Patient-reported outcome labeling claims and measurement approach for metastatic castration-resistant prostate cancer treatments in the United States and European Union

Abstract

BackgroundMetastatic castration-resistant prostate cancer (mCRPC) and its treatment significantly affect health-related quality of life (HRQOL). Our objectives were to evaluate and compare patient-reported outcome (PRO) claims granted by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for 5 recently approved mCRPC treatments and to examine key characteristics, development, and measurement properties of the PRO measures supporting these claims against current regulatory standards.MethodsFive products approved for treatment of mCRPC by the FDA and the EMA (2010–2013) were examined: enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and radium Ra 223 dichloride. United States (US) drug approval packages and European Public Assessment Reports were reviewed. PRO claims in the US labels and European Summaries of Product Characteristics and supporting measures were identified. For PRO measures supporting claims, a targeted literature review was conducted to identify information on key characteristics and measurement properties; this information was compared against FDA PRO guidance criteria.ResultsNine PRO “claims” were granted across 4 of 5 products reviewed. The EMA granted more claims (7 claims—4 for pain, 3 for HRQOL) than the FDA (2 claims, both for pain). The Brief Pain Inventory–Short Form (BPI-SF) worst pain item supported most pain claims and was the only measure supporting US claims. EMA pain claims were supported by BPI-SF worst pain (n = 2) and average pain (n = 1) items and the McGill Pain Questionnaire Present Pain Intensity component (n = 1). EMA HRQOL claims were supported by the Functional Assessment of Cancer Therapy–Prostate Module (n = 2) and the EuroQol 5 Dimensions with visual analogue scale (n = 1). Pain and prostate cancer–specific HRQOL measures supporting claims met US regulatory standards for construct validity, reliability, and responsiveness; these properties were strongest for the BPI-SF worst pain item. Only the BPI-SF worst pain item has documented content validity in mCRPC.ConclusionsPRO label claims were commonly granted across the mCRPC products reviewed. Among the measures reviewed, only the BPI-SF worst pain item supported US label claims. The BPI-SF worst pain item is recommended for pain assessment for the evaluation of new mCRPC treatments.

Patient-Reported Outcomes in Cancer Drug Development and US Regulatory Review

“…5,6 Data suggest that FDA, and the Office of Hematology and Oncology Products (OHOP) in particular, includes PROs less commonly in their labels than their European oncology counterparts, or US nononcology review divisions. 3,7 Although PRO-based labeling claims are granted to approximately one-quarter of all new drugs in the United States, it is a rare occurrence for oncology-related therapies. 7 For new oncology-related compounds approved between 2006 and 2013 by FDA, PRO-based labeling claims were granted to only 1 of 43 compounds.…”

“…3,7 Although PRO-based labeling claims are granted to approximately one-quarter of all new drugs in the United States, it is a rare occurrence for oncology-related therapies. 7 For new oncology-related compounds approved between 2006 and 2013 by FDA, PRO-based labeling claims were granted to only 1 of 43 compounds. This compares to 14 of 42 oncology products approved by the European regulators.…”

“…This compares to 14 of 42 oncology products approved by the European regulators. 7 Within this context, the industry faces major challenges when it comes to integrating PRO measurement in oncology clinical trials:…”

Impact of abiraterone on patient-related outcomes in metastatic castration-resistant prostate cancer: current perspectives

“…The instruments used to assess PRO include information about HRQoL, self-satisfaction with symptoms, compliance with therapy, and perceived value of treatment 18,19. In addition, the PRO claims are important in granting approval across varying agencies such as the US FDA and the European counterpart of the European Medicines Agency (EMA) 20. However, the challenge remains in standardizing these methods of qualifying PROs and quantifying and reporting of patients with mCRPC to have a meaningful interpretation in the clinic 13.…”

Development, Use, and Interpretation of Patient-Reported Outcomes for Clinical Decision Making in Ophthalmology

“…This document has increased the scientific rigor of patient reports, which are being used as a primary basis for regulatory approval of medical products in some therapeutic areas (eg, some gastrointestinal diseases). In other therapeutic areas, such as oncology, there has been an increasing trend to consider the patient perspective in evaluation of medical products (eg, symptoms of myelofibrosis, 2 pain in prostate cancer 3 ). The framework outlined in the US Food and Drug Administration guidance document can also be applied more broadly to other types of clinical outcome assessments, including observerbased assessments and physician rating scales.…”