Contributions of Robert T. O’Neill to the Evolution of Regulatory Statistical Science

Abstract

Dr. Robert T. O'Neill has been on the forefront of regulatory statistical science since he came to the Food and Drug Administration in 1970. He worked to shape the statistical framework for the drug approval process for all new drugs marketed in the United States following passage of the 1962 Kefauver-Harris Amendments. This article will focus on Dr. O'Neill's responses to challenges in the field of drug development and evaluation and Dr. O'Neill's broad and influential role in the conceptualization and evolution of a systematic, statistically based approach to answering the question “Does this drug really work?” Statisticians working in pharmaceutical science have learned from his pioneering work and sound instincts in a regulatory environment but have also profited from his willingness to communicate through talks, travel, and publications over the years. We will describe some of the statistical principles he articulated so well and consider the role of clinical trial related statistical methodology overall as it has been applied in the biomedical sciences both nationally and internationally. We will conclude with a look at the future of regulatory statistical science.

Key Words:

• Adequate and well controlled studies
• BEMAC
• Clinical trials
• DESI
• ICH
• Safety evaluation

Acknowledgments

The authors thank Cindy Lachin for providing valuable research assistance; and Edward Nevius, Susan Ellenberg, Scott Podolsky, and Peter Hutt for reading earlier versions of the article and their helpful comments and suggestions. We also thank Eric Sampson for his editorial support and assistance with formatting the references.