Richard K Zimmerman MD MPH

University of Pittsburgh School of Medicine

Research grants from Pfizer (adolescent vaccine) and Sanofi

Is the vaccine effective?Is the vaccine safe?Is the public health impact based on amount of

potentially preventable disease sufficient?Is it programmatically feasible to add more

injectionsIs it cost-effective?ACIP uses GRADE

Explicit, evidence-based grading process

CDC

Source ACIP meeting

WHO recommends the same composition for the Northern Hemisphere 2014-15 influenza vaccines as for 2013-14: an A/California/7/2009 (H1N1)pdm09-like virus; an A/Texas/50/2012 (H3N2)-like virus; a B/Massachusetts/2/2012-like virus. (Yamagata

lineage)for quadrivalent vaccines, add B/Brisbane/60/2008-like

virus (Victoria lineage)

60 mcg per strain compared to 15 mcg typically Prefilled syringesNo adjuvant or preservativeCurrently only trivalentLicensed in December 200913 million doses used in first three seasonsPenetrance in market 20% among elderly in past

32,000 persons >65 years in 126 study sites in US and Canada

Randomized and blinded trialLaboratory confirmation on NP swab:

PCRCulture

October 2013 ACIP Meeting

October 2013 ACIP Meeting

October 2013 ACIP Meeting

October 2013 ACIP Meeting

October 2013 ACIP Meeting

Two types:PPSV 23 – 23 valent pneumococcal polysaccharidePCV13 – 13 valent pneumococcal conjugate

Existing recommendation for PPSV23 for one dose at age >65 years

PCV13 is FDA licensed for adultsserotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F

and 23FDeferred recommendation until CAPITA data

available and until herd (indirect) effect data from childhood use of PCV13

ACIP Meeting

ACIP Meeting

ACIP Meeting

ACIP Meeting

ACIP Meeting

ACIP Meeting

 Health OutcomesChange in outcome compared to

existing PPSV23 recommendation

  IPD -226

  Inpatient NBP -4,961

  Outpatient NBP -7,252

Deaths (IPD) -33

Deaths (NBP) -332

QALYs 3,053

Life-years 4,627

Stoecker, ACIP June 2014

27

 OutcomesChange in outcome

compared to existing PPSV23 recommendation

Total Cost (Millions) $189

  Medical (Millions) -$132  Vaccine total cost (Millions) $321

Cost/QALY gained $62,065

Cost/Life-year gained $40,949

Stoecker, ACIP June 2014

28

Outcome Risk of

bias

Inconsis-

tency

Indirectness Impreci-

sion

Quality of

evidence

IPD No

serious

N/A Serious No serious 21

1Indirectness due to different comparison groupa. Placebo instead of PPSVb. PPSV efficacy against IPD among older adults = 50-80%

Pneumonia No

serious

N/A No serious No serious 1

Study/population Endpoint

Vaccine Efficacy

(95% CI)

CAPITA

Adults 65+

Netherlands

PCV13-serotype IPD 75% (41%, 91%)

CAPITA, ACIP June 2014

What effect might we expect among persons >65 years old in the US?

PCV13-serotype non-bacteremic

pneumonia 45% (14%, 65%)

1. PCV13-type IPD rate among adults >65 years old in the US. CDC, ABCs, 2013

2. Simonsen et al Lancet Resp. Med 2014

3. Nelson et al. Vaccine 2008

4. CAPITA

5. Number-needed-to vaccinate (NNV) =1 / (Ratebaseline – Ratevaccinated)

Outcome(PCV13-type)

Baseline incidence(per 100,000 population)

Vaccine efficacy (95% CI)

Number needed to vaccinate5

IPD 6.51 75% (41%, 91%)4

20,400 (16,950 - 37,000)

Caveat: VE vs. placebo

Inpatient CAP 137.52 45% (14%, 65%)4

1,620 (1,110 - 5,130)

Baseline estimates assume 10% of all CAP due to PCV13 -typesOutpatient CAP 2013 45%

(14%, 65%)4

1,110 (760-3,500)

Total CAP - - 656(454-2,110)

Outcome (PCV13 type)

2015•20% reduction due to herd effects*•PCV13 direct effects**•Coverage 10% (5%-30%)

2019•86% reduction due to herd effects* •PCV13 direct effects**•Coverage 30% (20%-60%)

IPD 160 (80-480) 80 (50-170)

Inpatient CAP 2,030 (1,020-6,090) 1,070 (700 -2,130)

Outpatient CAP 2,970 (1,480-8,900) 1,560 (1,040 – 3,120)

Total CAP 5,000 (2,500-14,990) 2,630 (1,740 – 5,250)

*Based on post-PCV7 reductions observed between 2003 and 2009**Assume PCV13 VE =75% (IPD) and 45% (CAP)

33

PCV13 should be given first when possible Interval between PCV13 followed by PPSV23:

6-12 months Interval for PCV13 when given post-PPSV23:

>1 year Include flexibility in the guidance if doses cannot be

administered within the recommended window: If a second dose cannot be given during this time

window, a dose can be given later during the next visit

34

*ACIP 2012 recommendations for PCV13 use among adults with immunocompromising conditions (MMWR October 2012)

35

Received PCV13 previously?

Yes No

No additional PCV13 doses needed*

Received one or more doses of PPSV23 previously?

Yes No

PCV13 dose

PCV13 dosefollowed by PPSV23

36

Adults >65 years who have not previously

received pneumococcal vaccine or whose previous vaccination history is unknown:

receive a dose of PCV13 first, followed by a dose of PPSV23

6-12 months laterIf not feasible, during next visitNot co-administered

ACIP meeting

Incidence~ 3-4 per 1,000 person years

1 million cases in U.S. annually Lifetime risk

30% overall50% of individuals living until 85 years of age

Complications:Post herpetic neuralgia (13% of those >60 years)OphthalmicNerve PalsiesBacterial superinfection

Gnann J et al. N Engl J Med. 2002; Katz J et al. Clin Infect Dis. 2004; Ragozzino M et al. Medicine 1982.

Recommended once by ACIP to persons >60 years of age

ACA requires commercial insurances subject to ACA to pay for ACIP recommended vaccines with first dollar coverage (no copays)

So, almost all commercial insurances pay Medicare is part D with doughnut hole possibilitySo, give it ages 60-64 when commercial insurance

offers first dollar coverage

Year, Setting Equipment misused Length of misuse

Persons at risk

2008, Hospital Insulin pen 7 months 908

2009, Hospital Insulin pen 7 months 2114

2009, Community Health Center

Multi-lancet finger stick device

6 months 283

2010, Health Fair Multi-lancet finger stick device

1 day 64

2011, HMO, certified diabetes educator

Multi-lancet finger stick device, insulin pen

5+ years 2345

Total at risk     5714

• Adults with diabetes without “Other” hepatitis B risk factors†

– Ages <60 years, 2X higher odds of hepatitis B

– Ages ≥60 years, 1.5X higher odds of hepatitis B*

†”Other” risk factors included injecting drug use, men who have sex with men, and HIV risk associated behaviors.

*Not statistically significant (small sample size) Reilly M. IDSA 2011

ACIP

~30% cases symptomatic; average 1-4 months ~40% cases hospitalized1%-2% cases fulminant liver failureNNDSS 2009, Sentinel Counties 2002-2005; EIP

Sites, 2005-2007 ;CDC unpublishedCase fatality rate

1.3% overall2%-4% ages ≥50 year6%-18% older adults in outbreak settings

• Nationally representative survey of noninstitutionalized adults; tested for antibody to

hepatitis B core antigen (anti-HBc)• Unadjusted prevalence of anti-HBc amongadults with diabetes (vs. without diabetes)*– Overall, 60% increase (p<0.001)– Ages 18-59 years, 70% increase (p<0.001)– Ages ≥60 years, 30% increase (p=0.032)* CDC unpublished data; updated 10/31/2011

• Seroprotection remains high in the majority of adults to age 60 years

• Younger age, fewer co-morbidities

– Vaccination soon after diabetes diagnosis maximizes protection

• Fewer adults ≥60 years fully protected

• No special safety concerns

AuthorEvent Rate

(%): PlaceboEven Rate

(%): Vaccinated

Vaccine

Efficacy

Adverse Events*

Coutinho 23.8 4.8 80 No serious

Crosnier 12.3 3.6 71 No serious

Dienstag 0.8 0.2 80 No serious

Francis 20.9 9.2 82 No serious

Szmuness80 35.0 7.6 78 No serious

Szmuness82 9.9 2.2 77 No serious*Study sizes not sufficient to detect rare adverse events, †Not reported by study, vaccine efficacy= incidence in placebo recipients minus incidence in vaccine recipients, divided by incidence in placebo recipients (0.75 and 0.15, respectively, for Dienstag), crude rate not accounting for person-time follow-up, ‡Does not include anti-HBc positivity without enzyme elevation

Age (years) at vaccination

Number needed to vaccinate

20-59 124

≥50 1071

≥20 261

T Hoerger et al. Research Triangle Institute, Int. 2011.

Age at vaccination Number vaccinated with 10% vaccine update

Cost per QALY saved

20-59 528,047 $75,094

60+ 774,394 $2,760,753

Vaccinate adults with DM who <60 years old Optional >60 years with DM

Increase Patient Demand Patient reminders

Enhance Access Office hours express vaccination After hours express vaccine-only clinics

Provider Reminders and Office Systems Standing order programs (SOPs) Prompts in EMRs

Combination of 2 or 3 strategic approaches led to a 16% point increase in rates.

Multiple interventions within a single strategic approach increased rates only 4% points.

4pillarstoolkit.pitt.edu

Extended vaccination season Starts when influenza vaccine arrives Continues into the influenza disease season for unvaccinated

Season unpredictable & some benefit possible2 waves of influenza may occur

Express vaccination servicesVaccination only services:

Dedicated evening or weekend vaccine-only services

Walk-in vaccination stationNursing vaccination visits

About Convenient Vaccination ServicesNotification Methods

AutodialerEmail/textOffice posters/videosAnswering service “on-hold” messagesMail

MMWR 1988;37:657-61

• Physician recommendation is essential to patient acceptance

• Makes a difference among patients hesitant to be vaccinated, as shown in figure

Pillar 2: Patient Notification

Providers should discuss serious nature of vaccine preventable diseases

Assessment of influenza vaccination as a routine part of the office visit by nursing staff:Prompts in EMRHealth maintenance or immunization section

review Routinely address “Is vaccination status up to

date?” as part of vital signsEmpowering staff to vaccinate by standing

orders Combination of assessment and SOPs should

reduce missed opportunities

• Ongoing motivation is a key to success• Set goals for improving rates• Identify an Immunization Champion • Champion monitors weekly progress towards

goals • Shares progress with team• Celebrate achievements

• Consider rewards

Effective office manager and lead physician (Immunization Champions)

Leaders inspired staff to take responsibility for assessing vaccination status and vaccinating patients, using SOPs

Staff appreciated regular feedback on performance and comparison with other sites

Staff believed that their performance made the difference vaccination rates

Age group

2010 (before 4 pillars toolkit)

2011 (after 4 pillars toolkit)

P value

18-49 years

23% 32% <.001

49-64 years

35% 46% <.01

≥65 years

52% 69% <.001

Influenza vaccination rates in one urban practice

www.immunizationed.org/shotsonline.aspx

Detailed information on specific vaccines Click on buttons for more details

CDC www.cdc.gov/vaccinesIAC: www.immunize.org