Lack of evidence for clinical and health policy decisions

A major frustration for clinical and health policy decision makers is the limited amount of relevant and credible evidence available to make evidence based decisions, a perspective conveyed in many health technology assessments and systematic reviews with some version of the following phrase: “Because of the paucity of high quality evidence, the data available—though voluminous—may have little meaning or value for informing clinical practice.”1 Many variations of this statement can be found, differentiated by subtle nuances of judgment reflected in the phrasing of the report’s executive summary—ranging from simple resignation to incredulity, exasperation, and hostility. This epidemic of ignorance is particularly perplexing given the fact that about 19 000 new randomized clinical trials are published each year, making one wonder how generating this amount of data while leaving so many gaps in knowledge is possible.

In seeking to understand this phenomenon, I have sought insights from a wide range of intellectual disciplines, eventually settling on the field of molecular biology, given the rapidly growing expectation that all health related phenomena be explained at the genome or molecular level. This work has led to the discovery of a potential explanation for the massive amount of uncertainty in healthcare and, more importantly, some insights regarding possible strategies to improve the quality and relevance of future primary research. My observations are shown in the figure⇓ as the “molecular basis of uncertainty.”

The molecular basis of uncertainty: a subcellular hypothesis to explain widespread gaps in evidence identified by systematic reviews. An earlier version of this diagram appeared in Asian Hospital and Healthcare Management (issue 19, 2009)

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The figure⇑ illustrates the flow of information from the extracellular environment of the clinical research enterprise to the intracellular milieu in which decision makers are generally confined. New scientific activities by clinical and health services researchers have generally been prompted by intellectual curiosity, often with limited awareness of or interest in the realities of the intracellular conditions that influence decision makers. Most of the resulting evidence moves slowly in the direction of decision makers through the cell membrane by passive diffusion, a process labeled “knowledge translation 1,” which is an energy consuming, inefficient pathway that contributes to the lengthy time lag between the publication of new evidence and the effect of that evidence on practice.2 The speed of translation can sometimes be increased through an active transport mechanism involving the systematic collection and analysis of scientific evidence by health technology assessment organizations (via knowledge translation 2—a pathway first demonstrated in a laboratory at Johns Hopkins). However, the efficiency of information transfer is significantly reduced after knowledge translation 2 by the presence of the low affinity receptors for evidence surrounding the decision makers, a phenomenon sometimes referred to as the “knowledge translation blockade,” and the focus of study in the field of implementation science.3

In addition to accelerating evidence transfer toward decision makers, the health technology assessment process produces a critically important intermediate byproduct—a detailed characterization of the gaps in evidence highlighted by the body of evidence reviewed. Several high priority research questions are generally identified in these reports, along with a description of the common methodological deficiencies that reduce their utility for decision making.4 Unfortunately, the communication of these research needs and methodological recommendations through the cell membrane and back to the clinical research enterprise is severely impaired by defective transport at knowledge translation 3. The failure to communicate these knowledge gaps back to the evidence generating community leads to the gradual accumulation of ignorance inside the cell, resulting in a toxic environment that may lead eventually to cell death.

It has not escaped my notice that the specific pathways I have postulated immediately suggest several potential mechanisms to improve the quality and relevance of future primary research.5 Above all, a need exists to identify targeted interventions that promote greater flow of information between clinical and health policy decision makers and the clinical research enterprise, ideally retaining some element of intellectual curiosity. The health technology assessment program at the National Institutes of Health has recognized the importance of the knowledge translation 3 pathway for the past 20 years.6 More recently, a dedicated research program in the United States has begun to focus substantial attention and resources to facilitate cross membrane signaling at knowledge translation 3, with an emphasis on direct involvement of patients in this process.7