doi: 10.1161/01.CIR.0000023219.51483.66
(Circulation. 2002;106:746.)
© 2002 American Heart Association, Inc.
Clinical Cardiology: New Frontiers |
Lessons Learned From Recent Cardiovascular Clinical Trials: Part I
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 |
|---|
This is the first installment in a 4-part series of articles about our experiences with cardiovascular clinical research during the past 2 decades. From our vantage points as statistical and clinical researchers, we derive a series of lessons from recent clinical trials and incorporate them into principles designed to guide the practicing clinician who cares for patients with heart diseases.
We are entering an era in which the imperative to understand the rational basis for diagnostic and therapeutic options has become a major force in medical care. Medical products (drugs, devices, and biologics) are proliferating simultaneously with a substantial restructuring of the delivery of health care, with a focus on evidence to support medical interventions. As the texture of evidence to support clinical practice becomes clearer, the imperative to investigate the effectiveness of behavioral interventions becomes more important. When coupled with concern about the rising cost of medical care, this proliferation of technological and behavioral intervention reinforces the view that we cannot afford to offer all possible diagnostic and therapeutic options to all patients. Recent publicity about therapies that were in widespread use and were later found to be detrimental1–3 has fueled this concern to extend well beyond the cost implications. The advent of genomics, proteomics, combinatorial chemistry, and advanced biomedical engineering will increase the importance of developing rational evidence about therapeutic risks and benefits. This effort to develop a rational basis for diagnostic and therapeutic decisions on the basis of quantitative assessments is a major component of evidence-based medicine.
This article has been cited by other articles:
 |
|
 |
|
  M. Tonelli, B. Hemmelgarn, T. Reiman, B. Manns, M. N. Reaume, A. Lloyd, N. Wiebe, and S. Klarenbach Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis Can. Med. Assoc. J., May 26, 2009; 180(11): E62 - E71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Lim, A. Brown, A. Helmy, S. Mussa, and D. G. Altman Composite Outcomes in Cardiovascular Research: A Survey of Randomized Trials Ann Intern Med, November 4, 2008; 149(9): 612 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. DeMaria Clinical trials and clinical judgment. J. Am. Coll. Cardiol., March 18, 2008; 51(11): 1120 - 1122. [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Hernandez, G. C. Fonarow, and E. D. Peterson Implantable Cardioverter-Defibrillators, Heart Failure, and Patient Characteristics--Reply JAMA, January 23, 2008; 299(3): 286 - 286. [Full Text] [PDF]
|
|
|
|
|
|
R. A. Harrington, V. Hasselblad, and R. M. Califf Defining and utilizing surrogates in the evaluation of coronary stents: what do we really want and need to know? J. Am. Coll. Cardiol., January 1, 2008; 51(1): 33 - 36. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mayer-Hamblett, B. W. Ramsey, and R. A. Kronmal Advancing Outcome Measures for the New Era of Drug Development in Cystic Fibrosis Proceedings of the ATS, August 1, 2007; 4(4): 370 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The TRIUMPH Investigators Effect of Tilarginine Acetate in Patients With Acute Myocardial Infarction and Cardiogenic Shock: The TRIUMPH Randomized Controlled Trial JAMA, April 18, 2007; 297(15): 1657 - 1666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Ferreira-Gonzalez, G. Permanyer-Miralda, A. Domingo-Salvany, J. W Busse, D. Heels-Ansdell, V. M Montori, E. A Akl, D. M Bryant, P. Alonso-Coello, J. Alonso, et al. Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials BMJ, April 14, 2007; 334(7597): 786 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M Califf Clinical trials bureaucracy: unintended consequences of well-intentioned policy Clinical Trials, December 1, 2006; 3(6): 496 - 502. [Abstract] [PDF]
|
|
|
|
|
|
C. B. Granger and J. J.V. McMurray Using Measures of Disease Progression to Determine Therapeutic Effect: A Sirens' Song J. Am. Coll. Cardiol., August 1, 2006; 48(3): 434 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Tardif, T. Heinonen, D. Orloff, and P. Libby Vascular Biomarkers and Surrogates in Cardiovascular Disease Circulation, June 27, 2006; 113(25): 2936 - 2942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Freedland, G. E. Miller, and D. S. Sheps The Great Debate, revisited. Psychosom Med, March 1, 2006; 68(2): 179 - 184. [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Brody, H. Sucharew, J. D. Campbell, S. P. Millard, P. L. Molina, J. S. Klein, and J. Quan Computed Tomography Correlates with Pulmonary Exacerbations in Children with Cystic Fibrosis Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1128 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Reddan, L. A. Szczech, V. Hasselblad, E. G. Lowrie, R. M. Lindsay, J. Himmelfarb, R. D. Toto, J. Stivelman, J. F. Winchester, L. A. Zillman, et al. Intradialytic Blood Volume Monitoring in Ambulatory Hemodialysis Patients: A Randomized Trial J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2162 - 2169. [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]
|
|
|
|
|
|
J. A. Blumenthal, A. Sherwood, M. A. Babyak, L. L. Watkins, R. Waugh, A. Georgiades, S. L. Bacon, J. Hayano, R. E. Coleman, and A. Hinderliter Effects of Exercise and Stress Management Training on Markers of Cardiovascular Risk in Patients With Ischemic Heart Disease: A Randomized Controlled Trial JAMA, April 6, 2005; 293(13): 1626 - 1634. [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]
|
|
|
|
|
|
D. Massel Composite confusion J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1926 - 1927. [Full Text] [PDF]
|
|
|
|
|
|
J. P. Casas, L. A. Cubillos-Garzon, and C. A. Morillo Regional Pathologies and Globalization of Clinical Trials: Has the Time for Regional Trials Arrived? Circulation, May 27, 2003; 107 (20): e194 - e194. [Full Text] [PDF]
|
|
|
|
|
|
K. M. Kessler, D. L. DeMets, and R. M. Califf Combining Composite Endpoints: Counterintuitive or a Mathematical Impossibility? * Response Circulation, March 11, 2003; 107 (9): e70 - e70. [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]
|
|
|
|
 |
|
 J. J. Bax, E. E. Van der Wall, M. J. Schalij, S. S. Gottlieb, M. L. Fisher, W. T. Abraham, and the MIRACLE Study Group Cardiac Resynchronization Therapy for Heart Failure N. Engl. J. Med., November 28, 2002; 347(22): 1803 - 1804. [Full Text] [PDF]
|
|