Henry K. Beecher

Ethics and Clinical Research

HUMAN experimentation since World War II has created some difficult problems with the increasing employment of patients as experimental subjects when it must be apparent that they would not have be...

Ethical problems created by the hopelessly unconscious patient.

Vex not his ghost: O, let him pass! he hates him That would upon the rack of this tough world Stretch him out longer. King Lear, v. iii THE following remarks are limited to the single situation of ...

Increased stress and effectiveness of placebos and "active" drugs.

Evidence is presented to indicate that placebos are far more effective in producing carefully defined relief of pathological pain than they are in the case of experimental pain. This is construed as further support for the view that placebos are more effective when stress is great than they are when stress is not so great. A similar situation holds for morphine. Certain drugs are effective in relieving visceral sensations only if an essential psychological state is present. This is, in effect, a new principle of drug action.

Experimental production of pain in man: Sensitivity of a new method to 600 mg. of aspirin

The acetylsalicylic acid equivalent of two standard commercial aspirin tablets significantly delays development of ischemic pain induced experimentally in man by the submaximum‐effort tourniquet technique. Results of the present study, in confunction with previous findings, indicate that a wide range of analgesic potency may be assessed with this method, and thus a long‐sought procedure for testing, in man, the potency of new analgesics, studied under controlled experimental conditions, is provided. Efforts are presently under way to refine and sensitize the method in order to increase its practical usefulness for study of analgesics with only modest potency.

Generalization from Pain of Various Types and Diverse Origins

Pain that arises from very different pathological origins responds in a quantitative fashion to a given dose of a given narcotic, but this is not true when the pain has been contrived by experimental means, in man, with customary techniques.

Some fallacies and errors in the application of the principle of consent in human experimentation.

Fallacies and difficulties in the application of the principle of consent will be considered here. More questions will be raised than answers given; questions must be stated before answers can be expected.

A Study of Deaths Associated With Anesthesia and Surgery

Ten teams consisting of an anesthetist, a surgeon, and a secretary worked for a 5-year period in 10 University hospitals scattered widely over the United States. All the deaths occurring on all of the surgical and surgical specialty services were examined and appraised as to their causes by the team working in each participating hospital. Final decisions were made by the local team in each hospital, usually after a full staff discussion. These decisions were made as soon after each death as those who were on hand at the time of the death could assemble the relevant material. It is to be emphasized that in this study, there was nothing voluntary or selective about the reporting of the deaths, once an institution with its team had agreed to participate. A point is made of this fact, because studies of intermittently, casually, or partially reported deaths can never get to the center of a problem of this kind. All deaths were categorized and reported. The designation of the cause of death was made in the institution where it occurred; this classification was not altered in the central office. Reports to the central office were made at 4-month intervals by each of the participating hospitals; thus each institution sent in 15 reports over a 5-year period. In these reports, the causes of death were characterized as patient’s disease, error in diagnosis, error in surgical judgment, error in surgical technique, or during anesthesia. For 2 weeks during each 4-month period, the numbers of certain key operations were tallied, to check the uniformity of the surgical material in the 10 institutions. A sampling of the ages and races of the patient material was made on all patients present in the 10 hospitals on 2 dates that were considered representative. From the data collected on 599,548 anesthesia treatments, the following observations can be made for the period of this study.

Response to the Ingersoll Lecture by a Physician

Dr. Pahnkes field of interest, just described, is of very great importance. I can say this even though he and I might have some differences as to methodology. Questions must be asked in terms in which they can be answered. Thus Dr. Pahnke has sketched for us a new and promising approach to problems in an old field, and I am with him all the way in this interest.

Report of the subcommittee on position and status of the clinical pharmacologist in drug research

The new F. D. A. regulations direct attention to the clinical pharmacologist and have suddenly created a broad demand for his services. Yet there is no clear‐cut de:6.nition of a clinical pharmacologist or of clinical pharmacology; there are no generally accepted standards for the education and training of clinical pharmacologists and, though a journal with such a title is now in its fourth annual volume, there exists no collected body of literature or any textbook. If only for the legal considerations, an authoritative statement on the meaning and scope of clinical pharmacology is urgently needed. Since an important public function is involved, this subcommittee puts forward the statement which follows in the hope it will lead to the establishment of appropriately high standards for clinical pharmacology and clinical pharmacologists.

Experimental Pharmacology and Measurement of the Subjective Response

Boundaries. Experimental pharmacology in the past has dealt largely with phenomena that can be measured objectively in response to drug administration, with changes in heart rate, rises or falls of blood pressure, neuromuscular action, and so on. Such experimental studies have usually been carried out in animals, and the basic controls have been observed in most cases. On the other hand, relatively little attention has been given to the nature of the controls that are essential in order to elicit true and clear information concerning subjective responses to drugs. Such work must usually be carried out in man. The need for measurement of subjective responses can be seen by taking a look at the general growth of medicine in recent years. Besides its direct benefits, this growth has served indirectly to emphasize areas where development has lagged. Notable, for example, is the slowness of enduring growth in experimental psychiatry. This is not to say that advances have not been made. They have been, of course. But it is possible that growth in this field has been retarded because pharmacology as it deals with the subjective response has not been given the attention it deserves. The experimental biochemistry, physiology, and pharmacology of the future will more and more concern man, and in studies of man answers will be sought to questions that involve man’s subjective responses. For success here we must recognize the needs of this kind of investigation; they differ from those that deal with objective responses. Definitions. Objective responses in the sense in which we use the term here are made evident in physical change (or can be made evident) to the senses of an onlooker (a physical sign). They can be mechanically recorded. Subjective responses are evident only to the individual