Debate Intensifies Over Transparency of Trial Data

A researcher from a top US institution has delivered strong criticism of Roche's promise to release full clinical study reports as part of its data transparency policy, signaling an escalation of the battle over publication of clinical trial results.

In a letter published by http://bmj.com, Peter Doshi, PhD, a postdoctoral fellow at Johns Hopkins University School of Medicine in Baltimore, MD argues that "instead of issuing press releases with more promises to release data, Roche should alert the world when it actually makes good on its long-standing pledges." He also claims that three of the four advisors selected to lead Roche's advisory board that will grant access to patient-level data for scientific review are not independent but have recent financial relationships with Roche.

The correspondence is posted online as part of the British Medical Journal's open data campaign, aimed at persuading Roche to honor its commitment made in December 2009 to make full clinical study reports for 10 treatment trials of Tamiflu available for independent scrutiny. The company has not yet provided even a single full study report, according to Doshi.

In a press release issued at the end of February, Roche explained that it was unhappy with how Tamiflu has been reviewed and approved by regulatory authorities in over 80 countries. However, Doshi thinks the company does not understand the meaning of independent review, and questions whether Roche has any plans to correct the scientific record after Roche authors published a paper in 2003 claiming the opposite to what the FDA concluded over a decade ago that "Tamiflu has not been shown to prevent" serious bacterial complications of influenza.

Roche's newly announced data transparency policy is "unclear, containing conflicting statements about which data will be released, and the mechanisms for access appear restrictive." He explains that rather than releasing patient-level data to third party researchers, with no strings attached, Roche apparently intends to grant researchers access to a "secure system" and only "following agreement." These conditions may render "independent" analysis a hollow concept, he warns.

Also during March, AbbVie sought an injunction to block the European Medicines Agency (EMA) from releasing "confidential" and "commercially-sensitive" information on its blockbuster rheumatoid arthritis drug, according to news reports from Financial Times (FT) and Reuters. The Chicago-based company, which was spun off from Abbott Laboratories, reportedly is keen to prevent EMA from releasing data on the effects in individual patients in clinical trials for its drug Humira.

The EMA has been criticized in the past for excessive secrecy, but now is "opening its data vaults to systematic scrutiny, a move that will let independent researchers trawl through millions of pages of clinical trial information," according to Reuters. The organization adds that "it is a blow for the pharmaceutical industry, which guards its commercial secrets fiercely and has not before been required to share its data with outside researchers."

The injunction, taken in the EU's general court, follows two Freedom of Information requests to the agency in 2012 to release "raw data" on the drug's safety and efficacy, noted the FT on March 11, 2013. A second legal action has been brought against EMA by InterMune, a Californian biotech company, and the European and US pharmaceutical industry bodies have lodged supportive pleas, the report stated.

"While public debate has concentrated on opening data to independent researchers to prevent any concealment of side effects of drugs by companies, the cases show that rival companies have been most active in seeking the information. UCB, the Belgian drugs company, was one of those seeking reports on AbbVie's Humira," asserted FT reporter Andrew Jack.

The legal decision will have important implications for a broader commitment made last year by EMA to release publicly by the start of 2014 all data on drugs submitted to it, once it has made a decision either to approve or reject them for use across the European Union, he continued. Industry remains concerned that full data transparency risks jeopardizing patient confidentiality, misinterpretation by non-experts, and undermining sensitive commercial information that weakens the incentive to invest in research and development.

The EMA has pledged to proactively publish clinical trial data and enable access to full data sets by interested parties, but it admits that a number of practical and policy issues need to be addressed before complex data sets can be made available. It held a workshop on this topic in London at the end of last year.

On March 13, the agency published its work program for 2013. Its main priorities are to ensure assessment activities are conducted to the highest levels of quality and consistency; to implement the pharmacovigilance legislation, depending on resources; to prepare for the implementation of the falsified-medicines legislation; to prepare for the outcome of the European Commission's impact assessment on revision of the veterinary-medicines legislation; and to develop the communication and transparency activities of EMA.

—Philip Ward