Science and Technology CommitteeWritten evidence submitted by the Committee on Publication Ethics (COPE)

Executive Summary

1. There are several stages in the review process for clinical trials at journals which could enable improvements in transparency of trials and their reporting.

2. COPE is committed to improving the transparency around clinical trial reporting and data disclosure. Specific actions that editors and journals can undertake are improving compliance with the requirement for registration of trials, clinical trial reporting and enabling increased availability of data from these trials.

3. However, it not realistic to assume that journals alone can enforce compliance with requirement for trial registration and trial reporting without overarching mandates from funders and government, accompanied by specific penalties for non-compliance.

Background on COPE

4. COPE[1] is a forum for editors and publishers of peer-reviewed journals to discuss all aspects of publication ethics. COPE was established in 1997 by a small group of medical journal editors in the UK but now has over 8500 members worldwide from all academic fields. Membership is open to editors of scholarly journals and others interested in publication ethics. Several major publishers have signed up all their journals as COPE members.

5. COPE does not investigate individual cases of publication ethics but encourages editors to ensure that cases are investigated by the appropriate authorities (usually a research institution or employer).

6. COPE also funds research on publication ethics, organises annual seminars worldwide and produces guidelines on a wide range of issues relevant to publication ethics. COPE has also created an audit tool for members to measure compliance with its Code of Conduct and Best Practice Guidelines for Journal Editors.

Declaration of Interests

7. I am an employee of the Public Library of Science (PLOS), whose journals belong to COPE. I am Chair of COPE; this is an unpaid position. COPE receives subscriptions from member journals and publishers, which fund its work.

The Committee Sought Submissions on the Following Questions

(a)Do the European Commission’s proposed revisions to the Clinical Trials Directive address the main barriers to conducting clinical trials in the UK and EU?

(b)What is the role of the Health Research Authority (HRA) in relation to clinical trials and how effective has it been to date?

(c)What evidence is there that pharmaceutical companies withhold clinical data and what impact does this have on public health?

(d)How could the occurrence and results of clinical trials be made more open to scrutiny? Who should be responsible?

(e)Can lessons about transparency and disclosure of clinical data be learned from other countries?

8. We address point d only in this submission, and only from the perspective of journal publication ethics.

How could the occurrence and results of clinical trials be made more open to scrutiny? Who should be responsible?

9. There are several steps that are essential in opening up trials to more scrutiny: ensuring that all trials are registered, that summary results are reported and that all the data behind trials are available.

10. Journals and the editors that run them have a crucial role in the dissemination of clinical trial results, as medical journals are the place where currently most of the final results of trials are published. Journal editors have expertise in the assessment of clinical trials and have led the way in several important initiatives around opening up trials to more scrutiny.

11. A key part of ensuring that trials are available for scrutiny is for there to be universal registration of clinical trials in an internationally or nationally recognized registry. In 2004 the International Committee of Medical Journal Editors (ICMJE) adopted a policy[2] that from 1 July 2005 all trials submitted to ICMJE member journals should be registered in an approved registry before the first participant was enrolled. They further indicated that unregistered trials would not be considered for publication in ICMJE member journals. Since then many other journals have adopted this policy. The COPE Code of Conduct endorses clinical trial registration.[3] However, registration is not universal, and even if registered the registration number is not always reported in the journal report of a trial.[4] In addition, the quality of data included in the registries is highly variable and often not complete.[5]

12. COPE has supported the AllTrials initiative, which is calling for all trials to be registered and all results reported. In our support of the initiative we said: “COPE supports the AllTrials initiative for all trials to be registered and all results reported. Publication ethics is not just about such issues as prevention of plagiarism and managing conflicts of interest, but is, more widely, about ensuring the integrity of the scholarly literature. Registration of trials and full reporting of results is a critical step in counteracting the bias towards positive results in the medical literature.”[6]

13. A further critical aspect of making clinical trials open for scrutiny is to ensure that they are fully reported. The CONSORT group has been the leader in raising the standards for reporting of clinical trials[7] and is part of a wider initiative to improve reporting guidelines overall, the EQUATOR initiative.[8] However, despite the CONSORT guidelines having been available since 2001 and then revised in 2010 and endorsed by many journals, implementation remains far from complete and there remain many poorly reported trials in the medical literature.[9] There is a clear need for funders to require and journals to enforce better reporting of trials.

14. A further problem contributing to lack of scrutiny of body of evidence from trials is the bias within the published literature against trials that are perceived to be “negative”. This bias stems from many causes, including unwillingness of sponsors and authors to submit negative trials for publication but can also be the result of journals being unwilling to consider such trials for publication as they are perceived as being less interesting. The COPE Code of Conduct specifically states that “Studies reporting negative results should not be excluded.”[3]

15. One specific effect of the relative lack of negative studies is that systematic reviews and meta-analyses of these studies can preferentially be skewed towards a more positive interpretation of the literature overall. This has been demonstrated in a number of different places, including a recent systematic review.[10]

Recommendations for Government Action

16. There is a role for UK legislation to ensure that all clinical trials, of all phases, ie from early phase to post marketing, which are conducted within the UK or which are funded or co-funded by UK organisations, are registered, with specific penalties for non-compliance

17. The government should support requirements for all clinical trial results, both summary and underlying data, to be made available within a specific time frame after trial completion in a journal or a publicly available independent site. There should be oversight and enforced penalties for non-compliance.

February 2013

References/Notes

[1] Committee on Publication Ethics (2013). Available: http://www.publicationethics.org Accessed 17 February 2013

[2] De Angelis C, Drazen J M, Frizelle F A, Haug C, Hoey J, et al (2004). Clinical trial registration: a statement from the International Committee of Medical Journal Editors. N Engl J Med 351: 1250–1251.

[3] COPE code of conduct. Available: http://publicationethics.org/files/Code_of_conduct_for_journal_editors.pdf Accessed 17 February 2013

[4] van de Wetering F T, Scholten R J P M, Haring T, Clarke M, Hooft L (2012). Trial Registration Numbers Are Underreported in Biomedical Publications. PLoS ONE 7(11): e49599. doi:10.1371/journal.pone.0049599

[5] Viergever R F, Ghersi D (2011). The Quality of Registration of Clinical Trials. PLoS ONE 6(2): e14701. doi:10.1371/journal.pone.0014701

[6] AllTrials campaign. Available: http://www.alltrials.net/ Accessed 17 February 2013

[7] The CONSORT Statement Website. Available: http://www.consort-statement.org/ Accessed 17 February 2013

[8] EQUATOR Network (2013). Available: http://www.equator-network.org/ Accessed 17 February 2013

[9] Turner et al: Does use of the CONSORT Statement impact the completeness of reporting of randomised controlled trials published in medical journals? A Cochrane review. Systematic Reviews 2012 1:60.

[10] Dwan K, Altman D G, Arnalz J A, Bloom J, Chan A-W, Cronin E, Decullier E, Easterbrook P J, von Elm E, Gamble C, Ghersi D, Ioannidis J P A, Simes J, Williamson P R: Systematic review of the empirical evidence of study publication bias and outcome reporting bias. PLoS ONE 2008, 3:e3081. doi:10.1371/journal.pone.0003081

Prepared 16th September 2013