Limitations
throat
RECRUITMENT
HALS was an open cluster-randomized pragmatic trial under real world conditions. The design made blinding impossible. Thus, we cannot exclude selective recruitment of patients. Though using a convenience sample we do not assume relevant limitations to representativeness of our data. By recruiting 520 patients we did not reach the planned number of 570 patients. We decided to randomize practices, in order to avoid contamination. By limiting the number of GPs per practice to two and the number of patients recruited per practice to 11 we tried to reduce at least some cluster effects. However, due to the unexpectedly high heterogeneity in the antibiotic prescription rate among practices the retrospectively calculated ICC of 0.37 was much higher than the ICC of 0.05 that we had assumed. This results in a lack of power. Excluding patients with only light impairment in whom the guideline did not recommend antibiotics might have led to higher prescription rates and smaller effects of the interventions. All practices were instructed in the technique of taking a throat swab, and the practices of the GL-RADT-group to perform the rapid test. However, we cannot rule out the possibility that also untrained practice staff collected swabs or performed the RADTs. Study throat swabs were cultivated and analyzed by the routine procedures described that might have missed some GAS. The GPs almost never used the prepared list for patients not included into the study, but we suspect that they did not recruit consecutively, so that a selection bias of patients can’t be excluded. Time constraints in daily practice are seen as the main reason [With these restrictions, the breadth and quality of the documented data still allowed a comprehensive analysis of the factors influencing the effectiveness of our interventions in daily practice.