Science and Technology CommitteeWritten evidence submitted by Michael Power

I am responding only to the fourth question “How could the occurrence and results of clinical trials be made more open to scrutiny? Who should be responsible?”

1. Clinical trials could be made more open to scrutiny by including a statement in the consent form that de-identified data would be made publically available.

2. The National Research Ethics Service (NRES) of the NHS Health Research Office have a template for informed consent on their website. This template should be updated to include a statement about making trial data freely available—even if this is not specifically required by the ICH guidelines on Good Clinical Practice (discussed in paragraph 4) or by the forthcoming European Union Regulation on Clinical Trials. The statement should include:

(a)A commitment to make all the data from the trials, suitably anonymized, publically and freely available on the internet without unreasonable delay. Data should be in a form suitable for statistical analysis. The Committee may want to clarify what delay would be reasonable. Because the end of a trial and the publication of a research report can be manipulated, their dates should not be used to define “reasonable delay”.

(i)Peter C Gøtzsche, director of the Nordic Cochrane Centre, makes similar recommendations for improvements to the new European Union Regulation on Clinical Trials—see Gøtzsche PC. Deficiencies in proposed new EU regulation of clinical trials. BMJ 2012;345:e8522 doi: 10.1136/bmj.e8522.1

(ii)The European Medicines Agency intends to require trial data to be made available in form suitable for statistical analysis—see European Medicines Agency. Access to clinical-trial data and transparency. Workshop report. 2012.2

(b)An explanation of how data will be anonymized, how it will made available, and when it will be published (for example within two years of the planned termination date, or within two years of the actual termination date if this is earlier.)

(c)Assurance that the results of this research will be made available to other researchers in complete detail, subject only to full protection of identity, and cannot be withheld by the organisation conducting the trial.

(d)Assurance that the ethics committee will ensure that these commitments are upheld, and that any investigators who do not comply would be subject to professional discipline and would not be allowed to conduct human research in the future.

3. The International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH) brings together the regulatory authorities and pharmaceutical industry of Europe, Japan, and the US. The ICH develops and publishes a number of guidelines that aim to ensure that “safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner”. A certificate of training in the ICH guidelines on Good Clinical Practice (GCP) is required for the principal investigator of clinical trials conducted in NHS facilities. The ICH should update its GCP to include the same statement suggested in paragraph 3 for the NRES template.

4. All UK universities and NHS Trusts require the protocols of clinical trials to be approved by their Research Ethics Committees. These committees should ensure that clinical trial protocols and consent form are made public, and that the consent form adheres to the standards set by the NRES template for informed consent.

5. The Research Councils UK (RCUK)—the strategic partnership of the UK’s seven Research Councils—should remove the hedging from the part of their definition of unacceptable research conduct that refers to failure to “make relevant primary data and research evidence accessible to others for reasonable periods after the completion of the research”. The statement should be reworded along the lines of “make all primary data accessible within a reasonable period after the start of the research”.

6. The RCUK, the Medical Research Council and other research funders, the UK University Research Ethics Committees Forum, and the Association of Research Ethics Committees should use their influence to ensure that researchers and their employers are aware of the need to include a statement about availability of data in the informed consent forms for clinical trials.

7. Guidelines on how clinical trials are reported3 should be updated to include an appropriate statement of data availability in the study consent form.

8. Journals should require authors of clinical trial reports to follow guidelines such as CONSORT.

9. Guidelines on assessing the quality of evidence (such as the GRADE system) and manuals for developers of evidence-based guidance (such as the NICE “Guidelines manual”) should include in their criteria for assessing the risk of bias in a research report the presence of a statement explaining how and when primary data will be publically available.

10. Declaration of interests. I have no potential or actual financial interests that would be affected by the Committee’s recommendations. However, as a clinical researcher, a tax-payer willingly funding the NHS (which funds both healthcare and research), a patient, the Evidence-Based Practice Lead in my NHS Trust, and someone whose request for de-identified data from a clinical trial has been refused, I have multiple interests in the Committee’s recommendations.

January 2013

APPENDIX

EVIDENCE SUMMARY ON WHAT UK-RELEVANT POLICIES/GUIDELINES THERE ARE ON MAKING CLINICAL TRIAL DATA AVAILABLE

Institution
Policy/guidance

Statement that data must be made available

Statement that informed consent should include making data available

Medical Research Council

Weak

Nil

Good research practice: Principles and guidelines

August 2012

www.mrc.ac.uk/consumption/idcplg?IdcService=GET_FILE&dID=36739&dDocName=MRC002415&allowInterrupt=1

“Extending access, through initiatives such as data sharing, promotes the efficient use of resources for new research, assures the quality of research outputs and helps to maximise the impact of outputs on health”

“For all research involving people as participants, their tissues or data, the relevant principles of Good Clinical Practice (GCP), an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects, should be followed (13). Where practicable, consent that is freely given and informed should be sought from all competent participants. Guidance on writing participant information is available from the National Research Ethics Service (NRES)(14); this includes guidance for research that involves adults who lack capacity to give consent or children (15).”

 

International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use.

Good Clinical Practice: ichgcp.net

Nil

Nil

“2.9 Freely given informed consent should be obtained from every subject prior to clinical trial participation.”

3.1.2 The IRB/IEC should obtain the following documents:

trial protocol(s)/amendment(s), written informed consent form(s) and consent form updates that the investigator proposes for use in the trial, subject recruitment procedures (eg advertisements), written information to be provided to subjects, Investigator’s Brochure (IB), available safety information, information about payments and compensation available to subjects, the investigator’s current curriculum vitae and/or other documentation evidencing qualifications, and any other documents that the IRB/IEC may need to fulfil its responsibilities.

 

NHS Health Research Office

National Research Ethics Service (NRES)

www.nres.nhs.uk/applications/guidance/consent-guidance-and-forms/

Medicines for Human Use (Clinical Trials Regulations) 2004. Informed consent in clinical trials

www.nres.nhs.uk/applications/guidance/consent-guidance-and-forms/?entryid62=66934

Nil

Nil

“25. The ethics committee that reviews a clinical trial (referred to in this note as ‘the main REC’) must consider various matters before giving its opinion. These include:

The adequacy and completeness of the written information to be given, and the procedures to be followed, for the purpose of obtaining informed consent to the subjects’ participation in the trial.”

 

NHS Health Research Office

National Research Ethics Service (NRES)

Consent form template

www.nres.nhs.uk/EasysiteWeb/getresource.axd?AssetID=143371&type=full&servicetype=Attachment

Nil

Nil

“I understand that relevant sections of my medical notes and data collected during the study, may be looked at by individuals from [COMPANY NAME], from regulatory authorities or from the NHS Trust, where it is relevant to my taking part in this research. I give permission for these individuals to have access to my records.”

 

University of Newcastle

Nil

Nil

 

Research and Enterprise Services
Consent Form

www.ncl.ac.uk/res/research/ethics_governance/ethics/toolkit/consent/consent_form.htm

“The use of the data in research, publications, sharing and archiving has been explained to me.”

 

Research Councils UK (RCUK)—the strategic partnership of the UK’s seven Research Councils.

Policy and Code of Conduct on the Governance of Good Research Conduct October 2011

www.rcuk.ac.uk/Publications/researchers/Pages/grc.aspx

Weak

NIL

UNACCEPTABLE RESEARCH CONDUCT

Mismanagement or inadequate preservation of data and/or primary materials, including failure to:

“Appropriate procedures to obtain clearly informed consent from research participants—should be in place”

make relevant primary data and research evidence accessible to others for reasonable periods after the completion of the research:

 

UK University Research Ethics Committees Forum

N/A

N/A

An informal forum for those involved in research ethics review in UK Universities

 

Association of Research Ethics Committees

N/A

N/A

www.arec.org.uk/

 

Universities UK

Weak

Nil

Our five current strategic priorities are:

5. research funding and governance

www.universitiesuk.ac.uk/PolicyAndResearch/Pages/default.aspx

The concordat to support research activity

www.universitiesuk.ac.uk/Publications/Pages/concordattosupportresearchintegrity.aspx

“Transparency and open communication in … in making research findings widely available, which includes sharing negative results as appropriate…”

 

Government Office for Science (www.bis.gov.uk/go-science)

Rigour, Respect, Responsibility: a Universal Ethical Code for Scientists

www.bis.gov.uk/assets/goscience/docs/u/universal-ethical-code-scientists.pdf

European Union Regulation on Clinical Trials

Weak

NIL

Proposal for a Regulation of the European Parliament and of the Council on clinical trials

on medicinal products for human use, and repealing Directive 2001/20/EC. European

Commission. 2012 ec.europa.eu/health/files/clinicaltrials/2012_07/proposal/2012_07_proposal_en.pdf

3.6 Directive 2001/20/EC contains relatively few rules on the actual conduct of trials. These rules are partly contained in Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products12, and partly contained in Commission guidance documents. The proposed Regulation brings together these rules.

3.13. In particular, the protocol shall include:

a description of the publication policy

duly substantiated reasons for submission of the summary of the results of the clinical trials after more than one year

1 Published online 20 December 2012 at www.bmj.com/content/345/bmj.e8522.

2 www.ema.europa.eu/docs/en_GB/document_library/Report/2012/12/WC500135841.pdf.)

3 Such as the CONSORT statement—www.consort-statement.org/

Prepared 16th September 2013