The full clinical study reports of drugs that have been authorized for use in patients should be made publicly available in order to allow independent re-analysis of the benefits and risks of such drugs, according to leading international experts who base their assertions on their experience with Tamiflu (oseltamivir).

Tamiflu is classed by the World Health Organization as an essential drug and many countries have stockpiled the anti-influenza drug at great expense to taxpayers. But a recent Cochrane review on Tamiflu has shown that even more than ten thousand pages of regulatory evidence were not sufficient to clarify major discrepancies regarding the effects and mode of action of the drug.

Writing in this week’s PLoS Medicine, Peter Doshi from Johns Hopkins University School of Medicine in Baltimore, USA, Tom Jefferson from the Cochrane Collaboration in Rome, Italy, and Chris Del Mar from Bond University in the Gold Coast, Australia say that there are strong ethical arguments for ensuring that all clinical study reports are publicly accessible. In the course of trying to get hold of the regulatory evidence, the authors received several explanations from Roche as to why it would not share its data. By publishing that correspondence and comment, the authors assert that experiments on humans should be made available, all the more so given the international public health nature of the drug.

They argue: “It is the public who take and pay for approved drugs, and therefore the public should have access to complete information about those drugs.

We should also not lose sight of the fact that clinical trials are experiments conducted on humans that carry an assumption of contributing to medical knowledge. Non-disclosure of complete trial results undermines the philanthropy of human participants and sets back the pursuit of knowledge.”

However, according to the authors, industry and regulators have historically treated clinical study reports as confidential documents, impeding additional scrutiny by independent researchers.

Using the example of Tamiflu, in which drug companies, drug regulators, and public health bodies such as the World Health Organization and the Center for Disease Control have made discrepant claims about its clinical effects, the authors argue that critical analysis by an independent group such as a Cochrane review group is essential. By recounting the details of an extended correspondence with Tamiflu’s manufacturer Roche, the authors argue that the company provided no convincing reasons to refuse providing access to clinical study reports.

The authors challenge industry to either provide open access to clinical study reports or publically defend their current position of randomized controlled trial data secrecy.

They say: “we hope the debate may soon shift from one of whether to release regulatory data to the specifics of doing so. But until these policies go into effect—and perhaps even after they do—most drugs on the market will remain those approved in an era in which regulators protected industry’s data.”

Funding: Peter Doshi is funded by an institutional training grant from the Agency for Healthcare Research and Quality #T32HS019488. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: All review authors have applied for and received competitive research grants. All review authors are co-recipients of a UK National Institute for Health Research grant to carry out a Cochrane review of neuraminidase inhibitors (http://www.hta.ac.uk/2352). In addition: TJ was an ad hoc consultant for F.Hoffman-La Roche Ltd in 1998-1999. TJ receives royalties from his books published by Blackwells and Il Pensiero Scientifico Editore, none of which are on neuraminidase inhibitors. TJ is occasionally interviewed by market research companies for anonymous interviews about Phase 1 or 2 products unrelated to neuraminidase inhibitors. Since submission of this article, TJ has been retained as an expert consultant in a legal case involving Tamiflu. CDM provided expert advice to GlaxoSmithKline about vaccination against acute otitis media in 2008-2009. CDM receives royalties from books published through Blackwells, BMJ Books and Elsevier. PD declares no further conflicts of interest.

Citation: Doshi P, Jefferson T, Del Mar C (2012) The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience. PLoS Med 9(4): e1001201. doi:10.1371/journal.pmed.1001201

CONTACT:
Peter Doshi
Johns Hopkins School of Medicine
Divisions of General Pediatrics and General Internal Medicine
Baltimore, Maryland
United States of America
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