Our study provides a framework for evaluating the cost-effectiveness of different regimens and the expected vial use of those regimens in different throughput clinics from the perspective of health providers and bite victims in order to inform policy decisions. Assuming the 4-site regimen can be effectively delivered from 3 rather than 4 clinic visits (i.e. d0: 4 x 0.1mL injections or a single 0.5mL vial divided between 4 sites, d7: 2 x 0.1mL injections, d28: 1 x 0.1mL injection) as proposed in ref. 36 means that the 4-site regimen would use less vaccine and become more cost-effective.

We have therefore calculated the cost-effectiveness per rabies death averted for the 3-visit 4-site regimen using the parameter values and methods described in the main text (i.e. based on the costs described in Table 2, and the probability of 0.19 that rabies-exposed bite victims develop rabies in the absence of PEP as per ref 19). In the attached note we compare the cost-effectiveness of the proposed 3-visit 4-site regimen with other regimens in Figure 1, but note that absolute cost-effectiveness varies with locale-specific costs. As suggested, a more intuitive comparison for health practitioners is vial use (thus relative costs to health care providers). Vial use for the 3-visit schedule of the 4-site ID regimen is compared to other PEP vaccination regimens in Figure 2 of the attached note. A comparison of the different regimens in terms of their cost to patients is also presented in Table 1 of the attached note.

These analyses imply that evaluation of the 4-site ID regimen using a 3-visit schedule is warranted by WHO, as this could be highly cost-effective for health practitioners and would reduce both indirect (travel and accommodation) and direct (PEP) costs for bite victims. In particular, curtailing the schedule to just 3 visits means that fewer vials would be opened and discarded in lower throughput clinics resulting in greater savings.

As per WHO requirements, clinical data from the administration of the 3-visit schedule for the 4-site regimen would need to be evaluated by WHO in order to include this regimen in their recommendations for its future use. These analyses suggest that clinical trials for this should be a research priority for effective translation to policy.