Friday, September 01, 2006

Another Case of Attempted Research Suppression: the Famvir vs Valtrex Study

Another story of apparent suppression of clinical research has surfaced, spotted first by Pharma Watch. The details come from an article just published reporting the results of two trials of famciclovir versus valacyclovir for recurrent genital herpes simplex (HSV) infections,(1) plus an accompanying editorial.(2)

Famciclovir (Famvir) was originally made by SmithKline Beecham, and valcyclovir (Valtrex) was made by Glaxo Wellcome. In 1997, SmithKline Beecham supported two clinical trials of Famvir versus Valtrex, under the assumption that Famvir would prove superior. It did not publish the results of these trials. When the firms merged in 2000 to form GlaxoSmithKline (GSK), US regulators forced them to sell Famvir to Novartis. This year, six years after the merger, and nine after the trials were conducted, their results were finally published.(1)

Briefly, the results of the first trial were that Famvir and Valtrex had similar effects on the rates of clinical recurrence, and on the time to clinical recurrence. Patients on Famvir manifested recurrence by laboratory test earlier than those on Valtrex. The result of the second trial was that patients on Famvir were somewhat more likely to shed virus than those on Valtrex. Thus, the clinical effects of the drugs were indistinguishable, while the laboratory data somewhat favored Valtrex, but the clinical significance of these results is debatable.
At the end of the trial report,(1) the authors noted:

We acknowledge that the process of analyzing data for publication beyond a study report and preparing a manuscript is labor intensive, and companies are understandably wary of devoting resources to a report that is not in favor of their product. We appreciate that Novartis Corporation made these data available after their own in-house review. Although we received data tables and listings for this study, we were not able to obtain data tapes to verify the analyses and to conduct what we consider the most clinically relevant analyses for these types of data, such as the monthly frequency of recurrent episodes or the frequency of days with lesions during the observation period.
The accompanying editorial observed:

These studies took over 7 years to publish and some of the analyses are limited. The role of the study sponsor in this report should be considered. The studies were originally funded by SmithKline Beecham when it owned the rights to famciclovir. A condition imposed by U.S. regulatory agencies permitting the merger of SmithKline Beecham and Glaxo Wellcome that created GlaxoSmithKline was that famciclovir (including these study data) be sold. Novartis was the eventual buyer of famciclovir. As stated by the authors, Novartis provided the authors with the study report and the data listings, but not the primary data itself. Was the delay in the release and publication of the study data a result of the corporate shuffling and movement of responsibility for the study data created by the sale of famciclovir? Alternatively, was it an effort to suppress potentially unfavorable data? Should the full dataset have been provided so that the authors could confirm the analysis and perform additional analyses? Is Novartis to be criticized for delaying and limiting the release of the study report? Alternatively, should Novartis be praised for permitting potentially unfavorable results to be published? The answers to these questions may depend on one's view of the pharmaceutical industry.
All authors of the trial report(1) acknowledged receiving research fjunding from SmithKline Beecham. One is currently a consultant to Novartis. The author of the editorial(2) received research funding from GlaxoSmithKline and Novartis, and is a consultant to GSK.

In summary, these studies' results failed to favor the product made by the company who originally sponsored them. That company delayed publication of the results for the following three years. When it transferred the product and the study data to another company, that company delayed publication for another six years. Eventually, the company transferred pre-analyzed data to the ostensible academic investigators of the study, who were not allowed access to the original study data.

The research sponsors' actions in this case resemble those of another sponsor of another study. That study's academic principal investigator was Dr Aubrey Blumsohn (see post here, and the links to earlier posts it contains, and Dr Blumsohn's Scientific Misconduct Blog). Unlike the investigators of the current study, Dr Blumsohn insisted on getting the raw data from his own study. His persistent efforts to do so got him fired by Sheffield University.

As we have said before, unreasonably delaying or attempting to suppress publication of results of clinical research betrays the trust of the research subjects. Research subjects usually volunteer with the understanding that results of research done on them would be published. Such results could only have been obtained because of their willingness to participate.

Furthermore, failure to let ostensibly academic investigators see and analyze the raw data from their own research undercuts academic freedom, and damages trust in the study's results.

Increasing numbers of research suppression by commercial research sponsors, usually pharmaceutical companies, unfortunately should make physicians very skeptical of all commercially sponsored research.

ADDENDUM (6 September, 2006) - See also related comments on the Scientific Misconduct Blog.

1. Wald A, Selke S, Warren T et al. Comparative efficacy of famciclovir and valacyclovir for suppression of recurrent genital herpes and viral shedding. Sex Transmitted Dis 2006; 33: 529-533.
2. Fife KH. Are the antiherpes nucleosides really all the same? Sex Transmitted Dis 2006; 33: 534-535

1 comment:

JB Harrison said...

Great info on an often over looked topic, thanks!