A systematic review of pregnancy exposure registries: examination of protocol-specified pregnancy outcomes, target sample size, and comparator selection

Abstract

No registries were designed to have sufficient power to assess specific malformations, despite the plausibility that most teratogens cause specific defects. Only half of the registries included a power analysis. Despite their common use, external comparators, including MACDP, have important limitations. In the absence of randomized controlled trial data in pregnant women, pregnancy registries remain an important tool as part of a comprehensive pregnancy surveillance program; however, pregnancy registries alone may not be sufficient to obtain adequate data regarding risks of specific malformations. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Registries supporting new drug applications

“…With regard to pregnancy data, in 2002 the FDA issued an amendment describing the requirement for the collection of pregnancy data through registries . A recent review concluded that these types of registries remain an important tool to collect safety data in the absence of randomized controlled trial data on pregnant women . Moreover, the FDA did accept registries for regulatory purposes in the evaluation of medical devices and is exploring further ways to use real‐world data in support of drug applications …”

A systematic assessment of key design and performance characteristics of drug exposure registries requested by the U.S. Food and Drug Administration

“…The authors suggest increased use of existing patient registries to minimize these challenges and improve timeliness of data collection. In comparison to a review of postmarket pregnancy registries in which only 50% performed power analyses, two thirds of the nonpregnancy product registries in the present study performed sample size calculations and/or considered patient accrual/retention efforts. The proportion was higher (76%) among the high‐performance registries, which emphasizes the importance of recruitment strategies (e.g., that support a continued enrollment) and retention efforts (e.g., that encourage continued participation) for ensuring an adequate number of patients.…”

Use and safety of disease‐modifying therapy in pregnant women with multiple sclerosis

“…Exposure pregnancy registries have been considered the first line of evidence because they are able to enroll women soon after drug approval . However, they often fail to enroll sufficient numbers of pregnancies to produce robust safety data, particularly for newly introduced drugs for relatively rare conditions . Health‐care databases may be an efficient resource to provide real‐world evidence for pregnant women with MS including (a) information on drug utilization patterns, (b) baseline risks for common pregnancy outcomes that can be used as a reference for new drugs registries, and (c) boundaries of safety for drugs already used with certain frequency .…”