The Discrepancy Between Subjective and Objective Clinical Endpoints in Gastroesophageal Reflux Disease.

Abstract

Therapeutic outcome in gastroesophageal reflux disease (GERD) is commonly determined by both subjective and objective clinical endpoints. Clinicians frequently use symptom improvement as a key benchmark of clinical success, in conjunction with normalization of objective parameters such as esophageal acid exposure and inflammation. However, GERD therapeutic trials have demonstrated that a substantial number of patients rendered asymptomatic, whether through medical, surgical, or endoscopic intervention, continue to have persistent abnormal esophageal acid exposure and erosive esophagitis. The opposite has also been demonstrated in therapeutic trials, where patients remained symptomatic despite normalization of esophageal acid exposure and complete resolution of esophageal inflammation. Moreover, there is no substantive evidence that symptomatic response to antireflux treatment requires complete esophageal mucosal healing or normalization of esophageal acid exposure. Thus, it appears that a certain level of improvement in objective parameters is needed to translate into meaningful changes in symptoms and health-related quality of life of GERD patients. This supports the need to reconsider the commonly used "hard" clinical endpoints to evaluate therapeutic trials in GERD.