HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Borer, J. S. Search for Related Content PubMed PubMed Citation Articles by Borer, J. S.

SPECIAL ARTICLE

Development of cardiovascular drugs

The U.S. regulatory milieu from the perspective of a participating nonregulator

Division of Cardiovascular Pathophysiology and The Howard Gilman Institute for Valvular Heart Diseases, Weill Medical College of Cornell University, New York, New York

Manuscript received May 21, 2004; accepted July 24, 2004.

^* Reprint requests and correspondence: Dr. Jeffrey S. Borer, New York-Presbyterian Hospital Weill Cornell Medical Center, 525 East 68th Street, New York, New York 10021 (Email: ero2002{at}med.cornell.edu).

The Food and Drug Administration (FDA) is responsible for assuring that drugs, devices, and biologicals available in the U.S. are effective and acceptably safe for their intended uses. Both law and regulation define the procedures to be followed by the FDA in judging the effectiveness and safety of therapies. The FDA comprises a cadre of highly skilled public servants who receive and evaluate all data collected by the manufacturer during therapy, not just the portion that reaches publication. To assist in reaching final conclusions about approvability, the FDA can empanel legally constituted advisory committees and external consultants when the need is perceived for additional specific scientific/technical expertise and substantial experience in clinical practice. Evidentiary standards for marketing approval of drugs, biologicals, and devices generally require direct demonstration of clinical benefit, rather than inferences drawn from "surrogate" pharmacologic/device-mediated effects, sufficient exposure to enable a reasonable assessment of countervailing risk, consideration of specific design elements in the pivotal clinical trials (including prespecified hypotheses [implicitly incorporated in "primary end points"], rigorous plans for statistical analyses, and so on), and assessment of persistence of effectiveness and associated stability of safety over time. Finally, sufficient information must be available so that practitioners can receive written instructions for use (the label) adequate to support the likelihood that recipients of the therapy will receive the expected benefits within the envelope of the stated risks. This article will discuss and expand on these issues, with examples.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   AE = adverse event   ECG = electrocardiogram/electrocardiographic   FDA = Food and Drug Administration

This article has been cited by other articles:

				J. S. Borer Angiotensin-converting enzyme inhibition: a landmark advance in treatment for cardiovascular diseases Eur. Heart J. Suppl., September 1, 2007; 9(suppl_E): E2 - E9. [Abstract] [Full Text] [PDF]

				K. Fox, R. Ferrari, S. Yusuf, and J. S. Borer Should angiotensin-converting enzyme-inhibitors be used to improve outcome in patients with coronary artery disease and 'preserved' left ventricular function? Eur. Heart J., September 2, 2006; 27(18): 2154 - 2157. [Abstract] [Full Text] [PDF]

				J. S. Borer Heart rate slowing by If inhibition: therapeutic utility from clinical trials Eur. Heart J. Suppl., September 1, 2005; 7(suppl_H): H22 - H28. [Abstract] [Full Text] [PDF]