1. ATP NVAC PIWG Report Pandemic Influenza Antiviral Strategies and Priority Groups Andrew T. Pavia M.D. University of Utah

2. ATP NVAC PIWG Report Outline Process Principles, Key Data, Assumptions Working Group Recommendations –Optimal size and minimal size –Drugs of choice –Priority Groups and Strategies for Limited Supply –International containment –Critical research issues

3. ATP NVAC PIWG Report Working Group Process Meeting April 19-20, 2005 Construction of “Straw Man” proposal Conference Call with Wisconsin DOH Conference Call May 24, 2005 Joint meeting in Atlanta June 15-16, 2005 Coordination with Vaccine working sub-group

4. ATP NVAC PIWG Report Presentations – June 15, 16 Meeting Goals Estimates of pandemic influenza impact Impact of annual and pandemic flu in different age and risk groups Impact of pandemic influenza on the healthcare system and options for prioritizing among healthcare workers Definition of critical infrastructure and possible prioritization of infrastructure support groups

5. ATP NVAC PIWG Report Presentations – June 15, 16 Meeting Ethical considerations Impacts of oseltamivir in a mouse model of H5N1 infection Mathematical modeling of strategies to contain an influenza outbreak and prevent pandemic spread CDC antiviral planning activities Implementation of an antiviral response at the State level.

6. ATP NVAC PIWG Report Principles of Antiviral Drug Use - 1 Primary goal of response is to decrease pandemic health impacts (social secondary; economic tertiary) Given the uncertainties about antiviral drug use and supply, strategies must be flexible, and must be re- addressed as a pandemic unfolds National guidelines provide guidance and achieve consistency. However, State and local health departments should have flexibility to meet local needs

7. ATP NVAC PIWG Report Principles of Antiviral Drug Use - 2 Delivery of antiviral drugs should be equitable within target populations and not constrained by ability to pay Antiviral drug use strategies must be –Feasible to implement –Acceptable to the public –Transparent

8. ATP NVAC PIWG Report Key Data Treatment with a NA inhibitor within 48 hours decreases lower respiratory complications and hospitalizations (RCT data). In BM transplant recipients and NH residents it can reduce mortality (uncontrolled observational studies) Earlier treatment has a greater impact Most isolates from SE Asia are resistant to M2 inhibitors. When used as treatment, they will result in shedding of resistant, virulent virus Mouse studies with H5N1 suggest shedding and replication are at higher levels and last longer –? need for longer treatment

9. ATP NVAC PIWG Report Assumptions - 1 Priority groups must be designated because the amount of antiviral drug available is likely to be less than the demand. Antiviral drug use will prevent or treat infection in the recipient but will have little impact on the course of the pandemic Given the supplies will be limited, strategies that require less drug and yield greater health impact per course are preferred

10. ATP NVAC PIWG Report Assumptions - 2 Military needs are a priority – but we assume that a separate stockpile will be established We assume attack rate of 35%; 75% will present within 48 hours for treatment Prophylaxis course estimated at 40 days; equivalent to 4 treatment courses Optimal dosing and duration for H5N1 could change Distribution to states and Tribal governments will be pro rata from SNS. A small reserve will be held back for outbreak response

11. ATP NVAC PIWG Report Recommendations -1 Sufficient antiviral drugs should be stockpiled to support a robust response because of the key role that antiviral drugs can play in reducing health impact. –133 million courses would provide drug to treat all who are infected and support prophylaxis of health care workers and highest risk patients –40 million courses is the minimum that would support critical pandemic responses

12. ATP NVAC PIWG Report Recommendations - 2 Oseltamivir should be the primary drug stockpiled. Zanamavir should also be included because it is effective against most oseltamivir resistant viruses and to support ongoing production and protect against disruption of supply M2 inhibitors, beyond the 5 million courses currently in the SNS should not be stockpiled due to the likelihood of resistance

13. ATP NVAC PIWG Report Recommendations - 3 Priority groups 1.Hospitalized patients with influenza 2.HCWs and EMS workers with direct patient contact 3.Highest risk outpatients 4.Pandemic health responders, public safety & key government decision makers 5.Other high risk outpatients 6.Outbreak response (eg PEP in nursing homes) 7.Prophylaxis HCWs in ER, ICU, EMS, dialysis 8.Pandemic societal responders & other HCWs 9.Other outpatients 10.Prophylaxis for highest risk outpatients 11.Prophylaxis for other HCWs w/ patient contact

14. ATP NVAC PIWG Report Proposed Priority Target Groups Target Group Estimated Population (millions) Strategy # Courses (in millions) Target group Cumulative Patients admitted to hospital10.0T 8.0 HCWs with direct patient contact 9.2T 2.4 10.4 Highest risk outpatients 2.5T 0.7 11.1 Pandemic health responders, pub safety & key gov decision makers 3.3T 0.9 12.0 Increased risk outpatients85.5T22.4 34.4 Outbreak responseNAPEP 2.0 36.4 HCWs in ER, ICU, EMS, dialysis 1.2P 4.8 41.2 Pandemic societal responders & other HCWs 10.2T 2.7 43.9 Other outpatients180T47.3 91.2 Highest risk outpatients 2.5P10.0101.2 Other HCWs w/ patient contact 8.0P32.0133.2

15. ATP NVAC PIWG Report Size of Priority Groups and Cumulative Need

16. ATP NVAC PIWG Report Recommendations - 4 Use of antivirals as part of an international response to contain an outbreak and prevent or delay a pandemic is recommended if the following conditions are met: –International guidelines are developed –Field exercises in the country suggest an ability to effectively respond and contain the spread –Other countries with antiviral stockpiles contribute to the effort

17. ATP NVAC PIWG Report Recommendations - 5 Critical research should be conducted to support optimal use of antivirals, including: –Impact of treatment at hospital admission on outcomes –Optimal treatment dose and schedule in a ferret model with H5N1 and other strains –Sensitivity of rapid diagnostic tests for H5N1 and other strains with pandemic potential –Safety and pharmacokinetics of oseltamivir among infants <1 year old –Investigation of the impact of other agents

18. ATP NVAC PIWG Report Ongoing issues Only the first 2 of these 4 steps were addressed in the charge to the subgroup: –Stockpile purchase –Priority allocation –Distribution –Dispensing Ongoing work is needed to further refine definition of target groups and to refine estimates of the population size