Assessment of patient-reported outcomes in clinical trials: the example of health-related quality of life.

As the patient is the primary recipient of treatment, there is a need to recognize and value the patient's perception of change in response to treatment in clinical trials. A new outcomes classification, patient-reported outcomes (PROs), has been proposed by regulators. The PROs are used as an umbrella term and include, for example measures of subjective symptoms, health-related quality of life (HRQL) and treatment satisfaction. In this sense, the PROs are unique and complementary indicators of disease activity as well as of treatment efficacy. Frequently, pharmaceutical companies desire to include PRO benefits in the product label in order to reach a broad range of customers, including prescribers as well as patients. Therefore such information must be based on results that are scientifically valid. The measurement strategy, i.e. the thinking about and decision-making related to PRO and HRQL evaluations, needs to be explicit for clinical trials. First of all it is necessary to specify and provide the rationale for measuring the PROs. Similarly, the reason for selecting particular instruments should be stated and, for the selected instruments, the psychometric evidence should be summarized. The key PRO domains must be prespecified and evidence of their importance to patients should be provided. The research question under study and potential claims need to be clearly delineated. Hence, instrument selection is a key initial step for planning successful and scientifically adequate clinical trials intended to support labelling and promotional claims of PRO benefits to patients. The scientific criteria and design issues of clinical trials are the same for clinical and PRO endpoints. However, important issues of particular relevance to PRO assessments, such as missing values, multiple outcomes, and the statistical analysis, require careful attention. The thinking and planning involved in developing the PRO component of the clinical trial need to be articulated. Successful evaluation of PROs in clinical trials relies on careful planning provided the treatment shows sufficient effectiveness.