Pain and Punishment

An article in the New England Journal of Medicine on July 8, 1997 suggested that these drugs caused heart valve damage and a rare condition, primary pulmonary hypertension. A class action suit followed on July 9. The drugs were withdrawn from the market in September 1997. The drug company agreed to pay up to $ 4.83 billion to settle thousands of claims from patients who may have suffered heart damage from taking the once-popular weight-loss treatment.

The story did not end there. In 1999, The New York Times published a news story (‘‘Fen-Pen wasn’t that bad after all!’’) referring to a small study in the Journal of the American College of Cardiology . The newspaper was also influenced by the editorial in the same journal: ‘‘Story of Fen-Pen is just a big scare!’’ It was a matter of research by others to discover that one of the writers of the article, and the author of editorial published in the journal, were both paid by American Home Products.

Indeed, Wyeth (daughter company of American Home Products) had hired Excerpta Medica, a PR firm, to hire writers and opinion makers to ghostwrite and edit medical articles to support their legal defense, and present findings favorable to the drug in scientific meetings!

A question asked by the scientists is: was Vioxx clearly responsible for fatal side effects, or was the US court moved by the public opinion, emotions, and anecdotes? For a drug to be responsible for a disease such as heart attack, it is necessary to establish a cause-effect relationship since the heart is affected in adverse ways by nearly 50 environmental and biochemical factors.

Further, most of the patients taking Vioxx were old, and thus more prone to heart problems. The population-based studies (as have been done by Dr Graham, see box), do indicate that this drug may be at fault, but this evidence is more circumstantial than a definite proof.

Despite these uncertainties, the role of Merck continues to be under cloud. Clearly, if there was even an iota of suspicion about the safety of the drug, Merck chose to hide some vital information, and delayed the public announcement of the key findings. If the drug is deemed to be at fault, it should be withdrawn, and not used in the market for profits, disregarding morbidity and death that it may cause. Indeed, during 2001-2004, a number of articles by the employees of Merck repeatedly reaffirmed favorable cardiovascular safety of Vioxx.

Dr. Eric Topol in his editorial in the New England Journal of Medicine wrote: ‘‘Neither of the two — Merck and FDA — in the five-and-half-year-affair fulfilled their responsibility to the public’’. It is estimated that the death of as many as 60,000 Americans (cited as more than the number of US soldiers killed in the Vietnam War), could be ascribed to the use of Vioxx.

How a FDA advisory panel has now again voted to allow the drug to return to the market is incomprehensible. It is a popular joke in the US that for the FDA to consider a drug dangerous, it apparently has to kill more than 60,000 Americans!

The public health implications for India are enormous, and a lesson to physicians, pharmaceutical companies and drug regulatory agencies. Approximately 70 companies were marketing Rofecoxib, and estimated sale from this drug exceeded Rs. 200 crore. It is unclear how many patients would be taking this drug, but the number would be in millions.

Furthermore, a substantial number of patients were also taking sister drugs: Valdecoxib and Celecoxib (see box). Even if these drugs cause a fraction of a per cent increase in the serious cardiovascular adverse effects, the number of those affected in India would be several million people.

The Indian drug regulatory authorities have acted fairly promptly in banning Rofecoxib, but many companies continue to market this drug freely in remote towns, and a number of physicians are unaware of the ban of this drug.

Further, unscrupulous pharmacists continue to sell these drugs to illiterate people asking for over-the-counter painkiller. These events also underscore the urgency required for an active vigilance of known and unknown adverse effects of newly introduced drugs in India.

The cardiovascular side-effects of any drug on Indians need a careful monitoring, since Indians are more prone to cardiovascular diseases. Establishment of a National Pharmacovigilance Commission and other planned changes in the drug regulation are positive steps, but much remains to be done. The physicians also need to update themselves continuously on the new adverse effects of drugs.

The writer is a professor at the department of Medicine AIIMS, New Delhi, and is also a member of an expert committee on drugs in the Health Ministry.Email: anoopmisra@gmail.com