The challenges in producing high-quality clinical evidence

In 1996, David Sackett opined that ‘‘Evidence-based medicine [EBM] means integrating individual clinical expertise with the best available external clinical evidence from systematic research’’. Clinicians, educators, investigators, and administrators seeking to improve clinical care have adopted these tenets, and now, EBM fuels activities that aim to produce high-quality clinical evidence. The adoption of EBM has resulted in an ever expanding number of best practice guidelines, pay for performance rules, and/or public policies. Sadly for perioperative medicine, this process of research, knowledge translation, and the resultant changes to the perioperative evidence base has not yielded the types of clinical improvements that many would have predicted. There are various explanations for these failures, but in my opinion, the blame lies mostly in our research methodology. Improving the quality of clinical investigation requires more than just a process of randomization. We are challenged to conduct efficient, expedient, and adequately powered trials, pursuing biologically sound hypotheses that enhance clinically important, clearly defined, outcomes. While the ideal of EBM is highly promoted, in practice, there are numerous obstacles. The biggest problem is classic economics; demand exceeds supply. The notion that each clinical question, of which there are too many to count, can be answered by a meta-analysis and/or systematic reviews of multiple randomized controlled trials (RCTs) is naive. In fact, there are only a few examples of studies in perioperative medicine that lead to the highest quality recommendations. Our failures are examples where clinical recommendations were based on information that was prone to any number of biases. The challenge now is to produce quality evidence. The RCT has become synonymous with unbiased evidence. Nevertheless, the ability to generate and reproduce a high-quality RCT is constrained by a second economic reality, funding. Funding is a constant impediment that limits perioperative clinical research and thus hinders EBM. The need for multidisciplinary personnel, infrastructure, increasing layers of bureaucracy, privacy issues, and the time to complete studies has added to the costs of conducting any study. At the same time, the amount of peer-reviewed funding available to Canadian investigators is stagnant or decreasing. Another aspect of the escalating expense for research is the realization that, to pursue clinically important outcomes, interventional trials require study samples large enough to capture meaningful and reproducible differences; often a trial will require several thousand patients. In Transforming Clinical Research in the United States: Challenges and Opportunities, it has been estimated that global interventional trials can cost more than 300 million dollars. In truth, this number overestimates the costs of recent perioperative trials by over 20 fold, but costs will continue to increase and trial opportunities must be optimized. This special edition of the Journal acknowledges an important step in this direction, a discussion to define clinically important and patient-centred outcomes. Meta-analysis of well-conducted RCTs is promoted as the pinnacle of evidence, in other words, findings that are reproducible. Future meta-analyses will be stronger when every trial pursues a set of universally accepted outcomes. W. S. Beattie, MD, PhD (&) Department of Anesthesia, University Health Network, University of Toronto, Toronto, ON, Canada e-mail: scott.beattie@uhn.ca