the use of a combination of diphtheria, tetanus, and whole-cell pertussis vaccine (DTwP); and

Transcription

1 Economic evaluation of use of diphtheria, tetanus, and acellular pertussis vaccine or diphtheria, tetanus, and whole-cell pertussis vaccine in the United States, 1997 Ekwueme D U, Strebel P M, Hadler S C, Meltzer M I, Allen J W, Livengood J R 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 evaluated two vaccination programmes for children: the use of a combination of diphtheria, tetanus, and whole-cell pertussis vaccine (DTwP); and the use of a combination of diphtheria, tetanus, and acellular pertussis vaccine (DTaP). Type of intervention Paediatric vaccination. Economic study type Cost-effectiveness analysis. Study population The study population was represented by a hypothetical US birth cohort of 4.1 million children, who were evaluated from birth until the age of 15 years. Setting The clinical setting was not stated, but presumably the screening can be conducted in a physician's office (primary care). The study was carried out in the USA. Dates to which data relate The effectiveness evidence and the resource use data were derived from studies published from 1976 to The price year was Source of effectiveness data The effectiveness evidence was derived from published studies and the opinions of experts. Outcomes assessed in the review The outcomes assessed from the literature, quoted per 100,000, were: the number of children with pertussis hospitalised (or not) with both the vaccine programmes; and the numbers of deaths, seizures, and cases of pneumonia and encephalopathy. Specific major adverse events, and related physician visits and hospitalisations, were also assessed. These included the following: Page: 1 / 7

2 hypotonic hyporesponsive episodes; anaphylaxis; uncomplicated seizures; protracted crying or screaming; acute encephalopathy; minor adverse events, for example, local reactions at the injection site (such as pain, redness and swelling) or mild systematic reactions (such as low-grade fever, vomiting and anorexia); and vaccination coverage. Study designs and other criteria for inclusion in the review Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included The effectiveness evidence was mainly derived from 8 primary studies. A further 23 studies were used to support the estimates assumed in the study. Methods of combining primary studies Investigation of differences between primary studies Results of the review Regardless of the vaccine used, the number of children with pertussis hospitalised was per 100,000 children, whilst the corresponding number not hospitalised was 2,708 per 100,000 children. There were 1.01 deaths, 3.42 seizures, cases of pneumonia, and 0.32 encephalopathy episodes. There were 8 (range: 4-14) hypotonic hyporesponsive episodes with DTaP (50% physician visits and 12.5% hospitalisations) and 57 with DTwP (50% physician visits and 12.5% hospitalisations). There were 2 cases of anaphylaxis in both groups of patients (100% physician visits and 100% hospitalisations). Page: 2 / 7

3 There were 10 (range: 4-26) uncomplicated seizures with DTaP (100% physician visits and 12.5% hospitalisations) and 57 with DTwP (100% physician visits and 12.5% hospitalisations). There were 63 (range: ) episodes of protracted crying or screaming with DTaP (10% physician visits and 0.5% hospitalisations) and 31 with DTwP (10% physician visits and 0.5% hospitalisations). Acute encephalopathy occurred in only 0.57 cases with DTwP (100% physician visits and 100% hospitalisations). The occurrence of minor adverse events was 37% with DTaP and 61% with DTwP. Finally, vaccination coverage was 93% with both vaccines. Methods used to derive estimates of effectiveness A panel of four members made assumptions about the effectiveness when there were no published data available,. Estimates of effectiveness and key assumptions The effectiveness estimates that were not directly derived from the literature were as follows (quoted for a population of 100,000 children). The number of children with diphtheria was 6,750 without the vaccine, whilst 0.05 children were hospitalised and died with both vaccines. The number of children with tetanus was 4.02 without the vaccine, whilst 0.28 children were hospitalised and died with both vaccines. For the case of pertussis without the vaccine, 66,686 children were not hospitalised and 3,314 were hospitalised (27.59 deaths, 117 with seizures, with pneumonia, with encephalopathy, and 2, with no complications). For the case of pertussis with vaccination, 96.6 children had some complications. The authors also assumed that DTaP was not associated with acute encephalopathy. Measure of benefits used in the economic analysis The benefit measure used in the economic analysis was the number of cases of diphtheria, tetanus and pertussis, and the related death rates associated with the two vaccines, quoted per 100,000 children. Direct costs Discounting was relevant because the time horizon of the study was 15 years. A 3% discount rate was used. The analysis included the costs associated with the disease and with the vaccine. The unit costs were reported for physician visits, telephone consultations, hospitalisation for diphtheria, tetanus and pertussis, the treatment of adverse events, and vaccination prices. The direct non-medical costs, such as those for travel (to the clinic or to the physician's office) and administration, were also included. It was assumed that 50% of the vaccinations were given in the public sector and 50% in the private sector. The costs were estimated from published studies, a hospital database, and unpublished data. The resource/cost boundary adopted reflected both the perspectives adopted in the study. The net present value (NPV), also defined as the net benefit of vaccination, was calculated for both vaccines. The NPV was the sum of the discounted benefits from the vaccination programme minus the sum of the discounted costs, where the benefit was calculated as the difference between the total disease burden without and with vaccination. The authors clarified that "disease burden is defined as the costs of all hospitalised cases plus costs of nonhospitalised cases". The benefit cost ratio (BCR) was defined as the total benefit (as defined above), divided by the total cost of the vaccination programme. The costs associated with the vaccine administration and transportation costs were assumed to be borne by the diphtheria and tetanus component. All the cost data were standardised to 1997 dollars by the medical care Page: 3 / 7

4 component of the consumer price index. Statistical analysis of costs A statistical analysis was not conducted because the cost data were treated deterministically. Indirect Costs The indirect costs, in terms of productivity losses, were included in the analysis and were discounted at a rate of 3%. This was consistent with the perspective adopted. The authors assumed that the caregivers took, on average, 2 hours off from work to take the child for vaccination. The hourly cost was derived on actual data obtained from the US Department of Labor. Currency US dollars ($). Sensitivity analysis One-way sensitivity analyses were conducted to test the robustness of BCR to variations in the following parameters: a lower (80%) and upper bound (98.5%) for acellular pertussis vaccine effectiveness; a higher programme cost of $12.2 million; a discount rate of 5%; and variations in the probabilities of the major vaccine-related adverse events. A threshold analysis was also performed. This was used to identify both the price and the effectiveness values of DTaP at which the NPV of DTaP vaccination equalled the NPV of the DTwP programme. Estimated benefits used in the economic analysis For a cohort of 4.1 million children, the analysis indicated that in the case of no vaccination, there would be 276,750 cases of diphtheria (with 27,675 deaths), 165 cases of tetanus (with 25 deaths), and 2,870,001 cases of pertussis (with 1,131 deaths). However, in the case of vaccination (regardless of the type of vaccine), there would be 2 cases of diphtheria (with 0.2 deaths), 12 cases of tetanus (with 2 deaths), and 116,224 cases of pertussis (with 41 deaths). Therefore, a vaccination programme with either vaccine reduced the number of diphtheria, tetanus, and pertussis cases by more than 99, 93, and 96%, respectively. Cost results From the societal perspective, the total costs (in millions) for the treatment of diphtheria, tetanus, and pertussis case were $23,563.5 without a vaccination programme. This comprised $18,772.4 for diphtheria, $21 for tetanus, and $4,770.1 for pertussis. With a vaccination programme, the total costs (in millions) for the treatment of diphtheria, tetanus, and pertussis case amounted to $ This comprised $0.1 for diphtheria, $1.5 for tetanus, and $184.9 for pertussis. The cost (in millions) of the vaccination programme was $866.5 for DTaP. This comprised $252.7 for vaccine, $230.5 for administration, $54.7 for transportation, $318.9 for parental productivity, and $9.7 for adverse events. The equivalent cost for DTwP was $ This comprised $104.1 for vaccine, $230.5 for administration, $54.7 for transportation, $318.9 for parental productivity, and $45.5 for adverse events. The total cost of the programme (in millions), in other words the cost of the disease plus the vaccination, was $1,053 Page: 4 / 7

5 for DTaP and $940 for DTwP. The net cost-savings (in millions) were $22,510.5 for DTaP and $22,623.3 for DTwP. The BCR was 27:1 for DTaP and 31:1 for DTwP. From the perspective of the health care system, the total costs (in millions) for the treatment of diphtheria, tetanus, and pertussis cases were $4,755 without vaccination and $99.7 with a vaccination programme. The cost (in millions) of the vaccination programme was $547.6 for DTaP and $434.8 for DTwP. The total cost of the programme (in millions) was $647 for DTaP and $534 for DTwP. The net cost-savings (in millions) were $4,107.7 for DTaP and $4,220.8 for DTwP. The BCR was 9:1 for DTaP and 11:1 for DTwP. The sensitivity analyses indicated that, compared with no vaccine, vaccination would always produce savings within the ranges used. The threshold analysis revealed the NPV of the programmes to be equal when the price of DTaP ranged from $13.87 at 98.5% vaccine effectiveness, to $7.65 at 96%. Synthesis of costs and benefits The costs and the benefits were not combined. Authors' conclusions The analysis showed the substantial cost-savings of the implementation of a population-based vaccination programme, "regardless of the vaccine used or the perspective taken". The use of DTaP (diphtheria, tetanus and acellular pertussis vaccine) instead of DTwP (diphtheria, tetanus and whole-cell pertussis vaccine) resulted in a small net increase in the vaccination programme costs, but a lower rate of adverse events. Nevertheless, both the vaccines were deemed costeffective, because the costs of disease burden avoided outweighed the costs of the vaccination programme and adverse events. CRD COMMENTARY - Selection of comparators The authors justified their selection of the vaccine programmes on the grounds that DTwP represented the routine vaccine before the introduction of DTaP. The vaccines were first compared with no vaccination and then compared with each other. You should consider whether they represent widely used interventions in your own setting. Validity of estimate of measure of effectiveness The effectiveness evidence was derived from the literature, and the estimated values were generally not combined, in that almost every primary study provided a single health outcome measure. However, the bulk of the effectiveness data were obtained from assumptions made by the authors and a panel of experts, to support the review of the literature. This could have limited the internal validity of the analysis, because sensitivity analyses were conducted for only a few variables. Further, the authors recognised that the analysis could have overestimated the economic benefits, because it was assumed that the disease burden without vaccination would have been equal to that of the pre-vaccination period. However, the incidence of the infectious disease considered in the study was already declining in developed countries. Validity of estimate of measure of benefit No single benefit measure was used in the economic analysis. However, indicators of the number of cases of disease or deaths avoided with the introduction of the vaccine were reported. The main problem was that the two vaccine programmes were considered to be equal in terms of their effectiveness, and they differed only with respect to the sideeffects. As a consequence, the benefit measures were mainly employed to estimate the resource use, necessary to Page: 5 / 7

6 estimate the economic impact of the reduced disease-related costs, rather than being a pure measure of benefit. In fact, the costs and the benefits were not combined. It therefore appears that a cost-consequence analysis was carried out, although the term "benefit" may suggest some form of effectiveness outcome. Finally, the programmes did differ in terms of the health outcomes, at least due to adverse events. Thus, the incremental cost-effectiveness should have meant the estimation of the change in health outcome with the change in cost between the two programmes. Validity of estimate of costs The analysis of the costs was carried out from two distinct perspectives. It appears that all the cost categories relevant to both perspectives have been included in the analysis. Although the cost data were treated deterministically, sensitivity analyses were carried out on the cost of the programme and on the discount rate. As for the effectiveness analysis, the estimation of the costs was obtained from different sources, including some unpublished data. This could have reduced the internal validity of the study. Other issues The authors compared their results with those from other studies. The generalisability of the study's findings to other settings was enhanced by the fact that the authors reported the unit costs for some items and conducted some, although perhaps not very extensive, sensitivity analyses. The authors' conclusions were in keeping with the study population, and all the results seem to have been reported. Implications of the study The authors indicate that the study highlights the importance of vaccine programmes at high coverage. In particular, DTaP should be preferred over DTwP, not only in consideration of the greater cost-savings, but also for the reduced side-effects and the major ease for quality control. The study would have been improved by showing more clearly the incremental improvement in health outcome of using DTaP, over DTwP, for the incremental cost increase. Source of funding None stated. Bibliographic details Ekwueme D U, Strebel P M, Hadler S C, Meltzer M I, Allen J W, Livengood J R. Economic evaluation of use of diphtheria, tetanus, and acellular pertussis vaccine or diphtheria, tetanus, and whole-cell pertussis vaccine in the United States, Archives of Pediatrics and Adolescent Medicine 2000; 154(8): PubMedID Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Child; Child, Preschool; Cost Savings; Cost-Benefit Analysis; Diphtheria Toxoid /economics; Diphtheria- Tetanus-Pertussis Vaccine /economics; Humans; Immunization Programs /economics; Infant; Infant, Newborn; Pertussis Vaccine /economics; Tetanus Toxoid /economics; United States AccessionNumber Date bibliographic record published 31/07/2002 Page: 6 / 7

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