (VRMM)<br />
June Ra<strong>in</strong>e<br />
Device Technology<br />
& Safety<br />
Clive Bray<br />
Devices <strong>Cl<strong>in</strong>ical</strong><br />
Susanne Ludgate<br />
Inspection, Enforcement<br />
and Standards<br />
Gerald Heddell<br />
Information<br />
Management<br />
Alison Davis<br />
Human Resources<br />
Geoff Le Fevre<br />
Operations and<br />
F<strong>in</strong>ance<br />
Peter Comm<strong>in</strong>s<br />
Policy<br />
Shaun Gallagher<br />
Communications<br />
Simon Gregor<br />
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MHRA: Licens<strong>in</strong>g Division<br />
Director<br />
Ian Hudson<br />
Deputy Director<br />
Siu P<strong>in</strong>g Lam<br />
Group Manager<br />
Liz Baker<br />
Group Manager<br />
David Hook<br />
Group Manager<br />
Andy French<br />
Unit Manager<br />
Leslie Whitbread<br />
PLAT 1 PLAT 2 PLAT 3 Statistics PLAT 4 PLAT 5 PLAT 6 PLPI 1 PLPI 2<br />
<strong>Cl<strong>in</strong>ical</strong><br />
<strong>Trials</strong><br />
Biologicals/<br />
Biotechnology<br />
Service<br />
Management<br />
Expert Committee<br />
Support<br />
Unit Manager<br />
Keith McDonald<br />
Unit Manager<br />
Krystyna Fielden<br />
Unit Manager<br />
Tim Berridge<br />
Unit Manager<br />
Rob Hemm<strong>in</strong>gs<br />
Unit Manager<br />
Julian Bonnerjea<br />
Unit Manager<br />
Sue Harris<br />
Unit Manager<br />
Maureen Riach<br />
Unit Manager<br />
David Guest<br />
Unit Manager<br />
Uche Abass<br />
Unit Manager<br />
Martyn Ward<br />
Unit Manager<br />
Gopalan Narayanan<br />
Service Manager<br />
Rob<strong>in</strong> Fraser<br />
PLAT (Product Lifecycle Assessment Team) Therapeutic Group<strong>in</strong>gs:<br />
PLAT 1: Cardiovascular; diabetes<br />
PLAT 2: Respiratory; ear, nose & throat (ENT); endocr<strong>in</strong>e; dermatology<br />
PLAT 3: Central nervous system (CNS); anaes<strong>the</strong>tics<br />
PLAT 4: Gastro<strong>in</strong>test<strong>in</strong>al (GI) & nutrition; blood<br />
PLAT 5: Anti-<strong>in</strong>fective; obstetrics & gynaecology; genitour<strong>in</strong>ary tract<br />
PLAT 6: Musculoskeletal; malignant disease<br />
PLAT: Risk Management, scientific advice, application assessment<br />
SMERUD MEDICAL RESEARCH GROUP<br />
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<strong>UK</strong> Regulatory Framework and <strong>the</strong> CTA<br />
• Integrated <strong>in</strong>to <strong>the</strong> International Conference on Harmonisation<br />
(ICH)<br />
• Conforms to EMEA and ICH Guidance/Regulation<br />
• Obta<strong>in</strong><strong>in</strong>g a <strong>Cl<strong>in</strong>ical</strong> Trial Authorisation (CTA)<br />
• All trials of an IMP must have a CTA approved MHRA prior to study<br />
start<br />
• EudraCT application<br />
• Review timel<strong>in</strong>e up to 60 days<br />
MHRA is currently provid<strong>in</strong>g 14-21 day review for Phase I studies<br />
• Timel<strong>in</strong>e for amendment review 35 days<br />
• Associated fees<br />
Phase I NHV £2322<br />
Phase I, Phase II or Phase III patient trial, unknown product £4202<br />
Phase I, Phase II or Phase III patient trial known product £3414<br />
Phase IV trial Protocol £262<br />
Additional protocol [same sponsor and same product (s)] £262<br />
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CTA Format<br />
• Components<br />
• Cover letter<br />
• Allocation of EudraCT Number<br />
• Application Form<br />
• <strong>Cl<strong>in</strong>ical</strong> Protocol<br />
• Investigator Brochure<br />
• Investigational Medical Product Dossier<br />
(IMPD)<br />
Format follows Directive 2001/20/EC<br />
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MHRA Interaction<br />
• Pre-Application Meet<strong>in</strong>gs:<br />
• MHRA offers pre CTA application meet<strong>in</strong>gs:<br />
Quality<br />
Safety<br />
<strong>Cl<strong>in</strong>ical</strong><br />
Paediatric forms and uses<br />
• Additional meet<strong>in</strong>gs dur<strong>in</strong>g development are available<br />
• Sponsor submits request form and provides<br />
background and questions<br />
• MHRA will assess package prior to <strong>the</strong> meet<strong>in</strong>g<br />
• Meet<strong>in</strong>gs last ~90 m<strong>in</strong><br />
• Sponsor sends meet<strong>in</strong>g notes to MHRA with 15 days<br />
• MHRA written response with 30 days of <strong>the</strong> meet<strong>in</strong>g<br />
• MHRA ; http://www.mhra.gov.uk<br />
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Multi-Regional Ethical Committee (MREC)<br />
• Application is sent to a central regional EC specific<br />
for <strong>the</strong> Pr<strong>in</strong>cipal Investigator<br />
• If more ECs are <strong>in</strong>volved <strong>the</strong>n <strong>the</strong> central EC<br />
becomes <strong>the</strong> MREC (Multi-Regional EC) which has<br />
overall responsibility for <strong>the</strong> approval process<br />
• MREC approval is required when ≥5 or NHS<br />
organisations are <strong>in</strong>volved <strong>in</strong> a study<br />
• Application to <strong>the</strong> MHRA can be performed <strong>in</strong><br />
parallel with <strong>the</strong> MREC<br />
• <strong>Cl<strong>in</strong>ical</strong> trial may commence follow<strong>in</strong>g receipt of<br />
MHRA ‘no objection’ letter and MREC approval<br />
• Notification of MREC approval is sent to <strong>the</strong> local EC<br />
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Local Research Ethical Committee (LREC)<br />
• For multi-centre studies notification of <strong>the</strong> MREC<br />
approval is sent to <strong>the</strong> Local Research EC (LREC)<br />
• For s<strong>in</strong>gle centre studies an application is made<br />
directly to <strong>the</strong> LREC<br />
• All applications to LRECs <strong>in</strong> <strong>the</strong> <strong>UK</strong> are made us<strong>in</strong>g<br />
<strong>the</strong> Integrated Research Application system (IRAS)<br />
• Timel<strong>in</strong>e for approval 60 days<br />
• No Fee applicable<br />
• Additional <strong>in</strong>formation on MREC and LREC available<br />
at<br />
• http://www.nres.npsa.nhs.uk<br />
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Additional Approvals<br />
• Research & Development (R&D) Approval<br />
• All NHS organisations must have R&D approval<br />
before any research <strong>in</strong>volv<strong>in</strong>g human participants,<br />
<strong>the</strong>ir organs, tissue or data commences<br />
• All applications for R&D approval are made<br />
us<strong>in</strong>g IRAS<br />
• No Fee applicable<br />
• F<strong>in</strong>ancial agreement<br />
• The model <strong>Cl<strong>in</strong>ical</strong> Trial Agreement (mCTA) is<br />
used by all NHS Trust sites for all cl<strong>in</strong>ical trials<br />
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<strong>Cl<strong>in</strong>ical</strong> Trial Insurance<br />
• Sponsor must provide evidence of <strong>in</strong>surance coverage<br />
• Level of coverage appropriate to risks posed, OR<br />
• If self-<strong>in</strong>sured evidence of f<strong>in</strong>ancial capacity to do so<br />
<br />
Usually judged on <strong>the</strong> basis of <strong>the</strong> latest Annual Report<br />
produced by <strong>the</strong> Sponsor<br />
• Multiple providers capable for issu<strong>in</strong>g coverage for <strong>the</strong> <strong>UK</strong><br />
First <strong>in</strong> man, 30 subjects, multiple dose ~£6,000<br />
<br />
Phase II/III dependent on risks, patient numbers etc<br />
• Study Sponsorship under EU Directive requires<br />
negligence claims are dealt with us<strong>in</strong>g standard<br />
procedures <strong>in</strong> <strong>the</strong> <strong>in</strong>dividual hospital where <strong>the</strong> patient<br />
concerned is treated<br />
• Insurance and Idemnification recommendations are<br />
available from <strong>the</strong> ABPI<br />
• http://www.abpi.org.uk/publications<br />
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<strong>UK</strong> Pharmaceutical Market<br />
• One of <strong>the</strong> world’s largest pharmaceutical markets<br />
• In 2009, <strong>the</strong> NHS budget is £98.2 billion<br />
• Estimated to be £102.3 billion <strong>in</strong> 2010<br />
• Between 2004-2008 <strong>the</strong> number of prescriptions<br />
• <strong>in</strong>creased by 22.1% (1,025.7 million)<br />
• Prescription value <strong>in</strong>creased by 3.4% (£10.3 billion)<br />
• In 2008 <strong>the</strong> lead<strong>in</strong>g <strong>the</strong>rapeutic areas<br />
• cardiovascular system (# prescriptions written)<br />
• central nervous system (<strong>in</strong> terms of value)<br />
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Population Information<br />
• Under a s<strong>in</strong>gle CA approval, access to large<br />
patient number<br />
• <strong>UK</strong> Resident Population Estimate mid 2008*<br />
• 61,383,000<br />
Median age overall: 39<br />
Even distribution up to 71 year, <strong>the</strong>n F>M<br />
< 16 years old: 3,100,000 (19%)<br />
> 65 years old: 2,600,000 (16%)<br />
• Race/Ethnicity<br />
• White British: 50,366,497 (85.67%)<br />
• White (o<strong>the</strong>r): 3,096,169 (5.27%)<br />
• Indian: 1,053,411 (1.8%)<br />
• Pakistani: 747,285 (1.3%)<br />
• White Irish: 691,232 (1.2%)<br />
• Mixed race: 677,117 (1.2%)<br />
• All o<strong>the</strong>r ≤1%<br />
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Geographic Factors<br />
• Small country<br />
• 245,000 km 2<br />
Number of People<br />
• Population dense<br />
• Metropolitan areas<br />
• London, Manchester,<br />
• Birm<strong>in</strong>gham,<br />
• Leeds-Bradford<br />
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Summary<br />
• Large commercial pharmaceutical market<br />
• Relatively High Population Density<br />
• S<strong>in</strong>gle CA approval provides relatively large<br />
capacity<br />
• <strong>Cl<strong>in</strong>ical</strong> Trial Centres<br />
Experienced <strong>in</strong>vestigators<br />
• Patient Population<br />
Medical conditions<br />
• Enrollment cont<strong>in</strong>gencies<br />
• Mature regulatory environment<br />
• Scientific advice<br />
• Strong history of drug development<br />
Extensive early phase knowledge<br />
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