Data transparency in clinical trials
Dr Trish Groves
Trish Groves provides an overview of the increasing demand to make clinical trial data transparent.
Why should patient level data from clinical trials be shared?
The best reasons for data sharing are to optimise the evidence base for healthcare and to maximise the altruistic contribution of the funders and sponsors, investigators, and – most importantly – the participants in trials. Concerns about breaching patient confidentiality and commercial sensitivity when opening up datasets are important, but surely surmountable1. Far too often, the outputs from trials are wasted. Making data available to other researchers can also improve the nuts and bolts of research: analyses can be reproduced and checked, secondary hypotheses can be tested, meta-analyses can be far more powerful and precise, design of future trials can be improved, and healthcare teaching can be enhanced2.
Back in January 2011, major research funders (including the US National Institutes of Health and the Wellcome Trust) released a joint statement on sharing research data. And in June 2012, the Royal Society’s inquiry on science as an open enterprise came out in strong support of data sharing, with a clear recommendation that “industry sectors and relevant regulators should work together to determine the approaches to sharing data, information and knowledge that are in the public interest. This should include negative or null results.”
Now such calls to make clinical trial data transparent – along with openly accessible protocols, papers, and summary results – are really burgeoning, and it’s easy to lose the plot. So here are the headlines:
• When planning a clinical trial: if you are responsible for your company’s or institution’s policy on reporting clinical trial results, commit to publishing all clinical trial results and make that commitment public. Once you’ve done that, consider signing the petition at www.alltrials.net.
• When designing a clinical trial: if you write up clinical trial protocols consider doing so in line with the evidence based SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) checklist.
• When recruiting for a clinical trial: if you’re involved with designing and conducting clinical trials, you’d be wise to seek participants’ consent for these things upfront (as well as consent to take part in the trial): consent / commitment to publication of all results, consent to sharing of the study dataset – possibly with full open access, and consent to any planned storage of tissue / blood samples.
“…calls to make clinical trial data transparent – along with openly accessible protocols, papers, and summary results – are really burgeoning…”
• When submitting clinical trial papers to journals: be prepared to also submit the protocol and trial registration details and to explain any deviations from these, and be ready to state what plans you have, if any, for sharing patient level data from the trial. The BMJ now requires authors submitting any drug or device trial to the journal to commit to making the relevant anonymised patient level data available on reasonable request3. Other journals may well follow suit.
I won’t dwell on the requirements to report results at clinicaltrials.gov or on the public commitments that some pharmaceutical companies have already made to publish all results. These are important and largely good things, though patchily implemented, but they’ve been around for a while and will not be news to most pharmaphorum users. Plus, it’s got much easier to publish all studies, with the growth of online megajournals with high acceptance rates, such as PLoS One and BMJ Open. What’s new is that governments, regulators, and major research funders are moving beyond exhortations and are coming up with concrete plans.
In November 2012 the European Medicines Agency (EMA) committed to “proactive publication [from January 2014 onwards] of the data from clinical trials supporting the authorisation of medicines to enable the independent re-analysis of the evidence used by the Agency’s committees to determine their benefits and risks”. The agency is now working with several advisory groups to work out the ethics, legal aspects, and logistics of sharing the data.
“…it’s got much easier to publish all studies, with the growth of online megajournals with high acceptance rates…”
In the UK, the House of Commons Health Committee said, in its January 2013 report on the National Institute for Health and Clinical Excellence (NICE), that the pharmaceutical industry should be obliged to release, in a publicly accessible form, all the information it possesses about trials of licensed drugs. Meanwhile, the House of Commons Science and Technology Committee is holding an inquiry on access to clinical trial data and is seeking written evidence by 22 March 2013 on questions that include: “What evidence is there that pharmaceutical companies withhold clinical trial data and what impact does this have on public health?” and “How could the occurrence and results of clinical trials be made more open to scrutiny? Who should be responsible?”
Crowdsourcing calls for transparency, the AllTrials campaign is aiming to get all clinical trials, past and present, registered and full methods and all results reported. This was initiated by charity Sense About Science, Ben Goldacre at Bad Science, the BMJ, the James Lind Alliance, and the Centre for Evidence-based Medicine. As I write this, the AllTrials petition has more than 10,000 individual signatures and has been signed by many influential organisations including the Medical Research Council and the Cochrane Collaboration.
“…the AllTrials petition has more than 10,000 individual signatures and has been signed by many influential organisations…”
Some of the AllTrials campaigners have been patients in trials and, along with other trial participants, they’ve written an open letter to the EMA asking the agency to ensure that “the protocols for all clinical trials from now on – and all clinical trials since the 1980s – are posted on a public register, and that the summary results, the “primary and secondary outcomes” measured in all these trials and the Clinical Study Reports are published. They are also urging people who are thinking of taking part in a clinical trial to agree to participate only in those trials that have been registered and that promise to publish the results in full4.
Lastly, if you write up clinical trial protocols it would be worth following the SPIRIT checklist. SPIRIT is an international initiative that aims to improve the quality of clinical trial protocols by defining an evidence-based set of items to address in a trial protocol. It adheres to the 2008 Declaration of Helsinki, and is compatible with the ICH GCP E6 guidance and both WHO and ICMJE trial registration requirements. The checklist specifically asks, in items 31a and 31c, for plans on dissemination of results and data. SPIRIT was published in December 2012 in the Annals of Internal Medicine and the BMJ, but other journals such as the Lancet are endorsing it, and IRBs/ethics committees are expected to do so soon5,6.
1. Hrynaszkiewicz I, Norton ML, Vickers AJ, Altman DG. Preparing raw clinical data for publication: guidance for journal editors, authors, and peer reviewers. BMJ 2010,340:c181, doi: 10.1136/bmj.c181
2. Whose data set is it anyway? Sharing raw data from randomized trials. Vickers AJ. Trials 2006, 7:15doi:10.1186/1745-6215-7-15.
3. Godlee F ,Groves T. The new BMJ policy on sharing data from drug and device trials. BMJ 2012,345:e7888. http://www.bmj.com/content/345/bmj.e7888
4. Chalmers I ,Glasziou P ,Godlee F. All trials must be registered and the results published. BMJ 2013,346:f105. http://www.bmj.com/content/346/bmj.f105
5. Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jeri? K, Hróbjartsson A, Mann H, Dickersin K, Berlin J, Doré C, Parulekar W, Summerskill W, Groves T, Schulz K, Sox H, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 Statement: Defining standard protocol items for clinical trials. Ann Intern Med 2013, In press (Online First version). http://annals.org/article.aspx?articleid=1556168
6. Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin J, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleža-Jeri? K, Laupacis A, Moher D. SPIRIT 2013 Explanation and Elaboration: Guidance for protocols of clinical trials. BMJ 2013,346:e7586.
About the author:
Dr Trish Groves is Deputy Editor of the BMJ and Editor-in-chief of BMJ Open.
Trish qualified in medicine and psychiatry before moving to the BMJ (British Medical Journal), where she has now worked for nearly 24 years. Trish leads the team that peer reviews original research and articles on research methods. She has been a member of the council of the Committee on Publication Ethics and of many international groups including those developing reporting statements for research (e.g. CONSORT2010 statement), European Medical Research Councils and European Science Foundation working groups on improving and speeding up medical research, and the IDEAL collaboration that is developing stronger surgical research methods and has worked with the US FDA devices division on improving regulatory pathways.
Conflicts of interest: Trish is a senior editor at the BMJ and BMJ Open, two journals that levy article processing fees to support open access to published research and which strongly encourage data sharing. She is also an author of the SPIRIT statement.
Have you signed the AllTrials petition?