Evidence-Based Emergency MedicineTen Challenges at the Intersection of Clinical Research, Evidence-Based Medicine, and Pain Relief*,**
Introduction
Pain arguably is the best studied of all symptoms. There is a rich tradition of pain relief research spanning the past 40 years. Luminaries of the field including, among others, Henry Beecher, Louis Lasagna, Ray Houde, and Stanley Wallenstein, laid down explicit rules about the design and conduct of pain trials.1 During the second half of the 20th century, the number of randomized controlled trials (RCTs) evaluating analgesic interventions doubled every 10 years.2 In January 2000, we searched the Cochrane Controlled Trials Register, the largest collection of clinical trials in the world, and found that “pain” or “analgesia” is mentioned in more than 23,000 citations of RCTs (almost 9% of the total).
Of the many methods to evaluate analgesic interventions, RCTs are a very powerful and simple tool. A special value of RCTs in pain relief is their ability to minimize the confounding effects of unknown factors that may influence patients’ responses. In addition, analgesic trials help account for specific issues such as patient and practitioner expectations, the source of funding, and the placebo response. RCTs enroll patients or healthy volunteers who receive one intervention or another (the “control”) by random assignment. Prospective, double-blinded RCTs are a powerful technique to reduce bias in clinical trials, particularly pain relief trials in which suggestibility and placebo effects may distort the findings.
New methods, derived from clinical epidemiology and using RCTs as their “raw materials”,1 are also evolving. These methods include systematic reviews and meta-analysis and are based on the rigorous search for all evidence and the systematic and quantitative analysis of research. Yet despite the abundance of RCTs and systematic reviews regarding pain relief practices, the actual transfer of research evidence into clinical practice can be slow. Evidence-based decisionmaking is one way that can help ensure that the information coming from research will be considered and, if appropriate, incorporated with reasonable speed into decisions.3 Dealing with the abundance of RCTs and the increasing number of systematic reviews in pain relief creates numerous challenges for researchers, clinicians, funding agencies, ethics boards, journal editors, and the public.
This article, which explores the intersection of evidence-based medicine with pain relief practice and research, reviews 10 challenges regarding analgesic clinical trials and the translation of pain relief evidence into clinical practice. In addition, strategies, drawn on a more general discussion of the future of RCTs,4 for meeting these challenges will be proposed.
Section snippets
Challenge 1: To avoid unnecessary duplication of effort
Before embarking on a new trial, researchers, patients, and funding agencies should be confident that the question addressed by the trial has not been answered already. Given the abundance of trials, 2 strategies could accomplish this efficiently: systematic reviews of the literature, and an international register of ongoing trials.
Challenge 2: To use all existing trials to guide clinical decisions
Frequently, more than one trial has addressed the same clinical question. Because these trials enrolled different groups of people, in different settings, and used the interventions differently, it is unlikely that they would all agree. Sometimes, trials on the same topic yield opposite results. Thus, it may be risky for clinicians or patients to make decisions based on a single trial. To take advantage of the best available knowledge, decisionmakers should consider as many relevant trials as
Challenge 3: To improve the quality of RCTs in pain relief
The following are examples of efforts needed to improve the usefulness of RCTs.
Challenge 4: To improve the quality of reporting of RCTs
RCTs in all areas of health care are reported incompletely, and pain trials are no exception.15 Most reporting problems could be eliminated if all journals that published pain relief research, funders, and researchers endorsed and embraced the CONSORT statement.16, 17, 18 Although more than 70 journals including the Annals of Emergency Medicine endorse the CONSORT statement, many journals devoted solely to pain research still do not. The CONSORT statement, the product of an extensive
Challenge 5: To find better ways to present the results of trials to frontline users
If RCTs are to influence decisions on the treatment of pain, better dissemination of their findings is required. Written by researchers for other researchers, most reports of RCTs are unpalatable to clinicians, patients, journalists, policymakers, and other audiences. Although narrow targeting may be appropriate for preliminary results, it should be avoided when a trial answers a clinically important question. The separation of research-oriented and clinician-oriented journals would be a good
Challenge 6: To ensure that all RCTs, once completed, are promptly available to the users
Trials have little value, even when perfectly designed, conducted, and reported, if they are not available to users. Delays in releasing research findings can have harmful effects, especially if trials with positive results are published years before those with negative results.26 Ensuring that all trials, regardless of whether findings are positive or negative, are published soon after completion will reduce publication bias and time lag bias.9
We should educate patients to demand publication
Challenge 7: To ensure that decisionmakers understand RCTs
Even if RCTs were perfectly designed and their results readily available, they could not influence health care decisions and outcomes if users could not understand them. Most people still do not understand the concept of randomization and its strengths, the sources of bias in RCTs, and the role of RCTs in health care decisionmaking. Most efforts to promote the understanding of RCTs (and of research in general) focus on researchers, particularly those in training. Little has been done to promote
Challenge 8: To integrate the findings of clinical trials with information from other types of research
Researchers, clinicians, funding agencies, and policymakers tend to place RCTs at the top of the evidence hierarchy, assuming that such trials are always better than other study designs. Although this hierarchy may be valid in theory, it may in practice be inappropriate because it is incorrect to give more weight to a flawed RCT than to a rigorous observational study (eg, a cohort study). Furthermore, RCTs are just one type of research design. Clinical decisions should take into account other
Challenge 9: To balance the findings of clinical research with other ways of knowing
Over thousands of years, human beings have developed powerful but nonscientific ways of knowing. These “hard-wired” primal knowledge tools still have a profound effect on all the decisions we make in our everyday lives, as well as on the health care we advocate, practice, or receive. They include anecdotes, rules of thumb, and tacit knowledge.30, 31 Efforts to increase our understanding of RCTs and other types of research in pain relief should be coupled with efforts to understand those other
Challenge 10: To balance the findings of clinical trials with our values, preferences, and circumstances
Research information is modulated, not only by other types of information, but also by the values and preferences of all the decisionmakers involved and the specific circumstances in which most decisions are made.23 Our efforts to understand the role of values, preferences, and circumstances should be extended beyond the individual level. We also need a better understanding of the dynamics of collaborative decisionmaking (ie, between nurses and physicians, pharmacists and hospital
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Editor’s Note:This article is based on an original article that appeared in the Summer 1999 edition of the newsletter Pain: Clinical Updates, published by the International Association for the Study of Pain (IASP). The original newsletter article has been modified and updated for Annals of Emergency Medicine. We gratefully acknowledge the support of Daniel B. Carr, MD, (newsletter editor), and Louisa E. Jones (IASP) for allowing us to use and revise the original article.
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Reprints not available from the authors. Address for correspondence: Alejandro R. Jadad, MD, DPhil, Department of Clinical Epidemiology and Biostatistics, McMaster University, HSC-3H7, 1200 Main Street West, Hamilton, ON L8N 3Z5 Canada; 905-525-9140; E-mail: [email protected].