Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs

Chapter 76

UGDP Trial

Curtis L. Meinert

76.1 Introduction

The University Group Diabetes Program (UGDP) was a multicenter, investigator-initiated, trial started in 1960 and finished two decades later designed to assess the value of established antihyperglycemic drugs for prevention of the late complications of adult-onset diabetes. It generated a firestorm of controversy starting in 1970 with presentation and publication of results suggesting that a widely used oral agent—tolbutamide (Orinase, Upjohn, Kalamazoo now part of Pfizer)—was of no value in reducing the risk of morbidity or in prolonging life, if not possibly unsafe. The Food and Drug Administration (FDA) used its results to revise the label for the drug to include a special warning regarding possible cardiovascular (CV) risks associated with the drug, but only after a legal battle that raged on for more than a decade, which was propelled by the Committee for the Care of the Diabetic (CCD). This battle ultimately wound up in front of the U.S. Supreme Court. (The CCD was a group of diabetologists from around the country formed in late 1970 to challenge results from the trial.)

The trial started in one era and ended in another. It started before Institutional Review Boards (IRBs) existed and finished with them in place. Indeed, it was finishing enrollment just as the U.S. Public Health Service notified recipients of NIH funds that more funding would be contingent on evidence of written informed consents from persons being ...