The creeping pearl: why has the rate of contraceptive failure increased in clinical trials of combined hormonal contraceptive pills?

Abstract

BACKGROUND Despite several drawbacks, the Pearl Index continues to be the most widely used statistical measure of contraceptive failure. However, Pearl indices reported in studies of newer hormonal contraceptives appear to be increasing. STUDY DESIGN We searched PubMed and MIS databases for prospective trials evaluating oral contraceptive (OC) efficacy to examine potential factors that could contribute to increasing Pearl indices. RESULTS Numerous potential factors were identified, including an increased rate of failures of newer OCs, deficiencies in methods of calculating contraceptive failure rates, differences in study design and changes in patient populations resulting in increased rates of contraceptive failures due to the inappropriate or inconsistent use of the method. CONCLUSIONS The two most likely important contributors to the increase in Pearl indices are more frequent pregnancy testing with more sensitive tests and less adherent study populations. Because study populations appear to be increasingly representative of the likely actual users once the product is marketed, we can expect to see even higher failure rates in ongoing and future studies. This result poses challenges for companies and regulatory agencies.

Extended-Cycle Levonorgestrel/Ethinylestradiol and Low-Dose Ethinylestradiol (Seasonique®): A Review of Its Use as an Oral Contraceptive

“…1 Median unscheduled bleeding and/or spotting and bleeding alone days per 91-day cycle (a) and per patient-month (b) during treatment with Seasonique Ò in adult women (n = 1006) in a 1-year, noncomparative, multicentre, phase III trial [21] endometriosis, iron deficiency and anaemia, and in others, monthly bleeding is an inconvenience that interferes with quality of life and productivity [3,5]. Additionally, it has been postulated that an extended-cycle OC may help to avoid missing first pills, which is a cause of pill failure and unintended pregnancy [27]. In a 1-year, noncomparative trial of healthy, sexually active women, Seasonique Ò was found to have acceptable efficacy for the prevention of pregnancy in terms of the Pearl index for the overall (typical use) and method-failure (compliant use) pregnancy rates (Sect.…”

“…Moreover, regulatory agencies have differing requirements for the calculation of the Pearl index [27]. For example, the US FDA calculated the Pearl index for Seasonique Ò as 1.77, based on 7 pregnancies that occurred on-treatment over 5125.…”

“…It is difficult to compare the efficacy and tolerability of different contraceptive products as there is no single accepted and uniformly used design for clinical trials [27]. Moreover, regulatory agencies have differing requirements for the calculation of the Pearl index [27].…”

▼Zoely: a new combined oral contraceptive

“…Currently two methods are used for measuring contraceptive efficacy: the Pearl Index and the life table. Despite several drawbacks, the Pearl Index continues to be the most widely used statistical measure of contraceptive failure 17. It is defined as the number of failures per 100 woman-years of exposure 18.…”

“…The Pearl Index for COCs is estimated at 0.3–4.0. The life table analysis provides the contraceptive failure rate for each month of use and can provide a cumulative failure rate for any duration of exposure 17. The failure rate with perfect use (true pill failure) is 0.1% and with typical use (user and method failure), it is closer to 5% 18.…”