1. Good Clinical Practice in Research Clinical Trial Regulations
Zoe Whale / Lynette Lane
GCP Facilitators, NISCHR CRC

2. Objectives At the end of this session, I hope you will be able to:
Understand there is a set of interwoven laws, guidelines and
frameworks which govern the set up and conduct of clinical research
Understand what CTIMP and non-CTIMP studies are, the differences
between them and the regulatory requirements which govern their conduct
See GCP as a ‘live’ subject which is about continually improving the way things are done
Share your experiences of applying GCP to your own research field

3. What is the significance of regulation and standards in clinical research?
Safeguard and protect research subjects
Risk reduction
Quality data/outcomes
Excellent research, good science

4. Can anyone give me examples of ‘bad’ or ‘poor’ research?

5. Ethical standards to protect people have been around for over 60 years
Standards in Research are not new
Ethical standards to protect people have been around for over 60 years

6. Research Governance Framework for Health and Social Care in Wales 2009
The framework applies to all research that relates to the responsibilities
of the Secretary of State for Health
“… research concerned with the protection and promotion of public health,
research undertaken in or by the Department of Health, its non
Departmental Public Bodies and the NHS, and research undertaken by or
within social care agencies. It includes clinical and non-clinical research”
The framework is not law but must be adhered to for all studies conducted in Wales

7. EU Legislation UK Legislation ‘Guidance’
Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 1031)
EC Commission
Eudralex – Volume 10 Clinical Trial guidelines
EU Clinical Trials Directive 2001/20/EC
Medicines for Human Use (Clinical Trials) Amendment Regulations 2006 (SI 1928)
ICH GCP Topic E6 – Good Clinical Practice
EU GCP Directive 2005/28/EC
Amendment 2006 (SI 2964)
Research Governance Framework for Health and Social Care
Amendment 2008 (SI 941)
Amendment 2009 (SI 1164)
Organisation/Sponsor SOPs
Amendment 2010 (SI 1882)

8. What is all the fuss about?
Prior to 2004 the standards were guidelines and dual standards
existed
For the first time ethical and scientific standards for the set up, and
conduct of clinical research involving human subjects receiving
investigational medicinal products, became subject to law

9. European Directives & UK Laws
EU Directives are legislation issued by the European Union defining an
outcome or change that is binding for each member state
EU Directives must be transposed into law in each member state to
become law in that country
In the UK this is achieved by the introduction of a Statutory Instrument
named within an Act of Parliament, which then becomes the law

10. European Clinical Trials Directive 2001/20/EC
Introduced to ensure that everyone follows the same GCP standards
Clarified and standardised practice for the safety of the subject and the
quality of the data
Refers to the Core Principles of ICH GCP (as a scientific guideline),
especially Principles 5,7,11,12 and 13
Major areas of change included:
- The ethics review system came under the law
- Each member state had to appoint a Competent Authority (MHRA in UK)
- Strengthened consent for vulnerable groups
- Amendments required to follow a process
- Additional safety reporting requirements
- All results have to be made available even if negative findings
were found

11. GCP principles are a standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality of trial subjects are protected
Imagine you have been asked to participate as
a subject in a clinical study or trial
What would you want to know about the study and the people involved in its conduct before taking part?

12. GCP elements : MHRA inspection areas
Trial initiation, approvals and completion
Responsibilities of organisations and individuals
Recruitment and informed consent processes,
Documentation and data quality
Safety reporting /pharmacovigilance

13. Medicines for Human Use (Clinical trials) Regulations 2004
Statutory Instrument 2004/1031
Transposed European Clinical Trials Directive 2001/20/EC into UK Law from
1 May 2004
Made amendments to the Medicines Act 1968 which regulated the supply of
medicines for a clinical trial, but did not cover standards of conduct on a
clinical trial
SI 2004/1031 regulates the commencement and conduct of a clinical trial and
the manufacture of medicinal products to be used (including placebo)

14. European Clinical Trials Directive 2005/28/EC
The second EU Directive clarified and extends the first
Major areas of change included:
- Duties can be delegated, but not responsibilities
- New requirements on sponsor and investigators in relation to Trial
Documentation
- Notification of serious breaches
Statutory Instrument 2006/1928
Transposed European Clinical Trials Directive 2005/28/EC into UK Law from
29 August 2006
Makes amendments to the Medicines for Human Use (Clinical Trials)
Regulations 2004

15. All are available on the MHRA website
UK Regulations
There have also been subsequent Statutory Instruments which govern the conduct of clinical research in the UK.
The Statutory Instruments are:
2004/1031 (1 May 2004) – EU Directive 2001/20/EC transposed into law
2006/1928 (29 August 2006) – EU Directive 2005/28/EC transposed into law
2006/2984 (12 December 2006) – A&E trials without consent for adults without
capacity
2008/941 (1 May 2008) – Research Ethics Committee membership and approval
2009/1164 (8 May 2009) – Urgent safety measures
2010/1882 (19 August 2010) – Advanced Therapy Medicinal Products
All are available on the MHRA website

16. In addition …
Researchers work within other guidelines and laws, including
Data Protection Act (1998)
Protection of Children Act (1999)
Mental Capacity Act (2005)
Human Tissue Act (2004)
Equality and Diversity Legislation
Freedom of Information Act (2000)
Welsh Language Act 1993/ 2011
Health Board Policies

17. Some update areas
2010 e-SUSAR reporting to MHRA : expedited safety reporting
2010 public consultation on proposals for amending adverse reaction reports (CT3)
2010 Academy of Medical Sciences Review – recommendations to streamline bureaucracy and reduce costs
2011 the DSUR (Development Safety Update Report) will replace the Annual Safety Report
2011 MHRA develops risk-adapted approaches to approvals, monitoring and inspection

18. CTIMPS and Non-CTIMPS
A Clinical Trial of an Investigational Medicinal Product (CTIMP) is a legal
definition and describes those trials which fall within the scope of the
Medicines for Human Use (Clinical Trials) Regulations 2004
Non-CTIMPS are studies which do not use IMPs as defined by the
Medicines and Healthcare products Regulatory Agency (MHRA)
The rules governing medicinal products in the European Union
Guidance documents on the MHRA website includes an algorithm to
help you decide whether your study is a CTIMP or non-CTIMP

19. CTIMP and Non CTIMP Requirements CTIMPs Non-CTIMPs
Must identify a sponsor
Require a favourable ethical opinion
from a research ethics committee
Require host (R&D) approval to conduct
the study
Must maintain a study master file
Must receive consent from the volunteer
Must collect accurate data
Must create a clear audit trail
Must be aware of the safety reporting
requirements
Must conduct the study to Good Clinical
practice guidelines
Must demonstrate financial transparency
Must be adequately funded
Must identify a sponsor
Require a favourable ethical opinion
from a research ethics committee
Require host (R&D) approval to conduct
the study
Must maintain a study master file
Must receive consent from the volunteer
Must collect accurate data
Must create a clear audit trail
Must be aware of the safety reporting
requirements
Must conduct the study to Good Clinical
practice guidelines
Must demonstrate financial transparency
Must be adequately funded

20. CTIMP and Non CTIMP Requirements CTIMPs Non-CTIMPs
Are governed by law and come under the
jurisdiction of the UK competent
authority: Medicines and Healthcare
products Regulatory Agency (MHRA)
Must receive a Clinical Trials
Authorisation
Must register for a EudraCT number
(European Clinical Trials Database)
Are subject to mandatory inspections
Introduced Good Manufacturing
Practice
Are governed by the NHS Research
Governance Framework

21. In summary …
We have standards to protect research participants and data quality
In health and social care research in Wales, we work to the standards set out
in:
- Research Governance Framework for Health and Social Care (2009)
- Statutory Instruments for CTIMPs brought into law through the Medicines for
Human Use (Clinical trials) Regulations 2004
A set of interwoven frameworks, guidelines and laws govern the set-
up and conduct of health and social care research
Requirements for CTIMP and Non-CTIMP studies are largely the
same, with some additional requirements for CTIMPs

22. Thank you - Any Questions?