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10 - Alternatives to randomized trials for estimating treatment effects

Published online by Cambridge University Press:  04 August 2010

Thomas B. Newman
Affiliation:
University of California, San Francisco
Michael A. Kohn
Affiliation:
University of California, San Francisco
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Summary

Introduction

We said in Chapter 9 that randomized blinded trials are the best way of determining treatment effects because they minimize the potential for confounding, co-interventions, and bias, thus maximizing the strength of causal inference. However, sometimes observational studies can be attractive alternatives to randomized trials, because they may be more feasible, ethical, or elegant. Of course the issue of inferring causality from observational studies is a major topic in classical risk factor epidemiology. In this chapter, we focus on observational studies of treatment effects rather than risk factors, describing methods of reducing or assessing confounding that are particularly applicable to such studies.

Confounding by indication

We discussed in Chapter 9 that confounding refers to the distortion of the effect of variable A on the outcome C by a third variable B, which is both associated with A and a cause of C. We focus on treatments that are supposed to be beneficial, that is, to have an RR < 1 for a bad outcome. One type of confounding makes treatments appear better than they really are – for example, finding a beneficial treatment effect when, in truth, the treatment either has no effect or causes harm. In this situation, a confounder is associated with receiving the treatment and reduces the risk of a bad outcome (Fig. 10.1).

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Publisher: Cambridge University Press
Print publication year: 2009

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References

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Cook, T. D., and Campbell, D. T. (1979). Quasi-Experimentation: Design & Analysis Issues for Field Settings. Chicago, IL, Rand McNally College Pub. Co.Google Scholar
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Hearst, N., Newman, T. B., et al. (1986). “Delayed effects of the military draft on mortality. A randomized natural experiment.” N Engl J Med 314(10): 620–4.CrossRefGoogle ScholarPubMed
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Katz, M. H. (1999). Multivariable Analysis: A Practical Guide for Clinicians. Cambridge, Cambridge University Press.Google Scholar
Miller, E. R., 3rd, Pastor-Barriuso, R., et al. (2005). “Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.” Ann Intern Med 142(1): 37–46.CrossRefGoogle ScholarPubMed
Psaty, B. M., Heckbert, S. R., et al. (1995). “The risk of myocardial infarction associated with antihypertensive drug therapies.” JAMA 274(8): 620–5.CrossRefGoogle ScholarPubMed
Rimm, E. B., Stampfer, M. J., et al. (1993). “Vitamin E consumption and the risk of coronary heart disease in men.” N Engl J Med 328(20): 1450–6.CrossRefGoogle ScholarPubMed
Selby, J. V., Friedman, G. D., et al. (1992). “A case-control study of screening sigmoidoscopy and mortality from colorectal cancer.” N Engl J Med 326(10): 653–7.CrossRefGoogle ScholarPubMed
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Turnbull, F., Neal, B., et al. (2005). “Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials.” Arch Intern Med 165(12): 1410–9.Google ScholarPubMed
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Booth, G. L., and Hux, J. E. (2003). “Relationship between avoidable hospitalizations for diabetes mellitus and income level.” Arch Intern Med 163(1): 101–6.CrossRefGoogle ScholarPubMed
Cook, T. D., and Campbell, D. T. (1979). Quasi-Experimentation: Design & Analysis Issues for Field Settings. Chicago, IL, Rand McNally College Pub. Co.Google Scholar
Eidelman, R. S., Hollar, D., et al. (2004). “Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease.” Arch Intern Med 164(14): 1552–6.CrossRefGoogle ScholarPubMed
Gum, P. A., Thamilarasan, M., et al. (2001). “Aspirin use and all-cause mortality among patients being evaluated for known or suspected coronary artery disease: a propensity analysis.” JAMA 286(10): 1187–94.CrossRefGoogle ScholarPubMed
Hearst, N., Newman, T. B., et al. (1986). “Delayed effects of the military draft on mortality. A randomized natural experiment.” N Engl J Med 314(10): 620–4.CrossRefGoogle ScholarPubMed
Johnston, S. C. (2000). “Effect of endovascular services and hospital volume on cerebral aneurysm treatment outcomes.” Stroke 31(1): 111–7.CrossRefGoogle ScholarPubMed
Johnston, S. C., Dudley, R. A., et al. (1999). “Surgical and endovascular treatment of unruptured cerebral aneurysms at university hospitals.” Neurology 52(9): 1799–805.CrossRefGoogle ScholarPubMed
Katz, M. H. (1999). Multivariable Analysis: A Practical Guide for Clinicians. Cambridge, Cambridge University Press.Google Scholar
Miller, E. R., 3rd, Pastor-Barriuso, R., et al. (2005). “Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality.” Ann Intern Med 142(1): 37–46.CrossRefGoogle ScholarPubMed
Psaty, B. M., Heckbert, S. R., et al. (1995). “The risk of myocardial infarction associated with antihypertensive drug therapies.” JAMA 274(8): 620–5.CrossRefGoogle ScholarPubMed
Rimm, E. B., Stampfer, M. J., et al. (1993). “Vitamin E consumption and the risk of coronary heart disease in men.” N Engl J Med 328(20): 1450–6.CrossRefGoogle ScholarPubMed
Selby, J. V., Friedman, G. D., et al. (1992). “A case-control study of screening sigmoidoscopy and mortality from colorectal cancer.” N Engl J Med 326(10): 653–7.CrossRefGoogle ScholarPubMed
Stampfer, M. J., Hennekens, C. H., et al. (1993). “Vitamin E consumption and the risk of coronary disease in women.” N Engl J Med 328(20): 1444–9.CrossRefGoogle ScholarPubMed
Turnbull, F., Neal, B., et al. (2005). “Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials.” Arch Intern Med 165(12): 1410–9.Google ScholarPubMed
Warram, J. H., Laffel, L. M., et al. (1991). “Excess mortality associated with diuretic therapy in diabetes mellitus.” Arch Intern Med 151(7): 1350–6.CrossRefGoogle ScholarPubMed

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