Drug regulation in the United States and the United Kingdom: the Depo-Provera story
Richard, B.W.; Lasagna, L.
Annals of Internal Medicine 106(6): 886-891
1987
ISSN/ISBN: 0003-4819 PMID: 2953290 DOI: 10.7326/0003-4819-106-6-886Document Number: 424332
In 1984, both the UK and the US received recommendations from panels of experts convened to consider the use of Depo-Provera as a long-term contraceptive agent. Despite access to essentially the same data, the UK panel recommended marketing approval while the US panel did not. It is posited that these 2 conclusions reflected differences in the underlying biases of regulatory policies in the US and the UK. The standard practice in the US is to approve a drug for use only after the completion of extensive human trials. In the UK, however, the practice is to accumulate much of the data on human safety after the drug has been marketed. The US board tended to emphasize proof that Depo-Provera was safe, while the UK panel appeared to look for evidence to prove that Depo-Provera was unsafe. In addition, the US board was mandated to consider a set of specific questions focused on a risk-benefit analysis of Depo-Provera in comparison with other contraceptive methods, while the UK panel was given a more general mandate to act as expert analysts. Another possible explanation for the divergence of outcomes concerns the committees' judgments about the practices of physicians in the respective countries and the extent of influence regulatory agencies should have over individual medical practice. Denial of approval of Depo-Provera in the US was viewed as making little difference to physicians since the drug is currently approved for use for other indications. In the UK, on the other hand, doctors would have been inhibited from prescribing Depo-Provera by possible legal consequences. Overall, it is concluded that policies concerning the extent of human trials required to gain marketing approval, the acceptability of prescribing drugs for unapproved indications, the evidence required to prove or disprove carcinogenic potential, and the general threshold of evidence required to establish causality accounted for the different decisions reached by experts in the US and the UK.