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The gold-standard of evidence to be included in a NMA are randomized controlled trials (RCTs) which include a control arm and whose populations are randomized to reduce bias and improve precision.
None were conducted in high-income countries and the only study to include a control arm (i.e. no fluid bolus arm; FEAST trial), found at 48 h a lower mortality in controls compared to those receiving saline or colloid boluses (relative risk for sepsis 0.69, 95% CI 0.54 0.89 and for malaria 0.64, 95% CI 0.46 0.91, respectively) [82].
This was the only study to include a control arm.
However, this study has generated the need to plan for a larger study that will include a control arm.
Second, we do not include a control arm in our trial, but rather sought comparison with values at baseline.
The reason why this study did not include a control arm was that this study was funded as a pilot.
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The current study included a control arm of best practice as recommended by guidelines, by offering physiotherapy [ 22].
To compensate for these components, we included a control arm in our study design, which is a strength of our study compared with, for example, the DAFNE Study (3).
For the studies that included a control arm (D9901, D9902A, D9902B/IMPACT, and PROTECT, as described below), the same procedures were followed in the control arm, except that PA2024 was omitted.
External validation of this multi-gene model will require an independent study that is adequately statistically powered and includes a control arm of patients who are not treated with cetuximab.
Section 4 presents the library of phase II designs, which are grouped according to the various design elements selected from the flow diagram (e.g., Trial Aim: Treatment selection; Outcome of interest: activity; Outcome measure: Binary; Randomisation: including a control arm; Design category: Two stage).
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