Question 10

Discuss the stages in designing a clinical trial.

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College Answer

An outline of the background literature review, defining the hypothesis, study design, ethics, funding, consent, conduct and follow-up was expected. Common omissions related to details on study design e.g. minimising bias and error. Some candidates misinterpreted the question as phases of clinical research (0-IV). 

Discussion

From the inclusion of this topic in the primary curriculum, one might think that the college expects their fellows to be competent in running and designing a clinical trial. 

In brief summary, the stages of clinical trial design are as follows:

  1. Research the question
  2. Define the hypothesis 
  3. Review the literature 
  4. Involve a statistician 
  5. Develop inclusion and exclusion criteria
  6. Calculate the sample size 
  7. Develop methodology (trial protocol)
    Steps taken to minimise bias may include: 
  8. Gain ethics approval
  9. Perform a pilot study
  10. Modify protocol as needed
  11. Perform the study (collect data)
  12. Measure the outcomes
  13. Analyse the data
  14. Compare to null hypothesis (is the difference statistically significant?)
  15. Consider sources of bias and errors
  16. Submit for publication

This is all as seen in LITFL. Much more detail can be seen in Myles and Gin (pp.135-145), in the section titled "How to design a clinical trial". Locally, an extensive rant-form "summary" is also available.

References

Statistical methods for anaesthesia and intensive care (P S Myles, T Gin - 1st 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.