Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

The impact of FDA and EMA guidances regarding Patient Reported Outcomes (PRO) on the drug development and approval process ***

Dr. Max Storf (Abschlußjahr: 2013)

Summary
Language: English
Patient reported outcome (PRO) is a measurement of the patient’s health status that comes directly from the patient himself. PRO data are collected in clinical trials via PRO instruments (e.g., questionnaires or diaries) completed by the patient or completed during an interview, provided that the interviewer records only the patient’s response.
In the light of patient-centered drug development, the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) are highly interested that pharmaceutical companies use PRO instruments in clinical trials to support claims in approved medicinal product labeling. Since 2005, the EMA and the FDA have issued several guidance documents regarding patient reported outcomes. The two central guidance documents are the EMA Guidance “Reflection Paper on the Regulatory Guidance for the Use of Health-Related Quality of Life (HRQL) Measures in the Evaluation of Medicinal Products” issued in July 2005 and the FDA Guidance "Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims" issued in December 2009.
This master thesis compares the EMA and the FDA PRO guidances and discusses the impact of the PRO guidance documents on the drug development and approval process.
Similarities:
Both agencies require the development of an endpoint model to document the hierarchy and relationship among all clinical trial endpoints that are intended to support label claims.
The EMA and the FDA evaluate the measurement properties (content and construct validity, reliability, ability to detect change, conceptual framework, cultural adaptation/translation, and the instrument characteristics) of a PRO instrument to assess if the instrument is appropriate for the clinical trial patient population. The sponsor has to establish and demonstrate the measurement properties by performing qualitative and quantitative research (e.g., cognitive interviewing of patients) and document the adequacy of a PRO instrument in the PRO Evidence Dossier.
Both regulatory agencies recommend the use of PRO instruments only in randomized, double-blind clinical trials to avoid bias.
Sponsors can seek scientific advice or drug development tool (DDT) qualification advice regarding PRO instruments. They are encouraged to apply in parallel to the EMA and the FDA for advice.
Differences:
The EMA Reflection Paper provides guidance specifically for HRQL-related label claims, whereas the FDA PRO Guidance covers all PRO-related claims (symptoms, functioning, and HRQL).
The FDA prefers placebo controlled clinical trials, whereas the EMA recommends active comparator and/or placebo-controlled clinical trials with a minimum duration of 3 months.
The FDA recommends short recall periods for PRO instruments (24 – 48 h) and favors the use of daily (electronic) diaries in clinical trials.
Within the FDA, the Study Endpoints and Labeling Claims Development (SEALD) group is responsible for the review of PRO Evidence Dossiers. The EMA requests review of HRQL Evidence Dossiers from external academic or clinical experts.
Pharmaceutical companies have to be aware that a thorough development, validation, and implementation of PRO instruments and close interaction with the regulatory authorities are inevitable to obtain a targeted PRO label claim.
Pages: 65, Annex: 1 pages: 6