Elsevier

European Journal of Cancer

Volume 45, Issue 3, February 2009, Pages 347-353
European Journal of Cancer

Review
Patient-reported outcomes: Assessment and current perspectives of the guidelines of the Food and Drug Administration and the reflection paper of the European Medicines Agency

https://doi.org/10.1016/j.ejca.2008.09.032Get rights and content

Abstract

Aims

Patient-reported outcomes (PROs) have recently gained greater credibility with regulatory bodies aiming to standardise their use and interpretation in RCTs, thereby supporting medicinal product submissions. For this reason, the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) have released guidelines. This review paper provides an overview of the current perspectives and views on these guidelines.

Method

To evaluate the FDA and EMEA PRO guidelines, 47 expert responses to the FDA guidance were qualitatively reviewed. Two reviewers independently extracted data from these letters and checked these responses to warrant consistency and agreement in the evaluation process. A PubMed literature review was systematically examined to obtain supporting evidence or related articles for both the guidance documents.

Results

Generally, there is agreement between regulatory authorities and the research community on the contents of the FDA and EMEA PRO draft guidance. However, disagreements exist on significant philosophical topics (e.g. the FDA focuses more on conceptual models and symptoms than the EMEA) and design topics (e.g. the FDA is more restrictive on issues of recall bias, blinding of oncology trials and degrees of psychometric validation than researchers and the EMEA). This could influence the approval of PRO claims.

Conclusion

PRO guidance from the EMEA and FDA has been valuable, and has raised the profile and active debate of PROs in oncology. However, our review of the current opinion shows that there are controversial aspects of the guidance. Consequently, greater latitude should be given to how the guidance is interpreted and applied.

Introduction

In the recent years, the use of patient-reported outcomes (PROs) has increased significantly.1 HRQOL measures involve subjective patient assessment or evaluation of important aspects of well-being2 that are affected by current disease and/or treatment. Prominent examples of cancer-related HRQOL tools are the EORTC QLQ-C30 and the Functional Assessment of Cancer Therapy General (FACT G).3, 4

Recently, the Food and Drug Administration (FDA) introduced the umbrella term PRO and attempted to standardise PRO use to provide a more systematic treatment-review process. For this reason, the FDA released draft guidance on PRO measures in February 2006: Guidance for Industry. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims.5 Also, the European Medicines Agency (EMEA) produced a reflective paper of regulatory guidance for the use of HRQOL measures in the evaluation of medicinal products in cancer in July, 2005.6

However, despite considerable effort to develop guidelines, it is not entirely clear what evidence the regulatory bodies would require in supporting claims when reporting PRO data. To date, established PRO measures are criticised by the regulatory agencies, leading to rejection of many PRO labelling claims.

The main objective of this paper is to review the current opinion relating to the guidance, and to make recommendations based on our review.

Section snippets

Materials and methods

The aim of the study is to provide an overview of the current opinion in relation to the two major guidance documents: the FDA Patient-Reported Outcomes draft (2006) and the EMEA HRQOL reflection paper (2005). A thematic qualitative approach was used to compare recommendations and requirements from each guidance. Written comments, invited by the FDA and submitted to the FDA web site (Table 1), have been reviewed. These reviewed responses related to the FDA guidance were also considered in

Results

The FDA PRO guidance generated 47 written responses, totalling to 364 pages of comments, which are accessible on the FDA web site. These comments mainly came from professional groups in both academia and the pharmaceutical sector (Table 1). No documents were found on the EMEA web site about the EMEA HRQOL reflection paper, but the literature search identified several studies (discussed later) that looked at these guidelines. The search on PubMed and the search of grey literature generated

Discussion

In oncology phase III RCTs and registration trials, PROs are increasingly used for providing information about HRQOL in patients who undergo new treatments. Both the FDA and EMEA increasingly appear to be willing to accept PROs in support of medicinal labelling claims or in the evaluation of medical products such as cancer drugs.

The views of the FDA on PROs could be described as extensive, with detailed requirements and a restrictive nature. The EMEA has provided more global statements and

Conflict of interest statement

EORTC and Andrew Bottomley have received an unrestrictive academic research grant funding from AstraZeneca, UK. Dave Jones is an employee of AstraZeneca. Lily Claassens’ Fellowship was in part funded by an academic grant from AstraZeneca.

Acknowledgements

We thank Dr. Bhash Parasuraman (AstraZeneca, USA) for her comments on our paper.

This research was funded by an educational academic grant from AstraZeneca, UK. In addition, part of the publication was supported by Grant Numbers 5U10 CA011488-37–5U10 CA011488-38 from the National Cancer Institute (Bethesda, Maryland, USA). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

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