Ray of Light: Access to clinical trial data

The European Medicines Agency (EMA) has taken the initiative to develop a policy on publication of clinical data. The rationale for such step is article 80 of Regulation (EC) No 726/2004:

The clinical data publication website was developed to implement EMA Policy 0070, and is maintained by the EMA communications department.

The policy covers clinical data, both clinical reports and individual patient data, submitted under the centralized marketing authorization procedure after 01-Jan-2015, and extension of indication / line extension applications submitted after 01-Jul-2015, or as part of a procedure under Article 58 of Regulation (EC) No 726/2004, or data submitted by a third party in the context of a Market Authorization Application (MAA) or post-authorization procedure, or as additional clinical data for scientific assessment.

There are two categories of access to the published clinical data:

The terms of use by definition exclude all commercial research as well as investors and sponsors who could use the data to analyze available evidence and to assess performance and value of new therapies under development and compare them to the current standard of care. Since many insurers and payers are commercial entities as well this resource is not available to them either. Many hospitals and research centers are public-private partnerships, would they count as non-commercial entities? The terms of use also exclude consultants who could use the resource to analyze and benchmark their clients’ data.

Clinical reports include the following types of documents:

  • Clinical overview: a critical analysis of the clinical data submitted in the dossier, that presents the risks and limitations of the study, the study results, analysis of benefits and risks of the medicinal product, and description how the study results support the prescribing information;
  • Clinical summary: a detailed factual summary of the clinical information, including information provided in clinical study reports from any meta-analyses or other cross study analyses, as well as post-marketing data for products that have been marketed outside of the EU;
  • Clinical study report: a detailed scientific document about the methods and results of a clinical trial addressing safety and efficacy. Protocol and protocol amendments describe the objectives, design, methodology, statistical considerations and organization of a clinical trial. Sample case report form is a questionnaire used by the trial sponsor to collect data from each participating site. Finally, documentation of statistical methods provides a description of the planned methods for collection, analysis, interpretation, presentation, and organization of the data.

The AllTrials initiative has been asking very legitimate questions about trials that are never published and never presented to the professional public.

“AllTrials is an international initiative of Ben GoldacreBMJCentre for Evidence-based MedicineCochrane CollaborationJames Lind InitiativePLOS and  Sense About Science and is being led in the US by Sense about Science USADartmouth’s Geisel School of Medicine and the  Dartmouth Institute for Health Policy & Clinical Practice. The  AllTrials petition has been signed by  89300 people and  703 organizations.”

The first version of ClinicalTrials.gov was made available to the public on February 29, 2000. In September 2005, the International Committee of Medical Journal Editors began requiring trial registration as a condition of publication Two years later, in December 2007, the expanded registration requirements of FDAAA began and were implemented. Both events substantially increased the numbers of registered trials.

Out of 228,575 trials on the database, 52% have been completed (see definitions)

Out of the 118, 981 completed studies registered in ClinicalTrials.gov, only 16% have posted results. The remaining 84% do not. Out of 110,565 trials completed more than a year ago, only 19,246 have results available to the public. Section 801 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) requires the submission of “basic results” for certain clinical trials, generally no later than 1 year after their Completion Date.

Charles Piller: Law Ignored, Patients at Risk (STAT, December 2015)

Under section 402(j) of the PHS Act, sponsors of certain clinical trials of FDA-regulated products have been required to register them at ClinicalTrials.gov since December 26, 2007. Summary results information for clinical trials of approved products has to be submitted as of September 27, 2008, and certain adverse events information since September 27, 2009.

This final rule clarifies which clinical trials of FDA-regulated products must be submitted to ClinicalTrials.gov. The final rule also describes an approach for evaluating, prior to registration, whether a particular clinical trial or study is an applicable clinical trial (see Section IV.A.5 and Section IV.B.2).

FR: Clinical trials registration and results information submission, a rule by the DHHS on 09/21/2016

So it seems that results from clinical trials are slowly but surely becoming publicly available for public scrutiny. The next issue to solve will be standardization of results to make them comparable.


Standardization of reporting of clinical trials is essential for their review and assessment. CONSORT 2010, as developed by the CONSORT group, contains a 25-item checklist and flow diagram. Extensions of the CONSORT Statement have been developed for different types of trial designs, different interventions, and different types of data.


An international group that included experienced COS developers, methodologists, journal editors, potential users such as clinical trialists, systematic reviewers, and clinical guideline developers, as well as patient representatives developed the Core Outcome Set–STAndards for Reporting (COS-STAR) Statement as a reporting guideline for COS studies.

On October 18, the group published their work in PLOS Medicine: Core Outcome Set–STAndards for Reporting: The COS-STAR Statement“. The COS-STAR Statement consists of a checklist of 18 items considered essential for transparent and complete reporting in all COS studies:

See post at LinkedIn