Review 2: "Effect of a Widespread Reduction in Treatment Duration for Group A Streptococcal Pharyngitis on Outcomes and Household Transmission"

RR\ID Evidence Scale rating by reviewer:

• Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review: The title of this manuscript is "Effect of a widespread reduction in treatment duration for group A streptococcal pharyngitis on outcomes and household transmission." It is written as an observational research study. As a research study, the analysis plan used by the investigators is inadequate to address the primary question. The authors used a simple pre/post quasi-experimental study design to compare clinical outcomes in two different time periods. The pre-intervention time period (Oct 2020 to Sept 2022) was compared to the post-intervention period (Sept 2022 to June 2024). Of note, there was a global rise in invasive GAS infections cases in late 2022 to 2023 reported in multiple countries including New Zealand (Taylor A et al. Emerging Infectious Disease. 2023;29:11) that may substantially affect the results of a simple pre/post analysis. The authors did not mention this in their discussion. Rather than a simple pre/post study design, performing an interrupted time series analysis displaying the outcome of interest over time including the time period before and after the intervention would be more appropriate in evaluating the effect of the intervention on the metrics over time. Without this analysis these data are difficult to interpret. Furthermore, given how infrequent some of these outcomes are (especially acute rheumatic fever, but also hospitalization for invasive GAS infection), it is unlikely that a change in such a rare outcome would have been noted in this population, and therefore this study would likely have been insufficiently powered to detect a change in these outcomes. A power calculation and additional discussion from the authors addressing the possibility of type II error in their study's analysis would be important to include.

What can be gleaned from this manuscript, however, is that duration of antibiotics for GAS pharyngitis declined significantly after introduction of a laboratory-based intervention. This manuscript may have been better suited if framed as a quality improvement (QI) study, with antibiotic duration therapy as the primary outcome measure and clinical outcomes (recurrence of infection, hospitalization, ARF) as balancing measures. As a QI study, more detailed description of the intervention itself would have been helpful to include.