Marsha A. Wilcox, EdD, ScD

Data sharing and data transparency are becoming the new standard in pharmaceutical and medical device science. Sharing of data collected through clinical research maximizes its value to the scientific and clinical communities and promotes follow-up studies of secondary research using existing data. Sharing also minimizes duplication of data collection by allowing novel research questions to be addressed using existing data, which in turn lowers research costs and reduces human subject burden-while positioning clinical trial data as a public good. Importantly, sharing encourages multiple examinations and interpretations of data, which both protects against faulty analyses and contributes to verification, refinement, or refutation of earlier work.

Several recent initiatives have raised awareness of and promoted data sharing and data transparency, including the Institute of Medicine’s report “Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risks”; the revised data sharing guidance recommended by the Pharmaceutical Research and Manufacturers of America and the European Federation of Pharmaceutical Industries and Associations, US and European pharmaceutical trade organizations; and the recent recommendations on data sharing from the National Institutes of Health (NIH) for supported research.

 Each of these initiatives has the potential to ensure that the clinical research community can better leverage existing data resources for scientific purposes, which increases the likelihood that patients and physicians are better equipped with evidence relevant to any research question or clinical decision.

The purpose of this article is to share information about an initiative launched by the Janssen Pharmaceutical Companies of Johnson & Johnson, the Yale University Open Data Access (YODA) Project, the National Institute of Mental Health (NIMH), Rutgers University Medical School, and the Harvard T. H. Chan School of Public Health: the Open Translational Science in Schizophrenia (OPTICS) Project.

The OPTICS Project is a pilot initiative designed to provide a forum for true translational science in schizophrenia research. The collaboration involves clinical trial data from Janssen Pharmaceutical Companies of Johnson & Johnson and studies made available through the National Center for Biotechnology Information Database of Genotypes and Phenotypes (dbGaP) and the NIMH Repository and Genomics Resource (NRGR), all of which are being made publicly available to investigators. This effort is distinct from other initiatives in that it is a time-limited proof of concept for an open-science analytic collaboration using both clinical trial and observational data sources as opposed to the development of a data resource to be used in perpetuity.

The OPTICS Project aims to demonstrate the value of an open-science approach to better understand the efficacy and safety of medicines used to treat schizophrenia and schizophrenia as a disease, including natural history, subtypes, and etiologies. The intent is to contribute to the development of novel research designs and analytic methods for disparate data types that leverage existing data sources.

A scientific advisory board that includes researchers from each of the participating organizations governs the OPTICS project. The role of the advisory board is to manage the project and evaluate the scientific merit of initial proposals and project summary abstracts submitted at the conclusion of the analysis period. Any researcher is eligible to participate in the OPTICS Project, and an open invitation to researchers has been issued worldwide. However, to collaborate, all researchers must:

• Meet the data access and use requirements of the data holders

• Agree that intellectual property generated from this project will be dedicated to the public and free for everyone to use

• Agree that all publications related to this project will first be published as a compendium of articles-the OPTICS volume-in a peer-reviewed, open-access online journal

Researchers who participate in the OPTICS Project will use at least one clinical trial made available in the collection of Janssen’s paliperidone clinical trials on the YODA site (

). The OPTICS Bundle contains data from 17 trials with approximately 7000 study participants; data from the OPTICS Collection, which includes schizophrenia genetic/genomic (dbGaP) data from 9 studies with approximately 18,000 study participants; and/or data from the NRGR, which includes 19 studies with more than 10,000 study participants. The 

Collaborations are encouraged across industry, academia, and elsewhere, including those in economics, business modeling, or computer science. The OPTICS Project will provide a workspace (web-based) in which such collaboration can occur. Groups with similar methods and/or research topics are encouraged to work collaboratively.

At the conclusion of the analysis period (anticipated Q1 2017), participants who have completed analyses will be invited to attend a meeting to present and discuss results. Groups with similar strategies or research topics will be encouraged to integrate efforts in a combined or companion manuscript(s). All results will undergo peer review with the goal of publication in an open-access journal. Finally, the pilot will be evaluated with the goal of replicating it for other neuropsychiatric disorders.

The YODA Project has been at the forefront of the clinical trial data–sharing movement since its inception in 2011, advocating for the responsible sharing of clinical research data, open science, and research transparency, while serving as an independent intermediary between data generators and data users to facilitate access to data. The Project is committed to supporting research focused on improving the health of patients and informing science and public health while protecting the rights of research participants.

Through partnerships with Johnson & Johnson and Medtronic, Inc, the YODA Project worked to establish standards to guide its efforts through experience and input from the public and stakeholders. The project iteratively developed a model to make shared data available to other investigators, including de-identified participant-level clinical research data and/or comprehensive reports of clinical research, such as full clinical study reports. This level of detail is not customarily found in journal publications.

The YODA Project aims to support and promote scientific research using shared clinical trial data that may advance science or lead to improvements in health as well as health care delivery. The project is guided by the following core principles, which reflect the overall mission of the project to promote open science:

• Promoting the sharing of clinical research data to advance science and improve public health and health care

• Promoting the responsible conduct of research

• Ensuring good stewardship of clinical research data

• Protecting the rights of research participants

In 2014, the YODA Project entered into an agreement with Johnson & Johnson to develop a policy to share clinical data for all trials of the company’s pharmaceutical products; data became available to external investigators through this initiative in October 2014. The scope of this agreement was expanded in 2015 to include trials of medical device products approved in 2014 and onwards. Clinical trial data are currently available for many medical conditions, including schizophrenia, bipolar disorder, and ADHD, as well as non-psychiatric conditions such as diabetes mellitus and rheumatoid arthritis. Johnson & Johnson schizophrenia clinical trial data are available independently of the OPTICS Project, as well as through the OPTICS Project.

Within the current YODA Project model, investigators can request access to available clinical trial data by submitting a research proposal that describes their aims, methods, and statistical analysis plan, among other information. There is no charge to access the data. The YODA Project evaluates each submitted request to ensure it has scientific merit and on this basis makes the decision to provide access to the requested data, which are made available via a secure data-sharing platform. Once investigators have access to the data, the expectation is that they will pursue their proposed research and publish their results in the peer-reviewed literature or report their findings on the YODA Project website, which ensures that their work informs the larger scientific community.

NIMH has a long-standing history in promoting data sharing for accelerating mental health research through initiatives and polices and is a strong proponent of endeavors such as the OPTICS Project.

 One of the transformative data-sharing initiatives led by NIMH was the NIMH Human Genetics Initiative, driven by the principle that making data and biospecimens rapidly available to the broader scientific community is essential to maximize scientific progress.

This initiative led to the establishment of the NRGR. The NRGR has become the primary repository and centralized resource for well-annotated, uniformly processed, high-quality biological samples, along with clinical and genomic data from large cohorts. Since the NIH Genome-Wide Association Study (GWAS) policy was published in 2007, the dbGaP has become the primary repository for genomics data for all studies funded by NIH, including NIMH. Taken together, the dbGaP and the NRGR currently have genome-wide data from over 43,000 subjects, including cases and controls, available to the scientific community for secondary data analysis. Although the majority of the data comes from the GWAS (over 38,000 subjects), there are increasing numbers of studies that deposit sequencing data.

Most of the data that are publicly available through controlled access at the dbGaP or the NRGR are derived from observational studies. To enhance the scientific value of these datasets, NIMH is eager to foster collaborations with industry partners who have a wealth of clinical trial data, including genomic screens that have not formally been made available to the broader scientific community. The combination of such data­sets, along with other large GWAS datasets, can provide fruitful opportunities that may expedite identification and prioritization of potential genetic targets for drug discovery.

To simplify identification of relevant datasets, the dbGaP OPTICS Project Collection was established. It links together all of the schizophrenia studies currently in the dbGaP that have been consented for general research use (

http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/collection.cgi?study_id=phs000887.v1.p1

). With the “collection” structure, interested researchers can submit a single application to the dbGaP rather than having to submit separate applications for each study.

Forging new scientific understanding for schizophrenia through the OPTICS Project

The OPTICS Project represents the first time genetic, observational, and interventional data on schizophrenia are being made available to researchers in one bundle. The ability to analyze all of these data sources enables researchers to address questions about the disease, therapies, and analytic methods in ways not before possible. While the value of sharing clinical trial data on its own is significant, by connecting with privately and publicly funded data, the OPTICS Project provides participating researchers with direct access to resources that have rarely been connected before-a linkage likely to forge new and better scientific understanding and treatment of schizophrenia.

The OPTICS Project also breaks down barriers that have slowed the pace of scientific research and discovery in the past. By connecting OPTICS researchers who are working toward the same goals and encouraging them to work collaboratively, the OPTICS Project will create new interdisciplinary teams of researchers who will generate novel hypotheses about improving the treatment of schizophrenia. Moreover, by ensuring that all results are reported and published in peer-reviewed, open-access journals, the findings from this work will be available to the entire scientific and clinical communities.

The OPTICS Project provides a unique opportunity for collaborative partnerships, sharing, and learning from schizophrenia data that have been collected by multiple organizations. This Project is breaking down barriers that have slowed the pace of scientific research and discovery in the past and has the potential to provide substantial benefit to patients and the wider scientific community.

The OPTICS Project is representative of a new paradigm in scientific research, which will lead to more widespread collaboration and data sharing among private industry and the broader research community. Such cooperative efforts are necessary to gain deeper insights into the biology of disease and to achieve the ultimate goal of developing better treatments and reducing the overall public health burden of devastating brain diseases. For more information, please visit the OPTICS website, the NIH dbGaP website, and the NRGR website or email optics.schiz@gmail.com.

The authors are grateful for the assistance of Jessica D. Ritchie, MPH and Emily B. Finn, MPH for background research and manuscript preparation. Both Ms Ritchie and Mrs Finn are employees at the Center for Outcomes Research and Evaluation at Yale-New Haven Hospital. We would also like to thank Dr Adam Savitz, Director, Neuroscience at Janssen and Clinical Leader for the OPTICS Project for reviewing the manuscript and contributing to the establishment of the project.

Dr Ross is Associate Professor in the Section of General Internal Medicine and the Robert Wood Johnson Foundation Clinical Scholars Program, Department of Internal Medicine, Yale University School of Medicine; Associate Professor in the department of health policy and management, Yale University School of Public Health; and Co-Director of the YODA Project at the Center for Outcomes Research and Evaluation, Yale-New Haven Hospital in Connecticut; Dr Addington and Dr Senthil are Health Scientist Administrators at the Genomics Research Branch, National Institute of Mental Health in Bethesda, MD; Dr Lehner is Director of the Office of Genomics Research Coordination, National Institute of Mental Health in Bethesda, MD; and Dr Wilcox is a Scientific Director and Fellow at Janssen Research & Development, LLC in Titusville, NJ.

The preparation of this article was not supported by any external grants or funds. The authors assume full responsibility for the accuracy and completeness of the ideas presented. Dr Ross receives support through Yale University from Medtronic, Inc and Johnson & Johnson to develop methods of clinical trial data sharing, from the Centers of Medicare and Medicaid Services to develop and maintain performance measures that are used for public reporting, and from the FDA to develop methods for post-market surveillance of medical devices. Dr Wilcox is employed by Janssen Research & Development, LLC.

Institute of Medicine. Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risk

. Washington, DC: The National Academies Press; 2015.

 European Federation of Pharmaceutical Industries and Associations. The Power of One: A Commitment to Collaboration; 2013. 

http://www.efpia.eu/uploads/documents/EFPIA-AR-2014.pdf

 European Federation of Pharmaceutical Industries and Associations and the Pharmaceutical Research and Manufacturers of America. Principles for Responsible Clinical Trial Data Sharing; 2014. 

 Trans-NIH BioMedical Informatics Coordinating Committee. NIH Data Sharing Policies; 2013. 

https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_policies.html

 National Institute of Mental Health. Data Sharing Expectations for Clinical Research Funded by NIMH; 2015. 

http://grants.nih.gov/grants/guide/notice-files/NOT-MH-15-012.html

 Lehner T, Senthil G, Addington AM. Convergence of advances in genomics, team science, and repositories as drivers of progress in psychiatric genomics. 

Articles

A report of initiatives that have raised awareness of and promoted data sharing and data transparency in order to advance science and improve public health and health care.

Marsha A. Wilcox, EdD, ScD

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The OPTICS Project: An Open-Science Framework for the Analysis of Clinical Trial Data