The appearance of a text which is almost completely devoted to the theory of drug action, and in fact covers no particular drug in a systematic fashion, emphasizes the remarkable growth of pharmacology as a science. At a molecular level and in an orderly manner it dissects and demonstrates the logic by which man has attained the ability to control living processes of all types by the use of chemicals. About a third of the text is devoted to drug-receptor interaction, absorption, distribution and elimination of drugs, and drug metabolism. Another large section is directed toward more general principles such as the time course of drug action, idiosyncrasy and pharmacogenetics, drug resistance and tolerance, and physical dependence. The newer fields of chemical mutagenesis and carcinogenesis as well as teratogenesis are extensively covered. A section which deals with drug development and the theoretical aspects of clinical pharmacology serves to illustrate some

https://jamanetwork.com/journals/jama/articlepdf/342512/jama_206_11_031.pdf

Principles of Drug Action: The Basis of Pharmacology

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

Experimental pharmacology and measurement of the subjective response. 1952.

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E.N.T. Examination

The number of hours of sleep gained by means of a soporific (sleep-inducing preparation) will generally vary from person to person. With the help of statistics we would like to make a statement on the average gain in the number of hours of sleep. We must also test whether the gain in the duration of sleep is statistically significant. Analyses of this type require not only knowledge of statistical methods but also a thorough familiarity with the field of study, because to determine the unique effects of specified causes we must be able to sort out the more important factors contributing to the phenomenon examined. These factors can be of a psychological or physical nature. In our example confidence in the medication and in the physician, as well as the physician’s attitude, are factors in the first category; charges in the diet, and in the daily routine belong to the second. To eliminate two influences of the first type, neither the physician nor the patient must know whether a soporific or a placebo is administered. This type of study is called a double blind trial. 
Guidelines for medical doctors on the ethical aspects of clinical research are the internationally accepted Declarations of Helsinki 1964 and Tokyo 1975 [cf., World Medical Journal 22 (1975),87–90 and 25 (1978),58–59].
Another point concerns the following: Suppose the original problem is replaced by the question on the effects particular conditions produce in certain attributes of a given set of objects. The exact state of an attribute is replaced by the observed state; the observations are expressed by symbols. Errors of substitution can occur at each point of transition. For many important substitutions the attributes are not closely related to the problem, and are accordingly not very informative. An attribute is informative if it is highly correlated with the parameter under study.

Statistical Methods in Medicine and Technology

Wird die Wirkung eines Schlafmittels an einem groseren Personenkreis gepruft, so ist der Gewinn an Stunden Schlaf fur verschiedene Personen im allgemeinen verschieden Was man durch statistische Untersuchungen erreichen mochte, ist einmal eine Aussage uber den durchschnittlichen Gewinn an Stunden Schlaf Weiterhin mus gepruft werden, ob sich der Gewinn an Schlaf statistisch sichern last Diese Art von Untersuchungen setzt neben der Anwendung der mathematischen Statistik eine gute Sachkenntnis des zu bearbeitenden Fachgebietes voraus, denn es soll die Wirkung nur als Funktion der vorgegebenen Ursachen bestimmt werden Das bedeutet in unserem Beispiel, das jede psychologische Beeinflussung des Patienten vermieden werden mus Es darf weder der Arzt noch der Patient wissen, ob das verabreichte Mittel das zu prufende Schlafmittel oder ein mit Sicherheit wirkungsloses Mittel (sogenanntes Placebo) ist Diese Art von Versuchen nennt man „doppelten Blindversuch“ Er beleuchtet die Schwierigkeiten nichtmathematischer Natur bei der Anwendung statistischer Prufverfahren

Die Anwendung statistischer Verfahren in Medizin und Technik

Introduction: Industry/Regulatory Agencies Semi-impasse on Drug Submissions/Applications (leneral Ameliorating Measures Descriptions of the Clinical Trial Planning the Trial (in Broad Terms) Relative to Time, Realism, and Communication What the Clinical Investigator Understands What the Statistical Advisor Understands Objectives of the Trial Cooperative Field and Institution Trials Staffing and Equipment Protocol Points and the Necessity for Biostatistics Self-Queries in Designing the Trial Controls, Their Necessity and Nature Selection of Subjects (Number, Population, Sample, Definition) 233 Types of Treatments (Specific, Con234 trol, Placebo, Supportive, Con234 comitant, etc.) Allocation of Subjects to Treatments (Randomization and Stra235 tification) Definition of Data, Primary and 236 Secondary Evaluation of Treatment Effects 236 (Criteria) 236 Assessment of Study Results (Clinical and Statistical Significance, 237 Protocol Deviations) 237 Final Report (Checklist) Conclusions, Including Future Tm238 peratives 238 Summary, Choice of Investigators, and Monitoring 240 References

F.R.S.M. J. Corboy Ryan M.D.

Papers

Management of clinical research "architecture".