Abstract
9590 Background: PROs are frequently used within industry-sponsored clinical trials and phase III registration trials. Recently, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) have produced draft PRO guidance. The aim of this study was to evaluate this regulatory guidance with reference to the current expert and literature evidence base on the use of PROs in cancer trials and existing QoL tools (EORTC QLQ C30 and LC13). Methods: We conducted a systematic evaluation of both FDA and EMEA guidance and undertook quantitative analyses of 47 leading world key cancer research organizations that provided a formal response to the FDA guidance. In addition, we evaluated grey literature, 25 websites, and consulted over 20 key opinion leaders. Finally, we undertook a systematic literature review (medline 1990–2007) to evaluate conformity between regulatory positions and the scientific literature. Results: In comparison with the EMEA, the FDA has a more prescriptive approach, requiring tools with robust conceptual frameworks and psychometric studies. Current state assessment, advocated by the FDA, was contradicted by 88% of 25 reviewers addressing this issue (p < 0.001). Most expert reviewers (79 % of 14 non-significant) challenged the EMEA’ s and FDA’ s views that a general QOL claim requires improvement in all domains. Minor modifications or translations triggering full re-validation, was not considered realistic by nearly all organizations (97% of 32 p < 0.0001). In addition, substantial disagreement with FDA and EMEA exists on the subject of blinding (100% of 17 p < 0.0001). However, the Minimum Important Difference (MID) is in general agreed with by organizations (86% of 28 p < 0.05). Limited literature exists to support the debatable issues of the PRO guidance. On the whole, existing instruments (e.g. EORTC QLQ-LC13, MDASI) appear to meet FDA and EMEA requirements sufficiently. Conclusions: The regulatory PRO guidance were appreciated by the research community. However, differences on philosophical and design topics are evident. While this guidance is already impacting on trial design, we hope our evaluation will encourage dialogue between all parties, bringing harmony to such positions. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca
Published Version
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