In 2009, there are still lessons to be learned from the rofecoxib (ex-Vioxx°) scandal (1).

During one trial, a team studied how the pharmaceutical company Merck had concealed the increased mortality due to rofecoxib observed in the Alzheimer’s disease trials that it had financed (a)(2,3).

Publications and reports submitted to regulatory agencies
included spotty data and inappropriate analyses In 2 studies, mortality was 3 times higher with rofecoxib than with placebo (3). But several of the authors of the two published trial reports were employed by the company, and in these articles, deaths were reported in an isolated manner, without adequate analysis. The authors even had the nerve to conclude that rofecoxib was "well tolerated"!

While it was in possession of alarming data, in particular a rigorous "intent-to-treat" analysis, in September 2001 the company sent the US Food and Drug Administration a reassuring report, without the "intent-to-treat" analysis (b). At the end of 2001, the company explained that it had not informed the ethics committees (in charge of evaluating the ethical or non-ethical nature of clinical trials) of the results in terms of mortality (c).

Independent analysis is necessary
This type of behaviour is predictable, given the major conflicts of interest that arise when firms are put in charge of evaluating the very drugs from which they derive their income.

Until a healthy source of financing is found for clinical research, the authors of the study have called for expert opinion that is independent of pharmaceutical companies, to carry out and supervise clinical trials, and to analyse and present their results (3).

That is the very least we can do to protect patients.

©Prescrire 2009

Source: "Réagir à la mainmise des firmes sur les données cliniques" Rev Prescrire 2009; 29 (303): 57.

Notes:
a- Rofecoxib was marketed primarily for relief of osteoarthritis pain, and was withdrawn several years later, after tens of thousands of patients experienced serious, even fatal, cardiac events (ref 1).
b- In the "intent-to-treat" analysis, the adverse effects data are analysed for all of the patients who began the trial, since a serious adverse effect can be the reason for dropouts, and can also show up after the end of treatment.
c- See reference 4.

References:
1- Prescrire Editorial Staff “How to avoid future Vioxx°-type scandals” Prescrire Int 2005; 14 (77): 115-117.
2- Prescrire Editorial Staff “Celecoxib still on the market” Prescrire Int 2005; 14 (79): 177-178.
3- Psaty B et Kronmal R “Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment: a case study based on documents from rofecoxib litigation” JAMA 2008; 299 (15): 1813-1817.
4- Prescrire Rédaction “Comités de protection des personnes: affirmer leur rôle éthique et scientifique” Rev Prescrire 2005; 25 (267): 862-863.