This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Califf, R. M. Articles by DeMets, D. L. Search for Related Content PubMed PubMed Citation Articles by Califf, R. M. Articles by DeMets, D. L. Related Collections Congestive Lipids Cardiovascular Pharmacology Secondary prevention Valvular heart disease Clinical Studies Catheter-based coronary and valvular interventions: other Catheter-based coronary interventions: stents Acute coronary syndromes Acute myocardial infarction Epidemiology

(Circulation. 2002;106:1015.)
© 2002 American Heart Association, Inc.

Clinical Cardiology: New Frontiers

Principles From Clinical Trials Relevant to Clinical Practice: Part I

Robert M. Califf, MD; David L. DeMets, PhD

From the Duke Clinical Research Institute (R.M.C.), Duke University Medical Center, Durham, NC, and the Department of Biostatistics and Medical Informatics (D.L.D.), University of Wisconsin, Madison, Wis.

Correspondence to Robert M. Califf, MD, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715.

Key Words: trials • cardiovascular diseases • therapy • outcome assessment • statistics

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The first 2 parts of this review discussed lessons learned from cardiovascular clinical trials about the design and interpretation of clinical trials. In the next 2 parts, we will attempt to apply these lessons to decision-making in clinical practice. We undertake this effort with trepidation, recognizing that translating research findings into the care of an individual patient is a frontier that has not been adequately explored. Yet the potential for an empirical-based medical practice that would improve on the intuitive-based practice of the past, when combined with traditional clinical skills and patient preferences, demands that we move forward to apply what we have learned in populations to the care of individual patients.

	Principle 1: Treatment Effects Are Modest

 
The benefit of most cardiovascular therapies is much smaller than was anticipated before the first large-scale outcome trials. Relative risk reductions of 25% are rarely exceeded, as demonstrated in Figure 1, for post–myocardial infarction (MI) patients. This means that the patient’s outcome is determined more by the natural history of the disease than by the treatments we deliver, and that multiple combined treatments will be needed in most cases to achieve the best possible outcome.

View larger version (29K): [in this window] [in a new window]   Figure 1. Overview of treatment effects in acute MI, secondary prevention, and heart failure. The major point of this figure is that the treatment effects are modest, with relative risk reductions (RRRs) of 10% to 25%. These small but important reductions require a quantitative, systematic approach to realize the potential for a substantial impact on the public health.

At the other extreme, . . . [Full Text of this Article]

This article has been cited by other articles:

				B. S. Coller and R. M. Califf Traversing the Valley of Death: A Guide to Assessing Prospects for Translational Success Science Translational Medicine, December 9, 2009; 1(10): 10cm9 - 10cm9. [Full Text] [PDF]

				M. A. Pfeffer, E. A. Burdmann, C.-Y. Chen, M. E. Cooper, D. de Zeeuw, K.-U. Eckardt, J. M. Feyzi, P. Ivanovich, R. Kewalramani, A. S. Levey, et al. A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease N. Engl. J. Med., November 19, 2009; 361(21): 2019 - 2032. [Abstract] [Full Text] [PDF]

				M. L. Kukin, R. Kapoor, J. R. Kapoor, and R. J. Myerburg Implantable Cardioverter-Defibrillators N. Engl. J. Med., February 26, 2009; 360(9): 937 - 938. [Full Text] [PDF]

				D. L. Mann, M. A. Acker, M. Jessup, H. N. Sabbah, R. C. Starling, and S. H. Kubo Clinical Evaluation of the CorCap Cardiac Support Device in Patients With Dilated Cardiomyopathy Ann. Thorac. Surg., October 1, 2007; 84(4): 1226 - 1235. [Abstract] [Full Text] [PDF]

				K. P. Anderson Risk Assessment for Defibrillator Therapy: Il Trittico J. Am. Coll. Cardiol., September 18, 2007; 50(12): 1158 - 1160. [Full Text] [PDF]

				S. V. Rao, J. A. Eikelboom, C. B. Granger, R. A. Harrington, R. M. Califf, and J.-P. Bassand Bleeding and blood transfusion issues in patients with non-ST-segment elevation acute coronary syndromes Eur. Heart J., May 2, 2007; 28(10): 1193 - 1204. [Abstract] [Full Text] [PDF]

				R. M. Califf The cycle of quality as a model for improving health outcomes in the treatment of hypertension Eur. Heart J. Suppl., May 1, 2007; 9(suppl_B): B8 - B12. [Abstract] [Full Text] [PDF]

				J. B. Perlin and J. Kupersmith Information Technology And The Inferential Gap Health Aff., March 1, 2007; 26(2): w192 - w194. [Abstract] [Full Text] [PDF]

				The National Heart, Lung, and Blood Institute Work Major Clinical Trials of Hypertension: What Should Be Done Next? Hypertension, July 1, 2005; 46(1): 1 - 6. [Abstract] [Full Text] [PDF]

				J. S. March, S. G. Silva, S. Compton, M. Shapiro, R. Califf, and R. Krishnan The Case for Practical Clinical Trials in Psychiatry Am J Psychiatry, May 1, 2005; 162(5): 836 - 846. [Abstract] [Full Text] [PDF]

				R. M. Califf Simple Principles of Clinical Trials Remain Powerful JAMA, January 26, 2005; 293(4): 489 - 491. [Full Text] [PDF]

				N. Rajagopalan, T. D. Miller, D. O. Hodge, R. L. Frye, and R. J. Gibbons Identifying high-risk asymptomatic diabetic patients who are candidates for screening stress single-photon emission computed tomography imaging J. Am. Coll. Cardiol., January 4, 2005; 45(1): 43 - 49. [Abstract] [Full Text] [PDF]

				G. A. Diamond and S. Kaul Prior convictions: bayesian approaches to the analysis and interpretation of clinical megatrials J. Am. Coll. Cardiol., June 2, 2004; 43(11): 1929 - 1939. [Abstract] [Full Text] [PDF]

				S. R. Majumdar, F. A. McAlister, and C. D. Furberg From knowledge to practice in chronic cardiovascular disease: a long and winding road J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1738 - 1742. [Abstract] [Full Text] [PDF]

				E. M. Antman and J. J. Ferguson Should Evidence-Based Proof of Efficacy as Defined for a Specific Therapeutic Agent be Extrapolated to Encompass a Therapeutic Class of Agents? Circulation, November 25, 2003; 108(21): 2604 - 2607. [Full Text] [PDF]

				R. M. Califf Supplement on Acute Coronary Syndromes: Introduction Circulation, October 21, 2003; 108(90161): III-1 - 5. [Full Text] [PDF]

				S. R. Tunis, D. B. Stryer, and C. M. Clancy Practical Clinical Trials: Increasing the Value of Clinical Research for Decision Making in Clinical and Health Policy JAMA, September 24, 2003; 290(12): 1624 - 1632. [Abstract] [Full Text] [PDF]

				R. M. Califf and L. H. Muhlbaier Health Insurance Portability and Accountability Act (HIPAA): Must There Be a Trade-Off Between Privacy and Quality of Health Care, or Can We Advance Both? Circulation, August 26, 2003; 108(8): 915 - 918. [Full Text] [PDF]

				N. Frasure-Smith and F. Lesperance Depression--A Cardiac Risk Factor in Search of a Treatment JAMA, June 18, 2003; 289(23): 3171 - 3173. [Full Text] [PDF]

				F. A. McAlister Applying Evidence to Patient Care: From Black and White to Shades of Grey Ann Intern Med, June 3, 2003; 138(11): 938 - 939. [Full Text] [PDF]

				D. J. Bradley Combining Resynchronization and Defibrillation Therapies for Heart Failure JAMA, May 28, 2003; 289(20): 2719 - 2721. [Full Text] [PDF]

				H. C. Lane and J. D. Neaton When To Start Therapy for HIV Infection: A Swinging Pendulum in Search of Data Ann Intern Med, April 15, 2003; 138(8): 680 - 681. [Full Text] [PDF]

				D. S. Sheps, K. E. Freedland, R. N. Golden, and R. P. McMahon ENRICHD and SADHART: Implications for Future Biobehavioral Intervention Efforts Psychosom Med, January 1, 2003; 65(1): 1 - 2. [Full Text] [PDF]