Book Review

Science, Politics, and the Pharmaceutical Industry: Controversy and bias in drug regulation

N Engl J Med 1996; 334:609-610February 29, 1996

Article

Science, Politics, and the Pharmaceutical Industry: Controversy and bias in drug regulation
By John Abraham. 308 pp. New York, St. Martin's Press, 1995. $49.95. ISBN: 0-312-12873-8

Since 1962, when Congress required proof of the efficacy and safety of drugs approved by the Food and Drug Administration (FDA), the FDA's summary opinions have been fairly consistent with those of the medical profession, as outlined in pharmacology textbooks. When the FDA arouses public wrath, it is often for moving more slowly than its European counterparts. Yet, according to John Abraham, a sociologist at the University of Reading in England, the story is not so simple. His book about testing drugs for efficacy and safety in the United States and the United Kingdom is illustrated by case histories and the progress of five nonsteroidal antiinflammatory drugs through the regulatory processes in the two countries.

The British process is unlike the American process. Because the British government wishes to ensure the success of its pharmaceutical industry, its regulatory agencies tend to be protective rather than adversarial, as they are in the United States, where the government is required to be more concerned about protecting patients than about protecting the firms that manufacture medicines. Even so, as Abraham shows, the self-interest of American companies can lead to approvals that must eventually be reversed. He suggests that “corporate bias” is a serious problem in drug testing. A reading of his case histories brings to mind words such as “inconsistencies,” “coverup,” “incompetence” — even “lies” — as synonyms for “bias.”

Abraham discusses the cases of naproxen (Naprosyn), piroxicam (Feldene), benoxaprofen (Oraflex), zomepirac (Zomax), and suprofen (Suprol). These cases exemplify problems that range from lack of provable efficacy to anaphylactoid reactions, gastrointestinal toxicity, cholestatic jaundice, and carcinogenicity. All five drugs managed to gain approval for marketing in both the United States and the United Kingdom, despite the lack of scientifically sound evidence of their efficacy in the treatment of rheumatoid arthritis and osteoarthritis — illnesses that promise very large markets for nonsteroidal antiinflammatory drugs. Four of the drugs were approved in the face of uncertainty about their safety. The scientific legerdemain carefully described by Abraham may be typified by the manufacturer of benoxaprofen, which blamed the sun, not the drug, for its phototoxicity. Three drugs had to be disapproved soon after their approval, as solid evidence of their toxic effects betrayed their sponsors' attempts to explain away these effects or to suppress the publication of negative reports in refereed journals.

Abraham has accomplished his enormous task dispassionately. Heretofore it has been nearly impossible to compile detailed case histories of the FDA approval process; the Freedom of Information Act alone permitted him to compile these stories. He can provide fewer details of the British experience with the same drugs, because the British government is more secretive about official actions, especially those in which the government believes it has a major stake.

Physicians can be excused from reading Abraham's first chapter, on sociological models for the biased behavior described in the case histories; it is not essential for understanding what follows. The second chapter, an accurate account of the evolution of drug regulation in the United States and the United Kingdom, is followed by the case histories and several self-evident recommendations for policy changes. The book should be read by anyone involved with or interested in the study, manufacture, and regulation of drugs. It provides a fascinating account of the interface between science and the public interest and could well find a place in business-school curriculums.

J. Worth Estes, M.D.
Boston University School of Medicine, Boston, MA 02118