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Interpreting and Using the Literature: Integrating Evidence-Based Trials with Real-World Practice
All things are subject to interpretation. Whichever interpretation prevails at a given time is a function of power and not truth.
Many of the groups… are far too small to allow of any definite opinion being formed at all, having regard to the size of the probable error involved.
▢ When reading a clinical trial, be able to describe the characteristics of the group being studied, and recognize ways in which they may be comparable or dissimilar to other types of patients (such as those whom you treat) before generalizing findings to a wider potential treatment group
▢ Recognize whether a study was purposefully designed from the outset to evaluate the outcome measures being reported, or whether reported findings are secondary and thus only provisional and hypothesis-generating, rather than hypothesis-testing
▢ Understand the importance of sample sizes and adequacy of statistical power, prospective versus retrospective designs, post hoc analyses, correction of statistical significance levels for multiple comparisons, noninferiority trials, how to interpret confidence intervals, sample enrichment, attrition, failed versus negative trials, and the difference between p-values (statistical significance) and effect sizes (clinically meaningful differences)
▢ Appreciate why the concept of randomization is often referred to as the “great equalizer” in clinical trials methodology (and why nonrandomized trials yield far less compelling data than randomized trials)
When investigators report the findings from a clinical trial, the results require interpretation. Peer review is the process through which the structure and execution of a clinical study is judged to be coherent, linear, and logical. The procedure is not unlike conducting a mental status exam: the evaluator is trying to discern if the content is credible at face value, if any underlying factors that could be biasing the results are accounted for, if the observed phenomena are being interpreted accurately, and if the conclusions drawn are valid. With varying degrees of provisionality or certainty, clinical trials give information about the narrow impact of (usually) one intervention versus a comparator (a placebo; an active comparator; or treatment as usual (TAU)) for a circumscribed period of time, with efforts made to hold other relevant variables constant (so, no other treatments are begun or altered, adherence must be near-perfect, substance use is grounds for ejection, and major life disruptions could botch the findings).
Clinicians trying to interpret the literature1 rely on the rigor of peer review and editorial filtering when judging if a finding is “ready for prime time” implementation, or more just an interesting idea or observation that needs further beta-testing and elaboration before it should be taken up into everyday practice. They must also judge how results obtained from a carefully controlled environment using hand-picked cases will translate into less meticulously structured treatment settings.
There is no shortage in the marketplace of simplified digests, newsletters and distillations of current literature that promise to boil down detailed research efforts into a single authoritative soundbite – helpful for gaining quick headline summaries, but also running the risk of equating a “Cliff Notes” version of a novel to actually reading and understanding the novel itself.2 For the sake of gaining up-to-date knowledge and true expertise, there is really no shortcut to searching, understanding, and applying the primary literature. Therefore, our aim in this chapter is to equip clinician-readers with the tools they need to assess for themselves the claims made by a clinical trial using the same kind of critical, forensic mindset they would apply to the self-reported history of a potentially complex patient during a clinical encounter.
As noted in Chapter 1, varying levels of rigor define the strength of evidence with which an intervention is supported, refuted, or unknown. Large, adequately powered, prospective, randomized, placebo-controlled trials that have been sufficiently replicated provide the most confident information about likely outcomes when a particular treatment is undertaken for a specific ailment. Smaller, underpowered, open-label, nonrandomized trials, case series, or anecdotal observations provide proof-of-concept data that can generate tentative hypotheses that must then be tested more extensively in a-priori-designed large-scale trials. The latter can then yield more definitive conclusions about the appropriateness and expectable effects of an intervention, strengthening the basis for its uptake into clinical practice.
Sourcing the empirical literature directly is the most scientific way a clinician can determine for himself or herself whether a candidate treatment for a particular ailment is evidence-based, and how well an existing evidence base may apply to a specific individual patient (as opposed to just a diagnosis, with no contextual information). Electronic database search engines such as MEDLINE, Ovid, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, PsycLIT, and Science Citation Index Expanded place access to the empirical literature literally at one’s fingertips. Do-it-yourself online searches not only allow anyone to find the most up-to-date information, but perhaps even more importantly, enable highly tailored searches and types of studies by specifying relevant search terms (for example, “stroke” + “depression” + “cancer” + “stimulant” + “randomized trial”).
To fully appreciate any given evidence base, let us now consider in greater detail the factors that make clinical trial designs and findings interpretable and comprehensible.
1 We differentiate the published peer-reviewed literature from the so-called “gray literature,” comprising scholarly works that have not been formally published in peer-reviewed journals, such as dissertations, conference proceedings, technical reports, and government reports (described further at www.opengrey.edu).
2 For those seeking a compromise between original source reports and a third party’s critical commentary, we would encourage readers to visit a website sponsored by the National Institute for Health Research and available through the Library of Medicine from the National Institute of Health, called the Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews. Devised and maintained by the Centre for Reviews and Dissemination (CRD) at the University of York, UK, the DARE site provides not only cogent summaries of published reports, but also appraises their quality, highlighting methodological strengths and weaknesses (www.crd.york.ac.uk/CRDWeb/).