On Monday September 29th, the European Ombudsman organized a panel discussion on “International Right to Know Day.” This day was established in 2002 by access to information advocates from around the world. This year, the panel’s theme was “Transparency and public health – how accessible is scientific data?”
This topic was well chosen for a week in which the board of the European Medicines Agency (EMA) published their long-awaited policy on publication of clinical data (1). The panel at the European Parliament consisted of representatives from all stakeholders that gave input to EMA’s draft policy over the preceding years. The European Ombudsman, Emily O’Reilly, opened the discussion by saying that while there is much good coming from the pharmaceutical industry, more trust is needed to convince patients that therapies are working, and the only way to create that trust is by opening up clinical trials results and data.
The actions of the industry will silence the critics
Both Ben Goldacre (physician and author of the book Bad Pharma) and Margrete Auken (European Parliament member and shadow rapporteur in the new 2014 clinical trial regulation of the European Union), expressed a lingering distrust against the pharmaceutical industry in how they are releasing data. Richard Bergström of the European Federation of Pharmaceutical Industries and Associations (EFPIA) presented the great progress in the last year by the European pharmaceutical industry in their drive to release clinical trial data in a controlled manner. “This is unprecedented,” said Bergström, with many EFPIA members going beyond the principles that his organization has laid out. These principles include sharing all information produced during a clinical trial, including Clinical Study Reports (CSR’s) and the complete set of (anonymized) individual patient data (IPD).
The European Medicines Agency releases their transparency policy
The EMA policy describes what clinical trial information will be released, when it will be released, and also that EMA itself intends to make it available to interested researchers. Guido Rasi, the Executive Director of EMA, received most of the attention with the publishing of the EMA policy the same week. Rasi pointed out that EMA was under no legal obligation to release the clinical trial information owned by the pharmaceutical companies, but did so to increase public trust in regulatory decisions about new products. According to Rasi, the policy intends to strike a balance between releasing clinical trial data and the commercial interests of pharmaceutical companies. Meanwhile, GSK, as the first global pharmaceutical company, decided last year to open up all clinical trial information – including anonymized IPD – for external researchers. This pharmaceutical giant is now providing external researchers the ability to apply for access to a clinical trial, host an independent review panel, and access a secure online data and analysis environment (SAS® Clinical Trial Data Transparency) that allows the applicants to gain access and re-analyze the patient-level clinical trial data.
Europe leads the way in transparency of clinical trials
The “EMA policy on publication of clinical data for medicinal products for human use” – as it is titled – will become effective January 1, 2015, and reflects a legal obligation for transparency in the new European Clinical Trials Regulation No 536/2014 adopted in late May 2014. The European regulatory agency will implement this policy step-by-step, release Clinical Study Reports (or parts of them) initially, and IPD (“individual patient data”) might follow as a result of a follow-on policy. EMA will release only certain modules of the CSRs, such as:
- Clinical overviews, (module 2.5 of ICH E3 guidelines), clinical summaries (module 2.7), and clinical study reports (module 5, 16.1.1 - protocol and protocol amendments, 16.1.2 – sample CRF, and 16.1.9 – statistical methods).
Sponsors can redact commercial confidential information (CCI), and these redactions need to be approved by the EMA. At a later date, the EMA will detail how and when individual patient data will be released. The policy that was released on October 2nd however, defines two levels of access;
- A simple registration process will provide access to the information in screen-only mode (no print capability).
- A second level (for academics and non-commercial users) will require proof of identity and enable downloading and saving information.
Towards full transparency of clinical trial information, step-by-step
In my view, the EMA policy is a great step forward that will contribute to a better understanding of the regulatory decision that resulted in approval or rejection of marketing authorization applications (MAAs). It should, however, only be seen as complementary to the industry’s initiatives in providing complete information, including complete (but redacted) CSR’s, blank CRF’s, IPD’s, protocol information and other types of supporting information from historical clinical trials (2). For example, at least 19 organizations are listed on EFPIA’s transparency website and currently, 9 organizations are joining GSK in allowing access to anonymized patient-level data on ClinicalStudyDataRequest.com. After an independent review board approves their requests, researchers can access an advanced statistical computing environment and a multi-sponsor repository where they can analyze and compare trials from different sponsors and extract new clinical knowledge about the medicinal products and devices.
If you are an academic researcher, you can now turn to different organizations for information about medical products: to the regulators for regulatory decisions and submitted reports and to pharmaceutical companies for the detailed trial information – including IPD and the ability to re-analyze the data and compare competing or complementary products.
The future of data transparency
I believe that both access and information sharing systems will continue to thrive in the long-term and provide complementary benefits to the public and external researchers. A growing list of pharmaceutical companies are now fully committed to provide detailed trial information and encourage secondary analysis; e.g. they are discussing how to apply clinical data standards such as CDISC for bringing de-identified data together and methods to de-identify the data (together with the help from industry associations like PhUSE and Transcelerate).
I’m hoping that academic trial research centers will now open up their information as well and consider providing centralized access to the data of clinical trials they’re running – preferably in the same multi-sponsor environment as the industry is currently using. While much progress has been made, some maturity and experience will be gathered by all involved stakeholders when researchers start making discoveries. Researchers can now make full use of these different complementary possibilities, start mining the clinical trials for all important confirmatory and secondary findings, and publish high-quality research to further increase the trust of the patients and physicians in medicines and devices approved for use by health care providers. After all, “the right to know”, as the theme of European Parliament panel was, can only be realized if researchers can make sense of the data in an advanced analytical environment.
- Publication of clinical reports: EMA adopts landmark policy to take effect on 1 January 2015.
- Krumholz et al. 2014, Sea Change in Open Science and Data Sharing Leadership by Industry, Circ Cardiovasc Qual Outcomes. 2014; (7) 499-504.