Clinical Trials

❘❙❚■ Chapter 1 | Randomized Clinical Trialsthe study, 886 patients (23%) in the candesartan group and 945 (25%) in theplacebo group (as predicted, 8% annual mortality) died from any cause(unadjusted hazard ratio 0.91 [95% CI 0.83, 1.00], P = 0.055), with fewercardiovascular deaths (691 [18%] vs 769 [20%], unadjusted hazard ratio 0.88 [0.79,0.97], P = 0.012) in the candesartan group. It was concluded that treatment of abroad spectrum of patients with symptomatic heart failure with candesartanresulted in a marginally significant reduction in deaths, notably because of asignificant 12% hazard reduction in cardiovascular deaths [14]. Results on theeffects of candesartan on cardiovascular death or CHF hospitalization in differentpopulations of patients with heart disease (CHARM-Preserved, -Added, and -Alternative) were reported in three separate articles [15–17].ConclusionRandomized clinical trials are a major investment in terms of patient andpersonnel involvement, and the funding needed to undertake the trial for theprogress of medical care. We have provided a short overview on the various typesof clinical trials, and the main types of errors that can arise and can seriouslycompromise our ability to draw valid conclusions from clinical trials.Many of the concepts mentioned in this chapter deal with minimizing bias andmaximizing precision. An appropriate design requires a clear definition of theprimary and secondary hypotheses in terms of measured outcomes and an explicitdefinition of the study population in order to avoid systematic errors. Statisticalanalyses deal with random errors due to sampling or random variation in theoutcome variables. Interpretation of these statistical measures of treatment effectand comparisons should consider the potential contribution of bias orconfounding. Finally, it is ethically imperative that a trial is conducted andmonitored in such a way as to minimize harm to patients, while looking to answerthe initial questions posed by the trial of whether the new treatment is better,worse, or similar to the comparison group.References1. World Medical Association Declaration of Helsinki. Ethical Principles for Medical ResearchInvolving Human Subjects. Available from: www.wma.net/e/policy/b3.htm. Accessed May 6, 2005.2. Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reportingrandomized trials: explanation and elaboration. Ann Intern Med 2001;134:663–94.3. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendationsfor improving the quality of reports of parallel-group randomized clinical trials. Lancet2001;357:1191–4.12