1. Patterns of Vaccination among Adolescents: Single and Concomitant Administration of Recently Licensed Vaccines in the Vaccine Safety Datalink Population
Presented by Stephanie Irving, MHS
for the Vaccine Safety Datalink team

2. Vaccine Safety Datalink (VSD)
Collaboration between CDC and 8 managed care organizations
Data from 8.8 million members captured annually
(2.9% of US population)
Group Health Cooperative
Northwest Kaiser Permanente
HealthPartners
Harvard Pilgrim
Marshfield Clinic
No. CA Kaiser Permanente
Quick overview of data source: VSD; all sites. Distributed Data Model (CDC: Hub access); vaccination info, events, characteristics linked by study IDs.
Kaiser Permanente Colorado
So. CA Kaiser Permanente
CDC

3. Adolescent Vaccination
Pre-2005: Td booster doses and catch-up immunization only
2005: ACIP recommends 2 vaccines for adolescent use
Meningococcal conjugate (MCV4)
Tetanus, diphtheria, acellular pertussis (Tdap)
2006: ACIP recommends quadrivalent human papillomavirus vaccine for adolescent females (qHPV)
Pre-2005 – aside from high risk groups

4. MCV4 Menactra™, Sanofi Pasteur
First ACIP recommendations: February 2005
June 2007: revised recommendations
All unvaccinated persons aged years
Increasing incidence of meningococcal disease in adolescence, 10-14% CFR, 11-19% rate of sequelae.
62% of U.S. meningococcal disease occurs in ≥11 years
Vaccination of college freshmen living in dormitories can prevent 16–30 cases of meningococcal disease and one to three deaths each year.
2005: y/o, those high school entry, and increased risk; increased risk: dorm residents, military recruits, travelers to hyperendemic areas, microbiologists exposed to Neisseria meningitidis. Rates highest in kids <1 year, but rate still higher than general public. # College frosh: ~ K. Revised recs: up coverage, simplify decision to vaccinate.

5. Tdap Adacel™, Sanofi Pasteur; Boostrix™, GSK
Recommended by ACIP in June 2005
Switch from Td booster to Tdap: number of reported pertussis cases had been steadily increasing, especially among adolescents and adults
8,897 (34%) of the 25,827 reported U.S. cases in 2004 occurred among adolescents aged years (incidence: 30 per 100,000 population)
High rates in adolescents during pertussis outbreaks
MMWR March During , 11 states had an annual incidence of reported pertussis in adolescents of >50 per 100,000 population during at least 1 year

6. qHPV Gardasil™, Merck Recommended by ACIP in June 2006
Routine vaccination of year old females
Catch up vaccination of girls aged years
HPV is the most common sexually transmitted infection in the United States; an estimated 6.2 million persons are newly infected every year
Goal of adolescent vaccination: protect prior to initiation of sexual activity
3.7% of females sexually active before age 13 (2005 YBRS)
March 2007 MMWR. YRBS = Youth Behavioral Risk Survey

7. U.S. Coverage Estimates
Tdap: Significantly higher among year olds then among those aged years
MCV4: No differences by age group
qHPV: No differences by age group
Survey captures adolescents aged years; first year HPV reported (initiation of series captured).

8. Concomitant Vaccination
Definition:
Two or more vaccines administered to one person during the same office visit, but in separate syringes
Evidence supports that concomitant administration of vaccines:
Is safe and effective
Decreases health care costs
Increases the probability that a person will be fully vaccinated at appropriate ages
Recommended by ACIP, CDC, Society for Adolescent Medicine for many vaccines
Also known as “simultaneous” administration.

9. Study Objective
Describe patterns of use, including individual and concomitant administration, of three recently licensed vaccines in persons aged 7-26 years
Potential implications for vaccination policy, practice, and further research

10. Methods
Vaccination information collected for persons aged 7-26 years with at least one vaccination between June 2006 and July 2008
Population divided into age groups:
7-10 years
11-12 years* (nested group: adolescent platform)
11-18 years*
19-26 years
Any vaccine, not just the “big 3”; at participating sites (listed in acknowledgements).
* Focus of current presentation.

11. Methods Data collected for all vaccine visits* in our population
Quantified total visits for each vaccine
Determined proportion of visits where a single vaccine was administered
Determined proportion of visits where multiple vaccines were administered (concomitant administration)
Determined most common vaccine combinations
Used chi-square analyses to examine differences in administration
Combinations: commonality, proportion of visits accounted for by each combination.
* Health care encounter in which any vaccine was administered.

12. Results Vaccine MCV4 252,097 72,421 (29) Tdap 261,671 117,416 (45)
No. Visits:
11-18 Yrs
11-12 Yrs
MCV4
252,097
72,421 (29)
Tdap
261,671
117,416 (45)
qHPV-1 (1st dose)
143,805
31,370 (22)
qHPV-2 (2nd dose)
90,475
16,739 (19)
qHPV-3 (3rd dose)
51,914
8,052 (16)
qHPV (any dose), MCV4 or Tdap
576,410
166,325 (29)
“Or” row: not total due to concomitant administration of above rows; parentheses indicate % of visits by age group.

13. Results Vaccine MCV4 82 92 Tdap 78 77 qHPV-1 70 87 qHPV-2 20 24 qHPV-3
% Visits
Concomitant:
11-18 Yrs
11-12 Yrs
MCV4 82 92
Tdap 78 77
qHPV-1 70 87
qHPV-2 20 24
qHPV-3 21 23
qHPV, MCV4 or Tdap 55 66
HPV 2 and 3: lower as expected, affect on total (% single inflated)

14. As expected, concomitant administration increased with the addition of the HPV vaccine (as seen in period 2).

15. Total visits ≥2 vaccines: 337,753 Total visits ≥2 vaccines: 116,880
Vaccine Combinations
11-18 Yrs
11-12 Yrs
Total visits ≥2 vaccines: 337,753
Total visits ≥2 vaccines: 116,880
Vaccine
Combination
% Total
Concomitant
Vaccination
MCV4 + Tdap
 12 13
MCV4 + Tdap + Varicella  6 11
Tdap + HepA  5
Tdap + Varicella 9
MCV4 + HPV-1 8
MCV4 + Tdap + HepA 4

16. % Administered Concomitantly
Analysis* by Gender
11-18 yrs
11-12 yrs
% Administered Concomitantly
Female
Male
p-value
MCV4 89 79
<.00001 95
Tdap 85 78 83
As expected, higher percentages among female vaccinees.
* chi-square

17. % Administered Concomitantly
Analysis by Season
11-18 yrs
11-12 yrs
% Administered Concomitantly
Summer*
Non
p-value
HPV-1 76 74
<.00001 90 89
0.003
MCV4 80 87 91 93
Tdap 85 86
Inconsistent findings undermine significance of seasonality. *Note: explain rationale for summer definition.
* Summer season defined as June 1 – August 31.

20. Differences in Administration by Provider Type
11-18 yrs
11-12 yrs
% Administered Concomitantly
FP*
Peds
Point Est.
95% CI
HPV-1 66 80
2.05
1.96, 2.14 85 90
1.58
1.38, 1.81
MCV4 83
1.14
1.09, 1.19 92
0.99
0.88, 1.11
Tdap 78
1.32
1.27, 1.37 79 81
1.13
1.06, 1.21
* FP: referent group.

21. Major Findings
<30% of “big 3” adolescent vaccination given during adolescent platform
Overall rates of concomitant administration high among those aged 11-18, higher among persons aged years
As expected, rates increased with introduction of qHPV vaccine
Individual administration accounts for largest proportion of any one vaccine studied
Pediatricians most likely to administer adolescent vaccines concomitantly
1) Big 3: qHPV, MCV4, Tdap, 2) “Overall” rate lowered by HPV doses 2 and 3, 3) Tables in extra slides section

22. Limitations Data collection Data quality
Unable to determine individual compliance with recommended schedules
Data collected at visit level rather than individual level (pilot/exploratory)
Data quality
Visits were only matched if the individual had an outpatient visit on the same day as the vaccine visit.
SOPHIA: ramifications of data quality issue? Didn’t collect info on inpt/ED encounters? Missed vaccine visits if administrative data were dated wrong?
We did not collect information on inpatient encounters. ED and URG encounters I believe can be captured through the outpatient file, as there is a department code for them. It is possible that we missed vaccine visits based on if the wrong date was entered for the visit.

23. Conclusions
Coverage improving and rates of concomitant administration high, but missed opportunities for adolescent vaccination exist
Educational efforts could be directed at certain types of provider
Individual level data is needed to make determinations regarding up-to-date status, compliance with recommended immunization schedules

24. Acknowledgements Participating sites Co-investigators
Group Health Cooperative
Harvard Pilgrim Health Care
HealthPartners Minneapolis
Kaiser Permanente Colorado
Marshfield Clinic
Northern California Kaiser Permanente
Northwest Kaiser Permanente
Southern California Kaiser Permanente
Co-investigators
Sophia Greer, MPH
Edward Belongia, MD
James Baggs, PhD
Eric Weintraub, MPH
Gabrielle Fowler, MPH
Funded through a subcontract with America's Health Insurance Plans (AHIP), under contract from the Centers for Disease Control and Prevention (CDC).
Acknowledge co-investigators, thank site which contributed data.

25. Extra Slides

26. Combination Tables: 11-18 yrs
HPV-1 Combinations
count %
MCV4+Tdap+Varicella+HPV1
7,005 5
MCV4+Tdap+HPV1
13,954 10
MCV4+HPV1
17,193 12
Tdap+HPV1
8,811 6
Varicella+HPV1
5,687 4
HPV1
43,195 30
MCV4 Combinations
count %
MCV4
45,977 18
MCV4+Tdap
39,717 16
MCV4+Tdap+Varicella
19,607 8
MCV4+Tdap+HepA
15,019 6
MCV4+Tdap+HPV1
13,954
MCV4+HPV1
17,193 7
Tdap Combinations 
count %
MCV4+Tdap
39,717 15
MCV4+Tdap+Varicella
19,607 7
MCV4+Tdap+HepA
15,019 6
Tdap
57,419 22
Tdap+Varicella
14,830
Tdap+HepA
18,276

27. Analysis by Provider Type
11-18 yrs
11-12 yrs
% Administered Concomitantly FP IM
Peds
HPV-1 66 59 80 85 90
MCV4 83 69 92 91
Tdap 78 74 79 81
FP=Family Practice, IM=Internal Medicine, Peds=Pediatrics

28. Analysis by Provider Type: Family Practice
11-18 yrs
11-12 yrs
% Administered Concomitantly FP
Non-FP
p-value
HPV-1 66 75
<.00001 85 89
MCV4 83 84 92
0.883
Tdap 78 81 79 80
0.025
Clarify (SOPHIA): “non” = all other types where vaccines were given, how provider type identified.
These proportion are among those visits in which a provider type was identified. Non is all other vaccine visits in which a provider type was identified. Does not include those visits in which a provider type was not identified. I believe the provider type was identified by the provider or somewhere in the medical record. (We may need to check this with the DD or Eric or James)

29. Analysis by Provider Type: Internal Medicine
11-18 yrs
11-12 yrs
% Administered Concomitantly IM
Non-IM
p-value
HPV-1 59 75
<.00001 85 89
0.018
MCV4 69 91 92
0.573
Tdap 74 81 79 80
0.382

30. Analysis by Provider Type: Pediatrics
11-18 yrs
11-12 yrs
% Administered Concomitantly
Peds
Non-Peds
p-value
HPV-1 80 58
<.00001 90 85
MCV4 81 92
0.537
Tdap 83 74 76