When published, a randomized parallel-group drug trial essentially includes a table listing all of the factors, otherwise called baseline characteristics, known possibly to influence outcome. E.g., in case of heart disease these will probably include apart from age and gender, the prevalence in each group of diabetes, hypertension, cholesterol levels, smoking history, other cardiovascular comorbidities, and concomitant medications. If the prevalence of such factors is similar in the two groups, then we can attribute any difference in outcome to the effect of test-treatment over reference-treatment. However, if this is not the case, we have a problem which can be illustrated by an example. Figure 1 shows the results of a study where the treatment effects are better in the males than they are in the females. This difference in efficacy does not influence the overall assessment as long as the numbers of males and females in the treatment comparison are equally distributed. If, however, many females received the new treatment, and many males received the control treatment, a peculiar effect on the overall data analysis is observed: the overall regression line is close to horizontal, giving rise to the erroneous conclusion that no difference in efficacy exists between treatment and control. This phenomenon is called confounding, and may have a profound effect on the outcome of a trial. In randomized controlled trials confounding is, traditionally, considered to play a minor role in the data. The randomization ensures that no covariate of the efficacy variable is associated with the randomized treatment.1 However, the randomization may fail for one or more variables, making such variables confounders. Then, adjustment of the efficacy estimate should be attempted. Methods include subclassification2, regression modeling1, and propensity scores.3,4 This paper reviews these three methods and uses hypothesized and real data examples for that purpose.
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References
Cleophas TJ, Zwinderman AH, Cleophas AF. Statistics applied to clinical trials. Springer, New York 2006, pp 141–50.
Cochran WG. The effectiveness of adjustment by subclassification in removing bias in observational studies. Biometrics 1968; 24: 295–313.
Rosenbaum P, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika 1983; 70: 41–55.
Rubin DB. Estimating causal effects from large data sets using propensity score. Ann Intern Med 1997; 127: 757–63.
SPSS Statistical Software. http://www.spss.com
Sobb M, Cleophas TJ, Hadj-Chaib A, Zwinderman AH. Clinical trials: odds ratios, why to assess them, and how to do so. Am J Ther 2008; 15: 44–53.
Cleophas TJ, Tuinenburg E, Van der Meulen J, Kauw FH. Wine drinking and other dietary characteristics in males under 60 before and after acute myocardial infarction. Angiology 1996; 47: 789–96.
Soledad Cepeda M, Boston R, Farrer JT, Strom BL. Comparison of logistic regression versus propensity scores when the number of events is low and there are multiple confounders. Am J Epidemiol 2003; 158: 280–7.
Wickramaratne PJ, Holford TR. Confounding in epidemiological studies: the adequacy of the control groups as a measure of confounding. Biometrics 1987; 43: 751–65.
Huppler Hullsiek K, Louis TA. Propensity scores modeling strategies for the causal analysis of observational data. Biostat 2002; 3: 179–93.
Begg CB. Commentary: ruminations on the intent to treat. Control Clin Trials 2000; 21: 241–3.
Beal SL, Sheiner LB. A note on the use of Laplace's approximations for non-linear mixed -effects models. Biometrika 1996; 83: 447–52.
SAS. http://www.prw.le.ac.uk/epidemiol/personal/ajs22/meta/macros.sas
Boeckman AJ, Sheiner LB, Beal SL. 1984 NONMEM user guide: part V. NONMEM Project Group, University of California, San Francisco.
Cleophas TJ, Zwinderman AH, Cleophas AF. Statistics applied to clinical trials. Springer, New York 2006, 329–36.
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(2009). Confounding. In: Cleophas, T.J., Zwinderman, A.H., Cleophas, T.F., Cleophas, E.P. (eds) Statistics Applied to Clinical Trials. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9523-8_19
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