Factors Influencing Completion of Multidose Vaccine Schedules in Adolescents

A Systematic Review

K. E. Gallagher; E. Kadokura; L. O. Eckert; S. Miyake; S. Mounier-Jack; M. Aldea; D. A. Ross; D. Watson-Jones

Disclosures

BMC Public Health. 2016;16(172) 

In This Article

Results

Of the 502 full texts reviewed (Fig. 1), 61 articles were eligible for inclusion (Table 3). Included articles reported completion rates for HPV (3-dose completion ranged from 27 %[15] to over 90 %[28]), HBV (27 % completion before a school mandate was introduced in California[29] to 95 % in a school-based programme in Canada[30]), varicella and hepatitis A vaccine (HAV). In the USA, the two dose series of varicella vaccine was completed within 1 year in 35.9 % of adolescents and 2 doses of HAV were completed in 40–48 %.[31] Searches returned no articles on completion of conjugate meningococcal vaccine, despite a multi-dose policy in the USA.[32] For the purposes of this review we have focused on results from multivariate analyses or qualitative findings. Data availability by country and vaccine is displayed in Table 4.

Individual Level Factors

Age. The association between age and completion was investigated in 31 articles. Multivariate analyses of at least 2 age categories within the age range of 9–19 years were conducted in 20 studies, in the USA (n = 17), Canada,[33] France,[34] and Australia.[35] Age recommendations vary across countries; results must be interpreted in context.

There is some evidence that completion rates decrease as age of vaccine initiation increases for HPV vaccine, HAV, and HBV.[15,31,36–38] In the USA, the HPV vaccine recommended age range is between 11 and 26 years; five studies state similar results among Medicaid enrolees, adjusting for insurance, race, region and year, 17 year olds were 0.84 times less likely to complete HPV vaccine compared to 11 year olds (95 % CI 0.74–0.95).[15] Among attendees of an urban hospital, in adjusted analyses, 14–17 year olds had 0.71 the odds of completion HPV vaccine when compared to 9–13 years olds (95 % CI 0.59–0.98).[37]

In the USA five further studies found no association[33,39–43] and two studies report the converse association, increased likelihood of completion with age between 13 and 17 years controlling for year, race, insurance status; this perhaps reflects the perception that it was an 'STI vaccine' in 2007–8.[44,45] No association between age and HPV vaccine completion was found in multivariate analyses in Canada although only one school grade was targeted.[33,39–43]

Race

Racial or ethnic identity was analysed in 31 studies from the USA, Australia and Greece; 18 conducted multivariate analyses. Analysis of >100,000 women in North Carolina adjusted for location, clinic, insurance, and age found Black (aOR 0.55; 95 % CI 0.53–0.56), American Indian or Alaskan (aOR 0.68; 0.61–0.77) and Hispanic (aOR 0.75; 0.72–0.79) women had 25–45 % lower likelihood of completion compared to White women.[43] Race was the only significant predictor of completion in the NIS-Teen household survey in USA.[44] Ten additional large database studies in the USA with multivariate analyses corroborate this association for both HPV and HBV vaccines.[15,16,36,37,39,40,42,43,46–48] However, no association between race and completion was found in 5 studies when controlling for gender, insurance and health clinic characteristics.[29,38,45,49,50] Hispanic adolescents were underrepresented in one survey with a low response rate.[29]

Greek non-nationals had lower completion rates (33 %) than nationals (60 %) for 2 doses of HAV.[51] In the northern territories of Australia, 3 dose coverage of HPV vaccine was lower in indigenous compared to non-indigenous groups (54 % vs. 64 %), but completion rates were the same (84 %).[52]

Insurance

Many countries have supplied HPV vaccine free-of-charge. In the USA, although the vaccine was not initially eligible for reimbursement in some health insurance plans, after it was recommended by the Advisory Committee on Immunization Practices it was included in the Vaccines for Children (VFC) programme which provides for underinsured and uninsured children.[1] Insurance status was investigated as a risk factor in 25 articles, 16 conducted multivariate analyses (15 USA, 1 France). In 2011, insurance status remained a significant predictor of HPV series completion in the USA; those publicly insured (Medicaid) were 2.08 times (95 % CI 1.16–3.7) more likely to complete compared to those with no insurance; those privately insured were not significantly more likely to complete than those on public insurance (aOR 1.16; 95 % CI 0.97–1.38) controlling for age, race, contraception use.[42] The association between insurance status and completion was stronger in 2006–8 reflecting policy changes.[16,43] In France completion rates were lower among recipients of complimentary social welfare compared to those with private insurance (aRR 0.88; 95 % CI 0.83–0.93).[34]

Longer enrolment on an insurance plan (>12 years) was associated with a 1–14 % increase in likelihood of completion of 2 doses of varicella vaccine; 9–12 % increased likelihood for HAV and 21–23 % for HBV in the vaccine safety database of almost 600,000 people in the USA between 1998 and 2004[31] controlling for age, gender, healthcare utilisation and provider characteristics.

Across the USA there are substantial differences across states in beliefs, policy, and the rapidity of implementation of changes made at the national level. In Oregon state in 2008, HPV vaccine was offered free of charge and no difference was found in completion rates between publicly and privately insured participants.[53] In Maryland in 2006–10 private insurance was found to be a risk factor for non-completion compared to those publicly insured (aOR 0.76; 95 % CI 0.59–0.98), controlling for race and age.[37] No association in multivariate analyses was seen in 5 studies in the USA.[29,39,40,44,50]

Gender

Gender was assessed in seven articles; no correlation between completion of HBV and gender was seen in unadjusted results from Greece,[51] nor in adjusted results in Australia.[35] In the USA, controlling for delivery site, age, insurance, year, chronic conditions and prior healthcare utilization, male gender was marginally associated with lower completion for varicella (aOR 0.93; 95 % CI 0.90–0.96), HAV (aOR 0.98; 0.97–0.99) and HBV (aOR 0.97; 0.96–0.98).[31] Included studies did not report completion of HPV vaccine in boys, recommendations to vaccinate boys were issued in 2015 in the USA; however, clinics in the USA with higher female:male ratios obtained higher completion rates of HPV vaccine among females (aRR 2.16; 1.13–4.13).[49]

Socio-economic Status

Socio-economic status (SES) was analysed in studies in the USA (n = 14), Canada (n = 2), UK (n = 1) and France (n = 1); 14 conducted multivariate analysis. Median neighbourhood income and average adult education,[54] parental income levels,[39,50,55] household income[56] and poverty status[45] were not associated with completion in multivariate analyses.

Every 10,000USD rise in median neighbourhood income was associated with a 15 % increase in HBV completion (aRR 1.15; 95 % CI 1.06–1.25)[47] and a 1 % increased likelihood of HPV completion in 20,000 9–17 year old American girls (aRR 1.01; 1.01–1.02).[57] Average census block education level was positively associated at a similar magnitude of effect (aRR 1.03; 1.02–1.05).[57] Adolescent girls living below the federal poverty level were signifıcantly less likely to complete vaccination compared to adolescents with household incomes > $75,000 (aOR 0.76; 0.63–0.92).[44]

The effect of SES may differ by delivery strategy; in Canadian public schools with in-school HPV vaccine delivery, completion increased as SES decreased, in Catholic schools in which the pupils relied on community delivery, completion decreased as SES decreased.[58] A linear trend with the Scottish multiple index of deprivation was found with completion but not with initiation; however, the difference between the most and least deprived groups was small (8 %) and disappeared with the administration of a catch-up dose 1 year later.[59] Girls in Canada in 2007–8 living in lower income neighbourhoods were significantly less likely to complete HPV vaccine than girls living in middle income neighbourhoods (aOR 0.45; 0.28–0.72).[33] In France compliance with the HPV vaccine schedule was lower in social welfare recipients compared to non-recipients (aRR 0.88, 0.83–0.93).[34]

Healthcare Utilization

History of health care utilization was inconsistently associated with completion. Seventeen articles from the USA, France and Australia analysed an individual's prior use of health care (defined by receipt of other recommended vaccines, or the number of prior visits to a primary health care provider) and completion of a multi-dose series of varicella, HPV or HBV vaccines. In adjusted analyses in the USA, >10 visits to a health care provider in the last year was associated with 15 % increased likelihood of HPV vaccine completion and a 4–6 % increase in HBV completion.[31] Similar findings were reported in France where compliance with the HPV vaccine regimen was 10 % higher if a girl had >6 consultations with a family physician in the past year.[34] The magnitude of the effect is supported by reports of a 2 % increased likelihood of completing the HPV vaccine series with every primary care provider visit in the past year.[36]

A further eight studies found no association between vaccine completion and the number of visits to a primary healthcare in the preceding 2 years,[60] non-acute care in the year preceding initiation,[29,33,39,44,55] previous prescriptions[47] or receipt of tetanus, diphtheria, and pertussis booster (Tdap) and meningococcal vaccines.[38]

Recorded contraceptive use (DMPA) at any time in the medical records by HPV vaccine recipients was associated with a two-fold increase (95 % CI 1.72–2.47) in the odds of HPV vaccine completion.[42] In Canada, HBV vaccination conferred 16.9 times higher odds (95 % CI 14.8–19.2) for HPV vaccine completion in comparison with those who had not received HBV. However, the association could be confounded by the differing vaccination policies and delivery strategies by school.[58] In Australia in an area with a high risk population, including young sex workers and drug users, a shorter time interval (<2 weeks) between first contact with the health care provider and initiation of vaccine series correlated with better HBV completion.[35]

Vaccine Related Knowledge

Three American studies examined knowledge in relation to completion in multivariate analysis.[45,47,55] The ability to correctly identify the number of required doses remained associated with series completion (aRR 1.38; 95 % CI 1.08–1.76).[55] Parents who remember receiving a provider recommendation for vaccination were more likely to have daughters who had completed the regimen (aOR 2.71; 1.99–3.70).[45] However, general knowledge of HPV and HBV vaccine was not associated with completion in adjusted analyses.[45,47]

Adverse Events

Three studies assessed whether experience of adverse events following HPV vaccination affected series completion in the USA. Parents of daughters who had completed the three dose series reported pain or discomfort as often as parents whose daughters were late for their second or third dose (OR 0.76; 95 % CI 0.33–1.77).[61] In a survey of over 3000 vaccine recipients[55] (response rate 27 %), multivariate analysis controlling for age, socio-economic status, health care utilization, showed reports of bruising or swelling at first dose did not affect completion of the series (aRR 0.88; 0.7–1.00). An association was not apparent for those reporting pain, syncope or dizziness.[55] A qualitative study of 18 women in the USA who did not complete the HPV vaccine series found none of them mentioned adverse events as a reason.[62]

Risk Behaviour

A variety of risk behaviours in seven studies were assessed in relation to completion of HBV or HPV vaccine schedules; no associations were found. Drug use, history of sexually transmitted infections (STIs), or alcohol use was not associated with completion in the USA.[38,47,63] In multivariate analysis in Australia, intravenous drug use, sex work, or hepatitis C status did not correlate with likelihood of completion of HPV in a health unit serving at-risk populations.[35]

Concomittant Healthcare

Three articles assessed the effect of concomitant health service delivery on adherence to HPV in the USA. Receipt of another vaccine at the time of HPV vaccination was not associated with odds of HPV completion controlling for socio-demographic and provider characteristics.[55] However, if the first dose was given at a health care provider visit which was attended primarily for another reason other than HPV, the odds of a mistimed 3rd dose were almost double (aOR 1.97; 95 % CI 1.39–2.80) than that if the first dose was at a vaccine only visit, controlling for age and race.[48] Type of visit was not associated in analysis investigating the effect of age and healthcare utilization.[41]

Access

Access to vaccination sites was assessed in two studies in the USA. Compliance to the schedule and completion of the series were not governed by proximity or mode of transportation to the clinical site.[47] Distance from home to clinic was not associated with completion controlling for age, race, and healthcare utilization.[40]

Qualitative Studies

One qualitative study investigated why 9–26 year olds did not return for the final dose of the HPV vaccine series, in non-exclusive responses: 33 % claimed they didn't know they were meant to obtain further doses, 23 % claimed they were too busy, 15 % cited inconvenience, 38.5 % claimed they were too busy or forgot, 7.7 % claimed they were too busy and times were inconvenient.[62] Two additional surveys of partially vaccinated university students in the USA and Australia indicated the potential problems with vaccinating older age groups who have competing priorities; reasons focused on inconvenience and lack of time.[64,65]

Maternal Characteristics

Three studies in the USA analyzed the relationship between maternal preventative behavior (cervical screening) and their daughter's HPV vaccine series completion. In multivariate analysis, controlling for demographic, socioeconomic, family, and health plan characteristics, all three studies found that girls whose mothers had received a pap smear in the past three years were more likely to complete the HPV vaccine series (aOR 1.07, 95 % CI 1.06–1.08);[56] 1.42, 1.31–1.54[54] and 1.87, 1.31–2.75[66]).

The relationship between maternal education and vaccine series completion was assessed in eight studies conducted in the USA (n = 7) and in Greece.[51] Adolescents whose mothers had less than high school education were less likely to complete the vaccine series in multivariate analysis;[44,66] both studies controlled for adolescent age, SES, and mother's health characteristics and found similar effect estimates (aOR 0.68; 95 % CI 0.56–0.84);[44] aOR 0.60; 0.41–0.87[66]). No association between maternal education and HPV or HAV vaccine series completion in multivariate analysis was found in three studies.[39,45,50]

Maternal age and marital status were found to have no or very slight associations with vaccine series completion in four of the five included studies.[39,44,45,66] In unadjusted analysis, one study found daughters with mothers aged over 40 years were more likely to complete the HPV vaccine series compared to mothers who were less than 40 years old.[56]

Provider/Organisational Characteristics

Delivery Model. There is strong evidence for high completion rates with school-delivery in high - income and low-middle income countries. Canadian in-school HPV vaccination completion rates were 75 % (95 % CI 74.7–75.8) compared to 36 % (95 % CI 35.3–37.2) for girls provided with a community-delivery model.[58] In-school vaccinations conferred 1.8 times the odds of completing the HBV series compared to if adolescents had to go off-site (95 % CI 1.15–2.8) in a parent survey in the USA controlling for age, race, insurance, SES, prior healthcare utilization.[29]

Only 2 articles included data from low and middle - income countries (LMIC); descriptive results are available regarding the success of different delivery strategies.[67] In Uganda, a school-based strategy appeared more successful (94 % completion) than a strategy in which the vaccine was given in the community with a child health programme (79–87 % completion year 1-year 2) although the delivery strategies had slightly different target populations. Peru's school-based strategy achieved 98.7 % completion, whilst combined school-based and health centre strategies in Vietnam achieved >99 % completion. In India, very similar completion rates were achieved in campaign and routine delivery approaches (97–98 %).[67] Differences in completion rates achieved in 21 demonstration projects in 14 countries implementing different models of delivery were insignificant;[68] however, the mixed model (school based delivery with mop-up activities at health centres) seemed to confer marginally higher completion (96.6 %), the school-only model was intermediate (88.6 %) and the health facility-only model was least effective (79.7 %)(p = 0.39).[69]

In Australia, high-risk groups, benefited from an accelerated schedule (0, 7, 21 days and 12 months), which increased the likelihood of HBV vaccine completion 1.35 times (1.01–1.80) controlling for drug use, and length of contact with the health facility.[35]

Provider Characteristics

Vaccine schedule completion was higher in an American school based programme when students returned the consent forms to their teacher compared to the school nurse.[70] In 1994–5 in Canada, initial parental consent was lower at private schools compared to public schools; however, private and public schools did not differ in completion rates. Different education providers (teachers or public health nurses) did not have an effect on completion, although education from teachers was associated with higher consent.[30]

A further 17 studies investigated health provider characteristics, of which 12 reported adjusted analyses. There was no evidence that the speciality of an adolescent girl's primary care physician influenced HPV series completion in multivariate analyses.[15,16,36,42,49,55] However, for women >17 years of age in the USA, those with a paediatric/internal medicine physician were slightly less likely to complete the HPV regimen than those with a family medicine physician. Female providers were not significantly associated with completion (male primary care provider aRR0.93 0.85–1.01).[36] In an American datalink study, those vaccinated at paediatric clinics had the highest completion (61 %) compared to family care practices (53 %; aOR 0.78; 95 % CI 0.76–0.80) and the local health departments (39 %; aOR 0.48; 0.47–0.50).[43]

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