OBJECTIVE: Many clinical trials include an HRQL assessment, but very few drugs have obtained labeling or promotional approval. This is due in part to the poor quality of HRQL assessment and reporting. The objective of the ERIQA group is to provide European regulatory authorities with guidance on how to assess the quality of HRQL studies in clinical trials, and how to evaluate the validity of HRQL claims, for appropriate decision-making. METHOD: A guidance document and a checklist have been designed following a literature search and using the experience of the ERIQA group's members, i.e. HRQL researchers, pharmaceutical industry representatives, academic people, and reviewers for regulatory authorities. RESULTS: The guidance document reviews the major issues of HRQL assessment in clinical trials, and especially practical considerations such as: selection of an HRQL questionnaire (i.e minimal properties required, validation of translated versions); implementation of a HRQL assessment (i.e. training of study personnel, mode of administration, eligibility criteria, data collection, prevention of missing data, respondent burden, multicenter trial); statistical analysis (i.e. justification of the sample size, handling of missing data, handling of multiple statistical tests), and interpretation. For each issue, recommendations are made, even when there is no definite answer (e.g. interpretation of results). All the issues to be prespecified in the research protocol are mentioned. The checklist summarizes all the issues. It is intended to help both regulatory authority reviewers in performing their clinical trial reviews and sponsors and investigators in conducting a clinical trial with HRQL data and writing the study report. CONCLUSION: The final objective is to reach a large European agreement upon this guidance document, to improve the quality of HRQL studies and to convince European regulatory authorities of the usefulness and scientific value of HRQL assessment.