How powerful is the evidence generated by different clinical trials?

20160909080000, Mak Wen Yao 
How powerful is the evidence generated by different clinical trials?
How powerful is the evidence generated by different clinical trials?
Healthcare professionals often rely on findings from clinical trials to provide critical information for their daily practice. Often times, however, this information may not be entirely appropriate to apply on patients.

Evidence-based medicine gaining popularity

It is critical to consider the level of evidence generated by various different trials when making any clinical decisions based on these outcomes. The practice of evidence-based medicine (EBM) is slowly gaining popularity, and the cornerstone of EBM is “the hierarchical system of classifying evidence” (1).

To comprehend the level of evidence, healthcare professionals should start by understanding the origin of such a concept. It was first described by the Canadian Task Force on the Periodic Health Examination in 1979. The task force was formed to investigate if periodic health examination would enhance or protect the health of the Canadian population, and it attempted to grade recommendations based on available evidence from the literature. They ranked the effectiveness of evidence in from I (at least one proper randomised control trial) to III (Expert opinions), in addition to grading the recommendation from A to E (2).

The hierarchy was based on the probability of biases being introduced into the process of generating evidence. It held randomised controlled trials (RCT) as the highest quality as these studies were designed to minimise the risk of errors and biases. Expert opinions were regarded as the lowest quality as these were most likely to be affected by various factors, and were expected to influence the authors' personal experience and conflict of interests in addition to the lack of control over these factors.

Randomised controlled trials not representative of the big picture

It is worth noticing that, in many instances, RCT may not represent the best quality evidence which health care professionals can refer to. There are many factors that may render the findings from an RCT incorrect, such as poor study design or small sample size. Recent studies also revealed that clinical studies sponsored by pharmaceutical companies were most likely to report favourable findings (3). This is the pitfall which many junior pharmacists may not be aware of, and it poses a good deal of danger when they provide recommendations to their colleagues.

Systematic critical appraisal yields better evidence

Systematic critical appraisal of all available evidence generated from different RCT may yield better evidence with reduced risk of bias. In the late 1970s and early 1980s, a group of Oxford health service researchers began the movement to systematically review the effectiveness of health care interventions. Their work eventually transformed into the Cochrane Collaboration (4). Clinical findings synthesised via systematic reviews of RCT provides the highest level evidence, and confer more impact to clinical practice compared to a single randomised controlled trial.

It is equally important to realise that the type and level of evidence is different according to different specialities. The type of studies that are most suitable to provide quality evidence to answer research questions in treatment, prognosis and diagnosis are different. For example, prognostic studies are "studies that examine selected predictive variables or risk factors and assess their influence on the outcome of a disease" (5). In this case, a cohort study or a systematic review of cohort studies will provide better evidence compared to RCT (1). MIMS

1. Burns PB, Rohrich RJ, Chung KC. The Levels of Evidence and Their Role in Evidence-Based Medicine. Plast Reconstr Surg. 2011 Jul;128(1):305–10.
2. Spitzer W, Bayne J, Charron K, Fletcher S, Frapper-Davignon L, Goldbloom R, et al. The periodic health examination. Canadian Task Force on the Periodic Health Examination. Can Med Assoc J. 1979;121(9):1193–254.
3. Lundh A, Sismondo S, Lexchin J, Busuioc OA, Bero L. Industry sponsorship and research outcome. In: Lundh A, editor. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2012.
4. ePPI Centre. History of systematic reviews [Internet]. ePPI Centre. 2015 [cited 2016 Aug 28]. Available from:
5. Mak K, Kum CK. How to Appraise a Prognostic Study. World J Surg. 2005 May 28;29(5):567–9.

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