Clinical Trials

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❘❙❚■ Chapter 37 | Critical Appraisal of a Report9. What are the implications of the study results and discussion?In the discussion section of the article, readers should expect to find a balancedinterpretation of the results, taking into account any previous work. A guide tothe format of a submission of a clinical trial is shown in Table 2. The biologicalplausibility of the results should be addressed, along with the impact on currentmedical practice. Although the authors will offer their interpretation of the data, thereader must draw their own conclusions about the importance and impact of theresults compared with conventional treatment strategies. A significant report maylead to changes in guidelines, but this usually requires either a very large definitivestudy or at least two large independent trials supporting the same conclusion.The conclusions of the publication might be biased or restricted in commerciallyfunded studies. Major journals have guidelines for the disclosure of industry’s rolein a clinical trial. These guidelines require the authors to disclose full details oftheir role (and the sponsors) in a study. Some journals insist that the responsibleauthor sign a statement indicating that he or she accepts full responsibility for theconduct of the trial, has had full access to the data, and has control of the decisionto publish, independent of the commercial sponsors funding the work [14].10. What were the limitations of the study?Having decided to read the full study manuscript, it is essential to appreciatethe limitations of a study. Indeed, most discussions with peers about a recenttrial report are won by the person who understands the flaws of a study, inaddition to the positive implications. The authors of a study are usually aware ofmost of their study’s limitations, but often they will only write about those that canbe defended. While these are valid tactics, the best investigators will discuss all thelimitations and recommend how future studies should be conducted to overcomethese. Some limitations are inherent to most studies – such as the phenomenonthat most participants in a trial are generally healthier as a result of exclusioncriteria – and so the ability of study results to be generalized should also bediscussed. A balanced discussion suggests the mark of careful and considerateclinical scientists and researchers, and lends the overall report more credibility.ConclusionInevitably, there is far more information being published then can be read andcommitted to memory. It is therefore natural to restrict our focus to titles relevantto our own work. For these titles, we scan the abstract and decide whether to read436
Clinical Trials: A Practical Guide ■❚❙❘the full paper. Mental notes can then be made about the number of patientsenrolled, the duration of follow-up, and the dose of the new therapy being tested.With a little more effort, a few more points can also be easily gleaned, allowinga more considered evaluation of the significance of a clinical trial report, which inturn might make the results more memorable.References1. Altman DG, Schulz KF, Moher D, et al. The revised CONSORT statement for reportingrandomized trials: explanation and elaboration. Ann Intern Med 2001;134:663–94.2. Moher D, Schulz KF, Altman DG, et al. The CONSORT statement: Revised recommendationsfor improving the quality of reports of parallel-group randomized trials. JAMA 2001;285:1987–91.3. Greenhalgh T. Assessing the methodological quality of published papers. BMJ 1997;315:305–8.4. Critical Appraisal Skills Programme Website, Learning and Development Public Health ResourceUnit. Available from http://www.phru.nhs.uk/casp/casp.htm. Accessed March 23, 2005.5. Joseph KS. Quality of impact factors of general medical journals. BMJ 2003;326:283.6. Pocock SJ, Hughes MD, Lee RJ. Statistical problems in the reporting of clinical trials.A survey of three medical journals. N Engl J Med 1987;317:426–32.7. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT-LLT). Major outcomes in moderately hypercholesterolemic, hypertensive patientsrandomized to pravastatin vs. usual care. JAMA 2002;288:2998–3007.8. Morrison DA, Sethi G, Sacks J, et al. Percutaneous coronary intervention versus coronary arterybypass graft surgery for patients with medically refractory myocardial ischemia and risk factors foradverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department ofVeterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative MortalityEvaluation (AWESOME). J Am Coll Cardiol 2001;38:143–9.9. Morrison DA, Sethi G, Sacks J, et al. Percutaneous coronary intervention versus coronary bypassgraft surgery for patients with medically refractory myocardial ischemia and risk factors for adverseoutcomes with bypass. The VA AWESOME multicenter registry: Comparison with the randomizedclinical trial. J Am Coll Cardiol 2002;39:266–73.10. Pocock SJ. Clinical Trials: A Practical Approach. Chichester: John Wiley & Sons, 1983.11. Olson CM, Rennie D, Cook D, et al. Publication bias in editorial decision making.JAMA 2002;287:2825–8.12. Simoons ML on behalf of the GUSTO Investigators. Effect of glycoprotein IIb/IIIa receptorblocker abciximab on outcome in patients with acute coronary syndromes without early coronaryrevascularisation: the GUSTO IV-ACS randomised trial. Lancet 2001;357:1915–24.13. Wang D, Bakhai A. Practical issues in trial design. Part 7: Choosing the right sample sizefor a randomized controlled trial. Clinical Researcher 2001;1(6):36–9.14. International Committee of Medical Journal Editors. Uniform requirements for manuscriptssubmitted to biomedical journals. Ann Intern Med 1997;126:36–47.15. Agency for Healthcare Research and Quality. Guide to clinical preventive services.3rd edition. 2000–2003. Report of the US Preventive Services Task Force. Available from:http://www.ahrq.gov/clinic/cps3dix.htm. Accessed March 23, 2005.437
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❘❙❚■ ContributorsStephen L
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Clinical Trials: A Practical Guide
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■■❚❙❘Part IVSpecial Trial
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