Clinical Trials

❘❙❚■ Chapter 37 | Critical Appraisal of a Reportwere removed from analysis in one group than the other. In randomized trials,outcomes should be compared among groups based on the original treatmentassignment rather than based on the treatment received, as results from strategiesother than intention-to-treat analysis are subject to potential bias.Confounding is another factor that can contribute to the observed treatmentdifference in an outcome variable. Confounding occurs when a baselinecharacteristic (or variable) of patients is associated with the outcome but unevenlydistributed between treatment groups. As a result, the observed treatment differencefrom the unadjusted (univariate) analysis can be explained by the imbalanceddistribution of this variable. When reading a report, the most useful way to detectpossible confounding factors is to examine the distribution of baseline characteristicsby treatment group, to assess if the treatment groups are comparable.6. Are negative trials worth reading in detail?A negative clinical trial is one in which the observed differences are not largeenough to satisfy a specified significance level (usually a P < 0.05 threshold), sothe results are declared to be statistically nonsignificant. The tendency to deferpublication of a negative trial creates so-called publication bias, with morepositive-result studies being published. Studies that have yielded disappointing ornegative results are less likely to be presented at scientific meetings, publishedpromptly, or published in high-impact journals.This reporting bias can imply that medical treatments are more useful than theyreally are. Despite evidence identifying investigators as the main cause ofpublication bias, investigators continue to claim that editorial bias is the mainreason for nonpublication of negative or null results, and that this is why theydo not submit negative findings. However, a study examining publication decisionsfor reports of controlled trials in JAMA found little evidence of a positivepublication bias in that journal [11].Thus, leading editors have an interest in publishing well-conducted negative orneutral trials. For the reader, it now becomes important to know not only whichtherapies benefit the management of certain diseases, but also those that do not.An example of a negative trial changing practice was the GUSTO-IV (Global Useof Strategies to Open Occluded Coronary Arteries) study [12]. This trial showedthat abciximab therapy did not confer benefit on patients with acute coronarysyndromes not needing urgent coronary investigations. Prior to this study,abciximab had been shown to be beneficial for almost all acute coronary syndromepopulations, but GUSTO-IV showed that there was an increase in bleeding432