# Presentation: 165833

## Monitoring the Effectiveness of Pandemic Influenza Vaccines

**VRBPAC, February 27, 2007**
**David K. Shay, MD, MPH**
**Epidemiology and Prevention Branch, Influenza Division (proposed)**
**Centers for Disease Control & Prevention**

## Pandemic Vaccines: Background 

**Limited immunogenicity and safety data will be available prior to distribution of a pandemic vaccine**
**Safety monitoring will be essential**
**Post-licensure safety studies can begin with pre-pandemic use of each product, and continue throughout the vaccine program **
**If desired, post-licensure immunogenicity data could be collected in the pre-pandemic setting**

## Pandemic Vaccines: Background 

**Data concerning clinical effectiveness of  pandemic vaccines will be essential**
**Immunogenicity and protection from illness imperfectly correlated**
**Different populations may receive vaccine in pre- and post-licensure situations**
**Vaccine match, need to change strain **
**But obviously must await onset of the pandemic and illness in populations eligible for vaccination**

## Pandemic Vaccine Effectiveness 

**Effectiveness: protection against influenza illness when vaccine is administered in an immunization program**
**Effectiveness may vary by age, medical history, and immunocompetence of patient  **
**Effectiveness may vary with outcomes**
**Lower for non-specific illnesses that can be caused by pathogens other than the pandemic virus**
**May vary by severity: illness, hospitalization, need for mechanical ventilation, death**
**Need to assess effectiveness after 1 and 2 doses of vaccine**

## CDC’s Existing Influenza VE Projects: Base for Pandemic VE Assessments

**Two projects build on existing surveillance systems for influenza**
**Emerging Infections Program (EIP)**
**New Vaccine Surveillance Network (NVSN) **
**Project with Marshfield Clinic was funded  to provide rapid, within season estimates of VE against a laboratory-confirmed outcome**
**All use laboratory-confirmed influenza  outcomes**

## EIP – 12 sites
Children <18 yrs hospitalized with laboratory-confirmed influenza infection
Adult surveillance began January 2006
NVSN – 3 sites
Children <5 yrs with inpatient or outpatient laboratory-confirmed influenza infection
Outpatient surveillance in 6-12 yrs started this season

**EIP – 12 sites**
**Children <18 yrs hospitalized with laboratory-confirmed influenza infection**
**Adult surveillance began January 2006**
**NVSN – 3 sites**
**Children <5 yrs with inpatient or outpatient laboratory-confirmed influenza infection**
**Outpatient surveillance in 6-12 yrs started this season**

## Emerging Infections Program Studies 

| Study Design | Case-control |
| --- | --- |
| Seasons | 2005-06, 2006-07 |
| Setting  | Hospitals in 6 (2005-06) and 9 (2006-07) states |
| Age | 6-23 mo (2005-06), 6-59 mo (2006-07) |
| Cases | Children hospitalized with laboratory-confirmed influenza. Tests ordered by clinicians. |
| Controls  | Age- and zip-code matched children not hospitalized with influenza |
| Vaccination data  | Health care providers and parent report |
| Source of other data | Medical chart review, parent interview   |
| Other data | Age, gender, race, insurance status, high-risk conditions, socioeconomic status |

## NVSN Studies 

| Study Design | Case-control |
| --- | --- |
| Seasons | 2003-04, 2004-05, 2005-06, 2006-07 |
| Setting  | Hospitals, emergency departments, and outpatient clinics in 3 counties (TN, NY, OH) |
| Age | 6-59 months |
| Cases | Children brought to medical attention with fever or ARI who test positive for influenza by culture or RT-PCR |
| Controls  | Children with fever or ARI who test negative for influenza by culture and  RT-PCR |
| Vaccination data  | Obtained from health care providers |
| Source of other data | Medical chart review, parent interview  |
| Other data | Age, gender, race, insurance status, high-risk conditions, socioeconomic status, and other risk factors |

## Marshfield Clinic Studies 

| Study Design | Cohort and case-control |
| --- | --- |
| Seasons | 2004-05, 2005-06, 2006-07 |
| Setting  | Clinic population in north-central WI |
| Age | All ACIP-recommended groups |
| Cases | Patients seeking care for acute respiratory illness who are influenza positive by culture or RT-PCR |
| Cohort/Controls | Cohort of adults and children for whom ACIP recommended annual influenza vaccination
Age-matched persons without ARI symptoms in same healthcare system; test-negative ARI |
| Vaccination data  | Obtained from regional electronic vaccine registry and patient report |
| Source of other data | Electronic medical record and interview  |
| Other data | Age, gender, race, high-risk conditions, use of health care |

## Underlying Rationale for Pandemic Vaccine Prioritization

**Everyone will be susceptible**
**US-based production capacity is not currently sufficient to provide vaccine rapidly for the entire population**
**Earliest doses of vaccine can be projected as becoming available at ~20 weeks after isolation and characterization of the pandemic virus **

## ACIP/NVAC Priority Groups 

**Joint work of the two HHS committees**
**Process included consideration of **
**Estimates of vaccine supply and effectiveness**
**Effects of pandemic by age and risk group**
**Potential effects on critical infrastructure and health care**
**Recommendations included in the 2005 HHS pandemic plan **
**As guidance for State/local planning **
**To promote further discussion **

## Top 2 ACIP/NVAC Priority Groups 

**1.A. Vaccine and antiviral manufacturers and others essential to manufacturing and critical support (~40,000) **
**	****Medical workers and public health workers who are involved in direct patient contact, other support services essential for direct patient care, and vaccinators (8-9 million)**
**1.B. Persons > 65 years with 1 or more influenza high-risk conditions, not including essential hypertension (approximately 18.2 million) **
**	****Persons 6 months to 64 years with 2 or more influenza high-risk conditions, not including essential hypertension (approximately 6.9 million) **
**	****Persons 6 months or older with history of hospitalization for pneumonia or influenza or other influenza high-risk condition in the past year (740,000) **

## Interagency Pandemic Vaccine Prioritization Working Group

**Participants from multiple federal agencies**
**Consideration of ACIP/NVAC recommendations**
**Consideration of National Infrastructure Advisory Council recommendations on critical infrastructure**
**Public engagement meetings and stakeholder meeting**** **

## Summary of 2 Public Engagement and Stakeholder Meetings

**At each of the 3 meetings, the most highly rated goals were the same**
**Maintaining critical societal functions**
**Protecting those who would help others during a pandemic**
**Protecting children as “our future”**
**Most other goals were considered moderately important**
**Including protecting those most likely to get sick or die during a pandemic**
**Ratings and rank order varied between meetings**

## Pandemic Vaccine Prioritization Interagency WG: Next Steps

**Draft prioritization guidance developed**
**Public & stakeholder meetings**
**Written comments**
**ACIP updated by Ben Schwartz, NVPO **
**The working group also will consider**
**Pre-pandemic vaccine prioritization**
**Modifying guidance at the time of a pandemic**
**Final guidance expected by May**

## Monitoring Pandemic Vaccine Effectiveness: 1

**Lab-confirmed outcomes will be studied**
**Hospitalizations captured in several systems**
**Additional more severe outcomes (e.g, all-cause mortality) may also be studied**
**Observational studies must collect data on possible confounding factors **
**Selection bias likely, but cannot assume direction**
**Need to link existing individual health data to vaccination and outcome data**

## Monitoring Pandemic Vaccine Effectiveness: 2

**Plans will evolve as vaccine priorities develop**
**Existing systems cover children well**
**Community-based studies may not be efficient if initial vaccine is prioritized to a few critical infrastructure sectors**** **
**Vaccine distribution and tracking methods **
**State, regional registries may be used to identify vaccinated individuals**
**Need to link pandemic vaccine receipt back to medical and demographic data**** **

## Monitoring Pandemic Vaccine Effectiveness: 3

**CDC will expand existing systems**
**Assess effectiveness among adults in EIP system**
**Rapid assessment methods in other sites**
**Potential for new systems**
**Consider using sentinel provider system and point-of-care tests being developed**** **
**CDC will work with governmental and other partners to meet needs for effectiveness data**

## Acknowledgments

**Emerging Infections Program sites**
**CA**
**CO**
**CT**
**GA**
**OR**
**TN**
**Marshfield Clinic Research Foundation**

**New Vaccine Surveillance Network sites**
**Children’s Hospital Medical Center Cincinnati**
**University of Rochester**
**Vanderbilt University**
**Ben Schwartz**
**Joe Bresee**
**Tony Fiore**
**Nancy Cox**

## Slide 20

## Basis for ACIP/NVAC Prioritization 

**Primary goal to mitigate adverse health outcomes **
**Pandemic severity assumptions**
**20-30% attack rate; up to 1% case fatality rate**
**Certain benefit of vaccinating high-risk versus unclear benefit of vaccinating critical infrastructure**
**Estimate of 10-15% absenteeism due to illness or caring for ill family members at pandemic peak**
**Much greater mortality risk among vulnerable persons than general population**

## ACIP/NVAC Priority Groups		  Personnel       Cumulative      Element and Tier				      (1,000’s)        total (1,000’s)

## Rationale for Reconsideration of Pandemic Vaccine Prioritization

**Public engagement meetings**
**Preserving essential services ranked as top goal**
**Evolving planning assumptions**
**More severe pandemic**
**Evolving pandemic response strategies**
**Community mitigation guidance**
**Additional analysis of critical infrastructures**

## EIP Surveillance Areas

**California: Kaiser Northern California members in 3 county San Francisco Bay area, and non-Kaiser children aged <2 years**
**Colorado: 5 county Denver area**
**Connecticut: 1 county New Haven area**
**Georgia: 8 county Atlanta area**
**Maryland: 5 county Baltimore area and Baltimore City**
**Minnesota: 7 county Minneapolis area**
**New Mexico: 1 county in Albuquerque area and 3 county Las Cruces area**
**New York: 8 county Albany area and 7 county Rochester area**
**Oregon: 3 county Portland area**
**Tennessee: 8 county Nashville area**
***Total: 4.7 million children aged <18, or ~7% of US population***** **

## NVSV Surveillance Areas

**Children aged <5 years in these communities:**
**Monroe County, New York:****	****43,720 **
**Davidson County, Tennessee:****	****56,466**
**Hamilton County, Ohio:****	****	****44,002**
***Total******	******	******	******	******         144,188***

## Marshfield Clinic Population

**The influenza study cohort was drawn from the Marshfield Epidemiologic Study Area (MESA), a dynamic, population-based cohort of approximately 54,000 residents living in 14 zip-codes surrounding Marshfield, Wisconsin**
**Nearly all MESA residents receive all inpatient and outpatient care from Marshfield Clinic facilities, which use an electronic medical record that captures ********90% of outpatient visits, 99% of deaths, and 95% of hospital discharges for the population**
**The 2004-05 study cohort included 11,565 people, including 1,881 (16%) with a clinical encounter for acute respiratory illness based on diagnosis codes in the electronic medical record during the 12-week study period**
**The 2005-06 study cohort included 18,542 residents**