Decision-making by the

Advisory Committee on Immunization Practices

Melinda Wharton, MD, MPHDeputy Director, National Center for Immunization

& Respiratory Diseases

Institute of Medicine9 February 2012

National Center for Immunization & Respiratory Diseases

Advisory Committee on Immunization Practices

q Establishes the standard of practice for immunization in the United States

q Evidence-based recommendations that consider:§ FDA Licensed indications and schedule

§ Disease burden overall and in high risk groups

§ Data on safety and efficacy in general and in specific groups§ Data on safety and efficacy in general and in specific groups

§ Feasibility in the context of existing recommendations

§ Equity in access to vaccine and good use of public funds (cost effectiveness)

§ Recommendations of other groups (i.e., AAP, AAFP, ACP, ACOG)

q Schedule represents a summation of individual vaccine recommendations, including recommendations for simultaneous administration

Morbid Mortal Wkly Rep 1995;43:959-960

How Much Risk is Too Much?Some Examples

q Smallpox vaccine§ Smallpox vaccine is associated with serious and sometimes fatal

adverse events

§ Smallpox vaccine recommended for laboratory workers who work with variola and related viruses

q Oral polio vaccine§ Vaccine-associated poliomyelitis: 1 in 750,000 first doses

q Rotavirus vaccines§ Intussusception following Rotashield: about 1 in 10,000 doses

Rotavirus Test Results at NREVSS Laboratories, 2000-2010

3

Tate J et al PIDJ in press

Estimated reduction in US hospitalizations 2008: >40,000

Gastroenteritis and Rotavirus-coded Hospitalizations in 18 States,

children aged <5 yrs, 2000-2008

Vaccine recommended

Curns A et al JID 2010

5

Number of Gastroenteritis and Rotavirus-confirmed Hospitalizations

NVSN 2006-2010

Payne D et al 20107

RV1: Post-marketing IS studies

8

RV5: Post-marketing IS studies

9

Estimate of Benefits: InputsRotavirus Burden and Vaccination

11

Updated inputs to model of Widdowson M, Meltzer M et al., Pediatrics 2007;119:684-97

Estimate of Benefits: ResultsRotavirus Disease Prevented with Vaccination

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Estimate of Risk : Input IS risk in one vaccinated birth cohort

13

Baseline Rate of Intussusception

000

5%

2%

<1%

18

68

0

0

7% Proportion of total rota1 doses given, by age group

14

Age at Rotavirus Vaccine Dose 1

National Immunization Survey 2009

1%1%

6%

3%

1%

15

66

<1%

9% Percentage of total Rota1 doses given, by age group

15

Estimate of Risk: Results Excess Intussusception Cases

1%1%4

4

Background: ~1,900 infants with IS annually

Number of cases caused by vaccine if RR = 4.6, by age group.TOTAL = 48

6%

3%

1%

15

66

<1%

9%

25

4

2

5

8

Percentage of total Rota1 doses given, by age group

16

Estimate of Risk: Results Excess Intussusception

17

Estimate of Risk: Results Attributable Intussusception Risk

18

Estimated attributable risk following Rotashield: ~1 case per 10,000 infants , Peter G et al. Pediatrics 2002

Benefits vs. Risks: Summary of Estimates One vaccinated birth cohort to age 5 years

19

Insurance Coverage for Vaccines

q In general, health insurance covers ACIP-recommended vaccines that are administered by an in-network provider, although deductibles and co-pays may result in substantial out of pocket costs

q The Affordable Care Act requires that new health insurance plans must provide coverage for ACIP insurance plans must provide coverage for ACIP recommended vaccines without deductibles or co-pays, when delivered by an in-network provider

Risks and Benefits

q ACIP’s decision-making process includes assessment of both risks and benefits of vaccination

q Vaccines – like any pharmaceutical product – do cause adverse events

q Vaccines are the most effective way to protect children from vaccine-preventable diseasesfrom vaccine-preventable diseases

q A decision to not vaccinate or to delay vaccination is not a risk-free decision

www.cdc.gov/vaccines

For more information please contact Centers for Disease Control and Prevention

1600 Clifton Road NE, Atlanta, GA 30333Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348E-mail: cdcinfo@cdc.gov Web: www.cdc.gov

National Center for Immunization & Respiratory Diseases

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Why Do We Give Vaccines at the Ages We Do?

q To provide protection from vaccine preventable diseases at the earliest age possible, or before periods of increased risk

q Given concurrently with other vaccines to coincide with established schedule of well-child visits

q Reflect ages at which vaccines are tested in clinical q Reflect ages at which vaccines are tested in clinical trials, and generally consistent with labeling

THE CHILDHOOD IMMUNIZATION SCHEDULE

Advisory Committee on Immunization Practices

Comparing Vaccinated, Unvaccinated, and Undervaccinated Children and their Households

q Undervaccinated compared with fully vaccinated:§ More likely to be Black than Hispanic or non-Hispanic white; young

mother; less likely to be married; more likely to have ≤12 years education; more likely to be poor; ≥4 children compared with only child

q Unvaccinated compared with undervaccinated:q Unvaccinated compared with undervaccinated:§ More likely to be non-Hispanic white; mother more likely to have

college degree and be ≥30 years old; household income >$75K; ≥4 children compared with only child

q Unvaccinated compared with fully vaccinated:§ More likely to be non-Hispanic white than Hispanic; more likely to

have ≥4 children compared with only child

§ A larger proportion of the unvaccinated were boys (57.3%)

Smith PJ et al. Pediatrics 2004;114:187-195

50

60

70

80

90

100

Per

cen

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cin

ated

(95

% C

I)

Cumulative percent of children born in 2007 vaccinated with 1 dose of MMR vaccine, by month of age, United States

Source: 2008-2010 National Immunization Survey

0

10

20

30

40

12 13 14 15 16 17 18 ≥19

Per

cen

t Vac

cin

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(95

% C

I)

Age (months)

National Immunization Survey, 2010

Vaccine %

MMR (≥1 dose) 91.5%

DTaP (≥3 doses) 95.0%

Varicella (≥1 dose) 90.4%

Hib (≥3 doses) 91.8%

PCV4 (4 doses) 83.3%

Morbid Mortal Wkly Rep 2011;60 (34):1157-1163

PCV4 (4 doses) 83.3%

Hep B (≥3 doses) 91.8%

Rotavirus (2 or 3 doses) 59.2%

Poliovirus 93.3%

4:3:1:3:3:1:4 70.2%

No vaccines 0.7%

50

60

70

80

90

100

Per

cen

t va

ccin

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(95

% C

I)Cumulative percent of children born in 2007 vaccinated with 1st

dose of DTaP vaccine, by month of age, United States

0

10

20

30

40

50

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 ≥19

Per

cen

t va

ccin

ated

(95

% C

I)

Age (months)

Source: 2008-2010 National Immunization Survey

National Immunization Survey (NIS)

q Primary coverage assessment tool for children 19-35 months and adolescents 13-17 years of age

q Random digit dialing survey

q Very large number of households contacted; for childhood survey§ ~1,000,000 households per year identified§ ~1,000,000 households per year identified

§ ~34,000 households per year complete interview

§ ~22,000 households per year used in analysis

q Provider-verified immunization histories are collected§ Survey instruments are mailed to providers who mail or fax back

responses

§ Only provider-verified vaccinations are used for estimation of vaccine coverage

The Science of Studying More than One Thing at a Time

q Rapid advances in multiple fields of biology have made it possible to study complex biological reactions at the cellular level

q These new “systems biology” approaches are beginning to be applied to questions about vaccines

Outpatient Visits for Fever by Day after Vaccine at Northern California Kaiser Permanente:

1995-2008Age 12-23 months

6241 total fever visits after 302,670 MMR+V, 147,762 MMR, 46,390 MMRV, 38,251 VZV

200

250

300

350

Even

ts /

100,

000

Dos

es

MMRMMR+VMMRVV

0

50

100

150

200

0 5 10 15 20 25 30 35 40Days after Immunization

Even

ts /

100,

000

Dos

es

Vaccine Safety Datalink; Immunization Safety Office, CDC

Data on Simultaneous Administration for a Licensed Vaccine: ROTARIX

q 484 healthy infants randomized into two groups

q All received Pediarix, PCV7, and ActHib at 2, 4, and 6 months and either ROTARIX concurrently at 2 and 4 months or separately at 3 and 5 months§ Co-administration: n=249

§ Separate administration: n=235

q Prespecified criteria for noninferiority of antibody response met for all antigens

Abu-Elyazeed et al, ICAAC 2007

Safety and Efficacy Issues Potentially Associated with the Childhood Vaccination Schedule

q Data generally available on concurrent administration at licensure

q Interference between concurrently administered vaccines theoretically possible but generally not observed§ Need for spacing of live virus vaccines

q Safety or efficacy issues associated with concurrent or antecedent exposure to vaccine components (e.g., diphtheria toxoid-containing vaccines)

q Cumulative exposure to vaccine components

Missed Opportunities

q Definition: Healthcare encounter in which a child is eligible to receive a vaccination but is not vaccinated

q What causes missed opportunities?§ Referrals from immunization provider

§ Deferrals of vaccination• Provider unaware that vaccines are due• Provider unaware that vaccines are due

• Failure to provide simultaneous vaccinations

• Inappropriate contraindications

• Office policies/administrative barriers

§ Non-vaccinating health care providers