Risk-benefit relationships in cancer clinical trials: the ECOG experience in non-small-cell lung cancer.

Although there is widespread recognition of the need to critically evaluate risks and benefits for patients participating in clinical trials, the actual implementation can be a difficult task. As an illustration of the analytic difficulties, we reviewed the experience of the Eastern Cooperative Oncology Group (ECOG) in advanced (inoperable) non-small-cell lung cancer over the past ten years (1973 to 1983). Of 2,714 ECOG patients analyzed, 15% showed objective tumor response. Median survival of all patients was 4.2 months, with approximately one half of patient's survival spent on protocol treatment. Thirty-nine percent of patients experienced at least one episode of severe or worse toxicity from therapy. Chemotherapy impact on this disease was assessed by examining trends in patient outcomes over the decade studied and by comparisons with patients receiving no treatment from earlier Veterans Administration Lung Protocols. Introducing more intensive chemotherapy regimens over this period appears to have resulted in some improvement in survival and response to therapy, but at the expense of greater toxicity. Despite modest survival gains achieved by these evolving trials, the community benefit from such trials seems clear, both in identifying ineffective therapies (and avoiding their general use) and as an important step in developing effective regimens. However, the decision for an individual patient to participate in a trial may involve difficult trade-offs between risk and benefit. This study suggests the need to identify subgroups of patients unlikely to benefit from trial participation and stresses the importance of incorporating patient preferences in the final decision. Some of the problems in patient communication are discussed.