# Presentation: 271681

## Pandemic Influenza Antiviral Strategies and Priority Groups

- Andrew T. Pavia M.D.
- University of Utah

## 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

## 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

## 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

## 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.

## 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

## 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

## 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

## 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

## 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

## 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

## 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

## Recommendations - 3 Priority groups

- Hospitalized patients with influenza
- HCWs and EMS workers with direct patient contact
- Highest risk outpatients
- Pandemic health responders, public safety & key government decision makers
- Other high risk outpatients

- Outbreak response (eg PEP in nursing homes)
- Prophylaxis HCWs in ER, ICU, EMS, dialysis
- Pandemic societal responders & other HCWs
- Other outpatients
- Prophylaxis for highest risk outpatients
- Prophylaxis for other HCWs w/ patient contact

## Proposed Priority Target Groups

| Target Group | Estimated
Population (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 |

## Size of Priority Groups and Cumulative Need

## 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

## 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

## 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