The rofecoxib case is bad news for industry, academics, journals, and the public. Merck was once one of the US's most publicly admired companies,w37
and its behaviour may not be different from that of others in the pharmaceutical or biotechnology industry. Journalists have questioned the ethics of industry and academic researchers.18
And yet, there is hardly a sense of outrage in the profession about the events that transpired.
Defenders of Merck may say that we do not know how rofecoxib's cardiovascular risk compares with that of other COX 2 inhibitors or traditional non-steroidal anti-inflammatory drugs. But the proper place of these drugs in the medical armamentarium is beside the point. With billions of dollars at stake, Merck conducted the trials, stored and analysed the data internally, paid academic researchers as consultants to the investigative teams and the safety monitoring boards, and maintained heavy involvement in the writing and presentation of findings. The journals published the studies, and the academic community accepted the findings without expressing much concern. Nearly 107 million prescriptions for rofecoxib were dispensed in the US between 1999 and September 2004,21
when the drug was withdrawn from the market, and none of the people picking up those prescriptions had the opportunity to consider the true balance of its risks and benefits.
What should we do going forward? Academic medicine, industry, medical journals, and government agencies need to come together to define a set of principles by which we can restore faith in collaborations on new treatments that can improve patient care. We might consider adopting some new approaches. Academics engaged in industry designed and sponsored studies should insist that the data are stored on an academic site, analysed by non-company investigators, and eventually made accessible to the public for scrutiny. Several early, large clinical trials of rofecoxib were not published in the academic literature for years after Merck made them available to the FDA,22
preventing independent investigators from accurately determining its cardiovascular risk using meta-analysis. In addition, independent audits should be conducted to ensure that companies follow a standardised, prespecified protocol.
Independent data and safety monitoring boards should be mandated and their governance should not be under the control of the company. Industry should not be allowed to select who serves on these boards or allowed to compensate members after their service.
In considering articles for publications, journals should understand that studies with immense financial implications require a higher level of scrutiny than others, especially when the study is conducted by the company with the financial stake. Journals should be prepared to go beyond the usual high quality review, paying particular attention to the possibility of bias. Articles should be accompanied by editorials by people without financial conflicts of interest. Moreover, ghostwriting constitutes a false statement of authorship or a false attribution of authorship, and academic researchers who sign off or “edit” original publications or reviews written by industry should be penalised unless there is full disclosure of the authorship, such as: “Representatives from XYZ drafted the manuscript; the authors were responsible for critical revisions of the manuscript for important intellectual content.”
Even the best oversight cannot always detect mistakes. When journals discover that information has been withheld or that results are incorrect, they need to rapidly disseminate that information and ensure that any web search that identifies the errant manuscript also identifies the correction. Authors should sign agreements that they will notify journals if such information becomes available or face being blacklisted by the journal.
Our system depends on putting patients' interests first. Collaborations between academics, practising doctors, industry, and journals are essential in advancing knowledge and improving the care of patients. Trust is a necessary element of this partnership, but the recent events have made it necessary to institute proper systems that protect the interests of patients. A renewed commitment by all those involved and the institution of these systems are the only way to extract something positive from this unfortunate affair.
Merck faces legal claims from nearly 30000 people who had an adverse cardiovascular event while taking rofecoxib (Merck denies liability)
Published studies of the drug obscured the risk
Merck had influence over all aspects, including data analysis, safety monitoring, and reporting
Academic medicine, industry, medical journals, and government agencies need to define a set of principles to restore trust in collaborations on drug development