European Clinical Trial Regulation 

Liz Philpots, head of research, AMRC

Summary

• About me & AMRC

• About the EU Clinical Trials Regulation – what’s new

• Implementation timeline

• What does this mean for UK ethicists?

AMRC established 1987

133 member charities…from large to the small

• All fund medical research

• Spend more than £1Bn on research

• 1/3 of medical research in UK

• Strong drive to benefit people affected by their condition

• 30% of studies in the NHS

A brief history of trial regulation

pre-2001 - national regulation (e.g. CTX Scheme in the UK)

2001 - GAFREC – ethics committees - EU ‘Clinical Trials’ Directive 2001/20/EC 2004 – UK law - Medicines for Human Use (Clinical Trials) Regulations

2005 - Good Clinical Practice Directive 2005/28/EC

BUT – EUCTD seen as a barrier to research:• 25% drop in trials in EU• increased costs• massive increase in delay to get trial started

2012 – proposal for new regulation

Some major issues with EUCTD

• interpretation by Member States not consistent

• lack of clarity over definitions and requirements

• cumbersome procedures, particularly for multi-centre clinical

trials in different Member States

The New EU Regulation on Clinical Trials

• the new EU Regulation (No 536/2014) on clinical trials on medicinal products for human use (and repealing Directive 2001/20/EC) was adopted on 16th April 2014

• it entered into force on 16 June 2014, but will apply no earlier than 28 May 2016 (in the meantime existing provisions continue to apply)

• it’s a regulation - will apply directly to each EU Member States

What’s different -processes?

• a streamlined application procedure via a single entry point - an EU portal and database

• a single authorisation procedure for all clinical trials

• a lighter regulatory regime for low risk clinical trials

• streamlined safety reporting

• strengthened transparency for clinical trials data

What’s different - principles

• clinical trials are a subset of clinical studies

• trial participants should represent the population that might benefit from the

treatment

• co- sponsorship

• encouragement for clinical trials in rare diseases or of orphan products

• ethics committees should be independent and involve lay people

What’s different - consent

• enrolment without informed consent in emergency situations

• simplified consent process for ‘cluster trials’

• special consideration for

• incapacitated subjects

• minors

• pregnant & breast feeding women

• military personnel, prisoners, people in residential care institutions

What’s different - jargon

• RMS

• CMS

• Low intervention clinical trials

Processes - streamlined application procedure

• sponsor must submit an application via an EU online portal

• single entry point for application, assessment and subsequent data

submission

• better communication between sponsor and authorities, and between

authorities in the relevant Member State

• greater transparency of CTs and of the results of CTs

• BUT - the portal needs to be built…..

Processes - single authorisation procedure - I

• for multinational CTs all Member States will be involved in the assessment,

although a ‘Reporting’ Member State (RMS) will lead and coordinate the

assessment

• Member States will retain responsibility for aspects which are entirely

national for example, informed consent, and compensation arrangements

• authorisation process timelines are specified whilst retaining the concept of

‘tacit authorisation’

• possible to extend the CT to additional Member States and clarifies when a

new CT authorisation is required

Processes - single authorisation procedure - II

Each country (CMS) inputs into Part I and conducts its own Part II assessment.

Part I: Reporting member state (RMS) –scientific assessment

Part II: National assessment by each country of site details, ethics, etc :

Processes for authorisation

Processes - low interventional clinical trials

• proportionate rules for monitoring, reporting, traceability and storage of investigational products

• ‘low interventional’ means - authorised medicines used within the terms of their

authorisation OR - ‘off-label’ use of medicines that is supported by appropriate

evidenceAND - trial procedures with minimal additional risk or burden to the

safety of the trial participants

Processes - transparency

• EU portal provides a systematic and transparent way to log CT lifecycle events

• sponsors must submit a publically available summary of the results of the CT within one year of its end, irrespective of the outcome of the trial

• where an EU Marketing Authorisation is granted, a full clinical study report will have to be submitted for publication on the EU database

• all CT must also provide a simplified summary of results for public audience

Implementation timeline

Adopted 16 April 2014

Portal fully functional…..

Dec 2015?

Entry into force28 May 2016

6 MONTHS

What does this mean for UK ethicists?

• Much stays the same

• It’s all about the portal …

• portal needed for implementation

• national systems need to ‘speak’ to the portal

• planned –Dec 2015 ….. watch this space

Thank you

Regulation: http://ec.europa.eu/health/files/eudralex/vol-1/reg_2014_536/reg_2014_536_en.pdf

Dr Liz Philpotsl.philpots@amrc.org.uk

www.amrc.org.uk