A reanalysis of the Cu-7 intrauterine contraceptive device clinical trial and the incidence of pelvic inflammatory disease: a paradigm for assessing intrauterine contraceptive device safety

Abstract

Objective: We calculated and compared the incidence of pelvic inflammatory disease in a 10% random sample of the Cu-7 intrauterine contraceptive device (G.D. Searle & Co., Skokie, Ill.) clinical trial with the rates reported to the Food and Drug Administration and those in subsequent trials published in the world literature.

Study design: A 10% random sample of the Cu-7 clinical trial was examined because calculations had demonstrated this random sample to be sufficient in size (n = 1614) to detect a difference in rates of pelvic inflammatory disease from those reported to the Food and Drug Administration. An audit of a subset of the patient files, compared with the original files in Skokie, Illinois, confirmed that the files available for analysis were complete. Standard definitions were used to identify cases of pelvic inflammatory disease and to calculate rates of pelvic inflammatory disease. The world literature on Cu-7 clinical trials was reviewed.

Results: The calculated crude and Pearl index rates of pelvic inflammatory disease were consistent with those rates previously reported to the Food and Drug Administration and published in the medical literature. Life-table pelvic inflammatory disease rates were not different between nulliparous and parous women and pelvic inflammatory disease did not differ from basal annual rates in fecund women.

Conclusion: On the basis of the analysis of this 10% sample, the pelvic inflammatory disease patient rates reported to the Food and Drug Administration for the entire Cu-7 clinical trial are accurate and are similar to those published in the world literature.

PIP: G.D. Searle asked a physician and research statistician to conduct an independent evaluation of the rates of pelvic inflammatory disease (PID) in a 10% random sample of the 1614 women using the Cu-7 IUD in the Searle clinical trial. The team compared these rates with the rates reported to the US Food and Drug Administration (FDA) and with rates of trials which followed the Searle trial and were published in the medical literature. The results would be used to make a judgement to the safety of the Cu-7 IUD and whether IUDs should be a viable contraceptive option for US women. The researchers conducted an audit of a subset of the patient files and compared them with the original files at G.D. Searle. They learned that the subset files were complete. The 20-month PID rates (crude = 2.23, and Pearl index rate = 2.06) among the 1614 women were not statistically different than those reported by G.D. Searle to the FDA (1.84). At 48 months the Pearl index rate was essentially the same as the plaintiffs' requested report in 1984 (1.89 vs 1.8). The overall Pearl index PID rate was less than 1% in an analysis of 27 separate clinical trials published between 1972 and 1989. Among the 1614 women no differences existed in PID life table rates between nulliparous and parous women (p = .29). PID did not differ from basal annual rates in fecund women. Based on the comparison between the 10% sample and the G.D. Searle trial and the 10% sample and the medical literature, the PID rates reported to the FDA for the complete Cu-7 IUD trial are correct and essentially correspond with those published in the world literature.