A Contribution to the Methodology of Clinical Appraisal of Drug Action

This study is concerned with the influence of the medical environment on drug action. We separated the pharmacologic action of a sedative and antispasmodic (meprobamate and tridihexethyl iodide) from the Medicinal Transactional Phenomenon (MTP). We defined MTP as consisting of the powerful interaction between the patient's interpretation of the medical environment with his psychological needs and drives. This interaction is made possible by the placebo, which acts as vehicle making the MTP socially and emotionally acceptable to the patient. This is not eliminated by the double blindfold test which attempts to eliminate the bias of the observer. Correction of this bias does not eliminate MTP, and its beneficial influence on the patient. We also describe the signaling effect as a factor in drug evaluation. It consists of a fantasy-interpretation of concomitant phenomena unrelated to drug action, as though they were the result of the doctor's influence, affecting the patient's sense of well being. We devised a method accounting for MTP rather than eliminating it. We divided this study into three parts. First we administered the real drug with a protective and solicitous demeanor, which was followed by a continuation of the same attitude but substituting for the drug a like looking placebo. Thirdly, we ceased our friendly demeanor and became abrupt and less protective, readministering the real drug in a physically different shape. The results substantiated the deep influence of MTP on the efficacy of even a potent drug. This study also demonstrated that Milpath has a significant, truly pharmacologic action.