Evidence,Belief,and Action: The Failure of Equipoise to Resolve the Ethical Tension in the Randomized Clinical Trial

See also Kass L.R. , Toward A More Natural Science: Biology And Human Affairs (New York: Free Press, 1985): at 196;.

Angell M. , “Patient Preferences in Randomized Clinical Trials,” N. Engl. J. Med., 310 (1984): 1385–87.

See, e.g., Freedman B. , “Equipoise and the Ethics of Clinical Research,” N. Engl. J. Med., 318 (1987): 141–55.

Baum M. Zilkha K. Houghton J. , “Ethics of Clinical Research: Lessons for the Future,” British Medical Journal, 299 (1989): 251–53.

Hellman S. , “The Patient and the Public Good,” Nature Medicine, 1 (1995): 400–02.

See Royall R. , Statistical Evidence: A Likelihood Paradigm (London: Chapman & Hall, 1997).

Id. at 4.

Lempert R. , “After the DNA Wars: Skirmishing with NRC II,” Jurimetrics, 439 (1997): 456–57.

“Frequentist” statistical method, which is the dominant method used in evaluating the results of clinical medical research, focuses on the frequency of outcomes. As the current method is used, the researcher calculates the probability that the observed result would occur due to chance alone if the null hypothesis (the hypothesis that there is no difference between the treatments being evaluated) were true.

Goodman S.N. , “Toward Evidence-Based Medical Statistics 1: The P Value Fallacy,” Annals of Internal Medicine, 130 (1999): 995–1004.

The combination of the Fisher and Neyman/Pearson methods that is standard practice today is widely recognized as theoretically incompatible. See, e.g., Goodman , supra note 9, at 997 (claiming that the Fisher and Neyman/Pearson methods “were incompatible but have become so intertwined that they are mistakenly regarded as part of a single, coherent approach to statistical inference”);.

Gill J. , “The Insignificance of Null Hypothesis Significance Testing,” Medical Research Quarterly, 521999): 647–74, at 649–50 (describing the “current null hypothesis significance test as a synthesis of two highly influential but incompatible schools of thought in modern statistics”).

As the p-value is calculated on the assumption that the null hypothesis is true, it “cannot, therefore, be a direct measure of the probability that the null hypothesis is false.” Goodman sees this misunderstanding as “reinforc[ing] the mistaken notion that the data alone can tell us the probability that a hypothesis is true” (emphasis added).

Id. at 996–97. Goodman explains well this familiar tradeoff between the virtues of inductive and deductive reasoning. He describes this as follows: “Under the assumption that two treatments are the same (that is, the hypothesis of no difference in efficacy is true), it is easy to calculate deductively the frequency of all possible outcomes that we could observe in a study. But once we observe a particular outcome, as in the result of a clinical trial, it is not easy to answer the more important inductive question, ‘How likely is it that the treatments are equivalent?’”.

Richard Royall makes precisely this point, see Royall R. , “Ethics and Statistics in Randomized Clinical Trial,” Statistical Science, 6 (1980): 52–88, at 56;

see also Hellman S. Hellman D. , supra note 4.

Federal regulations allow the use of “promising new drugs” to treat patients with a “serious or immediately life-threatening disease” if “no comparable or satisfactory alternative drug or other therapy is available.” 21 C.F.R. §; 312.34.

Nelson D. Weiss R. , “Penn Researchers Sued in Gene Therapy Death; Teen's Parents Also Name Ethicist as Defendant,” The Washington Post, Sept. 19, 2000,): at A3.

Emanual E.J. Patterson WB ., “Ethics of Randomized Clinical Trials,” Journal of Clinical Oncology, 16 (1998): 365–71.

Byar D.P. , “Design Considerations for AIDS Trials,” N. Engl. J. Med., 323 (1990): 1343–48;.

Concato J. Shah N. Horwitz R.L. , “Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs,” N. Engl. J. Med., 342 (2000): 1887–92.

See, e.g., Declaration of Helsinki, supra note 1.

In fact the National Institutes of Health funded trials of a shortened course of AZT which was given to pregnant women in developing countries in the attempt to reduce mother to infant transmission of HIV provoked controversy precisely because researchers defended giving some participants placebos on the grounds had the trials not taken place these women and their infants would receive no treatment. See Hellman D. , “Trials on Trial,” Report from the Institute for Philosophy and Public Policy, 18 (1998): 13–18 (evaluating the ethical permissibility of placebo-controlled trials of the efficacy of short course AZT therapies for reducing mother to infant transmissions of HIV in developing countries).