Question 8(p.2)

What are the strengths and weaknesses of the randomised control trial study design?

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College Answer

This question would best be answered by listing the relative merits and drawbacks of the
study design, with elaboration on the subjects of treatment allocation, randomisation to
eliminate selection bias, the need for adequate sample size to achieve power and a discussion
of the logistics of conducting multi-centre trials. Additional marks were awarded for
discussion of blinding, prospective design, “efficacy versus effectiveness” trials, applicability
and ethical considerations. The need for “equipoise” as a pre-requisite for randomisation in a
clinical trial was not discussed by candidates. Definition of Type I and Type II errors and the
relative merits of this study design in avoiding these errors required more detailed discussion.

Syllabus EBM 2.b, d, e;

Referrence: Statistical Methods for Anaesthesia and Intensive Care (Chapter 4), Myles and
Gin.

Discussion

Unlike the college answer to Question 6 from the first paper of 2014, the commentary here is actually useful to the revisiing candidate. Particularly helpful is the text reference. That chapter from Myles and Gin is still not as good as the LITFL page on randomised controlled trials, which offers an excellent breakdown of what would be relevant to a good detailed answer.

So:

Advantages of randomised control trial study design:

Comparative:
- One treatment is directly compared to another to establish superiority.
- This study design can make causal inferences, i.e. it is the strongest empirical evidence of a treatment's efficacy
Minimises bias:
- Randomisation minimises allocation bias and selection bias
- Blinding minimises performance bias
- Double-blinding minimises assessment bias
- Allocation concealment minimises both performance and assessment bias\
- Prospective design minimises recall error and selection bias
Minimises confounding factors:
- Randomisation minimises confounding due to unequal distribution of prognostic factors
- Randomisation makes groups comparable according both known and unknown factors
- Blocked randomisation makes groups comparable within known confounding factors
Statistical reliability
- Statistical test of significance is readily interpretable when the study is randomised
- Sample size - when adequately powered- avoids both Type 1 error (where the null hypothesis is incorrectly rejected) and Type 2 error (where the null hypothesis is incorrectly accepted)
Publishable
- Considered the gold standard: more publishable

Disadvantages of randomised control trial study design

Logistics:
- Power calculation might demand vast samples size, which require more resources from the investigators
- Validity requires multiple sites, which will be difficult to manage
- Long trial run time may result in the loss of relevance as practice may have moved on by the time the trial is published
Statistics
- A disadvantage of block randomization is that the allocation of participants may be predictable and result in selection bias when the study groups are unmasked
Applicability
- Trials which test for efficacy may not be widely applicable. Trials which test for effectiveness are larger and more expensive
- Results may not always mimic real life treatment situation (e.g. inclusion / exclusion criteria; highly controlled setting)
Ethical limitations
- Randomisation requires clinical equipoise: one cannot ethically randomise patients unless both treatments have equal support in the clinical community
- Informed consent is often impossible
- Some research cannot be ethically performed as an RCT (classically, RCT of the effects of parachutes on the survival of sky-divers)

References

Statistical methods for anaesthesia and intensive care (P S Myles, T Gin - 1^st ed - Oxford : Butterworth-Heinemann, 2001)

Ospina-Tascón, Gustavo A., Gustavo Luiz Büchele, and Jean-Louis Vincent. "Multicenter, randomized, controlled trials evaluating mortality in intensive care: doomed to fail?." Critical care medicine 36.4 (2008): 1311-1322.

Smith, Gordon CS, and Jill P. Pell. "Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials." BMJ: British Medical Journal 327.7429 (2003): 1459.

Vincent, Jean-Louis. "We should abandon randomized controlled trials in the intensive care unit." Critical care medicine 38.10 (2010): S534-S538.

Hébert, Paul C., et al. "The design of randomized clinical trials in critically ill patients." CHEST Journal 121.4 (2002): 1290-1300.

Jadad, Alejandro R., and Murray Enkin. Randomized controlled trials: questions, answers, and musings. Blackwell Pub., 2007.

Walker, Wendy. "The strengths and weaknesses of research designs involving quantitative measures." Journal of research in nursing 10.5 (2005): 571-582.

Sanson-Fisher, Robert William, et al. "Limitations of the randomized controlled trial in evaluating population-based health interventions." American journal of preventive medicine 33.2 (2007): 155-161.

Levin, Kate Ann. "Study design VII. Randomised controlled trials." Evidence-based dentistry 8.1 (2007): 22-23.

Efird, Jimmy. "Blocked randomization with randomly selected block sizes." International journal of environmental research and public health 8.1 (2010): 15-20.

Stang, Andreas. "Randomized controlled trials—an indispensible part of clinical research." Deutsches Ärzteblatt International 108.39 (2011): 661.

Singal, Amit G., Peter DR Higgins, and Akbar K. Waljee. "A primer on effectiveness and efficacy trials." Clinical and translational gastroenterology 5.1 (2014): e45.

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