W 22: Best Practices for Pregnancy Outcome Monitoring in the Post Marketing Environment
Merck & Co., Inc. United States
Drug and vaccine development generally excludes enrollment of women who are or may become pregnant during clinical trials. This review describes best practices for initiation, execution, and closure of pregnancy registries to detect safety signals of important pregnancy related adverse effects.
Pregnancy registries are voluntary, enhanced post-marketing surveillance programs that collect health information on women who take prescription medicines or vaccines during pregnancy, and are used to inform product safety. The analysis of cumulative outcome data is provided through annual reports.
A pregnancy registry may be implemented when mandated by a health authority, the product is used widely by women of reproductive age or existing data suggest a potential for harm. Pregnancy registries provide a structured approach to collect data on safety in a patient population that is exposed to prescription drugs (or vaccines) during pregnancy. Precise methods of registry enrollment and data collection are critical to ensure that complete and accurate data is obtained for analysis. Enrollment of a patient is voluntary and requires: identification of a healthcare provider (HCP); a unique patient identifier; and a documented drug (or vaccine) exposure during pregnancy. A patient or provider may decline to participate in a registry at any time. Reports are classified as prospective or retrospective. Prospective reports are those received before the outcome of the pregnancy is known; retrospective are those received after the outcome of pregnancy is known. Prospective reports comprise the primary cohort available for rate calculations. Due to inherent reporting bias concerning abnormal pregnancy outcomes, retrospective reports are analyzed separately from prospective reports. Pregnancy outcomes are ascertained from HCPs through questionnaires completed voluntarily at the time of the initial report and at the estimated date of delivery. Enhanced follow-up includes phone calls to HCP’s or patients to obtain pregnancy outcome information. Efforts are made to obtain newborn and pediatric medical records. The cumulative data presented in the annual report is reviewed by a teratologist. FDA Guidelines state that a pregnancy registry should continue until sufficient information has accumulated to meet the scientific objectives of the registry or the feasibility of collecting sufficient information diminishes to unacceptable levels due to: low exposure rates; poor enrollment; or loss to follow-up. Merck collaborates with Health Authorities regarding registry closure.
Merck has a history of managing pregnancy registries with the highest standards of excellence. Over the past 20 years, Merck has established and supported six pregnancy registries, allowing for the collection and analysis of post-marketing data on exposures to specific drugs or vaccines during pregnancy. Post-marketing surveillance relies upon the voluntary reporting by individuals and HCPs and it is often a challenge to collect adequate data. Reports are frequently incomplete and require diligent follow-up to obtain accurate information. Pregnancy registries allow for a more rigorous collection of pregnancy outcomes. Limiting loss to follow up in prospective reports by intensive follow up improves both the quality and quantity of the data. The annual report, with a detailed analysis of pregnancy and fetal outcomes, is provided to HCPs seeking additional information and to share with concerned patients. For example, in the varicella-containing-vaccines and human papillomavirus vaccine registries, the rates of spontaneous abortions and major birth defects were not greater than those in the general population of pregnant women in the absence of vaccine use. The information furnished by pregnancy registries allows the health care provider and patients to make more informed decisions regarding drug/vaccine use during pregnancy. Pregnancy Registry Programs serve an important public health need through the systematic collection and analysis of real world product safety in pregnancy and on fetal outcomes, and helps assure safe use of drugs and vaccines in women of childbearing age.