10.06.2009
Pfizer conceals study data
Drug manufacturer hinders the best possible treatment of patients with depression
The pharmaceutical company Pfizer is concealing data on the effect of a drug (Edronax® containing the agent reboxetine) for the treatment of depression. Despite repeated requests by the Institute for Quality and Efficiency in Health Care (IQWiG), Pfizer has refused to provide a complete list of all published and unpublished trials on reboxetine. The Institute discovered through its own literature search that the drug approved in Germany has been tested in at least 16 trials. However, in 9 of these 16 trials, key information is missing that would enable an evaluation of reboxetine's performance.
According to Peter T. Sawicki, IQWiG's Director, "By concealing study data, the manufacturer is depriving patients and doctors of the opportunity to make an informed decision on different therapy options." Furthermore, it hinders the work of institutions such as IQWiG. IQWiG's aim is to draw reliable conclusions concerning the benefit and harm of drugs.
No trivial offence
The fact that study results are only partially published has been known by the term "publication bias" for over 20 years. In this respect, it has been shown that particularly "negative studies", in which, for example, the company's drug did not produce the hoped-for result or even proved to have no effect, are published only years later or not at all. This means that, on the sole basis of published reports, patients and doctors receive an overoptimistic picture of the effects.
This trend is still one of the most important and dangerous sources of error in medicine. "Deception through concealment is no trivial offence," says Sawicki. "In extreme cases, patients may even receive useless treatments if information is incomplete."
For example, in the treatment of depression other researchers have already shown that the effect of several agents has always been exaggerated in the published literature - up to 70% (on average about 30%). In the case of some agents, it is even doubtful whether a benefit is detectable at all, if all trials are considered.
In the case of reboxetine, the Institute only had evaluable data for about 1600 patients, whereas at least 3000 more patients had participated in the incompletely published trials. According to this information, data on about two-thirds of the total number of patients are missing.
Voluntary self-commitment is not enough
It is particularly dangerous that doctors and researchers are often totally unaware that unpublished trials exist. In order to solve this problem, IQWiG concluded a basic agreement on the transfer of such data with the German Association of Research-based Pharmaceutical Companies (VFA) as early as 2005. Furthermore, in January 2005 the international associations of the pharmaceutical industry announced a voluntary self-commitment to disclose information on clinical trials.
However, these announcements from the pharmaceutical industry cannot be relied upon. In recent years, companies have repeatedly refused to provide the Institute with study documents required for the benefit assessment of drugs. Frequently, clinical trial registries, which have been set up in recent years, do not contain these data either. Pfizer did not give IQWiG any reasons for refusing to disclose the trials.
Trials should also be published retrospectively
IQWiG's experience has shown that the existing countermeasures, which are primarily based on voluntary solutions in Germany and Europe, are inadequate. It is not known when and how statutory regulations aimed at solving the problem will actually take effect. IQWiG is therefore calling for an EU-wide legal obligation, bound by tight deadlines, to publish the results of clinical trials.
"In the USA this obligation has been clearly implemented in law since 2008," explains Sawicki. "We need a comparable, definite and transparent implementation for Europe as soon as possible." In this context, it is essential that such an obligation must also apply retrospectively to drugs already approved. Moreover, statutory regulations are necessary so that all data are provided on request to institutions such as IQWiG or the Federal Joint Committee (G-BA).
By concealing data, manufacturers are also breaking agreements that were made with study participants, who take part in experiments both voluntarily and altruistically. Through their participation and the publication of the results, they also want to help others who are ill. Sawicki concludes, "Keeping the results of a trial secret is cheating the participants."
Reservations also exist regarding a further agent
The project commissioned by the G-BA is concerned with assessing the benefit of the three agents, reboxetine, mirtazapine and bupropion XL, in the treatment and prevention of depression. In the case of mirtazapine (Essex Pharma), it is also possible that not all trials were disclosed. Consequently, the result of the preliminary assessment is to be viewed with reservation.
Only in the case of bupropion XL could the Institute assume that it had access to a full database, as the manufacturer (GlaxoSmithKline) provided all the information requested.