The Committee reviewed an application from the Department of Reproductive Health and Research, WHO, for the inclusion of valaciclovir as a better example within a therapeutic group than aciclovir (currently listed in section 6.4.1 Antiherpes medicines) on the grounds of superior bioavailability and a simpler treatment regimen (valaciclovir can be administered as twice daily doses rather than as 4-6 doses per day as required with aciclovir). In the case of sexually transmitted infections (STIs), compliance is a key issue in ensuring the effectiveness of treatments. Successful treatment is important for reducing the transmission of HIV and for promoting the credibility and acceptance of the syndromic approach to treatment.

The Committee noted the comprehensive review of studies on the comparative efficacy and safety of valaciclovir and aciclovir that was provided as part of the application. The studies compared the two medicines as treatments for the first clinical episode of genital herpes, as treatments for recurrent infections or as suppressive therapy, and presented the dosage regimen for each indication.

The Committee recognized that none of the randomized controlled trials and studies of comparative effectiveness revealed significant differences between the two medicines and that both valaciclovir and aciclovir are effective when compared with a placebo. However, none of the trials reported adherence to treatment or patient preferences as an outcome measure. The Committee also noted that the treatment regimens for some of the indications involved twice-daily dosing for both medicines.

Given the assessment of comparative clinical performance and the lack of evidence of any benefit from better adherence to treatment, the appropriate economic evaluation would be a cost-minimization analysis. On this basis, the cost per course (i.e. 5 days treatment) with aciclovir is in the range US$ 1.46-31.69 whereas the cost per course (i.e. of 5 days treatment) with valaciclovir is higher, at US$ 36.72. Such a cost differential could only be justified if other direct and indirect non-medicine costs (e.g. physician visits, hospitalization, adverse events, productivity losses) associated with use of aciclovir are substantially greater than those associated with treatment with valaciclovir. Based on the available clinical trial evidence, this is unlikely to be the case.

The Committee also noted the scarcity of published data on the cost-effectiveness of treatment of herpes simplex with valaciclovir and aciclovir in HIV-infected patients. According to the results of one trial (19), in which the cost-effectiveness of the two medicines for the treatment of herpes simplex virus were compared, relative to aciclovir, the use of valaciclovir reduced direct medical costs by an average of 17% (US$ 60.01) and indirect medical costs by an average of 25% (US$ 46.54). However, this particular analysis was based on a cost-consequence approach and was not a true cost-effectiveness analysis. Moreover, as the analysis was highly system specific, the Committee did not consider it necessarily applicable to other settings.

The Committee concluded that valaciclovir could only be considered cost-effective if its price were to be reduced sufficiently, or if evidence were to be presented that adherence to treatment and treatment outcomes are considerably better than those achieved with aciclovir. In the absence of such information, the Committee recommended that valaciclovir should not be added to the Model List, but that aciclovir should take a box symbol for this indication, with valaciclovir identified as one of the alternatives in the same pharmacological class.