Considerations in the Assessment of Clinical Benefit with a Focus on Pain: a Regulatory Perspective.

In the USA, the regulatory standard for demonstration of efficacy of a drug is evidence of clinical benefit from adequate and well-controlled clinical trials. Understanding the natural history of disease and how treatment is expected to alter its course, and gathering input from relevant stakeholders, such as patients, caregivers, and clinicians, is essential to understand the best way to measure clinical benefit in a clinical trial. Though pain intensity has been the primary outcome measure in clinical trials for pain, an array of measures assessing clinical outcomes from multiple perspectives can allow for more comprehensive interpretation of how a treatment affects patients' lives. Careful consideration should be given to how pain affects the feeling and functioning of each distinct patient population and which outcome assessment, or combination of outcome assessments, may be necessary to provide a more comprehensive view of the patient experience. The early stages of medical product development are an important opportunity to engage with regulatory agencies to discuss potential approaches to clinical trial design and outcome measurement strategies.