The role of patient reported outcomes in the regulatory process needs to be better defined
PROmote* group, Rome, Italy
(*) Patient-Reported Outcomes MOving Toward Evidence
We read the editorial with great interest and we strongly support its
conclusions on the necessity to standardise the patients reported outcomes
(PROs) measures and stimulate their appropriate use. The growing amount of
applications in clinical research of these outcomes has stimulated the
regulatory agencies, in the United States and Europe, to take into
consideration PROs in the regulatory process and to produce documents
where this topic is addressed.
In 2004 the European Medicines Agency’s (EMEA) Committee for Medical
Products in Human Use published a “Reflection Paper on the Regulatory
Guidance for the Use of Health-Related Quality of Life Measures in the
Evaluation of Medicinal Products” 1. In 2006 a draft guidance for
industry, the “Patient-Reported Outcome Measures: Use in Medical Product
Development to Support Claims”, was published by the Food and Drug
Administration (FDA)2. The two documents have some agreement points and
several different aspects.
- Agreement points between the agencies: both documents not only have
recognized the usefulness of patient-centred measures for health outcomes
assessment, but also have expanded on methodological aspects, such as
study design, statistical analysis and hypothesis testing, reliability and
validity of patient centred measures.
- Disagreement points: FDA stated that all PROs, including health related
quality of life (HRQoL), can be used as “effectiveness endpoints” in
clinical trials, and in particular for drugs to be licensed for chronic
diseases (e.g., cancer, HIV). EMEA does not assign at the moment the same
weight to all the PROs measures. In fact, whereas the core symptoms of a
disease (e.g. pain, migraine, …), assessed by the patient himself, are
well-accepted as primary and secondary efficacy endpoints in registration
trials, the HRQoL assessment is regarded to be an optional endpoint of
drugs efficacy, as “the basis for the approval of a new medicinal product
is its clinical efficacy and safety in a given condition”1.
In 2005, a
review analysing the use of PROs measures for the approval of new
pharmaceutical products was published3 by the EMEA. According to the
authors, the regulatory decision-makers should develop and update
harmonized procedures to adequately use PROs information in the regulatory
decision processes. They concluded that the reflection paper released by
EMEA1 on HRQoL research is a promising step towards achieving this aim.
As a multidisciplinary group of health care researchers and physicians
(PROmote group), coordinated by the Italian National Institute of Health
(Istituto Superiore di Sanità), it is our opinion that the EMEA reflection
paper is based on preliminary assumptions but needs a urgent update. We
strongly encourage both the International and National regulatory
authorities to align their documents with the current thinking that all
PROs, including HRQoL, should have a significant role in the evaluation of
efficacy and safety of medicines.
1. European Medicine Agency. Reflection paper on the regulatory
guidance for the use of health-related quality of life (HRQL) measures in the evaluation of
medicinal products; EMEA/CHMP/EWP139391/2004. London, 2004 www.emea.eu.int
2 U.S. Department of Health and Human Service Food and Drug
Administration. Guidance for Industry – Patients-Reported Outcome Measures: Use in
Medical Product Development to Support Labeling Claims; February 2006. www.fda.gov/cder/guidance/5460dft.pdf
3. Szende A, Leidy NK, Revicki D. Health-Related Quality of Life and
Other Patient-Reported Outcomes in the European Centralized Drug Regulatory
Process: A Review of Guidance Documents and Performed Authorizations of Medicinal Products
1995 to 2003. Value in Health, 2005; 8(5): 534-548
Damiano Abeni Istituto Dermopatico dell'Immacolata - I.R.C.C.S.,
Raffaella Bucciardini Dipartimento del Farmaco - Istituto Superiore di
Ernesto Costabile Dipartimento del Farmaco - Istituto Superiore di Sanità,
Vincenzo Fragola Dipartimento del Farmaco - Istituto Superiore di Sanità,
Maria Teresa Greco Istituto di Ricerche Farmacologiche Mario Negri,
Giovanni Guaraldi Università degli Studi di Modena e Reggio Emilia.
Marco Lauriola Facoltà di Psicologia 1, Università degli Studi di Roma "La
Valerio Manno CNESPS, Istituto Superiore di Sanità, Roma.
Sergio Mariotti CNESPS, Istituto Superiore di Sanità, Roma.
Maurizio Massella Dipartimento del Farmaco - Istituto Superiore di Sanità,
Rita Murri Università Cattolica del Sacro Cuore, Roma.
Luca Padua Università Cattolica del Sacro Cuore, Roma.
Raffaele Pezzilli Ospedale Sant'Orsola Malpighi, Bologna.
Emilio Romanini Gruppo di Lavoro Ortopedia basata su prove di Efficacia,
Francesca Sampogna Istituto Dermopatico dell'Immacolata - I.R.C.C.S Roma.
Luciana Scalone Università degli Studi di Milano; Fondazione CHARTA,
Stefano Tabolli Istituto Dermopatico dell'Immacolata - I.R.C.C.S Roma.
Marina Torre CNESPS, Istituto Superiore di Sanità, Roma.
Competing interests: No competing interests