Sponsors Struggle with Data Disclosure Requirements

Policies to widen access to patient level data from clinical trials are gaining traction, despite strong opposition from research sponsors that such initiatives will undermine patient privacy and incentives for new drug development. There is general agreement that clinical data sharing can improve the efficiency of clinical trials, validate regulatory decisions, and increase public confidence in clinical research. But sponsors are concerned about who controls access to data, the purposes of disclosure, and safeguards to protect all parties. 

To head off a plan by EMA for public release, or "sharing," of study data in registration dossiers, sponsors are rolling out voluntary data sharing programs, as outlined in a "principles" document issued in July by the Pharmaceutical Research and Manufacturers of America (PhRMA) and the European Federation of Pharmaceutical Industries and Associations. Companies are advised to establish independent scientific review boards to evaluate outside data requests, plus procedures to protect patient privacy. The aim is to delay full data disclosure by EMA in January 2014, so that standards, third-party programs, and voluntary initiatives have more time to demonstrate their ability to enhance research transparency while protecting patients and research companies.

Industry objects that the EMA plan fails to limit access only to bona fide researchers seeking to address valid scientific questions. And the prospect of releasing full regulatory dossiers could expose proprietary formulation and manufacturing data and information on product development and future indications. Broad release of clinical data, moreover, could undermine product exclusivity in countries such as Australia, Brazil, China, and Korea that link exclusivity to data confidentiality, explained Pfizer Senior Vice President Justin McCarthy at a PhRMA briefing in October. He warned that companies may rethink their development and registration strategies if the EMA proceeds with its plan for full release of regulatory submissions. Sponsors may decide to delay submissions for approval in Europe or seek to eliminate or redact more confidential commercial information in dossiers.

Sponsors also are concerned about a June 2013 proposal from FDA to make available masked and de-identified data submitted in applications, possibly limited to information aggregated across drug classes. FDA reopened comments to this proposal in October, seeking additional information on what factors to consider in masking study data and if there are ways to identify patients after removing names, birth dates, death dates, and geographic information.

Industry is more comfortable with FDA's more narrowly focused data sharing plan, although still wary that outside researchers with advanced computer systems and access to extensive genomic information will be able to re-identify patients, particularly those involved in studies on rare diseases or cancers that affect small patient cohorts. And permitting non-experts to gain access to data, comments PhRMA, could result in "unjustified second-guessing of FDA's regulatory decisions" that raises alarm among patients and providers and discourages appropriate treatment.

Seeking consensus

These controversies are spurring efforts to reach consensus on achieving data transparency while enhancing biopharmaceutical innovation. An Institute of Medicine committee began deliberations last month on "Responsible Sharing of Clinical Trial Data," with the intent of issuing guiding principles and a framework for such initiatives. An interim report is due in January, and a final report in December 2014 to assess the benefits and risks of data sharing and opportunities for responsible disclosure.

While more pharma companies will launch data sharing programs in January, these voluntary initiatives have limitations. Firms don't plan to hand over clinical data sets to outsiders, but to run their queries through in-house data systems and provide results. And there are concerns about the real independence of a company-appointed scientific review board.

Patient representatives at the PhRMA briefing noted problems with informed consent if clinical data is to be used by outside parties for other purposes. FDA requires sponsors to advise clinical trial participants as part of the consent process that a summary of data from the study will be posted on clinicaltrials.gov, but that this information will not identify specific patients, attorney Mark Barnes pointed out at the October Clinical Trial Disclosure conference sponsored by the Drug Information Association. Weakened privacy safeguards, however, could invalidate that assurance.

Sponsors insist that they should decide how to share research information-not government regulators. And patient advocates are fearful of questionable secondary statistical analyses that challenge regulatory decisions and sponsor assessments. But there's optimism that the disclosure movement will spur data interoperability standards and open sourcing models, all key to transforming clinical research.