Firstly, using adefovir as a comparator, although appropriate at the time of the ETV-048 study, does not necessarily reflect the current treatment practice in the US since tenofovir is now also approved for the treatment of CHB patients with decompensated cirrhosis.
Although the Mayo regimen was used as a comparator in international trials at that time, this was not universally accepted in the UK.
For example, crossover trials involve randomizing patients to treatment at one time (or several times) and to no treatment (or treatment with a comparator) at another time (or other times).
Two HIV tests were performed in parallel for each patient, comprising a locally-available POC blood test provided for routine use at the clinic, and a comparator POC blood test provided by the study.
In total 3,547 patients were enrolled: 1,814 patients (32% children under five years) received DP and 1,733 received a comparator antimalarial at 12 different sites and were followed for 28 63 days.
27 This population comprised 28 061 patients receiving vildagliptin, and 15 294 receiving a comparator: final HbA1c change at 12 months was −1.19% in vildagliptin-treated patients.
Firstly, while it would have been preferable to use a comparator model that was at the same level of care as that of the intervention (that is, a primary care comparator) it was difficult to obtain relevant data to do so because of the paucity of relevant studies in the South African context.
There are different tools in use for assessment of evidence and for generating recommendations, but all those systems require controlled trials to show efficacy against placebo or at least a proven comparator drug.
Thus, one possible way to circumvent this pitfall would be to enroll at least a small comparator arm with complete pharmacokinetic characterization.
In recruitment for EPICure 2 this was extended to include all births at 26 weeks gestational age (that is, 26 weeks and 0 days to 26 weeks and 6 days) both because of a lack of reliable data for babies born at 26 weeks and because babies at this gestation routinely receive active care at birth, forming a useful comparator group.
