Major issues in the organization and implementation of the National Cooperative Gallstone Study (NCGS).

The National Cooperative Gallstone Study (NCGS) was a cooperative, randomized, controlled trial of a drug, chenodiol, for the medical dissolution of gallstones. The design and procedures of the NCGS were complex, having developed as a result of extensive involvement of many experts in the field of gallstone disease and biliary lipids. During the design and implementation of the protocol, many important issues required consideration and resolution. The aim of this article is to review these issues and the deliberations surrounding their resolution and provide personal conclusions and recommendations that may be helpful to other investigators involved in cooperative, controlled trials.

Recruitment for the National Cooperative Gallstone Study.

The National Cooperative Gallstone Study (NCGS) recruitment experience is reported, and the factors determining recruitment performance at a center are evaluated. Recruitment performance was grouped into four major areas: coordinating center, protocol, patient population, and treatment center. At the treatment centers, no relationship was found between performance and the prior experience of the clinic staff in clinical trials or expertise in gallstone research, lack of institutional support was not initially apparent, and ancillary studies did not appear to stimulate performance. Neither the population density nor the annual rate of cholecystectomy were predictive of the monthly rate of patient randomization. After the initial biopsy study and in the major study, changes in eligibility criteria and procedural requirements were followed by an augmented randomization rate. No significant correlation was found between the rating given to a center at the time of selection and the subsequent randomization rate. In conclusion, the criteria used by the NCGS for treatment center selection were inadequate to predict subsequent performance.