Only Small Steps Toward European Data Transparency

Weary followers of the European data transparency debate will derive no comfort from the responses to the latest efforts to steer a middle path between indefensible secrecy and excessive disclosure. In late July, the European drug industry agreed on its long-awaited and carefully-worded position on the release of clinical trial data. But within days, leading figures in the key constituencies of academia, patient groups, and healthcare campaigners had issued statements ranging from the cautious to the downright dismissive. For Health Action International (HAI), the industry proposals "fall woefully short." For the European Patient Forum (EPF), no limitation is acceptable on publication of results. And the scholarly assessment of the European Organization for Research and Treatment of Cancer (EORTC) of the pros and the cons of the industry approach concluded with an expression of regret.

What the European Federation of Pharmaceutical Industries and Associations (EFPIA) has offered—in conjunction with its US counterpart, the Pharmaceutical Research and Manufacturers of America (PhRMA)—is a series of "joint principles for responsible clinical trial data sharing." They say these commitments "will dramatically increase the amount of information available to researchers, patients, and members of the public."

Notably, companies will share clinical trial data at patient level and study level "with qualified scientific and medical researchers." The same facility will be offered for clinical trial data, full clinical study reports, and protocols from clinical trials. But there are some qualifications and conditions. It concerns only trials in patients "for medicines approved in the United States and the European Union." Data will be shared only "upon request." The data access will be "subject to terms necessary to protect patient privacy and confidential commercial information." And the industry will establish scientific review committees to vet the credentials of those seeking data access.

At the same time, companies will work with regulators "to provide a factual summary of clinical trial results to patients who participate in clinical trials." And once a new medicine or indication has been approved in the European Union or the United States, the synopses of clinical study reports for clinical trials in patients will be made publicly available.

As part of this proclamation, biopharmaceutical companies have also reaffirmed "their commitment to publish clinical trial results regardless of the outcome." According to EFPIA, what this translates into is that "as a minimum," results will be "submitted for publication" from all Phase III clinical trials "and clinical trial results of significant medical importance." The industry claims the principles will "enhance research and scientific knowledge, advance patient care, and improve public health."

Interesting, but…

Françoise Meunier, director general of EORTC, said the industry proposals are "very interesting"—adding, "but, as you know, the devil is in the detail." EORTC welcomed the initiative as it would "guarantee some minimal level of access to trial results and data on a more global level, and not only for trials run or submitted as part of a registration dossier in the European Union." This is, it believes, an improvement on the policy of the European Medicines Agency (EMA) or EU regulations—even though its application is not worldwide.

Other features which EORTC welcomes include the apparent "willingness to increase CT data transparency from the industry," and the recognition of "the important contribution of independent academic partners and the need to share information with them." It considers it important that industry "clearly engages to make trial results public (in the form of a synopsis of the clinical study report), whether they be positive or negative, and including in the case where development programs are discontinued."

There is also praise for the industry intention to allow independent review boards to review applications for access to data, and for the "high degree of transparency on the precise procedures that will apply." This is "consistent with the EORTC approach to data sharing," which Meunier contrasts with the EMA position, where no plans exist to make any assessment of the professional skills or proposed methodology of those seeking data access.

EORTC regrets

Deficiencies that EORTC identifies include the limitation to Phase III trials only in the industry engagement for publication of results. "More and more drugs, at least in oncology, are getting conditional approvals and being prescribed based on Phase II trial results," EORTC points out, recommending an extension of this minimum engagement to cover Phase II trials as well, at least if the drug received provisional or definitive approval without Phase III data. Similarly, if drug development was discontinued before any Phase III could be run, these results should be shared too. EORTC wants a clearer commitment to publication of results for all clinical trials, irrespective of where they are run.

It also foresees obstacles in the nature of the scientific review committees that industry envisages for handling data sharing requests. Since these are to be set up at each company, smaller firms may find it a challenge, and researchers may need to contact many companies and undergo multiple reviews for a single project—notably in the case of meta-analyses. Instead, EORTC suggests that EFPIA puts in place a central review committee (at least for oncology) that companies could use on a voluntary basis, thus simplifying the tasks.

Patient views

The comments from Nicola Bedlington, Executive Director of the European Patients' Forum, are shorter, and more direct. "Industry's new overarching commitments on transparency are an important step," she said. "But it is a much longer journey." EPF remains firm on its standpoint: "We continue to call for the publication of all results of all clinical trials, be they industry or publicly funded, in an EU database with appropriate access for researchers and the public. Results should be made available in a timely manner after the end of the trial, regardless of the outcomes."

Woefully short

HAI Europe has urged the drug industry to "truly commit to clinical trial data transparency." And while it "welcomes any initiative that grants increased access to clinical trial data," the commitments made by EFPIA and PhRMA "fall woefully short of the data transparency that is needed." HAI questions the industry's "overall commitment to transparency," because "while they claim to support greater access" to clinical trial data, "they actually do the opposite," it says, citing a recently-leaked industry briefing paper that was widely seen by industry critics as proof of industry opposition to greater data transparency.

From the point of view of HAI, mandatory public disclosure of all clinical trial data is important to minimize the risks that industry will practice selective reporting of trial results, leading to an overestimation of the benefits of medicines and an underestimation of the risks, and posing a significant threat to public health. Accordingly, the industry proposal to make only the synopsis of clinical study reports available, after marketing authorization has been granted, is inadequate. ''Disclosing only synopses of clinical study reports will not solve the prevailing dangerous practices of reporting bias and misuse of data by the pharmaceutical industry," according to Ancella Santos of HAI. It is crucial that the full clinical study report, including raw data, is available in a publicly accessible database, so as to ensure independent reviews of the safety and efficacy of medicines and to enable informed decision-making by healthcare professionals and consumers, she says.

In addition, the industry's extensive list of restrictive conditions raises "serious doubts on whether the commitments put forward will in practice increase the set of publicly available clinical trial data." In particular, HAI is alert to the risk that the definition of who may be granted data access "potentially excludes independent review by any other qualified experts including public health organizations."

Industry concerns

Industry has attempted to ward off accusations of undue secrecy by spelling out its reasons for seeking some control on access. Although "companies routinely publish their clinical research," companies will provide access to patient-level data and other clinical trial information "consistent with the principle of safeguarding patient privacy." In addition, "where co-development agreements or other legal restrictions prevent companies from sharing particular data, companies will work with qualified requestors to provide summary information where possible."

The qualification process for data requestors is explained at length by the industry. They will be "required to submit a research proposal to document the legitimacy of the research question and the qualifications of the requestor." The evaluation will take account of "any potential conflicts of interest, including potential competitive use of the data." And "researchers must agree not to transfer the shared data or information to parties not identified in the research proposal, use the data for purposes not contained in the research proposal, or seek to re-identify research participants."

"In a sustainable research ecosystem, companies must be certain that their proprietary information will remain secure from disclosure to competitors," the industry statement insists. That is why access will be given to "confidential commercial information—which could be used to help gain approval of a competing medicine—only for legitimate scientific and medical research." These data sharing principles "are not intended to allow freeriding," industry states unambiguously. "It would be appropriate for companies to refuse to share proprietary information with their competitors."

Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.