Regarding randomised clinical trials:
a) What is a noninferiority trial? (10% marks)
b) What is the null hypothesis in a noninferiority trial? (10% marks)
c) Why would a noninferiority trial be undertaken instead of a superiority trial? (40% marks)
d) What are the limitations of noninferiority trials? (40% marks)
This question is identical to Question 24 from the first paper of 2018.
a) What is a noninferiority trial?
b) What is the null hypothesis in a noninferiority trial?
In superiority trials, the hypothesis is that the experimental treatment is different (better) to the standard treatment, and two-sided statistical tests are used to test the null hypothesis (because the experimental treatment could be better or worse). The null hypothesis is therefore that there really is no difference. In equivalence trials the null hypothesis is that the treatments are significantly different, by a specified margin (the "equivalence margin"). In non-inferiority trials the null hypothesis is that the experimental treatment is worse than the standard treatment - and the pre-specified equivalence margin determines how much worse.
The diagram below is borrowed and modified from Ian A Scott (2009), and demonstrates the results and confidence interval ranges expected of the three different types of trials, when they have demonstrated that the null hypothesis is false.
Superiority trials have to have their results well over to the "favours experimental treatment" side, usually by a pre-specified margin. Equivalence trials need to have their results and confidence intervals within that margin to confirm that the two treatments are in fact equivalent. Non-inferiority trials also need to have their results within that margin, but there is no need to prove that the treatment is superior (i.e the confidence intervals and results simply need to remain within the not much worse margin, the "+1%" line in the diagram).
c) Why would a noninferiority trial be undertaken instead of a superiority trial?
A non-inferiority trial is appropriate when:
d) What are the limitations of noninferiority trials?
Snapinn, Steven M. "Noninferiority trials." Trials 1.1 (2000): 19.
Lesaffre, Emmanuel. "Superiority, equivalence, and non-inferiority trials." Bulletin of the NYU hospital for joint diseases66.2 (2008): 150-154.
Murray, Gordon D. "Switching between superiority and non‐inferiority." British journal of clinical pharmacology 52.3 (2001): 219-219.
Scott, Ian A. "Non-inferiority trials: determining whether alternative treatments are good enough." Med J Aust 190.6 (2009): 326-330.
Piaggio, Gilda, et al. "Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement." Jama 308.24 (2012): 2594-2604.
Garattini, Silvio. "Non-inferiority trials are unethical because they disregard patients' interests." The Lancet 370.9602 (2007): 1875-1877.
Fleming, Thomas R. "Current issues in non‐inferiority trials." Statistics in medicine 27.3 (2008): 317-332.