(A-293) One Problem, Multiple Solutions

Background: The United States (US) Food and Drug Administration (FDA) often requires sponsors to conduct pregnancy safety studies as post-marketing requirements/commitments (PMR/PMCs). Typically, these studies are pregnancy exposure registries or database studies.
Sponsors with registry PMR/PMCs for multiple products in the same class have a key decision to make: to conduct separate studies (1 registry per product), to conduct a combined study (1 registry for multiple products), or to build participate in a multi-sponsor registry (if one doesn’t exist). The first 2 options also apply to database studies as well.

Pfizer has separate registry and database studies for rimegepant and zavegepant (2 registry studies, 2 database studies, 4 PMRs). AbbVie has the same 4 PMRs for ubrogepant and atogepant and has a combined registry study and separate database studies. Many sponsors participate in multi-product pregnancy registries (eg, antiretrovirals, antiepileptics, antidepressants).

Objectives: To quantify the number of applicable PMR/PMCs and discuss strengths and limitations of each approach.

Methods: FDA’s PMR/PMC database was searched for pregnancy studies. Product class was assigned to each record in FDA’s PMR/PMC database using the first 5 digits of the Anatomical Therapeutic Chemical code. Sponsor experiences with migraine products are discussed.

Results: 227 of 2566 PMR/PMCs are pregnancy studies. 16 sponsors had pregnancy PMR/PMCs for multiple products in the same class. 29 product classes had pregnancy PMR/PMCs for multiple sponsors.

With separate studies, sponsors have more flexibility (eg , to expand only one study to additional countries if product uptake is low or to complete a PMR early if enrollment exceeds expectations). Key disadvantages are operational inefficiency (ie, duplicate effort) and competition for patients.

Combined studies require fewer resources (eg, 1 study team, 1 protocol, 1 set of data collection forms). The benefits extend to patients and providers, improving recruitment and retention. However, products are typically approved at different times and revising the study protocol, data collection forms, etc. after data collection has started is challenging. Added scientific complexity can be addressed in the statistical analysis.

Key advantages of multi-sponsor registries are combined resources and less competition for patients. Indeed, FDA has recommended this approach to reduce redundancy and patient/provider burden. However, efficiency gains may decline with multiple stakeholders and sponsor-specific protocols.

Conclusions: All solutions are scientifically sound. Sponsors can weigh the importance of operational efficiencies versus less complex statistical analyses and the flexibility of maintaining separate PMRs.