New England Journal of Medicine
June 2, 2016 Vol. 374 No. 22
http://www.nejm.org/toc/nejm/medical-journal

.
Editorial
Clinical Trials Series
Janet Woodcock, M.D., James H. Ware, Ph.D., Pamela W. Miller, John J.V. McMurray, M.D., David P. Harrington, Ph.D., and Jeffrey M. Drazen, M.D.
N Engl J Med 2016; 374:2167 June 2, 2016 DOI: 10.1056/NEJMe1601510
Clinical trials are our best vehicle for turning medical information that we may think is true into evidence that we know, within reasonable limits, to be true. Since the introduction of random assignments to treatment in the 1930s,1 the clinical trial has been in continuous evolution. Among the major milestones have been the development of methods to perform randomization; the convening of data and safety monitoring committees; the formulation of stopping guidelines for safety, efficacy, and futility; and many others. Indeed, the clinical trial landscape is far different today from what it was over 80 years ago, when investigators first confronted the conundrum of how to obtain unbiased data that could be used to guide clinical practice. Today, trials range from a single person2 to 100,000 people, from a single lab to hundreds of centers around the world, from simple two-arm randomizations to increasingly complex study designs.

In this issue, we inaugurate a series of articles called “The Changing Face of Clinical Trials,” in which we examine the current challenges in the design, performance, and interpretation of clinical trials. The series will deal with contemporary challenges that affect clinical trialists today. It is not meant to be a course in clinical trial performance; rather, the articles are written by trialists for trialists about issues that face us all. We plan to cover new trial designs, current issues related to the performance of clinical trials, how to deal with unexpected events during the progress of trials, difficulties in the interpretation of trial findings, and challenges faced by specific sectors of trialists, including those working for large or small companies; the viewpoint of regulators who use trial data in their decision making will also be included. Each review article will define a specific issue of interest and illustrate it with examples from actual practice. The articles will occasionally be accompanied by Perspective pieces to bring additional history and color to the topic. We begin with an article on integrating comparative effectiveness trials into patient care,3 accompanied by a history of clinical trials.4 We have enjoyed putting the series together for you, and we hope that it will stimulate thought and discussion.

.

Review Article
Integrating Randomized Comparative Effectiveness Research with Patient Care
Louis D. Fiore, M.D., M.P.H., and Philip W. Lavori, Ph.D.
N Engl J Med 2016; 374:2152-2158 June 2, 2016 DOI: 10.1056/NEJMra1510057
Clinical trials of interventions in common practice can be built into the workflow of an electronic medical record. The authors review four such trials and highlight the strengths and weaknesses of this approach to gathering information.

.

Medicine and Society
Assessing the Gold Standard — Lessons from the History of RCTs
Laura E. Bothwell, Ph.D., Jeremy A. Greene, M.D., Ph.D., Scott H. Podolsky, M.D., and David S. Jones, M.D., Ph.D.
N Engl J Med 2016; 374:2175-2181 June 2, 2016 DOI: 10.1056/NEJMms160459
Over the past 70 years, randomized, controlled trials (RCTs) have reshaped medical knowledge and practice. Popularized by mid-20th-century clinical researchers and statisticians aiming to reduce bias and enhance the accuracy of clinical experimentation, RCTs have often functioned well in that role. Yet the past seven decades also bear witness to many limitations of this new “gold standard.” The scientific and political history of RCTs offers lessons regarding the complexity of medicine and disease and the economic and political forces that shape the production and circulation of medical knowledge…