Title: Cochrane individual participant data (IPD) repository: a pilot with trials on progesterone for preterm birth prevention
Funder: Department of Health and Social Care

Abstract: Our project will create and pilot a Cochrane approach to hosting and sharing clinical trial datasets comprising individual participant data (IPD). The data repository will provide best evidence for clinical decision-making by enabling more Cochrane systematic reviews to include individual participant data meta-analysis (IPD-MA). The project is a test of concept to establish an online portal to allow users to search for and apply to share trial data and to establish governance for responsible data sharing. Cochrane Pregnancy & Childbirth will lead the project. Most systematic reviews obtain trial data directly from trial publications and combine these in aggregate-data meta-analysis. The IPD-MA approach offers considerable advantages to this standard method. With IPD, researchers have more complete data sets and are able to standardise and verify data; they can perform more flexible and powerful analyses, and, importantly, explore whether particular types of individuals benefit more (or less) from interventions. Currently available data sharing platforms are not designed with IPD in mind. In 2015 just 1% of Cochrane reviews used IPD, but Cochrane seeks to improve upon this to provide best evidence and to keep Cochrane reviews current, relevant and cutting edge. IPD-MA is labour-intense, requiring time to collect, check, recode and standardise data. Historically, most IPD-MAs have been constrained in onward sharing because of terms of agreement with trialists and lack of infrastructure for long-term data management. Changing attitudes have led to the development of generic data repositories, such as clinicalstudyrequest.com. However, these general repositories provide gateway access to data coded variously as in the original trials, requiring wasteful repetition of data standardisation each time data are shared. Further, because any analysis takes place within each repository, and trials may be distributed across several repositories, accessing and combining data from all available trials may not be possible. Finally, few academic trials contribute to general repositories. A new model for data-sharing is warranted for systematic reviews and other evidence synthesis including network meta-analyses. Our repository will assemble IPD from trials evaluating progesterone for prevention of preterm birth. We will build on a collaboration between the Cochrane Collaboration, the National Institute for Health Research (UK) and the Patient-Centered Outcomes Research Institute (PCORI), a non-profit organisation authorised by the US Congress, who recently commissioned and funded an IPD-MA on progesterone trials (awarded to our collaborator Prof Stewart). We will develop a governance infrastructure and a prototype data-sharing platform to manage data request and access. Our aim is to design a generalizable system and outputs that will extend to other Cochrane Pregnancy & Childbirth topics beyond progesterone. Further, we aim to conceptualize systems suitable for wider implementation in other Cochrane groups Researchers will not need to be affiliated with Cochrane to access repository data. It is envisaged that access to IPD will be contingent on applicants submitting a full protocol that would be subject to peer review and made publicly available on the repository website. We will establish a pool of content and methodological peer reviewers and a governance panel to assess applications and recommend whether access to data should be granted. Original trial investigators may reserve the right to withhold access should proposed projects be considered unacceptable. Release of data would also be contingent on due academic credit been given to the original trial investigators. All decisions would be reported transparently on the repository website. We aim to place Cochrane and the NIHR firmly at the centre of international data sharing. The proposed repository will facilitate sharing assembled progesterone trial data with potential to support diverse types of evidence synthesis. The repository project presents a significant opportunity for Cochrane to think practically about its role in global data sharing, in order to remain at the forefront of innovation in evidence-based medicine and research synthesis.

Lay abstract: Finding better answers to questions about health care There are many unanswered questions in health care. For example, “Does taking regular exercise prevent diabetes?” Health researchers write papers called systematic reviews to summarise the results of clinical trials on a given topic, in order to answer just such questions. Doctors, nurses and the wider public may then read systematic reviews to find out about the advantages of or problems with different medical treatments. Cochrane Pregnancy & Childbirth produces systematic reviews to do with many treatments for pregnant women. Cochrane hopes to improve these systematic reviews to find better answers for pregnant women, and a key way to do this is to provide more complete information to the researchers who write reviews. Our project will create and test an online system for sharing clinical trial data. We will create a website where researchers can search for and apply to share clinical trial data directly, so that they can then write more complete systematic reviews. We want to know how difficult and time-consuming it is to create an online data sharing system that is both responsible and fair. The model data repository will concentrate on clinical trials that look at the drug progesterone – something often given to pregnant women to help them avoid giving birth too early, or before they are full-term. Researchers who write systematic reviews most often get their information about clinical trials from papers published in medical journals. With the data repository we plan, researchers would be able to have the full data set from a trial, with much more complete information than they would find in a medical journal. More, and better information will make the benefits and drawbacks to different treatments clearer and, in the end, help all who need to make decisions about healthcare treatments. Sharing clinical trial data sets is not new, but in the past data sharing has not been easy or straight-forward. Governments and other organisations that pay for clinical trials now want the trial data to be open to the public. To meet this goal, we need new systems to allow sharing of trial data in a way that is responsible and fair to the authors of the trial. Our data repository is one way forward. Cochrane Pregnancy & Childbirth will work together with government agencies in the US and the UK to come up with an online system for data sharing.

Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE