1. Christine Babbel, MSPH University of Colorado Denver
Physician Knowledge and Practice Regarding Use of Hib Vaccine During Recent Shortages: A National Survey
Christine Babbel, MSPH University of Colorado Denver

2. Disclosures The authors have no relevant
financial relationships with any
commercial interests to disclose
No reference will be made to the use of
medications in manners not licensed by
the Food and Drug Administration

3. Background Haemophilus influenzae type B (Hib) Disease
Occurs primarily in infants and children < 5 years
Invasive Hib infection can cause: meningitis, pneumonia, sepsis, epiglotittis, otitis media, skin infections, and arthritis
In the U.S., Hib disease now primarily occurs in underimmunized children and infants
3%-6% of cases are fatal
Up to 20% of surviving patients have other long-term side effects (e.g.: hearing loss)
-At risk: Infants and young children , household contacts, and day-care centers, as well as American Indian/Alaska Native populations are also at increased risk.
-In 50-60% of reported invasive Hib infection causes meningitis, but can also lead to…..
-Under immunized among vaccine refusers and among infants who have not been fully vaccinated with the primary series

4. Hib Vaccination
Hib vaccine licensed in 1987 and recommended for all U.S. infants since 1991
Incidence of invasive Hib disease has decreased by 99% since licensure
Dosing schedules/Formulations
Merck (PedvaxHIB® and COMVAX® )
– 2, 4 months + 1 booster at months
Sanofi Pasteur (ActHIB® and Pentacel®)
– 2, 4, 6 months + 1 booster at months
-Licensed in 1987, recommended…..
-The incidence of invasive Hib disease in the prevaccine era was approximately cases per 100,000 children younger than 5 years old.
-COMVAX is a combo vaccine of Hep B and Hib
-Pentacel – Hib, DTaP, IPV

5. Hib Shortages
In Dec 2007, Merck voluntarily recalled ~ 1 million doses due to concerns about sterility of equipment used in manufacturing
CDC/ACIP issued interim recommendations:
Defer Hib booster in healthy month old children
Continue primary series for all children and booster dose in high-risk month olds
Shortages expected to continue through mid-2009
-Doses recalled as a precautionary measure because Merck was unable to assure the sterility of equipment used to manufacture certain lots of vaccine
-ACIP: Advisory committee on immunization practices
-HEALTHY month olds; still administer booster to children at high risk for Hib disease

6. Recent Outbreaks of Hib Disease
During ‘08-09 in Minnesota and Pennsylvania:
10 children aged 5 months to 4 years old were reported with invasive Hib disease
3 of those children died
Data suggest that most cases of Hib disease occurred in children that were not fully vaccinated
Parental refusal
Too young
-Data does suggest that the recent outbreak is unlikely due to CDC interim recommendations, but are likely linked to shortages as most cases of Hib disease occurred……
-MN cases: 1 case in a 5-month-old child too young to have finished its first series of Hib shots. Another case was in a child who got all the shots but who turned out to have an immune deficiency; the other 3 were vaccine refusers.
-PA cases:

7. Study Objectives
To determine in a nationally representative sample of pediatricians (Peds) and family medicine (FM) physicians:
1) Knowledge and attitudes about CDC’s interim recommendations
2) Current practice regarding Hib administration
3) Factors associated with not adhering to recommendations

8. Methods – Study Population
Surveyed physicians in existing sentinel network (Vaccine Policy Collaborative Initiative)
Recruited from random samples of AAP and AAFP
Quota sampling to ensure networks similar to overall AAP and AAFP memberships
Previous study* compared sentinel network to physicians randomly sampled from AMA
Sentinel networks comparable to AMA sample with respect to:
Physician demographics
Practice characteristics
Responses regarding vaccine-related issues
-Surveying the AMA is currently the most commonly used survey method
*Ref: Crane LA, Eval & Health Prof, 2008

9. Methods – Survey Administration
Survey period: April 2008
4 months post interim recommendations
Due to quick turn-around time, survey administered ONLY to sentinel network members who agreed to be surveyed by (~2/3 of each network)
Participants received an initial with link to internet survey* and up to 3 additional reminders
Because this was a short turn around survey and CDC needed results in 4 weeks, only those who wanted to be surveyed by were used
* (VoviciTM, Dulles, VA)

10. Results: Survey Response
Overall Response rate: 60% (N=372)
68% Peds, 51% FM
FM physicians who don’t immunize < 2 years excluded (n=18)
Generally, respondents were similar to non-respondents with respect to physician and practice characteristics with 2 exceptions:
FM respondents less likely to be male (52% vs. 65%)
Peds respondents had higher participation in VFC (88% vs. 77%)

11. Knowledge Regarding Interim Hib Recommendations
98% of Peds and 81% of FM aware of interim recommendations (p<0.0001)
Of those aware, 100% Peds and 99% of FM understood to defer Hib booster in healthy month olds
Main source of information for recommendations
Peds – 93% from American Academy of Pediatrics
FM – 59% from physician’s respective local/state health department

12. Attitudes Regarding Interim Recommendations
Strongly / somewhat agree that. . .
Peds FM
P-value
Interim recommendations were not clear
21%
37%
<0.01
Patients who have received the primary series of Hib vaccine will not be adequately protected until they receive their booster dose
60%
39%
FM physicians were more likely to believe that the interim recs were not clear, while Peds more likely believed that Pts. Who have received the primary series will not be adequately protected until they receive their booster dose.

13. Percent of Physicians Reporting They Experienced Shortages Requiring Deferral
When physicians were asked is they felt that their practice has experienced a Hib shortage and had to defer in any of their patient groups, 73% of Peds and 45% of FM

14. Hib Administration Practices
-about 50% of FM physicians who were not aware of recommendations were non-adherent

15. Percentage of Physicians Reporting Need to Defer Any Doses of Primary Series in 2-6 Month Olds
57%
43%
*Distributions between Peds and FM are different at p=.01 using Kolmogorov-Smirnov test

16. Factors Associated with Non-Adherence to Recommendations for Healthy 12-15 Month Olds
Peds
Adjusted OR*
(95% CI) FM
Practice has had sufficient vaccine supplies
101.1 ( )
11.0 ( )
Physician not aware of interim recommendations NS
25.3 ( )
*Adjusted for physician demographics and practice characteristics (such as gender, region, location of practice, type of practice, practice size, volume of newborns, % pts enrolled in Medicaid), attitudes and current practice
-The odds for non-adherence to recs was times higher in Peds and 11 times higher in FM if they believed that their practice had sufficient supplies and did not need to defer vaccination in any of their pt. groups.
-Additionally, the odds of non-adherence was 25.3 times higher for FM if they were not aware of interim recs
-odds ratios overestimate the effect when the outcome is common...in this case, the outcome is 20-30%

17. Strengths and Limitations
Only national survey to assess attitudes and practice regarding Hib shortage
Physicians surveyed during Hib shortage - recall bias unlikely
Limitations
Physicians surveyed only by (prior work suggests and mail responses don’t differ)
Sentinel physicians may differ from physicians overall (prior work suggests that they are representative)
Survey results represent reported practice; actual practice not observed
-Sentinel physicians may differ from physicians overall ,however, as mentioned previously, prior work shows that our sentinel networks are representative of reported physician practices nationally

18. Conclusions Knowledge:
Most physicians aware of CDC’s interim recommendations and understood to defer booster in healthy month olds
Current Practice:
Majority of Peds and close to half of FM reported experiencing shortages and > 20% reported deferring primary doses in 2-6 month olds 10% or more of the time

19. Conclusions Current Practice:
20-30% of physicians were NOT adhering to recommendations
Peds and FM physicians who reported having sufficient supplies of vaccine significantly more likely to be non-adherent
Additionally, FM physicians who reported not being aware of interim recommendations were more likely to be non-adherent

20. Discussion Non-adherence to recommendations may include:
Misinterpretation of interim recommendations: Belief that “shortages” refer to supplies at practice level rather than national level
Desire to use up vaccine supplies at the practice level due to:
Recoup up-front costs
Poor mechanisms for redistribution
No need to ration vaccine because of belief that shortage will be short-lived

21. Discussion
Confusion regarding recommendations may be related to different dosing schedules and formulations
Reported deferral of primary series is of concern and could be leading to increase carriage of Hib bacteria and decrease herd immunity, as suggested by recent Hib outbreaks
The recalled vaccine manufactured by Merck consists of a 2-dose schedule for vaccinating with the primary series, but the primary series that is available consists of 3 doses 21

22. Implications
Need for continued clarification that interim recommendations are based on supplies at national versus practice level
Clarifications regarding use of different Hib containing vaccines (e.g. Pentacel) will help to decrease confusion
Frequent updates regarding duration of shortages will be helpful for physicians in planning
Need to assure completion of the primary series in 2, 4, 6 month olds in the face of prolonged shortages
-will help to decrease confusion about different dosing schedules and formulations
-will be helpful for physicians in planning to assure that all children get vaccinated with the primary series

23. Vaccine Policy Collaborative Initiative
University of Colorado Denver
Principal Investigator - Allison Kempe, MD, MPH
Matthew F. Daley, MD
Brenda L. Beaty, MSPH
L. Miriam Dickinson, PhD
Jennifer Barrow, MSPH
Sandra Black, DVM
Christine Babbel, MSPH
Lori A. Crane, PhD, MPH
Christina Kim, MD
CDC Collaborators
Greg Wallace, MD, MS, MPH
Shannon Stokley, MPH
Funding
CDC, through Rocky Mountain Prevention Research Center

24. Additional Slides

25. Creation of Sentinel Site Network (1)
Subjects recruited from random sample of:
2500 American Academy of Pediatrics (AAP) members
3000 American Academy of Family Physicians
Up to 2 mail/ s sent to ask to participate in 2-4 surveys per year
Respondents practicing < 50% primary care excluded

26. Creation of Sentinel Site Network (2)
Respondents stratified by 3 characteristics:
Region of country (NE, S, MW, W)
Location (urban, suburban, rural)
Setting (private, managed care, community/hospital-based) – Did not have this information for AAFP participants
36 possible “cells,” (12 possible “cells” for FM), each with expected frequency based on AAP and AAFP memberships
For cells with excess (>110% predicted) respondents, a subset randomly selected for study

27. Sampling Matrix for Sentinel Sites

28. Comparison of Respondents, Non-respondents and Total Sentinel Network
Peds FM
Characteristic
Respondents
(n=220)
Non-respondents
(n=105)
Total Sentinel Network (n=429)
(n=153)
(n=149)
Total Sentinel Network (n=419)
Year of graduation, mean
1986
1987
1984
Male gender,% 53 49 51
52*
66 * 57
Region of the country, % 16 20 31 26 30
Northeast 29 23 28 14 15
South 34 43 37 32
West 18 27
Location of practice, %
Urban, inner-city 42 39 44 22
Urban non-inner-city/suburban 46 45
Rural 12 10
Type of practice, %
Private practice 87 80 86 82 76 79
Community- or hospital-based 11 19
Managed care organization 1 4 2
Participate in VFC, %
88*
77* 83 66 59 61
*p<0.05 for comparison between respondents and non-respondents within each specialty using chi-square, t-test, or Wilcoxon as appropriate.

29. Reported Ordering Information Prior to Shortages
Prior to Dec 2007:
64% of FM and 66% of Peds used Sanofi product
54% of FM and 61% of Peds used Merck product
Some physicians claimed to use both products
Ordering information:
20% of data missing
Physicians not asked about use of products during shortage
Data may not be fully reliable