There is a growing trend toward evidence-based medicine, in which patient-oriented data are valued more highly than disease-oriented evidence (DOEs). In the vernacular of evidence-based medicine, the old DOEs are slowly being replaced by POEMs (patient-oriented evidence that matters). Unfortunately, POEMs do not yet exist to meet every family-practice need. When there are no POEMs to determine an appropriate therapeutic choice, another decision-making method must be used. This method includes liberal use of DOEs combined with thoughtful use of causal pathways to provide preliminary direction. This article applies that method to an example from the growing basic science surrounding endothelial functioning. (J Fam Pract 2000; 49:362-368)
There is a well-described gap in clinical medicine. Research is published at an ever-increasing rate, and it is far beyond the capabilities of any individual to stay abreast of all the latest developments. Despite this rapid advance in knowledge, most published data describe advances in disease-oriented, cell-oriented, or molecule-oriented medicine. These advances are seldom applicable to clinical medicine.
This is not a small matter. The first 2 articles in a recent issue of the New England Journal of Medicine were dedicated to the prophylaxis and treatment of gastritis and ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs).1,2 These 2 articles were disease-oriented evidence (DOEs), emphasizing NSAID-induced ulcer management and using disease-oriented (endoscopic evidence of ulcer) rather than patient-oriented (pain or other symptoms) outcomes. The articles received much publicity, especially from the developers of the “better” treatment. This publicity, both through possible direct-to-consumer advertisements and academic detailing aimed at supporting DOE-based behavior, influences physician behavior.
Of course, all fault does not lie with the medical literature, since clinicians do not always follow patient-oriented evidence that matters (POEMs). For example, a series of POEMs stretching across more than a decade demonstrated that post-myocardial infarction (MI) patients experience improved outcomes (with such significant patient-oriented outcomes as survival) when given a b-blocker.3-5 Still, many candidates for such treatment are not given a b-blocker after an MI.
All POEMs are important; those demonstrating clinical effectiveness, however, are of the greatest value to physicians. Clinical trials are designed to assess either efficacy or effectiveness.6 Efficacy describes biology (ie, whether a given intervention works under ideal conditions). Most randomized trials are efficacy studies. In family medicine this is important (we like to know that something works), but efficacy is not as significant as effectiveness. Effectiveness confirms that the intervention works in the context of real world problems, such as issues of compliance (both physicians’ and patients’) and competing priorities. Efficacy is a valuable measurement tool for the Food and Drug Administration and the National Institutes of Health. Effectiveness is the measurement of a patient’s experience.
The problem is two-fold. First, there are fewer POEMs than DOEs. Second, even when provided with the appropriate POEMs (ie, those about effectiveness), physicians are often slow to change their practices. This article addresses the first issue, the relative paucity of POEMs for guiding clinical practice. What should physicians do? Should they abandon all evidence-based science? Should they blindly rely on DOEs while waiting for POEMs? Is there another alternative?
Many physicians have practiced an alternative for years. This method includes liberal use of DOEs (when available) combined with thoughtful use of causal pathways to provide preliminary direction to guide clinical decisions. This article applies that method to an example from the growing basic science surrounding endothelial functioning. The endo-thelium was chosen because its basic science is not everyday reading material for the family physician. Thus, this topic provides an excellent model for applying these techniques to any new knowledge.
The causal pathway
A causal pathway is a description of how physicians view the pathophysiology of disease. Usually the causal pathway reflects elements that are temporally and causally related. A causal pathway may be simple (eg, hypertension leads to atherosclerosis, which leads to stroke); however, a detailed pathway is more useful. Figure 1 depicts a simplified pathway for coronary heart disease.7 This pathway is based on the assumption that lowering high-serum cholesterol results in a lower risk of coronary heart disease. This pathway further assumes that early detection of hypercholesterolemia is possible.
A causal pathway has several uses. First, it explicitly states our understanding of mechanisms of action. This leads to testable hypotheses that can advance our knowledge. Second, it provides a series of proposed links between an early potential causative agent and an outcome. This is important, because the proposed links provide a mechanism for testing several smaller questions instead, of a large one. This has obvious cost and time advantages. The causal pathway in Figure 1 can be used as an example. A question may arise about whether screening for hypercholesterolemia can lead to a lower risk of coronary heart disease. The best way to evaluate that question is through a randomized trial as depicted in line 5 of Figure 1. However, such a trial would take a significant period of time and be expensive. Instead a series of smaller studies, each testing a different link in the causal pathway (eg, 1, 2, and 3, or 1 and 4 in Figure 1), could provide important evidence. Certainly, the larger trial is superior. However, when faced with a lack of documented evidence, supportive evidence from the links of a causal pathway can be reassuring. This is precisely what occurred during the past 20 years to establish the link between cholesterol and coronary heart disease. First, a series of epidemiologic POEMs followed by clinical trial DOEs supported the cholesterol-cardiac disease causal pathway. Recently, randomized controlled trial POEMs provided the final support for the model. Likewise, nonsupportive evidence, while not eliminating a causal link, suggests that the cause-and-effect relationship is less likely.