Setting The study setting was primary care. The economic analysis was conducted in the USA.

Predicted effects of a new combination vaccine on childhood immunization coverage rates and vaccination activities Meyerhoff A S, Greenberg D P, Jacobs R J Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The study investigated the use of a new combination vaccine, the diphtheria-tetanus-acellular pertussis (DTaP)-hepatitis B (HepB)-inactivated poliovirus vaccine (IPV) (DTaP-HepB-IPV). This intervention was compared with a control intervention. The control intervention consisted of other vaccines, including combination vaccines other than DTaP- HepB-IPV. Type of intervention Primary prevention. Economic study type Cost-effectiveness analysis. Study population The study population included private paediatric-clinic patients born in mid-2001 in the USA. Patient entry criteria into the study were a visit that day, visit age younger than 2 months, and no known prior outpatient visit to any other provider. Children were excluded if records indicated no dose of any vaccine by age 25 months, no visit at age 18 to 25 months, and one or more invalid doses of DTaP, HepB-Haemophilus influenzae type B (Hib) or IPV, according to the Advisory Committee on Immunization Practices minimum age and time-interval criteria. Setting The study setting was primary care. The economic analysis was conducted in the USA. Dates to which data relate The effectiveness and resource use data were collected for patients who visited centres between 31 July 2001 and 1 May 2002. The price year was 2003. Source of effectiveness data The study population was identified by a review of records. Empirically observed vaccination histories for these children were compared with modelled vaccination histories. The modelled histories were obtained using decisionanalytic techniques to apply a series of decision rules to predict how DTaP-HepB-IPV would be used if available. Modelling A two-step model was used to assess the use of the combination vaccine. The model was applied to medical records of 775 children born in mid-2001 who received primary care. DTaP-HepB-IPV use was predicted by applying decision rules to selectively substitute it for component vaccines. The model considered the effects of DTaP-HepB-IPV on use of HepB at age less than 6 weeks, and HepB, HepB-Hib, Hib, DTaP and IPV at age 6 weeks to 2 years. To model HepB Page: 1 / 5

birth doses, the authors relied on survey research conducted prior to DTaP-HepB-IPV availability, in which paediatrician respondents were asked how their use of HepB containing vaccines might change when the new combination vaccine became available. Outcomes assessed in the review The outcomes assessed were the responses on the use of HepB-containing vaccines in current practice and in practice assuming DTaP-HepB-IPV availability. Study designs and other criteria for inclusion in the review The authors only used results from survey research (Cooper et al. 2001, see 'Other Publications of Related Interest' below for bibliographic details). Sources searched to identify primary studies Not reported. Criteria used to ensure the validity of primary studies Not reported. Methods used to judge relevance and validity, and for extracting data The validity of the primary studies does not appear to have been assessed. Number of primary studies included The authors used only results from a survey research in which 270 paediatrician responders were asked how their use of HepB-containing vaccines might change when DTaP-HepB-IPV became available. Methods of combining primary studies Not relevant. Investigation of differences between primary studies Not relevant. Results of the review Out of the 270 responders: 18 were currently starting HepB series with monovalent vaccines with a birth dose, and if the DTaP-HepB-IPV vaccines were to become available they would start HepB series with combination vaccines with a birth dose. 30 were currently starting HepB series with monovalent vaccines with a birth dose, and if the DTaP-HepB-IPV vaccines 29 were currently starting HepB series with combination vaccines with a birth dose, and if the DTaP-HepB-IPV vaccines were to become available they would start HepB series with combination vaccines with a birth dose. 20 were currently starting HepB series with combination vaccines with a birth dose, and if the DTaP-HepB-IPV vaccines Page: 2 / 5

1 was currently starting HepB series with monovalent vaccines, but not at birth, and if the DTaP-HepB-IPV vaccines were to become available he/she would start HepB series with combination vaccines with a birth dose. 29 were currently starting HepB series with monovalent vaccines, but not at birth, and if the DTaP-HepB-IPV vaccines 4 were currently starting HepB series with combination vaccines, but not at birth, and if the DTaP-HepB-IPV vaccines were to become available they would start HepB series with combination vaccines with a birth dose. 73 were currently starting HepB series with combination vaccines, but not at birth, and if the DTaP-HepB-IPV vaccines Using these survey responses, the authors transformed these data into probabilities to use in their model. Measure of benefits used in the economic analysis The measures of health benefits were the receipt of three or more valid doses of each of DTaP, HepB and IPV by 2 years of age, vaccine injections, and coverage rates at 1, 1.5 and 2 years. Direct costs The direct costs included in the analysis were those to the health care system. These were for vaccine administration and vaccine acquisition. Vaccine administration covered clinic costs for vaccine supplies and labour, vaccine preparation and administration, immunisation record entries, securing informed consent for vaccination, and vaccine inventory management. The vaccine acquisition costs were weighted to reflect a 50%/50% distribution of public and private sector vaccine purchases, and private and public sector costs per dose were obtained from the US Centres for Disease Control. The health system costs associated with vaccine-preventable illness morbidity and mortality were not considered. Although the costs were incurred during 2 years, discounting was not performed. The study reported the average costs. The price year was 2003. Statistical analysis of costs The costs were treated stochastically. A paired t-test was used to test differences in the costs. Differences were considered significant at p<0.05. Indirect Costs The indirect costs were not included. Currency US dollars ($). Sensitivity analysis A series of one-way sensitivity analyses were performed by varying selected parameter values by +/- 30%. Such parameters included the probabilities of starting the HepB series with a birth dose, the rate of deferring one or more doses for visits at which five antigens are due, DTaP-HepB-IPV acquisition cost and vaccine administration costs. Estimated benefits used in the economic analysis At 2 years of age, DTaP-HepB-IPV would increase the proportion of children receiving three or more doses of DTaP (95.6% versus 96.4%; p=0.02), HepB (91.7% versus 95.2%; p<0.001), IPV (90.7% versus 96.3%; p<0.001), and each of these vaccines (86.2% versus 94.6%; p<0.001), compared with those receiving each component in singular or combination vaccines other than DTaP-HepB-IPV. Page: 3 / 5

The use of DTaP-HepB-IPV showed that all the DTaP-, HepB- and IPV-coverage rates were significantly (p<0.05) increased at each of the ages 1, 1.5 and 2 years, with the exception of four or more DTaP doses at ages 1.5 and 2 years. The use of DTaP-HepB-IPV reduced the number of vaccine injections per child at age 0 to 2 years by 16%, (p<0.001). Cost results The costs of DTaP-HepB-IPV vaccination were found to be $681 per child, compared with $698 per child when using single or combination vaccines other than DTaP-HepB-IPV. This difference did not reach statistical significance, (p=0.35). Synthesis of costs and benefits The costs and benefits were not combined as DTaP-HepB-IPV was found to be more effective, and at a minimum as costly as other single or combination vaccines. Varying parameter estimates in the model by +/- 30% had no impact on the model's results. Authors' conclusions The diphtheria-tetanus-acellular pertussis (DTaP)-hepatitis B (HepB)-inactivated poliovirus vaccine (IPV) (DTaP-HepB- IPV) improved immunisation coverage rates whilst reducing the number of vaccine injections and costs. CRD COMMENTARY - Selection of comparators A justification was given for using monovalent or combination vaccines other than DTaP-HepB-IPV as the comparator. These vaccines represented current practice in the authors' settings. You should decide if the comparator used represents current practice in your own setting. Validity of estimate of measure of effectiveness The study population was identified by a review of records. Empirically observed vaccination histories for these children were compared with modelled vaccination histories obtained using decision-analytic techniques to apply a series of decision rules to predict how DTaP-HepB-IPV would be used if available. The authors adequately reported how their study population was identified, and provided details of the survey used to derive the probabilities of further DTaP use. Validity of estimate of measure of benefit The estimation of benefits was modelled. The model was difficult to understand because of the number of decision rules the authors introduced into their model. Validity of estimate of costs All the cost categories relevant to the perspective of the health care system were included in the analysis. However, some relevant costs were omitted from the analysis. For example, the authors did not include the costs associated with vaccine-preventable illness morbidity. As the new combination vaccine was found to have higher coverage rates than old vaccines, it is likely that this omission biased the results in favour of the comparator (i.e. old vaccines). Resource use and costs were not reported separately, which will limit the generalisability of the authors' results. The costs were derived from published sources. Appropriate sensitivity analyses were performed by varying the costs of vaccine acquisition and administration by +/- 30%. Discounting was relevant, as the costs were incurred during 2 years, but was not performed. The price year was reported, which will aid any future inflation exercises. Other issues Page: 4 / 5

Powered by TCPDF (www.tcpdf.org) The authors did not compare their results with any other economic evaluation; this might indicate that this is the first study to assess the cost-effectiveness of the DTaP-HepB-IPV vaccine. The issue of generalisability to other settings was partly addressed in the sensitivity analysis. The authors do not appear to have presented their results selectively, although the model used was difficult to follow and understand given the great number of decision rules the authors used. The authors reported a number of further limitations to their study. First, they relied on a physician survey to predict DTaP-HepB-IPV availability, and not empirical information. Second, their decision rules were simply predictors of practice. Third, their model was based on patients from patient paediatrician clinics, which might not be representative of all children. Fourth, the authors did not assess hepatitis B surface antigen (HBsAg) status, and, therefore, the model might have included children born of HBsAg-positive mothers. Finally, the costs were measured for a health system perspective and, accordingly, did not assess financial effects on paediatricians. Implications of the study The authors reported that well-designed empirical studies will better assess compliance effects and coverage rates. Source of funding Funded through an unrestricted research grant from GlaxoSmithKline. Bibliographic details Meyerhoff A S, Greenberg D P, Jacobs R J. Predicted effects of a new combination vaccine on childhood immunization coverage rates and vaccination activities. Disease Management and Health Outcomes 2005; 13(5): 317-326 Other publications of related interest Cooper A, Yusuf H, Rodewald L, et al. Attitudes, practices, and preferences of paediatricians regarding initiation of hepatitis B immunisation at birth. Pediatrics 2001;108:E98. Meyerhoff AS, Jacobs RJ. Do too many shots due lead to missed vaccination opportunities? Prev Med 2005;41:540-4. Meyerhoff AS, Weniger BJ, Jacobs RJ. Economic value to parents of reducing the pain and emotional distress of childhood vaccine injections. Pediatr Infect Dis J 2001;20(11 Suppl):S57-62. Indexing Status Subject indexing assigned by CRD MeSH Cost-Benefit Analysis; Diphtheria-Tetanus-acellular Pertussis Vaccines; Hepatitis B Vaccines; Humans; Immunization Programs /economics; Immunization Schedule; Infant; Poliovirus Vaccine, Inactivated; Vaccines, Combined /administration & dosage /economics AccessionNumber 22005001592 Date bibliographic record published 28/02/2007 Date abstract record published 28/02/2007 Page: 5 / 5