Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.

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Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.

Health systems worldwide struggle to meet increasing demands for health care, and Norway is no exception. This paper discusses the new, comprehensive framework for priority setting recently laid out by the third Norwegian Committee on Priority Setting in the Health Sector. The framework posits that priority setting should pursue the goal of "the greatest number of healthy life years for all, fairly distributed" and centres on three criteria: 1) The health-benefit criterion: The priority of an intervention increases with the expected health benefit (and other relevant welfare benefits) from the intervention; 2) The resource criterion: The priority of an intervention increases, the less resources it requires; and 3) The health-loss criterion: The priority of an intervention increases with the expected lifetime health loss of the beneficiary in the absence of such an intervention. Cost-effectiveness plays a central role in this framework, but only alongside the health-loss criterion which incorporates a special concern for the worse off and promotes fairness. In line with this, cost-effectiveness thresholds are differentiated according to health loss. Concrete implementation tools and open processes with user participation complement the three criteria. Informed by the proposal, the Ministry of Health and Care Services is preparing a report to the Parliament, with the aim of reaching political consensus on a new priority-setting framework for Norway.