1. Salcido, Richard "Sal" MD

Article Content

The sine qua non of evidenced-based medicine or the "gold standard" is a large multicenter, randomized, double-blind, placebo-controlled trial (RDBPCT) conducted during a significant epoch of time (years not months). Its attributes should include significant power (large numbers of subjects that produce statistically significant results) to support the safety and efficacy of a given treatment, surgical procedure, or pharmacologic agent. Typically, clinicians, professional societies, regulators, and payers embrace these studies as meeting a standard of a given practice. Patients, who have access to and can interpret information from various venues, including media, believe that the treatment options generated by the aforementioned trials are a safe bet. Studies that meet criteria for the "gold standard" usually receive the highest strength of evidence ratings (SOER) and recommendations under the rubric of numerous SOER grading scales, which are inherently complex, owing to problematic taxonomic variability.

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The limitations of the "gold standard," however, are significant. These studies require significant numbers of patients, significant capital, and significant influence by the funding source. The funding sources range from industry, National Institutes of Health, and the Veterans Administration to the pharmaceutical companies. Correspondingly, the funding source also has a significant say in what gets funded, and, of course, it possesses a keen interest in the outcome, which develops an inherent bias.



Although these large multicenter RDBPCTs are highly respected, they must also meet the standard of generalizability; ergo, will the results of the study be applicable or generalizable to the patients in regional or local hospitals? In summary, if the study was carried out in a large quaternary health system by clinicians trained in the appropriate research methods, protocols, and procedures, where the patients were closely monitored, can this evidence-based medicine (EBM) recommendation be carried out in a reproducible manner in general clinical practice? In addition, persons with multifactorial comorbidities, or complex diseases, such as patients with chronic nonhealing wounds, are not often included in studies and the results of these studies are not easily generalizable. In my experience, a large, planned RDBPCT had to be scrapped because the company funding the study insisted that the inclusion criteria include only patients with wounds and exclude patients with diabetes and other confounding real-world comorbidities.



There has been an inherent bias to publish papers that are peer reviewed and demonstrate positive outcomes. This method uses analytical learning, which is not always applicable to the real-world environment. Alternatively or coincidently, we learn by experiential methods. To use a well-worn metaphor, "We can learn what not to do by observing others' mistakes," and we could learn about practice pitfalls by reading about trials that failed. We certainly should seek out information that has a negative finding or negative trials; we need to know if a certain wound care modality or dressing actually works. In today's environment, we must consider other methods of published information, including online journals and reviews, to have access to the full array of information-beyond the traditional print journal. According to the authors of a relatively new journal, The Journal of Negative Results in Biomedicine, "It is useful and important to publish well-documented failures, such as with drugs that show no benefit or clinical improvement, as well as with the use of methods that are unreliable, but for which the shortcomings have not been publicized."



The intent of EBM practices helps to guide the clinician to practice the state of the art. In The Limits of Evidence-Based Medicine, Tonelli advises that "the knowledge gained from clinical research does not directly answer the primary clinical question of what is best for the patient at hand" and suggests that EBM should not discount the value of clinical experience. In other words, the clinician should supplement the experiential to the analytical found in the RDBPCTs.



It is not uncommon in the industry for certain practices to prevail. For example, the issue of ghostwriters has received recent attention nationally, by the Congress, and in this journal recently. In addition, issues of appropriate inclusion and exclusion criteria potentially biasing the study are common concerns in large clinical trials. In wound care, as pointed out by Ayello and Sibbald in their "Letter to the Editor" below, it may be unethical to withhold treatment in the control arm of the RDBPCT for the purposes of conducting a funded trial.


Although we strive for the best evidence for our practices in wound care, we must remain cognizant that there may not be evidence for caring for and trying to heal wounds, especially at the end of life. We must do so for the dignity of man.


Richard "Sal" Salcido, MD

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Selected References


Pfeffer C, Olsen BR. Editorial. J Negat Results Biomed 2002;12:1-2.


Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence-based medicine: what it is and what it isn't. BMJ 1996;312(7023):71-2.


Salcido R. Ghostwriters in the fray: the implications for science, industry, medical journals, and our patients. Adv Skin Wound Care 2009;22:494-6.


Salcido R. The language of wound care: taxonomy of discourse. Adv Skin Wound Care 2000;13:252-4.


Tonelli MR. The limits of evidence-based medicine. Respir Care 2001;46:1435-40.