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

Chapter 17

Clinical Trials, Early Cancer and Heart Disease

Marvin A. Schneiderman and Edmund A. Gehan

17.1 Introduction

Early developments in controlled clinical trials at the National Institutes of Health (NIH) took place mainly at the National Cancer Institute (NCI) and what was then the National Heart Institute (NHI) [subsequently the National Heart, Lung, and Blood Institute (NHLBI)] beginning in the 1950s. This article reviews the developments from the early 1950s to the late 1960s at both institutes, summarizing the early efforts in clinical trials, the organizations set up to conduct and monitor the clinical trials, and the developments in statistical methodology that have formed the basis for conducting many of the present day randomized controlled trials. The early history of clinical trials at these institutes has been reviewed in more detail at NCI by Gehan and Schneiderman and at NHLBI by Halperin et al. [28, 32].

17.2 Developments in Clinical Trials at the National Cancer Institute (NCI)

A major advance in the development of chemical agents for the treatment of cancer came from observations of the treatment of children with acute lymphocytic leukemia, which was a rapidly fatal disease until 1948 when Sidney Farber, in a nonrandomized study of methotrexate, observed complete remissions and longer survival among some pediatric patients [21]. However, results did not meet with uniform acceptance and questions were raised about diagnosis, selection of patients, and reporting. ...