Clinical Data Disclosure: PhRMA Principles Rely On Review Boards To Screen Research Proposals

PhRMA and EFPIA issue joint principles that urge firms to release the synopses of clinical study reports; PhRMA objects to FDA’s proposal to release masked, de-identified data on the grounds of patient privacy, competitive secrecy.

The pharmaceutical industry is trying to change the direction of clinical trial data disclosure so companies can retain control over who has access to the information.

On July 24, the European Federation of Pharmaceutical Industries and Associations and the Pharmaceutical Research and Manufacturers of America issued joint principles for clinical trial data sharing that call for each biopharmaceutical company to establish a scientific review board to review requests from researchers to access trial data. The approach offers an alternative to the European Medicines Agency’s policy, which would proactively make data submitted in support of a marketing authorization application available to researchers once the decision-making process is completed.

The two associations have been adamantly opposed to EMA’s policy, arguing that the release of individual patient data could impact patient confidentiality and result in disclosure of confidential commercial information (Also see "Clinical Trial Data Disclosure: As EMA Pushes For Patient Level Info, What Control Will Firms Have?" - Pink Sheet, 3 Dec, 2012.). They are offering an alternative approach that they say will protect patient privacy and proprietary information.

It is uncertain whether their principles will shift EMA’s position. “For PhRMA and EFPIA to change the direction we are now heading – broad disclosure requiring no gatekeeper – they would have to change the context in which the debate is taking place, and that is hard to do,” said Jonathan Schur, a partner at Dechert.

“Industry is inaudible,” he added. People see it “as placing financial interests above patients” and credit the views of critics of industry without listening to what industry has to say.

PhRMA and EFPIA’s new document may help industry get its message across and counter the public perception that drug makers are unwilling to disclose certain data.

Access To Be Denied If Patients Can Be Re-Identified

The “Principles for Responsible Clinical Trial Data Sharing” list five commitments that companies are to make on a voluntary basis. The first is to enhance data sharing with researchers. Those seeking clinical trial data will be required to submit a research proposal. A company’s review board, to include outside scientists and healthcare professionals, would then evaluate the requestor’s qualifications and the legitimacy of the research proposal. The proposal must include the hypothesis to be tested, the rationale for the proposed research, a publication and posting date, and a description of any potential conflicts of interest, among other things.

Under EMA’s approach, researchers must submit a registered protocol to get access to data but the agency does not scrutinize the protocol.

The principles note that companies will not be required to provide access to patient-level data “if there is a reasonable likelihood that individual patients could be re-identified.” They could also deny access to data subject to co-development agreements or other legal restrictions.

The principals also require companies to:

• Make publicly available the synopses of clinical study reports (CSRs) filed with regulators on or after Jan. 1, 2014. They will also evaluate requests for full CSRs;
• Work with regulators to adopt mechanisms to provide a factual summary of clinical trials results and make the summaries available to research participants;
• Certify procedures for sharing clinical trial information on a publicly available website; and
• Reaffirm commitments to publish clinical trial results irrespective of whether they are positive or negative.

“The commitments recognize the importance of sharing clinical trial data in the interest of patients, healthcare and the economy,” Robert Hugin, chairman of PhRMA and chairman and CEO of Celgene Corp., said in a release. “Imperative to the success of this initiative are safeguards that ensure patient privacy, respect for integrity of regulatory systems worldwide and greater incentives for more investment in medical innovation.”

EMA Establishes Three Categories Of Data

An EMA spokesperson said she had not yet reviewed the EFPIA-PhRMA principles and could not comment on them.

EMA’s draft policy on the publication and access to clinical trial data, released in June, defines three categories of data that have different levels of access: commercially confidential information; open access; and controlled access.

The first category, commercially confidential information, covers clinical trial data or documents that may contain commercially confidential information, such as some in vitro studies or bioanalytical data characterizing the product. The open access category covers trial data and information that does not contain patients’ personal data. And the controlled access category covers data with patients’ personal data, including individual patient data sets, patient line listings, and individual case report forms.

But Schur said that even with these three categories there will be broad disclosure of data. “Industry will be fighting an uphill battle if it wants to claim that data is confidential,” he said.

GlaxoSmithKline PLC, which in contrast to PhRMA has supported full data disclosure, is critical of EMA’s policy.

“In particular, we do not believe that the EMA’s proposals for a controlled access model are sufficient to ensure valid science is conducted with the data or that they will have the resources needed,” a GSK spokesperson said in an email. “At the present time, we believe our system, with progression to a broader system with other sponsors, remains the best way to share data from industry and academic clinical trials.”

GSK announced the establishment of its system in October. Like the EFPIA-PhRMA principles, it requires researchers to submit a scientific protocol that is to be reviewed by external independent experts appointed by GSK. The GSK spokesperson said some aspects of its system go further than the principles. For example, it is making available full CSRs, which provide more detail on the design, methods and results of clinical trials, rather than a synopsis.

PhRMA Says FDA Proposal Could Benefit Sponsor’s Competitors

FDA is also responding to the push for greater access to trial data. In June it announced a proposal to allow experts outside the agency to analyze nonsummary trial data, including patient-level data that has been de-identified and masked so the data is not linked to a specific product or application. The agency explained that the data could be used to help further understanding of potential biomarkers, endpoints and drug development tools (Also see "FDA’s Trial Data Disclosure Policy Diverges From EMA’s By Masking Products" - Pink Sheet, 4 Jun, 2013.).

PhRMA submitted comments to FDA on July 24, the day it released the joint principles, urging the agency to reconsider its proposal in favor of PhRMA’s data sharing initiatives.

“While PhRMA shares the agency’s commitments to promoting biopharmaceutical innovation and enhancing transparency, the proposal summarized in FDA’s notice raises significant concerns,” the association stated. “Although the scope of the proposal is not clearly defined, it appears that FDA contemplates wide release of masked, deidentified data and may even release the data to the entire public.”

The association said such disclosure faces practical, policy and legal challenges. First, PhRMA said, FDA would have to ensure that data could not be reidentified and unmasked. It noted that in recent studies, researchers were able to use computational methods and publicly available information to deduce the identity of subjects from deidentified data.

Second, the association said the widespread, public release of non-summary data would have unintended consequences, including increasing risks to patient privacy. The release also “could result in unjustified second-guessing of FDA’s regulatory decisions and prompt patients to forego medically appropriate treatments and vaccinations,” the association said.

PhRMA also expressed concern that a sponsor’s competitors could use the masked data to overcome hurdles in drug development or to develop patentable inventions and then exclude the original submitter from using them. The association also asserted that FDA lacks statutory and regulatory authority to release non-summary data on a broad basis.