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

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

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

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 12-15 months Sanofi Pasteur (ActHIB® and Pentacel®) – 2, 4, 6 months + 1 booster at 12-15 months -Licensed in 1987, recommended….. -The incidence of invasive Hib disease in the prevaccine era was approximately 20-90 cases per 100,000 children younger than 5 years old. -COMVAX is a combo vaccine of Hep B and Hib -Pentacel – Hib, DTaP, IPV

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 12-15 month old children Continue primary series for all children and booster dose in high-risk 12-15 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 12-15 month olds; still administer booster to children at high risk for Hib disease

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:

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

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

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 e-mail (~2/3 of each network) Participants received an initial e-mail with link to internet survey* and up to 3 additional e-mail reminders Because this was a short turn around survey and CDC needed results in 4 weeks, only those who wanted to be surveyed by email were used * (VoviciTM, Dulles, VA)

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%)

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 12-15 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

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.

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

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

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

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 (31.8-321.3) 11.0 (3.1-38.8) Physician not aware of interim recommendations NS 25.3 (4.9-130.8) *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 101.1 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%

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 e-mail (prior work suggests e-mail 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

Conclusions Knowledge: Most physicians aware of CDC’s interim recommendations and understood to defer booster in healthy 12-15 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

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

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

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

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

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

Additional Slides

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/emails sent to ask to participate in 2-4 surveys per year Respondents practicing < 50% primary care excluded

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

Sampling Matrix for Sentinel Sites

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.

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