Do clinical trials sponsored by the pharmaceutical industry show bias in research findings?Public health advocates in the United States have long questioned bias and conflict of interest in industry sponsored clinical trials. Now, a recent study from Germany indicates that industry trials report out their findings with favorable findings for drugs they are sponsors of. This has certainly been the concern of American public health advocates. In this Guest Commentary Professor Gerhard Fortwengel reviews two articles regarding the German study. Gerd’s commentary certainly contributes to the discussion on pharmaceuticaal influence in publication of results of clinical trials. The articles he reviews provide a strong case for research that is independently sponsored and reviewed. The Blog certainly welcomes alternative viewpoints. Let me know what you think.
Comparison of Industry and Independent Clinical Trial Results
The results of clinical trials funded by the pharmaceutical company who is the owner of the investigational drug, are often more favorable in support of the drug under investigation compared to clinical trials with independent financial support.This has been confirmed by German scientists, who evaluated 57 systematic review publications with publication dates between November 2002 and December 2009. In the articles (part 1 and 2) the authors describe that published drug trials that were financed by pharmaceutical companies, or whose authors declared a financial conflict of interest, were found to yield favorable results for the drug manufacturer more frequently than independently financed trials whose authors had no such conflicts. Looking at the pure outcome figures it is also stated that the interpretation of the results was more often favorably than in independently financed trials.
The article states that evidence was found that pharmaceutical companies influenced study protocols in a way that was favorable to themselves. On the other hand the methodological quality of trials financed by pharmaceutical companies was not found to be any worse than that of trials financed in other ways. Coming back to the authors´ statement about study protocols and how they are designed to favor the drug under investigation, following ways of doing so were listed e.g. usage of lower than routine dosages in treatment arms for comparison, selection of endpoints supportive for the new drug, but not state of the art and disregarding relevant objective endpoints.
What are the consequences? Do we, as we are all somehow affected by or directly involved in drug development, want to accept this? No, never – we want to be part of a reliable business as well as we want to rely ourselves in all conscience on publications referring to new potent drugs. But what can be done?
Would a higher degree of transparency help to bring some light into this and to regain credibility? What would this look like? The countries in the European Union have already implemented certain steps, such as initial regulatory approval for any type of trial and subsequently of any substantial amendment to an approved trial protocol, in addition to the worldwide implemented IRB/EC approval requirements. Of course I would expect that a regulatory approval includes the review of the scientific value of the trial and consequently “wrong” endpoints or trials with active comparators with a too small dosages should not have been approved, shouldn’t they? A (publicly) accessible clinical trial registry, including a module with trials results, mandatory to be completed by any trial sponsor (industry or academia) in a pre-defined time period after trial completion could help, particularly when the structure for the results would be clearly defined in order to avoid to focus e.g. on secondary objectives or even corollary results, instead of providing a clear result with regard to the initial study objective. At least such registries would be supportive for any agency after receiving an application for a market license to be able to check if all trials have been properly included in the package submitted and to identify missing trials with equal and negative results.
Everyone, who was ever involved in critical appraisals knows, that the reading of scientific papers requires routine and a strong background regarding the topic of the publication. So, finally this type of trial results publication channel would address more the need of the scientific community and consequently a different way must be found for the lay public.
By Prof. Dr. Gerhard Fortwengel, MPH
University of Applied Science and Arts Hannover, Germany
18 May 2010
[Schott, G; Pachl, H; Limbach, U; Gundert-Remy, U; Ludwig, W; Lieb, K.: The Financing of Drug Trials by Pharmaceutical Companies and Its Consequences: Part 1. A Qualitative, Systematic Review of the Literature on Possible Influences on the Findings, Protocols, and Quality of Drug Trials
Dtsch Arztebl Int 2010; 107(16): 279-85;
Schott, G; Pachl, H; Limbach, U; Gundert-Remy, U; Lieb, K; Ludwig, W.; The Financing of Drug Trials by Pharmaceutical Companies and Its Consequences: Part 2. A Qualitative, Systematic Review of the Literature on Possible Influences on Authorship, Access to Trial Data, and Trial Registration and Publication Dtsch Arztebl Int 2010; 107(17): 295-301]
In the United States, a leading critic of the pharmaceutical industry is Dr. Marcia Angell. Her new article is in the Boston Review is called Big Pharma, Bad Medicine.
There is more than one side in this discussion and you can read information from the pharmaceutical industry on the PhRMA homepage.
As always, The Blog welcomes Your comments.