Présentation PowerPoint - EBMT

Clinical Trials (General Talk) Liz Clark, EBMT CTO London London – 9th April 2013

www.ebmt.org

Agenda

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Definitions and acronyms Clinical trial process Regulations, Ethics and Pharmacovigilance Quality Trial Coordination Further information

Clinical Trials (General Talk) – Liz Clark

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Definitions and Acronyms

Clinical Trials (General Talk) – Liz Clark

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Definitions • A clinical trial = – Investigation in human subjects – To discover or verify the clinical, pharmacological and/or pharmacodynamic/pharmacokinetic (PD/PK) effects of one or more medicinal products – To identify adverse reactions • CTIMP – Clinical Trial of an Investigational Medicinal Product – CTIMP is a legal definition Clinical Trials (General Talk) – Liz Clark

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Definitions • Prospective clinical trials – Investigate future events, following a clinical trial protocol. – Prior ethics committee and regulatory approval are needed. – For drugs without a marketing approval or for a new indication.

• Non-interventional prospective studies – Investigate future events, following standard hospital practice (no protocol). – Data collection does not interfere with the choice of treatment, sample collection, procedures, or the treatment itself.

• Retrospective studies – Use information on past events (from the registry plus requests for new data on past events).

• Algorithm - http://www.mhra.gov.uk/home/groups/lunit1/documents/websiteresources/con009394.pdf Clinical Trials (General Talk) – Liz Clark

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Definitions • Prospective clinical trials – Investigate future events, following a clinical trial protocol. – Prior ethics committee and regulatory approval are needed. – For drugs without a marketing approval or for a new indication.

• Non-interventional prospective studies – Investigate future events, following standard hospital practice (no protocol). – Data collection does not interfere with the choice of treatment, sample collection, procedures, or the treatment itself.

• Retrospective studies – Use information on past events (from the registry plus requests for new data on past events).

• Algorithm - http://www.mhra.gov.uk/home/groups/lunit1/documents/websiteresources/con009394.pdf Clinical Trials (General Talk) – Liz Clark

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Common jargon / terms • Randomised:

which arm depends on chance • Placebo-controlled or gold standard treatment

• Treatment blinding: • Double-blind: • Single-blind: • Open:

neither doctor nor patient know the patient does not know everyone knows

• Study design: • Crossover: • Parallel group:

subjects receive all arms sequentially different groups receive different arms

• Pharmacovigilance: safety reporting • Investigator initiated trials (IIT) / post-marketing trials

Clinical Trials (General Talk) – Liz Clark

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Common Acronyms • • • • • • • • • • • • •

(S)AE – (serious) adverse event CRA – clinical research associate (monitor) CRF – case report form CRO – contract research organisation CSR – clinical study report DSMB – data safety monitoring board / committee (IDMC) IB – Investigator’s Brochure ICF – information and consent form / patient information leaflet (PIL) IEC – independent ethics committee / IRB – institutional review board IMP – investigational medicinal product GCP – good clinical practice (GLP, GMP, GxP) SMO – site management organisation TMF – trial master file (essential documents)

Clinical Trials (General Talk) – Liz Clark

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The Drug Development Process

License approved

Clinical Trials (General Talk) – Liz Clark

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Trial Phases Phase

Aim

Subjects

Preclinical

In vivo and in vitro tests to determine toxicity profile and effective doses of an NME

N/A

0

Initial PK – micro-doses (radiolabeled) – select drug candidates Reduced data package needed for regulatory No safety or tolerability

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1

Safety and tolerability (pharmacology) Dose range selection (FTIM, SAD, MAD) Identify side effects

20-80 healthy volunteers (not oncology = 20-30 patients)

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Effectiveness (exploratory) Dose response Safety

50-300 patients

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Effectiveness (confirmatory) Compare to common treatments Safety and side effects

100s-1000s patients

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Post-marketing surveillance Effectiveness and safety in general population Optimising treatment protocols