Analysis of patient-reported outcomes in the approval of novel oncology drugs in the United States, 2017-2022

Abstract

Background: With the growing notion of patient-focused drug development, the quality of life and other patient-reported outcomes (PROs) of cancer patients are gaining considerable attention. Several drug regulatory agencies, including the U.S. Food and Drug Administration (FDA), are calling attention to PROs. This review aims to comprehensively characterise the application of PROs and regulatory considerations for PROs in the FDA-approved novel oncology drugs.

Methods: The FDA review documents and labels for novel oncology drugs approved from July 2017 to July 2022 were retrieved. We collected and analysed drug approval information, types of endpoints for PROs, PRO measures, designs of trials including PROs, and regulatory comments on PRO-related contents.

Findings: Results demonstrated that PROs were used more commonly for solid tumours than hematologic malignancies, which might be correlated with the disease characteristics. We further categorised and analysed existing PRO measures, providing insight for tool selection in future oncology trial design. Our findings also indicated that PROs currently do not play a significant role in oncology drug approvals. The major deficiencies related to PROs commented on by FDA reviewers were analysed, followed by recommendations for improvements.

Interpretation: This review demonstrates that PROs currently do not play a significant role in oncology drug marketing review, and how they can be used to support the approval of new oncology drugs is still in the exploratory stage. This current situation is not only related to the deficiencies in the design and implementation of PRO-related contents in oncology trials, but more importantly, it is a reminder that we should pay more attention to patient experience in the development of oncology drugs.

Funding: This study was not supported by any funding.

Keywords: Novel oncology drug; Patient-reported outcome.

Fig. 1

Use of different types of PROM in oncology trials with different indications. PROMs are classified into three major categories, generic quality of life (QoL) measures (olive), measures for symptom, function or safety (cyan) and indication-specific measures (purple). (A) The measure counts (y axis) are plotted versus the number of pivotal trials corresponding to indications mentioned on the x axis. Generic QoL measures are further divided into EQ-5D, EORTC QLQ-C30, FACT-G and other generic QoL measures; Indication-specific measures are divided into EORTC QLQ modular, FACT modular and other indication-specific measures. (B) The numbers in the Venn diagram indicate the number of included pivotal trials, using the Venn diagram to represent the use of multiple different types of PROMs in a single trial. Abbreviations: EQ-5D, EuroQol Five Dimensions Questionnaire; EORTC QLQ, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; FACT, the Functional Assessment of Cancer Therapy; EORTC QLQ-C30, EORTC QLQ-core questionnaire; FACT-G, FACT- General.

Fig. 2

Key comments and regulatory decision on PRO results. The key comments extracted from the clinical review documents were categorised and shown on the top of the figure. Study designs of the pivotal trials supporting each drug approval were colour-coded and indicated on the left of the figure. FDA's decisions on PRO results were indicated by a symbol after the established name of listed products. A circle indicated that the PRO result was not considered part of the efficacy benefit evidence but were considered as important data for the review of safety and tolerability, and a star indicated that it supported efficacy benefit and was included in the original labelling. The absence of a circle or a star indicated that the PRO results were not endorsed by the FDA. Issues that were not addressed by the FDA reviewers could also exist in the related studies. Abbreviations: FDA, US Food and Drug Administration; MCID, minimal clinically important difference; PROM, patient-reported outcome measures.