BACKGROUND: Despite increasing inclusion of patient-reported outcomes (PROs) in pivotal trials, PRO data often do not make it into labeling for approved products. This is particularly true in the field of oncology, where assessment and reporting of PROs in clinical trials remains suboptimal and most product labels do not mention patient experience data. The aim of this review is to better understand potential issues that may prevent PRO data from being included in product labeling.
METHODS: Submission packages for 60 new drug applications (NDAs) for oncology drugs approved by the US Food and Drug Administration (FDA) from 2018 to 2021 were obtained from the FDA website. Full-text submission packages were reviewed to identify comments expressing criticism or concern about PRO data, with a focus on primary or secondary endpoints. Two separate raters classified each critical comment into the following categories: fit for purpose, study design, data quality, statistical analysis considerations, administration considerations, no treatment benefit, and other.
RESULTS: Of the 60 oncology NDAs reviewed, 45 (75.0%) included PRO data. About 73% (33/45) of these NDAs included at least one critical comment related to the PRO data. The most frequently identified issues described in critical comments focused on statistical analysis considerations and study design in 54.5% (18/33) of submissions. Open-label and single-arm trial designs, lack of hierarchical testing for PRO endpoints, and no establishment of a clinically meaningful threshold of treatment benefit caused concern. Comments on data quality and fit for purpose selection of PROs were the next most identified challenge mentioned in 27.3% and 24.2% of submissions, respectively. Missing data, use of generic measures, and lack of evidence that measures were valid for use in the population of interest were some of the key issues identified by the FDA. All comments identified were provided by reviewers in the Oncology Center of Excellence.
CONCLUSIONS: This review identifies areas of greatest concern voiced by the FDA with respect to PRO data, which helps explain the limited appearance of these data in labeling for FDA-approved oncology products. Considering that regulatory agencies increasingly require incorporation of the patient experience in the drug development process, careful planning and early dialogue with the FDA are critical for designing PRO strategies capable of supporting labeling claims.
