Leaving Therapy to Chance

clinical trials of anticancer drugs are incompatible with the ethics of the patient-physician relationship. If this problem cannot be resolved, then either a key procedure for achieving scientific knowledge in medicine must be given up or unethical behavior by physicians must be tolerated. Since the issue applies to randomized clinical trials in general but is particularly intractible in the context of anticancer drug trials, I will focus my ethical analysis on this type of trial. Furthermore, I will consider only "two-arm" studies, those in which one of two anticancer drugs or drug combinations is assigned to patients enrolled in the study solely on a randomized basis. Randomization is intended to ensure that any statistically significant difference in responses to the drugs is due solely to the difference in the efficacies of the drugs. The scientific value of randomization in clinical trials can be best appreciated by considering the alternative. It might seem that to compare adequately a new drug to a standard drug, one need only compare results obtained when the new drug is given to a group of patients to the results obtained when the standard therapy had been given to patients in the past. Such comparisons are inadequate for a number of reasons. Consider an evaluation of the difference in the response rates by a tumor to two different drugs. It is extremely important that the criteria for what counts as a response by the tumor have been carefully standardized. Even so, the degree of response to the drugs by the two patient populations may be affected by all sorts of factors other than the difference in the drugs, including the medical condition of the patients, their age, the extent of previous treatment with other anticancer drugs, and other medical care they receive. In addition, although physicians may agree concerning the drug of choice for a given cancer at a given stage, they may disagree about the amount and frequency of administration of the drug. Even the notion of standard therapy is not as clean as might first appear. Suppose, it is argued, statisticians can find ways of accounting for these other factors so as to identify the precise difference in effect of the two drugs under investigation. There are many serious difficulties with such a procedure. First, the precise extent of the effects of these other factors DON MARQUIS is associate professor of philosophy, University of Kansas. may not be known-and usually isn't. But unless it is known, it will be impossible to determine the precise extent of the difference due to these other factors. Second, precise data concerning these other factors may not be available for the patient populations that are tested. Third, the success of such a nonrandomized study depends upon knowing all the factors that might affect a difference in the responses to the drug in the two samples of patients. But many things are unknown about cancer. Obviously, then, it is possible that there are some unknown and therefore unaccounted-for factors that actually do make a difference in the response rate of two particular populations. Fourth, patients may receive different therapies because they have different physicians who will assign therapies based on different clinical judgments. Their judgments are based not entirely on well-documented, impeccably researched studies in medical journals, but also on their own experiences and the theories about the disease process they accept. It is nearly impossible to account for these individual differences in judgment. Since randomized studies avoid these problems, they are often the only way of achieving reliable scientific knowledge in clinical medicine.'