System Analysis: A Strategy for Drug Experimentation and Evaluation

SYSTEM ANALYSIS: A STRATEGY FOR DRUG EXPERIMENTATION AND EVALUATION SAMUEL IRWIN, Ph.D.* The organisms and tissues the biologist investigates are not static, rigid systems. They undergo continuous change in response to numerous internal and external factors that may greatly modify them. As a consequence , a datum in biology has no fixed value; it reflects only the capacity ofa particular tissue or organism to respond at a particular time under a particular set ofexperimental conditions, many ofwhich are unknown to the experimenter or beyond his control. How, then, does one establish TABLE 1 The Meaning of Information A.Blood pressure ....................A. Fighting behavior B.Cardiac rate ..................... B. Arousal level C.Cardiac strength .................C. Motor activity D.Cardiac output ..................D. Muscle tone E.Peripheral resistance ..............E. Co-ordination Note.—The meaning of a drug-induced change is contingent on other sources of information simultaneously derived from each subject. the reliability and meaningfulness of biologic data? How precise need measurement be? A datum in biology also conveys little meaning until paired and correlated with the information that enables one to interpret it. For example, a drug that reduces fighting behavior may do so directly or indirectly by reducing locomotion, response to provoking stimuli, or skeletal muscle tone (paralysis), or by simply impairing motor co-ordination (Table i). Unless such relevant information is obtained, the inferences drawn from findings are less likely to be correct. * Department ofPsychiatry, University ofOregon Medical School, Portland. Oregon Regional Primate Research Center, Beaverton. I wish to thank Dr. LyIe D. Calvin ofOregon State University for helpful advice on the section dealing with statistical analysis, and Rexine M. Hayes, secretary, for editorial assistance in the preparation of this manuscript. Publication costs were kindly contributed by Hoffman-La Roche, Inc., and Smith Kline & French Laboratories. Research was supported in part by U.S. Public Health Service grant MH 10990. 654 Samuel Irwin · Drug Evaluation Perspectives in Biology and Medicine · Summer 1968 Many scientists are aware of these requirements and respond accordingly , but studies where the relevant interactional organismic variables are neither defined nor measured dominate much ofthe research effort today; greater attention seems given to the precision ofmeasurement than to its scope and content. This more conventional approach to investigation often misleads and thus not only fails to advance knowledge significantly but may even detract from it. Required and recommended as the basic strategy for biologic research is a general systems approach, that is, one where investigations are kept sufficiently broad in scope to include the multiple organismic data and other information that enables one better to understand and interpret one's findings [i]. The biologic system is complex. The study that views it as a simple, static system unresponsive to the conditions ofmeasurement, failing to take the general state ofthe organism into account , is a poorly conceived one. System Analysis System analysis is based on the proposition that every measurement involves a complex system (including the organism or tissue, the environment , the instruments of measurement used, and the observer) and that the variables within the system can greatly modify and influence the outcome ofmeasurement. This creates the need to define and study the relevant variables of the system itself in order to understand the discrete changes produced in it. Asnoted by Müller [2], "Any single event involves the entire system in which it takes place." Phenomena, also, can be described only in terms ofthe operations used to observe them; the operation itselfbecomes the unit ofknowledge [3]. As already noted, meaningful information and inference are rarely possible from a single unit ofmeasurement only; additional information is almost always required. The ideal méthodologie approach is to obtain all such information simultaneously from the same subject, where each measure exists in quantitative relationship to the other and where the conditions for measurement are the same. Such quantitative relationship is impossible to achieve when the separate units ofinformation are obtained from different subjects (different systems ofmeasurement), as illustrated in Table 2. As noted by Schueler [4], "All levels are linked functionally with one another,just as they are linked structurally, through the process ofsuccès655 sive combination to give moreand more complex interacting aggregates," but such linkage exists only within subjects...