Suggested NI margin M3 for different scales of trial outcomes.

<p>Sample sizes are calculated according to Farrington and Manning <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103616#pone.0103616-Farrington1" target="_blank">[28]</a> (for binary outcome), Rothmann <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103616#pone.0103616-Rothmann2" target="_blank">[29]</a> (continuous) and Crisp and Curtis <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103616#pone.0103616-Crisp1" target="_blank">[27]</a> (survival).</p><p>*overall number of events required.</p><p>**The sample size is calculated for a two-arm trial with 1∶1 randomisation comparing the lower bound of a two-sided 95% CI with the margin.</p

Aspects of identification of NI trials with data on margins and data extraction.

<p>*details described in Gladstone and Vach (17).</p>†<p>observed success rate used when assumed was not reported.</p>§<p>derived from available measures of variance using standard formulas (34), when not reported.</p>‡<p>expressed as values below 0.</p>||<p>expressed as values below 1.</p

Scenarios of true effect distribution used in the calculation of likelihood of degradation.

<p>Scenarios of true effect distribution used in the calculation of likelihood of degradation.</p

Distribution of non-inferiority margins in the NI trials for continuous outcomes.

<p>Distribution of non-inferiority margins in the NI trials for continuous outcomes.</p

Distribution of non-inferiority margins in the NI trials for survival outcomes.

<p>Distribution of non-inferiority margins in the NI trials for survival outcomes.</p

Flowchart of identification of non-inferiority trials and their margins – a) registered trials from trials register data b) published trials from four major journals.

<p>Flowchart of identification of non-inferiority trials and their margins – a) registered trials from trials register data b) published trials from four major journals.</p

Likelihood of degradation (moderate scenario) among the NI trials stratified by medical field and sorted by the median value. o represents each trial.

<p>Likelihood of degradation (moderate scenario) among the NI trials stratified by medical field and sorted by the median value. o represents each trial.</p

Distribution of the likelihood of degradation among the current NI trials.

<p>The diamonds represent the worst possible likelihood of degradation values and the dot represents the median likelihood of degradation in the moderate scenario.</p

Trial characteristics of the Non-inferiority trials studied.

<p>Trial characteristics of the Non-inferiority trials studied.</p

Scatterplot of the assumed success rate in the control arm versus allowed success rate in the treatment arm.

<p>The diagonal is shown as a line corresponding to a risk difference of 0. The two parallel lines correspond to risk differences of −0.1 and −0.2. The two curved lines correspond to an OR of 2/3 and 1/2.</p