Value of drug-licensing documents in studying the effect of postmenopausal hormone therapy on cardiovascular disease

Lancet. 2000 Feb 12;355(9203):566-9. doi: 10.1016/S0140-6736(99)03432-7.

Abstract

Background: In a previous study of pooled data from published trials, we found no evidence to support the claim that postmenopausal hormone therapy (PHT) is associated with a decrease in cardiovascular disease. The purpose of this study was to see whether reports of clinical trials attached to drug-licensing applications in Finland could be obtained for scientific purposes, whether they are useful for studying cardiovascular events resulting from PHT, and if so, whether these unpublished reports corroborate the results of published reports.

Methods: Since clinical trials in drug-licensing documents are confidential, we had to obtain special permission from the Ministry of Social Affairs and Health to use the data for research purposes. After permission was granted, we studied the clinical sections of licensing documents for PHT drugs sent by drug companies to the Finnish Drug Agency. We aimed to identify trials that compared PHT and a placebo (or no therapy, or vitamin-mineral drugs), and that reported on cardiovascular and thromboembolic events or superficial phlebitis. New trials were identified and their data were pooled with those of published trials.

Findings: 17 licensing applications for drugs used as PHT were found. The number, type, and quality of reporting of clinical trials varied widely between applications. The trials and their reporting of unanticipated adverse events were mostly inadequate. Six new trials (ie, those fulfilling the inclusion criteria and not included in our earlier report) were found. The new trials added little to the conclusions of previously published studies: the calculated odds ratios of cardiovascular and thromboembolic events for women taking PHT versus those not taking it was 1.97 (95% CI 0.84-4.63), compared with 1.65 (0.65-4.21) in our previous study.

Interpretation: In this case, unpublished trials added only a little to the data available from published trials, mainly due to the type of clinical data used in the licensing applications. The new data did not change the previous conclusion that clinical trials do not support a beneficial effect of PHT on cardiovascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / prevention & control*
  • Clinical Trials as Topic
  • Data Collection / methods
  • Drug Approval*
  • Female
  • Finland
  • Hormone Replacement Therapy* / adverse effects
  • Humans
  • Middle Aged