Prospective randomized trial is the gold standard in clinical research. Randomized trials tend to reduce and even eliminate investigator and patient bias. A poorly-designed or improperly randomized study involving human subjects that will not or cannot answer a scientific question is by definition unethical. However, a well-designed clinical trial is not inherently ethical. Physicians involved in a randomized trial must make the intellectually honest admission that the best therapy for the individual's disease is not yet known. The ultimate protection for human subjects who volunteer to participate in clinical trials is the responsible investigator himself. In patients with advanced cancer there are three primary factors motivating participation: hope that the new treatment will offer a better chance for controlling disease; altruism that even if the treatment did not help them as an individual it might ultimately help others; and trust that the physician would not recommend that the patient enter investigational therapy unless he thought it might be helpful.