Rome Foundation Endpoints and Outcomes Conference 2009: Optimizing Clinical Trials in FGID

The meeting was successful in accomplishing the stated objectives. The main issues addressed and recommendations made include the following: Global composite measures of response such as adequate or satisfactory relief are viewed by the FDA as incompletely validated, though recent data provide supportive evidence. Since FGID treatment must lead to relief of symptoms, a good PRO is directly related to the symptoms and its impact; it needs to capture the most important outcomes and consider adverse events. Defining cut points for clinically important improvement is preferred to using statistically significant changes on rating scales. Thus, the MCID is considered highly relevant to PROs, as it is the smallest difference in a rating that is perceived by patients as beneficial and that leads to a change in management. In drug development, it is important to evaluate both the risk and the benefit. Several effective medications for FGIDs have been removed from the market because of adverse events. In balance, studies now show that because patients with IBS have major impairments in health, they are willing to accept higher levels of risk (e.g., of death) than previously recognized in order to achieve meaningful clinical benefit from a medication. The severity of IBS and FGIDs is a multi-component concept, and neither symptoms nor HRQOL are sufficient to explain it. It has not been well studied, yet clinicians make diagnostic and treatment decisions based on the patient's perceived severity. Accordingly, recommendations were made to develop and validate patient-based severity measures for research and clinical practice. Further work is needed to develop PROs and clinical end points for the pediatric FGID population; it was recommended that this be done by international consensus. The challenges to drug development, including for conditions such as FGIDs, relate primarily to the absence of agreed-on or validated PRO instruments. This led the FDA to publish guidelines in the form of a PRO guidance document and develop a PRO Consortium committee to work on the development of such instruments.