ATPNVAC PIWG Report

Pandemic Influenza Antiviral Strategies and Priority Groups

Andrew T. Pavia M.D.University of Utah

ATPNVAC 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

ATPNVAC 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

ATPNVAC 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

ATPNVAC 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.

ATPNVAC 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

ATPNVAC 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

ATPNVAC 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

ATPNVAC 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

ATPNVAC 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

ATPNVAC 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

ATPNVAC 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

ATPNVAC 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

ATPNVAC PIWG Report

Proposed Priority Target Groups

Target GroupEstimatedPopulation

(millions)Strategy

# Courses (in millions)

Target group

Cumulative

Patients admitted to hospital 10.0 T 8.0 8.0

HCWs with direct patient contact

9.2 T 2.4 10.4

Highest risk outpatients 2.5 T 0.7 11.1

Pandemic health responders, pub safety & key gov decision makers

3.3 T 0.9 12.0

Increased risk outpatients 85.5 T 22.4 34.4

Outbreak response NA PEP 2.0 36.4

HCWs in ER, ICU, EMS, dialysis 1.2 P 4.8 41.2

Pandemic societal responders & other HCWs

10.2 T 2.7 43.9

Other outpatients 180 T 47.3 91.2

Highest risk outpatients 2.5 P 10.0 101.2

Other HCWs w/ patient contact

8.0 P 32.0 133.2

ATPNVAC PIWG Report

Size of Priority Groups and Cumulative Need

0

20

40

60

80

100

120

140

Cou

rses

in m

illion

s

ATPNVAC 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

ATPNVAC 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

ATPNVAC 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