Dr. Browning, entering his fellowship in pulmonary medicine, is assigned to carry out an institutional review board (IRB)-approved study designed by Dr. Sedgwick. The study of patients with cystic fibrosis is designed to determine whether an experimental drug improves pulmonary function and reduces the incidence of new infections. The study is double-blinded, and the patients receive inhalers with either placebo or the experimental drug. Preclinical studies were promising, but potential problems had included an allergic reaction to the drug and a direct, adverse chemical effect on the lung passages.

The clinical study for which Dr. Browning is responsible consists of a three-month trial of either the drug or placebo, a one-month drug-free period, then a three-month trial of the other arm of the study. Forty patients are to be entered by the completion of the trial. They are to be evaluated by a lung function test.

The experimental drug is so effective that, shortly after the trial begins, Dr. Browning finds it easy to know who is receiving the drug and who is receiving placebo. After 20 patients are entered in the trial, Dr. Browning asks Dr. Sedgwick about ending the protocol. Dr. Sedgwick responds, "We are not only testing efficacy here; we are also testing for adverse effects that may not be common but may be quite serious. What would you think about using the drug if one percent of recipients had a bout of life-threatening anaphylaxis? Furthermore, we are also going to follow the patients to see if there is a reduction of the rate of infection, hospitalization, and need for antibiotics."

Dr. Browning responds that the statistical power of the study is not sufficient to determine whether an effect would occur in one percent of subjects, nor is the duration long enough to obtain meaningful data on infections. For that, a different experiment, monitoring the treatment of large numbers of subjects over a longer period of time would be required. Because the degree of improvement is sufficient to demonstrate efficacy after only 20 subjects, there is no need to continue the placebo controls or to continue the current study.

Dr. Sedgwick points out that the FDA requires 40 cases from their institution for the efficacy study, and their requirements take priority over the power calculations for statistical analysis in most cases.