Open access innovating in clinical trial reporting
Angela Wipperman, Helene Faure and Iain Hrynaszkiewicz
Online, open access medical publishing has provided new opportunities for increased transparency and innovation in clinical trial reporting, which if widely adopted can ultimately help enhance the quality and reliability of evidence. Through free, immediate and universal – open – access to trial information, from study registration through to sharing of raw data, open access publishers are taking steps to improve trial reporting.
Journals remain the foremost medium for communicating trial research and results, and open access journals are innovating in the way trials are reported. Open access journal Trials, has been publishing trial results, protocols, methodologies, and reviews since 2006, and has continually adapted to fit the needs of the clinical trial and research community, both in terms of policy and in the author services offered by the journal. The journal’s article types reflect the diverse nature of clinical trials research, although study protocols make up about half of publications. Protocol publication improves outcome reporting by providing a record of the intended method, and allowing readers to critically assess the outcome in light of the original study aims. Authors also benefit as reviewer recommendations can potentially prompt improvements in protocols.
Amendments to protocols do not necessarily cease at publication. Changes are often made in response to evolving needs during a trial, but such changes can be at risk of being lost to the scientific record. In 2011, Trials introduced a novel article type called an ‘Update’, which allows authors to extend and update previously published trial protocols, and results, without the need for developing an entirely new article. This means that changes to a published protocol, or new evidence that complements previous results, can be added to the existing literature. An update to the 3rd International Stroke Trial (IST-3)1 provided a platform for the authors to make known important changes to the previously published study protocol2– and present baseline characteristics of the patients recruited. The results of the IST-3 trial3 which showed that stroke thrombolysis is effective in patients over 80 years, have since been published in The Lancet, and this transparent approach to publishing the whole “thread” of publications about a trial has been applauded in other peer reviewed journals4. The same group were able to make effective use of Trials’ open access model, and best practice guidelines developed by the journal’s editors5, when seeking to make public data from the first International Stroke Trial. Sandercock et al. published anonymized data from 19,435 stroke patients collected over a period of five years during the nineties in their article, The International Stroke Trial database6. This made valuable data available for secondary analyses and to help facilitate the planning of future trials.
“This made valuable data available for secondary analyses and to help facilitate the planning of future trials.”
Sandercock et al.’s article reflects a wider shift in attitudes towards clinical data sharing. Calls for access to clinical results and data have emerged from a number of stakeholders in research including journals and publishers, such as the BMJ, PLoS and BMC, funders of research such as the Medical Research Council, and regulators of research, such as the EMA. Leaders in evidence-based medicine the Cochrane collaboration also now strongly support access to data, to help end selective reporting and reduce harm to patients. Patient-focused organisations such as 23 and Me, and PatientsLikeMe are beginning to provide individuals with more autonomy in the use of and access to their data. As ownership – whether by researchers, funders, governments, industry or individuals – and consent for reuse of clinical data continues to be debated7, facilitating wider, public understanding of clinical research will become increasingly important. Current Controlled Trials (CCT), the database for administering trial registration on behalf of ISRCTN, has introduced ‘lay summaries’ for this purpose. When trialists register their trials on the ISRCTN Register, they can provide a lay summary of their research. This information is fed into the UK Clinical Trials Gateway (UKCTG), a UK government initiative providing information on ongoing trials to the general public and health professionals. Current Controlled Trials continues to engage with organisations that require research summaries as part of their funding process to encourage the use of high quality lay summaries throughout the life cycle of clinical trials.
CCT was itself an innovation in trial reporting when established in 2000. The database now holds over 10,600 records dealing with completed, ongoing or sometimes stopped trials in all areas of healthcare, with each trial assigned a unique eight digit ID. The Declaration of Helsinki made public registration an ethical requirement from 2008, and over the last decade, in line with International Committee of Medical Journal Editors recommendations, a growing number of medical journals have insisted on prospective registration: trials should be publicly listed before participants are recruited. The proportion of trials registered retrospectively still makes up the majority of trials included in the ISRCTN Register but there has been a growing awareness among trialists of the importance of prospective registration8. This change in attitudes is reflected in the growing number of registries available to authors, in 2000 there were two publicly available trial registers, now The World Health Organization pools data from 15 registries, including the ISRCTN Register.
Registration records, protocols, results and updates all contribute to the online record of a trial, and the concept of tying this information together, ‘threaded publications’, first arose more than twelve years ago in The Lancet9, when Altman and Chalmers envisaged electronic publication of study protocols in online journals followed by a subsequent “thread” of all results, any secondary analyses and ultimately the raw data set.
“Registration records, protocols, results and updates all contribute to the online record of a trial…”
Better connecting all trial related publications, regardless of publication venue, to enhance discoverability and enable more effective systematic reviews of the evidence, is another aim of this joined-up, more open approach to publishing. By working with CrossRef, the organisation founded by scholarly publishers to help ensure permanence of content on the web, we are making threaded publications a reality, and hope to implement the concept across publishers of evidence-based medicine. With the vast store of information spread across the web, threaded publications should allow researchers, clinicians, patients, policy makers and systematic reviewers to better follow research from inception to conclusion.
While open access provides more effective ways to wider disseminate research and associated data, there remains a vast amount of research that remains unpublished. Prevailing attitudes in the type of findings to publish, inherent biases in the peer review and publication process, and, historically, suppression of “unfavourable” scientific results and selective reporting contribute to the problem of publication bias10. This issue of distorted medical evidence, which can ultimately harm patients, has been widely recognised in healthcare11. In an attempt increase their visibility, in 2002 the Journal of Negative Results in Biomedicine launched as an open access venue for research that promotes discussion of unexpected, controversial, provocative and negative results in the context of current tenets. A number of other open access journals which promote the concept of publishing all scientifically sound results, regardless of outcome or direction of conclusions, have since emerged. These include BMC Research Notes, Nature Publishing Group’s Scientific Reports, Public Library of Science’s PLoS One, and Trials. As well as negative results, incomplete results from stopped or abandoned trials can prove informative in subsequent trial design and research, and will help reduce wasteful duplication of research. Developing an effective method for disseminating such research despite its incompleteness is a future challenge for open access, clinical trials journals.
The results of clinical trials, if published, form a mass of evidence that contributes ultimately to treatment decisions. Systematic reviews draw on this store and are becoming an essential facet of evidence based medicine. The open access journal, Systematic Reviews, launched this year as a new venue for systematic reviews in healthcare. Taking lessons from the clinical trials community, the journal encourages registration of systematic reviews prior to publication to help ensure transparency in reporting, although registration of systematic reviews is not yet as widely accepted or enforced as for clinical trials.
“One of the greatest attributes of online only, open access publishing is space.”
One of the greatest attributes of online only, open access publishing is space. Removing restrictive page number and figure limits results in more complete reports that can adequately describe in detail methods, results and support large data sets for analysis and re-use. In clinical trials, specifically, unlimited space means authors are better able to comply with standards of reporting set out by the CONSORT initiative – an evidence-based checklist for reporting randomized controlled trials, which is endorsed by many major medical journals. Open access publishing models which utilise Creative Commons licenses also ensure that copyright remains with the authors, which aids the unrestricted sharing and reuse of research, promotes collaboration and means that published work can be built upon with future research efficiently.
Sharing research and associated data is core to the open access ethos and improving access to online research forms a large part of the future for the open access movement. Not just researchers, but increasingly educated patients require accessible information, while technological developments in data collection and analysis means storage of large datasets needs to be a consideration for journals. Access to original research remains the driving force behind the growing open access movement, recently exemplified by a Whitehouse petition for open access publication of tax funded research, the negative reaction to the controversial Research Works Act, and the announcement by the UK’s science and universities minister of the British government’s support for open access. Improving availability of data, increasing access to research in developing countries and creating new services for easier location and reuse of clinical information, including the forthcoming Cases Database of medical case reports, are all priorities for the future and can contribute to the advancement of clinical medicine.
1. Sandercock et al. Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited Trials. 2011, 12:252 http://www.trialsjournal.com/content/12/1/252
2. Sandercock et al. The third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke Trials. 2008, 9:37 http://www.trialsjournal.com/content/9/1/37
3. The IST-3 collaborative group: The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. The Lancet. May 2012 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2960768-5/fulltext#article_upsell
4. Lyden, Patrick D. In Anticipation of International Stroke Trial-3 (IST-3). Stroke. 2012 http://stroke.ahajournals.org/content/early/2012/05/03/STROKEAHA.112.656876.citation
5. Hrynaszkiewicz et al. Preparing raw clinical data for publication: guidance for journal editors, authors, and peer reviewers. Trials 2010, 11:9 http://www.trialsjournal.com/content/11/1/9/
6. Sandercock et al. The International Stroke Trial database. Trials 2011, 12:101 m http://www.trialsjournal.com/content/12/1/101
7. SF Terry, P F Terry. Power to the People: Participant Ownership of Clinical Trial Data. Sci. Transl. Med. 3, 69cm3 http://stm.sciencemag.org/content/3/69/69cm3.abstract
8. Califf, Robert M. et al. Characteristics of Clinical Trials Registered in ClinicalTrials.gov, 2007-2010 AMA. 2012,307(17) http://jama.jamanetwork.com/article.aspx?articleid=1150093
9. Chalmers I, Altman DG. How can medical journals help prevent poor medical research? Some opportunities presented by electronic publishing. The Lancet. 1999 353:9151, p490 – 493 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2898%2907618-1/fulltext
10. Gwendolyn B et al. Testing for the Presence of Positive-Outcome Bias in Peer Review A Randomized Controlled Trial Arch Intern Med. 2010,170(21) http://archinte.jamanetwork.com/article.aspx?articleid=226270
11. McGauran et al. Reporting bias in medical research – a narrative Review Trials 2010, 11:37 http://www.trialsjournal.com/content/11/1/37
About the authors:
Angela Wipperman, Journal Development Manager at BioMed Central
Angela Wipperman studied biochemistry as an undergraduate at Manchester University before joining BioMed Central in 2010 as a Journal Development Editor, working on bioinformatics and cell biology journals. Angela has since moved to BioMed Central’s Open Science team as Journal Development Manager, overseeing the development of a group of broad scope biology and medical journals, including BMC Research Notes, Trials and Journal of Medical Case Reports and data driven journals.
Helene Faure, Database Manager at BioMed Central
Helene Faure worked for 6 years at IMS the information and solution provider for the health industry, in operations and product management roles for databases tracking doctors’ prescribing habits. Helene joined BioMed Central in 2002 and manages the content of two non journal databases, including Current Controlled Trials’ ISRCTN register of clinical trials.
Iain Hrynaszkiewicz, Journal Publisher at BioMed Central
Iain Hrynaszkiewicz’s academic background is in microbiology and journalism which, after working in medical information for pharmaceutical clients, led him to join the open access publisher BioMed Central as an Assistant Editor in 2006. Iain has held various editorial and publishing positions at BioMed Central and now, as Publisher (Open Science), has overall responsibility for the strategy and development of journals with specific interests in promoting data sharing and publication, such as BMC Research Notes, Trials and GigaScience, and leading BioMed Central’s open data publishing strategies. These strategies include development of guidelines for sharing of patient data, which were published in the BMJ and Trials in 2010. Iain is also responsible for BioMed Central database products including Current Controlled Trials, and new publishing product developments such as BioMed Central’s Threaded Publications initiative.
How can we improve open access innovation in clinical trial reporting?