Randomized controlled trials criticisms

Cochrane Library. The Cochrane Library [44] includes The Cochrane Database of Systematic Reviews, a collection of regularly updated, systematic reviews of the effects of health care. It is maintained by contributors to the Cochrane Collaboration. Cochrane reviews are reviews mainly of randomized controlled trials. To minimize bias, evidence is included or excluded on the basis of explicit quality criteria. Data are often combined statistically, with meta-analysis, to increase the power of the findings of numerous studies, each too small to produce reliable results individually. Database of Abstracts of Reviews of Effectiveness is also included. It consists of critical assessments and structured abstracts of good systematic reviews published elsewhere. The Cochrane Controlled Trials Register with bibliographic information on controlled trials and other sources of information on the science of reviewing research and evidence-based health care are part of the Cochrane Library. It is commercially available on CD-ROM or the Internet. 

Three hundred critically-ill septic adults were enrolled in a randomized controlled trial of severe sepsis within 12 hours of diagnosis. Subjects were randomized... 

In a randomized controlled trial conducted by Nemoto et al, 98 patients were assigned to either conventional treatment or PMX B (Nemoto et al., 2001). The overall survival was significantly better in the treated group. When looking at subgroups, the authors concluded that this therapeutic approach was more likely to improve survival when applied earlier in sepsis. One criticism of this conclusion is that the subgroups contained a low number of patients to make a definitive statement in this regard. 

Kuperman GJ, Teich JM, Tanasijevic MJ, Ma Luf N, Rittenberg E, Jha A et al. Improving response to critical laboratory results with automation Results of a randomized controlled trial. J Am Med Inform Assoc 1999 6 512-22. 

However, the validity of these findings has been questioned, because some papers chosen for meta-analysis by the Cochrane group were suggested to have been incorrectly included (14,15). The results obtained from the meta-analysis have also been challenged by another meta-analysis of albumin administration in critically ill patients, which showed no increased risk in mortality (16). This illustrates the need for high-quality, randomized, controlled trials to generate definitive evidence. 

In July 1998, The Cochrane Injuries Group Albumin Reviewers published a meta-analysis comparing the use of albumin with the use of crystalloids or no treatment in critically ill patients (12). The review was based on 30 randomized, controlled studies, involving a total of 1419 patients with hypovolemia due to trauma, surgery, burns, or hypoalbuminemia. There was excess mortality in the albumin group of about 6%, and the authors concluded that albumin should not be used outside rigorously conducted randomized controlled trials. The review elicited numerous mostly critical comments. For example, it was commented that a meta-analysis is not exact and that in this specific studythe study had conflated three separate indications that were not comparable (5). 

Chalupa P, Atherstone A, Penzes I, Kubler A, Knaub S, Keinecke HO, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM KyberSept Trial Study Group. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis a randomized controlled trial. JAMA... 

The Cochrane Collaboration is named after Archie Cochrane, a British epidemiologist. He emphasized that the effectiveness of healthcare interventions should be based on evidence from randomized controlled trials. He argued that evidence-based healthcare could encourage the wise use of resources. Cochrane also recognized that people who want to make informed decisions about healthcare did not have access to reliable reviews of the available evidence when in 1979, he wrote It is surely a great criticism of our profession that we have not organized a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomized controlled trials. ... 

There are two levels of criticism applied to evidence-based medicine. The first relates to the widespread dependence on the randomized controlled trial, and the second relates to the patient-population dichotomy. 

Other critics state that EBM considers randomized, controlled trials (RCTs) as the only evidence to be used in clinical decision making. AcmaUy, EBM seeks the best existing evidence from basic science to clinical research with which to inform clinical decision. For example, a decision about the accuracy of a diagnostic test is best informed by evidence from a cross-sectional study, not an RCT. A cohort study, not an RCT, best answers a question about prognosis. However, in selecting a treatment, the randomized trial is the best study design to provide the most accurate estimate of treatment efficacy and safety. 

Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients Systematic review of randomized controlled trials. BMJ 1998 317 235-240. 

Gomersall CD, Joynt GM, Freebairn RC, et al. Resuscitation of critically ill patients based on the results of gastric tonometry A prospective, randomized, controlled trial. Crit Care Med 2000 28 607-614. 

The pathophysiology of anemia of critical illness would lead to the hypothesis that treatment with pharmacologic doses of EPO might be beneficial. Few randomized, controlled trials have evaluated the role of EPO in critically ill patients, and these have resulted in mixed findings regarding EPO s ability to decrease transfusion requirements. A recently published literature review found that EPO cannot be recommended to reduce the need for RBC transfusions in critically ill patients with anemia. Even though EPO administration... 

Critical reviews of available randomized controlled trials comparing EN to PN in the critically ill adult patient with an intact GI tract suggest a significant reduction in infectious complications associated with EN. Decreased infectious complications have been documented in patients with abdominal trauma, burns, or severe head injury given EN compared to PN. The use of EN has been recommended over PN as the preferred route of feeding in the critically ill patient requiring specialized nutrition support. ... 

Strong evidence supports the natural idea that recanalization of the occlusion and resulting tissue reperfusion translate into improved clinical outcomes (Fig. 12.4) [6, 9, 10]. While there is no randomized controlled trial data comparing lAT and intravenous therapy for PAO, multiple studies demonstrate improved rates of revascularization with lAT [6,11-13]. The promise of endovascular stroke therapy has led to the recent emergence of multiple stroke devices. Prospective, industry-sponsored trials of these devices have utilized reperfusion as their primary endpoint [6, 14, 15]. However, there is growing criticism of this emphasis on revascularization in lieu of clinical outcome [16,17]. Indeed, the clinical success of the endovascular approach is highly variable for incompletely understood reasons. 

Lu, D., Chen, B., Liang, Z., Deng, W., Jiang, Y., Li, S., Xu, J., Wu, Q., Zhang, Z., Xie, B., Chen, S. Comparison of hone marrow mesenchymal stem cells with hone marrow-derived mononuclear cells for treatment of diabetic critical hmh ischemia and foot ulcer A douhle-hUnd, randomized, controlled trial. Diahetes Research And Clinical Practice 92, 26—36 (2011)... 

Jones C, Skirrow P, Griffiths RD, et al. Rehabilitation after critical illness a randomized, controlled trial. Grit Care Med 2003 31 2456-2461. 

Apte NM, Karnad DR, Medhekar TP, Tilve GH, Morye S, Bhave GG. Gastric colonization and pneumonia in intubated critically ill patients receiving stress ulcer prophylaxis a randomized, controlled trial. Crit Care Med 1992 20 590-593. 

Beraprost is a stable, orally active analogue of PGI2. It has been tested in patients with intermittent claudication in a randomized, placebo-controlled trial (1). Beraprost improved walking distance more often than placebo. It also reduced the incidence of critical cardiovascular events, but the trial was not powered for statistical validation of this effect. As with iloprost, headache and flushing were the most common adverse effects. 

Corwin HL, Gettinger A, Rodriguez RM, Pearl RG, Gubler KD, Enny C, Colton T, Corwin MJ. Efficacy of recombinant human erythropoietin in the critically ill patient a randomized, double-blind, placebo-controlled trial. Crit Care Med 1999 27(ll) 2346-50. 

---