Maternal varicella antibodies in children aged less than one year: Assessment of antibody decay.

OBJECTIVES: To investigate maternal antibody levels to varicella in infants <12 months of age in Ontario, Canada. STUDY DESIGN: In this study, we included specimens from infants <12 months of age, born at ≥37 weeks gestational age, who had sera collected at The Hospital for Sick Children (Toronto, Canada) between 2014-2016. We tested sera using a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). We measured varicella susceptibility (antibody concentration <150mIU/mL) and mean varicella antibody concentration, and assessed the probability of susceptibility and concentration between one and 11 months of age using multivariable logistic regression and Poisson regression. RESULTS: We found that 32% of 196 included specimens represented infants susceptible to varicella at one month of age, increasing to nearly 80% at three months of age. At six months of age, all infants were susceptible to varicella and the predicted mean varicella antibody concentration declined to 62 mIU/mL (95% confidence interval 40, 84), well below the threshold of protection. CONCLUSIONS: We found that varicella maternal antibody levels wane rapidly in infants, leaving most infants susceptible by four months of age. Our findings have implications for the timing of first dose of varicella-containing vaccine, infection control measures, and infant post-exposure prophylaxis recommendations.

Cost-effectiveness analysis of nirsevimab and maternal RSVpreF vaccine strategies for prevention of Respiratory Syncytial Virus disease among infants in Canada: a simulation study.

Background: The cost-effectiveness of immunisation strategies with a long-acting monoclonal antibody (nirsevimab) and/or a protein-based maternal vaccine (RSVpreF) for protecting infants from Respiratory Syncytial Virus (RSV)-associated illness has not been previously determined for Canada. We estimated the health benefits and cost-effectiveness of nirsevimab for immunising the entire birth cohort, regardless of gestational age or other risk factors. Additionally, we evaluated the health benefits and cost-effectiveness of a combined strategy of year-round vaccination of pregnant women with RSVpreF and immunisation of infants at high risk, including those born preterm or with chronic conditions, with nirsevimab during the RSV season. Methods: We developed a discrete-event simulation model, parameterized with the data on medically-attended RSV infections among infants under one year of age from 2010 to 2019, including outpatient care, hospitalisations, and deaths. Intervention scenarios targeting twelve monthly birth cohorts and pregnant women, reflecting the 2021 census data for Ontario, Canada were evaluated over a follow-up time horizon of one year from birth. Taking into account the costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using the quality-adjusted life-year (QALY) gained. Further, we determined the range of price-per-dose (PPD) for nirsevimab and RSVpreF within which the program was cost-effective. Cost-effectiveness analyses were conducted from both healthcare and societal perspectives. Findings: Using a willingness-to-pay of CAD$50,000 per QALY gained, we found that immunising the entire birth cohort with nirsevimab would be cost-effective from a societal perspective for a PPD of up to $290, with an annual budget impact of $83,978 for 1113 infants per 100,000 population. An alternative, combined strategy of vaccinating pregnant women and immunising only infants at high risk of severe disease would lead to a lower budget impact of $49,473 per 100,000 population with a PPD of $290 and $195 for nirsevimab and RSVpreF vaccine, respectively. This combined strategy would reduce infant mortality by 76%-85%, comparable to a 78% reduction achieved through a nirsevimab-only program of the entire birth cohort. The PPD for cost-effective programs with nirsevimab was sensitive to the target population among infants. Interpretation: Passive immunisation of infants under 6 months of age with nirsevimab and vaccination of pregnant women with RSVpreF could be a cost-effective strategy for protecting infants during their first RSV season. Funding: This study was supported by the Canadian Immunisation Research Network (CIRN) and the Canadian Institutes of Health Research (CIHR). Seyed M. Moghadas acknowledges support from the Natural Sciences and Engineering Research Council of Canada (MfPH and Discovery grants). Alison P. Galvani acknowledges support from the The Notsew Orm Sands Foundation.

Effectiveness and cost-effectiveness of RSV infant and maternal immunization programs: A case study of Nunavik, Canada.

BACKGROUND: Despite passive immunization with palivizumab to select high-risk children under two years of age, the health and economic burden of respiratory syncytial virus (RSV) remains substantial. We evaluated the effectiveness and cost-effectiveness of immunization programs with new generations of RSV prophylactics, including long-acting monoclonal antibodies (LAMA) and maternal vaccines, in terms of reducing hospitalizations in Nunavik, a Canadian Arctic region. METHODS: We developed an agent-based model of RSV transmission and parameterized it with the demographics and burden of RSV in Nunavik, Québec. We compared various immunization strategies, taking into account the costs associated with program delivery and calculating the incremental cost-effectiveness ratio (ICER) using quality-adjusted life-years (QALYs) gained as a measure of effectiveness. Scenario analyses included immunization with palivizumab and LAMA for infants under one year of age, and maternal vaccination in mild, moderate, and severe RSV seasons. Data were analysed from November 1, 2019 to May 1, 2021. FINDINGS: We found that a Nunavik pilot program with palivizumab which included healthy full-term infants aged 0-2 months in addition to those considered high-risk for complicated RSV disease is not cost-effective, compared to offering palivizumab only to preterm/chronically ill infants under 1 year of age. Using LAMA as prophylaxis produces ICER values of CAD $39,414/QALY (95% Credible Interval [CrI]: $39,314-$40,017) in a mild season (moderately cost-effective) and CAD $5,255/QALY (95% CrI: $5,222-$5,307) in a moderate season (highly cost-effective). LAMA was a dominant (cost-saving with negative incremental costs and positive incremental effects) strategy in a severe RSV season. Maternal vaccination combined with immunization of preterm/chronically ill infants 3-11 months was also a dominant (cost-saving) strategy in all seasons. INTERPRETATION: The switch from palivizumab in RSV immunization programs to new prophylactics would lead to significant savings, with LAMA being an effective strategy without compromising benefits in terms of reducing hospitalizations.

Pertussis vaccination in pregnancy in Canada: a cost-utility analysis.

BACKGROUND: The Canadian National Advisory Committee on Immunization recommends universal vaccination against pertussis in pregnancy. We assessed the cost-effectiveness of vaccination with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in pregnancy in Canada. METHODS: We conducted a cost-utility analysis comparing a vaccination program to no program corresponding with the 2017 Canadian guideline for economic evaluation from the Canadian Agency for Drugs and Technologies in Health. We developed 2 models - part decision tree, part Markov model - to estimate the long-term cost and quality-adjusted life-years (QALYs) for pregnant women and their infants. We obtained epidemiologic data from 2006 to 2015, and derived costs and utility values from relevant sources. Results were reported in 2019 Canadian dollars. We obtained expected values through probabilistic analysis, with methodologic and structural uncertainty assessed through scenario analyses. The analysis adopted an acquisition price of Tdap vaccine of $12.50, with scenario analysis conducted to identify the threshold price for vaccination to be cost-effective. RESULTS: In the base-case scenario, for every 1000 pregnant women vaccinated, the program would lead to a gain of 0.3 QALYs, occurring solely in infants, at an increased total cost of $12 987, or $44 301 per QALY gained. Based on a threshold of $50 000 per QALY gained, vaccination would have been cost-effective in 6 of the 10 years included in the model (range of incremental costs $20 463-$100 348 per QALY gained). The threshold cost for Tdap vaccine to be cost-effective over the 10-year horizon was $14.03. INTERPRETATION: Based on a threshold of $50 000 per QALY gained, vaccination against pertussis in pregnancy would be cost-effective if the acquisition cost per vaccine were $14.03 or less. Province- and territory-specific analyses should be done to inform local decision-making.

Active surveillance of acute paediatric hospitalisations demonstrates the impact of vaccination programmes and informs vaccine policy in Canada and Australia.

Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases' surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.

Burden of Children Hospitalized With Pertussis in Canada in the Acellular Pertussis Vaccine Era, 1999-2015.

BACKGROUND: Recent increases in pertussis morbidity and mortality rates among young infants have led to a recommendation in some countries for vaccination against pertussis during pregnancy. Having data on the burden of pediatric pertussis in a large population over time is important for establishing the true burden of disease in the acellular pertussis (aP) vaccine era. Here, we describe age-specific epidemiology and morbidity and mortality rates in children hospitalized with pertussis over 17 years across Canada in the aP vaccine era. METHODS: Patients aged ≤16 years who were admitted to 1 of 12 pediatric tertiary-care hospitals across Canada between 1999 and 2015 with confirmed (laboratory-confirmed or epidemiologically linked) or probable (clinically diagnosed) pertussis were included. RESULTS: Overall, 1402 patients with pertussis were included. Infants aged <2 months had the highest mean annual incidences of pertussis hospitalization and intensive care unit (ICU) admission (116.40 [95% confidence interval (CI), 85.32-147.49] and 33.48 [95% CI, 26.35-40.62] per 100 000 population, respectively). The overall proportion of children who required ICU admission was 25.46%, and the proportion was highest in infants aged <2 months (37.90%). Over the span of this study, 21 deaths occurred. Age of <16 weeks, prematurity, encephalopathy, and a confirmed pertussis diagnosis were independent risk factors for ICU admission. Age of <4 weeks, prematurity, and female sex were independent risk factors for death. CONCLUSIONS: In the aP vaccine era, endemic pertussis still contributes considerably to childhood morbidity and death, particularly in infants aged <2 months. Vaccination against pertussis during pregnancy has the potential to reduce this disease burden.

Assessment of population immunity to measles in Ontario, Canada: a Canadian Immunization Research Network (CIRN) study.

Canada eliminated measles in 1998. We conducted a sero-epidemiology study to estimate population immunity to measles in the province of Ontario, Canada and to identify groups at higher risk of outbreaks. We used a previously developed modified enzyme immunoassay to test 1,199 residual sera from patients aged 1-39 years. We re-tested negative and equivocal sera using a plaque reduction neutralization assay. We interpreted our results in the context of Ontario's immunization program and vaccine coverage data. Of 1,199 sera, 1035 (86.3%, 95% confidence interval (CI) 84.4, 88.2) were above the measles threshold for protection, 70 (5.8%, 95% CI 4.5, 7.2) were equivocal and 94 (7.8%, 95% CI 6.3, 9.4) were negative. The proportion of positive sera was highest for those 1-5 years, with 180/199 (90.5%, 95% CI 86.4, 94.5) positive sera, and lowest for those age 12-19 years, at 158/199 (79.4%, 95% CI 73.8, 85.0). Adjusted for age, females were more likely than males to have antibody titers above the threshold of protection (odds ratio = 1.60, 95% CI 1.14, 2.24). Most of the study cohort were eligible for two measles vaccine doses, and vaccine uptake in Ontario is >90% for school-aged cohorts. We observed a higher than expected proportion of sera with antibody levels below the threshold of protection, suggesting that immunity in some Ontario age-groups may be waning, despite high vaccine coverage. Alternatively, the traditional measles correlates of protection may not be an appropriate measure of population protection in measles-eliminated settings.

The role of healthcare provider attitudes in increasing willingness to accept seasonal influenza vaccine policy changes.

BACKGROUND: This research explored the role of attitudes in acceptance of organizational change initiatives. METHODS: A survey assessed factors associated with health care provider (HCP) likelihood to accept seasonal influenza vaccine policy changes. We evaluated the impact of knowledge and individual attitudes on this outcome measure. RESULTS: Knowledge of seasonal influenza vaccine and influenza recommendations was a significant predictor of HCP's attitudes toward vaccine at the individual (p<0.001), organizational (p<0.05), and legislative level (p<0.05). Mixed results were obtained when investigating the impact of knowledge on actual willingness to accept vaccine, suggesting that knowledge was only a significant predictor at the organizational (p<0.05) and legislative levels (p<0.05). Attitudes fully mediated the impact of knowledge at both the organizational and legislative levels. INTERPRETATION: Knowledge of seasonal influenza and vaccine recommendations is an important, but insufficient predictor of willingness to accept policy change.

Hospitalization for Influenza A Versus B.

BACKGROUND: The extent to which influenza A and B infection differs remains uncertain. METHODS: Using active surveillance data from the Canadian Immunization Monitoring Program Active at 12 pediatric hospitals, we compared clinical characteristics and outcomes of children ≤16 years admitted with laboratory-confirmed influenza B or seasonal influenza A. We also examined factors associated with ICU admission in children hospitalized with influenza B. RESULTS: Over 8 nonpandemic influenza seasons (2004-2013), we identified 1510 influenza B and 2645 influenza A cases; median ages were 3.9 and 2.0 years, respectively (P < .0001). Compared with influenza A patients, influenza B patients were more likely to have a vaccine-indicated condition (odds ratio [OR] = 1.30; 95% confidence interval [CI] = 1.14-1.47). Symptoms more often associated with influenza B were headache, abdominal pain, and myalgia (P < .0001 for all symptoms after adjustment for age and health status). The proportion of deaths attributable to influenza was significantly greater for influenza B (1.1%) than influenza A (0.4%); adjusted for age and health status, OR was 2.65 (95% CI = 1.18-5.94). A similar adjusted OR was obtained for all-cause mortality (OR = 2.95; 95% CI = 1.34-6.49). Among healthy children with influenza B, age ≥10 years (relative to <6 months) was associated with the greatest odds of ICU admission (OR = 5.79; 95% CI = 1.91-17.57). CONCLUSIONS: Mortality associated with pediatric influenza B infection was greater than that of influenza A. Among healthy children hosptialized with influenza B, those 10 years and older had a significant risk of ICU admission.

Toward more specific and transparent research and development costs: the case of seasonal influenza vaccines.

BACKGROUND: The ability to calculate the development costs for specific medicines and vaccines is important to inform investments in innovation. Unfortunately, the literature is predominated by non-reproducible studies only measuring aggregate level drug research and development (R&D) costs. We describe methodology that improves the transparency and reproducibility of primary indication expected R&D expenditures. METHODS: We used publically accessible clinical trial data to investigate the fate of all seasonal influenza vaccine candidates that entered clinical development post year 2000. We calculated development times and probabilities of success for these candidates through the various phases of clinical development. Clinical trial cost data obtained from university based clinical researchers were used to estimate the costs of each phase of development. The cost of preclinical development was estimated using published literature. RESULTS: A vaccine candidate entering pre-clinical development in 2011 would be expected to achieve licensure in 2022; all costs are reported in 2022 Canadian dollars (CAD). After applying a 9% cost of capital, the capitalized total R&D expenditure amounts to $474.88 million CAD. CONCLUSION: Clinical development costs for vaccines and drugs can be estimated with increased specificity and transparency using public sources of data. The robustness of these estimates will only increase over time due to public disclosure incentives first introduced in the late 1990s. However, preclinical development costs remain difficult to estimate from public data.

Approved but non-funded vaccines: accessing individual protection.

Funded immunization programs are best able to achieve high participation rates, optimal protection of the target population, and indirect protection of others. However, in many countries public funding of approved vaccines can be substantially delayed, limited to a portion of the at-risk population or denied altogether. In these situations, unfunded vaccines are often inaccessible to individuals at risk, allowing potentially avoidable morbidity and mortality to continue to occur. We contend that private access to approved but unfunded vaccines should be reconsidered and encouraged, with recognition that individuals have a prerogative to take advantage of a vaccine of potential benefit to them whether it is publicly funded or not. Moreover, numbers of "approved but unfunded" vaccines are likely to grow because governments will not be able to fund all future vaccines of potential benefit to some citizens. New strategies are needed to better use unfunded vaccines even though the net benefits will fall short of those of funded programs. Canada, after recent delays funding several new vaccine programs, has developed means to encourage private vaccine use. Physicians are required to inform relevant patients about risks and benefits of all recommended vaccines, publicly funded or not. Likewise, some provincial public health departments now recommend and promote both funded and unfunded vaccines. Pharmacists are key players in making unfunded vaccines locally available. Professional organizations are contributing to public and provider education about unfunded vaccines (e.g. herpes zoster, not funded in any province). Vaccine companies are gaining expertise with direct-to-consumer advertising. However, major challenges remain, such as making unfunded vaccines more available to low-income families and overcoming public expectations that all vaccines will be provided cost-free, when many other recommended personal preventive measures are user-pay. The greatest need is to change the widespread perception that approved vaccines should be publicly funded or ignored.

Cost effectiveness of infant vaccination for rotavirus in Canada.

INTRODUCTION: Rotavirus is the main cause of gastroenteritis in Canadian children younger than five years of age, resulting in significant morbidity and cost. The present study provides evidence on the cost effectiveness of two alternative rotavirus vaccinations (RotaTeq [Merck Frosst Canada Ltd, Canada] and Rotarix [GlaxoSmithKline, Canada]) available in Canada. METHODS: Analysis was conducted through a Markov model that followed a cohort of children from birth to five years of age. Analysis used pertinent data on the natural history of rotavirus and the effects of vaccination. Estimates of heath care costs for children requiring hospitalizations and emergency department visits were derived from the Canadian Immunization Monitoring Program, Active (IMPACT) surveillance, emergency department studies, as well as other Canadian studies. The model estimated the effect of vaccination on costs and quality-adjusted life years (QALYs). RESULTS: The incremental cost per QALY gained from the health care system perspective was $122,000 for RotaTeq and $108,000 for Rotarix. From the societal perspective, both vaccination strategies were dominant - both cost saving and more effective. The cost-effectiveness of vaccination is dependent on the mode of administration, the perspective adopted and the cost of the vaccine. CONCLUSIONS: From a societal perspective, a universal vaccination program against rotavirus will be both cost saving and more effective than no vaccination. Becasue the majority of rotavirus infections do not require emergency department visits or hospital admission, from a health care system perspective, a program would not be considered cost effective.

INTRODUCTION: Le rotavirus est la principale cause de gastroentérite chez les enfants canadiens de moins de cinq ans, ce qui s'associe à une morbidité et à des coûts considérables. La présente étude expose des données probantes sur le rapport coût-efficacité de deux vaccins contre le rotavirus (RotaTeq [Merck Frosst Canada Ltée, Canada] et Rotarix [GlaxoSmithKline, Canada]) offerts au Canada. MÉTHODOLOGIE: Les chercheurs ont effectué l'analyse au moyen d'un modèle de Markov qui consistait à suivre une cohorte d'enfants entre la naissance et cinq ans. L'analyse faisait appel à des données pertinentes sur l'évolution naturelle du rotavirus et sur les effets de la vaccination. Les évaluations des coûts de santé à l'égard des enfants devant être hospitalisés et consulter à l'urgence étaient tirées de la surveillance du Programme canadien de surveillance active de l'immunisation (IMPACT), d'études des départements d'urgence et d'autres études canadiennes. Le modèle a permis d'évaluer l'effet de la vaccination sur les coûts et les années de vie ajustées en fonction de la qualité (AVAQ). RÉSULTATS: Le coût incrémentiel par AVAQ épargné par le système de santé s'élevait à 122 000 $ à l'aide du vaccin RotaTeq et à 108 000 $ à l'aide du vaccin Rotarix. Sur le plan sociétal, les deux stratégies vaccinales étaient dominantes, c'est-à-dire qu'elles étaient à la fois rentables et plus efficaces. Le rapport coût-efficacité de la vaccination dépend du mode d'administration, de la perspective adoptée et du coût du vaccin. CONCLUSIONS: Sur le plan sociétal, un programme de vaccination universel contre le rotavirus sera à la fois rentable et plus efficace que l'absence de vaccination. Puisque la majorité des infections à rotavirus n'exigent pas de consultation à l'urgence ou d'hospitalisation, le programme ne serait pas rentable pour le système de santé.

The hidden costs and characteristics of childhood rotavirus emergency visits in Canada.

BACKGROUND: Administrative databases are often used to determine burden of rotavirus disease in emergency departments (EDs). Our objective was to describe rotavirus ED visits to include healthcare utilization pre- and postvisit to estimate true societal costs. METHODS: During rotavirus seasons in 2007, 2008, and 2009, a convenience sample of children <3 years of age with vomiting and/or diarrhea and rotavirus in stool samples at ED visits was identified at 5 pediatric hospitals in Canada. Interviews took place within 24 hours and 2 weeks after diagnosis, and ED charts were reviewed. Using unit costs for all resources, healthcare and societal costs were determined in Canadian dollars. RESULTS: A total of 199 children (mean age, 16 months; range, 1-35 months) had rotavirus and had a completed initial questionnaire on record. Prior healthcare provider visits had occurred in 104 (52.3%) before and 50/172 (29.1%) children 2 weeks after the ED visit. The mean healthcare cost of the ED visit alone was $218.10 (95% confidence interval [CI]: $198, $238), and the mean societal cost was $261.40 (95% CI: $240, $283). Including both total healthcare and parental costs, this increased to a mean total societal cost of $674.80 (95% CI: $578, $771) per episode of rotavirus infection. CONCLUSIONS: Both the pre- and postvisit costs contribute substantially to the societal costs associated with an ED visit for rotavirus infection. In Canada, we estimate that the annual healthcare cost for children requiring a rotavirus ED visit ranges from $4.5 to $9.3 million, but when parental costs are included, the total societal cost ranges from $8.9 to $18.4 million.

Optimizing Canadian public immunization programs: a prescription for action.

Recent expansion of public vaccination programs for children and youth offers new health benefits but at substantially increased cost. As with other large public investments, immunization programs ought to be systematically evaluated for safety, effectiveness and economic value. At present, program evaluations are suboptimal in most provinces and territories. Experts in public health and vaccinology who attended a workshop in 2009 reviewed the shortcomings and produced "prescriptions for action" to improve matters. Six key recommendations were made: 1) a formal requirement should exist to evaluate all public vaccination programs appropriately; 2) greater voluntary harmonization of programs will facilitate evaluations; 3) a mechanism is needed to prioritize and coordinate program-specific evaluations; 4) new funding mechanisms are needed for basic jurisdictional studies and joint studies of broad relevance; 5) strong emphasis is needed on capacity development and training; and 6) administrative barriers to accessing health information systems and publishing evaluation studies need to be overcome. The expert group considered the need to improve program evaluations as urgent and compelling, with success achievable with dedicated funding and effective leadership. Demonstrating that Canadian immunization programs are among the world's best and safest is a sound strategy for maintaining public participation in those programs.

Assessment of the compatibility of co-administered 7-valent pneumococcal conjugate, DTaP.IPV/PRP-T Hib and hepatitis B vaccines in infants 2-7 months of age.

This study assessed compatibility of concurrently administered 7-valent pneumococcal conjugate (PCV7), hepatitis B (HB) and DTaP.IPV/Hib vaccines. Infants were given DTaP.IPV/Hib and HB at 2, 4, 6 months and randomly assigned (2:1) to receive PCV7 concurrently or sequentially (at 3, 5, 7 months). Antibody levels were compared in 246 concurrent and 122 sequential vaccinees. Responses to PCV7, DTaP.IPV/Hib and HB were generally unaltered with concurrent administration except that Hib responses were increased (p=0.008) and HB responses were reduced (p=0.006) with concurrent dosing, the latter possibly from same thigh injection with DTaP.IPV/Hib. We conclude that PCV7, DTaP.IPV/Hib and HB are compatible with concurrent, separate injections.

Canadian Association for Immunization Research and Evaluation (CAIRE) guidelines for industry-sponsored clinical trial and epidemiology contract research.

In response to concerns about interactions of academic and public health investigators with industry, the Canadian Association for Immunization Research and Evaluation (CAIRE), in collaboration with six major vaccine manufacturers, developed guidelines for participation in industry-sponsored clinical trial and epidemiology contract research within Canada. Topics addressed include definition of investigators, data ownership, protocol development, data management, data analysis, producing a study report and publication of the results of the study.

A pilot study to quantify parental anxiety associated with enrollment of an infant or toddler in a phase III vaccine trial.

We sought to measure the anxiety felt by parents at the time of entry into a randomized controlled vaccine trial, and to determine if anxiety level was associated with parental demographic variables or past experience. The children were 2-month-old infants entering a randomized controlled clinical trial (RCT) of a diphtheria-tetanus toxoid-acellular pertussis vaccine adsorbed with Haemophilus influenzae B conjugate, or toddlers enrolling in a RCT of a Meningococcal C conjugate vaccine. Nurses interviewed parents to collect demographic data and parents self-administered the Spielberger Self-evaluation Questionnaire (State Anxiety STAI-Y-I) [Manual for the State-Trait Anxiety Inventory (Form Y) (Self-evaluation Questionnaire), Consulting Psychologists Press Inc., Palo Alto, 1983], a validated instrument measuring the temporary condition of "state anxiety." A regression tree (CART) (S-Plus) was used to identify factors associated with higher anxiety scores. Parents of 97 children enrolled. Anxiety scores ranged from 22.75 (lower anxiety) to 36.43 (higher anxiety). The regression tree identified a structured tree with six branches. The highest anxiety scores occurred in fathers with education less then grade 8, mothers with education less than high school, birth order of the child less then the third, previous serious illness in the family, or lack of experience with research. In a group of parents agreeing to enroll their infant or toddler in a vaccine study, certain attributes and experiences were associated with higher anxiety at the time of immunization in the context of a RCT. These factors should be considered by vaccine researchers in the recruitment process of clinical trials.