Date of Award

Spring 6-8-2022

Degree Type

Dissertation

Degree Name

PhD Health Sciences

Department

Health and Medical Sciences

Advisor

Deborah DeLuca, J.D., M.S.

Committee Member

Genevieve Zipp, Ed.D.

Committee Member

Paula Abreu, Ph.D.

Keywords

Accelerated approval, confirmatory study, regulatory affairs, FDA, regulatory modeling, regulatory prediction

Abstract

Background and purpose of study: Pharmaceutical drugs are commonly used to treat various ailments and the pharmaceutical industry is increasingly leveraging expedited pathways to market, like the FDA’s accelerated approval pathway. Thus, these pathways are becoming more prevalent and thus more scrutinized for reliability. A consequence from this increased utilization is observed variability in time to reach full approval from the point accelerated approval was received. Variables that may impact time and ability to reach full approval should be further investigated. The purpose of this study was to explore, identify and predict variables that may influence time from accelerated approval (AA) to full approval (FA) of a drug or drug combination brought to market via the accelerated approval regulatory pathway.

Methods: This was a data-driven, predictive, exploratory, observational (cross-sectional) study utilizing information obtained from publicly available sources, such as the FDA database of accelerated approvals, Drugs@FDA (database of drugs approved for human use) and ClinicalTrials.gov. SAS OnDemand for Academics was utilized to conduct descriptive, regression and time to event analyses. N=269, as obtained from FDA’s Center for Drug Evaluation & Research (CDER) Current List (as of June 30, 2021) of Accelerated Approvals Based on a Surrogate Endpoint.

Results: Out of 269 applications in the accelerated approval program since inception, 67% (N=179) were in the oncology therapeutic area, 10% (N=28) of applications in the program involved a therapy that required an FDA approved test to be used for prescribing the drug, 67% (N=179) of applications were sponsored by large companies (>10,000 employees), 45% (N=120) of applications involved therapies that were considered second-line therapies or greater, and the majority of applications in the program did not involve pediatric populations (66%, N=177). A total of 132 (49%) applications converted to full approval at time of data collection. Median time between accelerated and full approval was 1169 days. Of those that converted to full approval, 57% (N=75) of applications obtained orphan designation for the indication under review, 58% (N=77) of applications involved single-agent therapies, 63% (N=83) of applications involved oral therapies, and 78% (N=103) of applications involved non-biologic drugs. Regression linear analysis was applied to identify variables that help predict time to FA and to study association of potential predictors that impact ability to obtain FA. Analyses demonstrated that the variables orphan designation, drug type (biologic vs. non-biologic), monotherapy vs. combination therapy, pediatric indication, confirmatory study ongoing at time of initial approval, as well as the ‘orphan*PED’ interaction impacted time from initial to full approval and thus were included in a final predictive statistical model.

Conclusion: Although standards to obtain drug approval tend to vary across drug development programs globally, variables have been identified within one expedited pathway to market in the US (accelerated approval pathway) that may provide important insight for pharmaceutical companies to better understand and quantify risk and timing of obtaining approval for their asset based on specific characteristics of the development program/therapy. Additional research should be conducted to confirm the impact of these variables in other expedited as well as non-expedited pathways to market.

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