OBJECTIVES: FDA regulatory evidence requirements currently focus on a product’s pharmacology, efficacy, and safety. In 2021, FDA released draft guidance on benefit-risk assessment for new drug and biological products. This emerging guidance suggests an evolution towards more holistic approaches to drug evaluation, incorporating evidence on disease burden and unmet need, particularly from patient/caregiver perspectives, alongside product efficacy and safety.

METHODS: The anticipated FDA benefit-risk assessment guidance provides manufacturers opportunities to update approaches to disease-state and clinical research supporting product development, starting at the preclinical stage. Our recommendations for new product planning incorporate the four dimensions discussed in the draft guidance: analysis of condition, current treatment options, benefit, and risk/risk management. We include considerations for preclinical, early clinical, pivotal trial planning, and NDA submission stages. These include disease state research efforts (eg, literature-based research, patient/caregiver experience, real-world evidence), clearly defining benefit and risk in the indication, and designing clinical trials to measure more broadly defined risk and benefit.

RESULTS: In general, activities to support FDA evaluation under the new guidance are also relevant to US payers and value assessors (eg, ICER) and would inform global health technology assessment (HTA) submissions, but with key differences. The FDA guidance considers disease burden and unmet need through the lens of risk, rather than direct and indirect costs, imposed on patients, caregivers, and society. Likewise, the drug’s clinical outcomes are weighed as risks and benefits but are not ultimately translated into economic outcomes such as cost-effectiveness.

CONCLUSIONS: The draft FDA guidance on benefit-risk assessment provides an opportunity to optimize evidence planning starting at the preclinical stage and continuing throughout product development, in a manner largely consistent with preparation for regulatory evaluation and HTA in key global markets. Our approach outlines how early evidence planning can incorporate both benefit-risk and economic considerations to optimize regulatory and payer submissions.