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Cost-effectiveness of hepatitis B vaccination in haemodialysis patients |
Taal M W, van Zyl-Smit R |
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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 health technology studied was Hepatitis B vaccination (3 micro grams into the deltoid region at 0, 1, 2, and 4 months) of chronic haemodialysis patients, preceded by testing for antibodies to HBsAg (anti-HBs) and for antibodies to hepatitis B core antigen (anti-HBc IgG). HBsAg levels were measured at months 3, 4, 5 and 6 months after the first dose. A plasma-derived vaccine containing heat-inactivated HBsAg and aluminium phosphate was used (Heppaccine-B Vaccine, Cheil Foods and Chemicals Inc). HBsAg was detected using a radio-immunoassay (AUSRIA, Abbots Laboratories). Antibodies to HbsAg and anti-HBc IgG were both measured with microparticle enzyme immunoassays (Imx AUSAB and Imx CORE, Abbot Laboratories).
Type of intervention Screening and primary prevention.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised chronic haemodialysis patients who tested negative for HBsAg.
Setting The setting was a hospital. The economic study was carried out in Groote Schuur Hospital, Cape Town, South Africa.
Dates to which data relate No dates were given except for the exchange rate at the time of going to press.
Source of effectiveness data Effectiveness data were derived from a single study and from assumptions made by the authors.
Link between effectiveness and cost data Resource use was based on the same patient sample as for the effectiveness data, with an extrapolation beyond the study period based on the authors' assumptions.
Study sample Out of 79 pre-vaccination chronic haemodialysis patients, 48 were negative for both antibodies. Three received renal transplants and were excluded, leaving 45 who received the first dose of vaccine. Baseline characteristics were given as demographic and possible risk factors for Hepatitis B Virus (HBV) infection, including:
prevalence of previous infection in black patients, 40%;
prevalence of previous infection in patients of mixed racial origin, 30%; and
prevalence of previous infection in white patients, 0%.
No power calculation for the determination of the sample size was reported.
Study design This was essentially a before-and-after design since there was only one group of patients. The implicit assumption was that vaccination only improved health. In other words effectiveness was hypothesised to be greater than prior to the introduction of vaccination (which involved monthly HBsAg monitoring). Patients were followed-up for 6 months. 9 patients were lost to follow-up: one died and 8 received renal transplants, although it was not stated at which point during the vaccination program this occurred.
Analysis of effectiveness The basis for the analysis of effectiveness (intention to treat or completers only) was not stated but appears to have been treatment completers only. The measures of effectiveness were the percentage of patients who responded (presence of anti-HBs) and the percentage deemed to have a protective titre (>=10 IU/l). The latter was not given for the comparator group. Also, for the intervention, the percentage of patients with both anti-HBs and anti-HBc, indicating prior infection and clearance of HBV, was reported. The incidence of HBV over a period of 40 months prior to vaccination was also assessed.
Effectiveness results The results for vaccinated patients were given in a bar chart by month, which showed the minimum protective antibody level at different times post-vaccination. There was a progressive increase in the number responding and the number achieving protective levels from month 3 to month 6. The maximum response rate was achieved at 2 months after the fourth dose (i.e. 6 months) of vaccine, when 72% were anti-HBs-positive and 69% had achieved protective levels.
The results of anti-HBs and anti-HBc IgG testing prior to vaccination showed that 33% of patients were positive for both antibodies, and 6% were positive for anti-HBs but negative for anti-HBc. The incidence of HBV prior to vaccination was 0% over 40 months.
Clinical conclusions A programme of Hepatitis B screening and vaccination resulted in a marked increase in the numbers of hospitalised haemodialysis patients protected against infection from hepatitis B.
Methods used to derive estimates of effectiveness The authors made an implicit assumption about the relationship between the measures of effectiveness in the study and the incidence of HBV.
Estimates of effectiveness and key assumptions Since the main measure of effectiveness of vaccination was percentage of patients achieving a level of anti-HBs sufficient to confer protection against HBV, it would be logical, in order to make a comparison with the technology prior to vaccination, to use the same measure. However, this information was lacking. What was provided was the percentage of patients who had any level of anti-HBs, indicating prior vaccination, and any level of both anti-HBs and anti-HBc, indicating prior infection and clearance of HBV. The authors stated that because the incidence of HBV prior to vaccination was 0% it would be difficult to demonstrate added benefit by vaccination. The implicit assumption therefore is that vaccination and the concomitant surveillance measures proposed, are equally as effective as the surveillance measures prior to vaccination. If it is the case that it is through prevention of HBV that effectiveness is ultimately achieved, then the assumption is that the anti-HBs levels achieved are sufficiently better than prior to vaccination in order to permit the proposed reduction in surveillance.
Measure of benefits used in the economic analysis There was no summary measure of benefit and, as stated above, there was an implicit assumption that the effectiveness (in terms of cases of hepatitis B infection) was equal between the intervention and the comparator. The principal benefit was therefore associated with the increased protection against HBV, as recorded in the effectiveness results above.
Direct costs Cost categories were antibody testing, vaccination and HBsAg testing, for which quantities and unit costs were given. Costs were only given for the intervention itself. The difference between the costs for the intervention and those for the comparator were reported as the intervention costs minus savings from reduced HBsAg surveillance. It was assumed that there would be a saving due to patients having protective levels of HBs not requiring monthly HBsAg testing, but only yearly anti-HBs level testing. In fact, it was further assumed that only those patients (n=16/25 who had protective levels) with an antibody titre of <200IU/l would be expected to need a booster dose. Savings were also included arising from the discontinuation of monthly testing for those with immunity due to prior infection (the 26/45 (33%) positive for anti-HBc and anti-HBs), since they would have been discovered by testing for antibodies as part of the vaccination programme. The resource quantities for the study period were those incurred during the study period. Unit costs were from the South African Institute for Medical Research for testing and the Groote Schuur Hospital tender price for vaccination. Discounting was not appropriate for the first year, although the net annual cost after this was given without discounting. The cost boundary was that of the institution. The price year was not given although the authors stated that the exchange rate was the date of going to press.
Statistical analysis of costs There was no test of difference, but costs were treated stochastically.
Indirect Costs No indirect costs were reported.
Sensitivity analysis No sensitivity analysis was reported.
Estimated benefits used in the economic analysis There was no summary measure of benefit: please refer to the effectiveness results reported earlier.
Cost results The total cost of the intervention during the study period and up to end of first year (pre-vaccination testing, vaccination and 4 anti-HBs levels) was R19,763.90.
The annual cost after the first year (based on 25 anti-HBs tests and 16 doses of vaccine) was R1,480.00.
Savings for the first year were R10,826.20 (those who were vaccinated) plus R16,161 (those with immunity after infection) making a total of R26,987.80.
Savings per subsequent year were R15,540 (vaccinated) plus R16,161.60 (immune after infection) to give a total of R31,701.60.
Net cost (first year) = -R7,223.90.
Net cost (each subsequent year) = -R30,092.00.
There was no discounting.
Synthesis of costs and benefits Authors' conclusions The authors stated that "In view of the high prevalence of chronic hepatitis B carriers in the South African population, the reduction in the number of patients at risk of infection, combined with a net cost saving, makes it reasonable to recommend vaccination in all non-immune haemodialysis patients despite a reduced response rate."
CRD COMMENTARY - Selection of comparators The comparator was justified as being the technology prior to vaccination. However, it was not clear given only the use of the word 'vaccination' to describe the intervention, that it did included pre-vaccination testing, which was critical in that it permitted the avoidance of HBsAg testing. It is also unclear why antibody testing was not already routine or, since it was not routine, why it was not investigated as a separate strategy.
Validity of estimate of measure of effectiveness Although the before-and-after design of the study introduces the potential for confounding due to other changes over time, in this case it was an appropriate approach as the same cohort was used. It should be noted that the increased protection of the programme did not result in a reduction of cases of contracted HBV, as the incidence in the pre-intervention period was zero. Therefore the effectiveness results are an intermediate outcome that may prevent infection and thus generate potential health benefits. In this respect the authors assumed that the vaccination programme would provide equal effectiveness, although risk of infection in the community would be an additional (unmeasured) benefit due to the high prevalence of HBV in South Africa.
Validity of estimate of measure of benefit Health benefits in terms of the incidence of HBV for the pre and post-intervention periods were the same, implying a cost-minimisation approach. The health benefits were therefore associated with the increased protection against HBV infection (the effectiveness measure of the study).
Validity of estimate of costs A good feature of the study was that costs were based on actual resource use, the quantities for which were given with the unit costs. However, no price year was given, preventing reflation, and unit costs would only be valid for South Africa, there being no sensitivity analysis. The main problem, alluded to above, was that vaccination was being recommended on the basis of savings, which could only occur if effectiveness did not fall in terms of preventing HBV. Also, as the authors acknowledged, there could be much larger savings if effectiveness improved, namely by preventing HBV and its consequent resource implications. However, these are all suppositions and evidence to support them was not provided.
Other issues The authors made comparisons with the results of other studies and do not seem to have presented their results selectively. However, they did not consider the issue of generalisability, their consideration being for the high prevalence population of South Africa. Finally, their conclusions were consistent with this population.
Implications of the study The authors make a clear recommendation to adopt the vaccination programme but make no explicit recommendation for further research.
However, as has been discussed above, evidence is lacking to support this. Further research, perhaps using modelling to show the correlation between antibody level and risk of HBV as well as the implications for quality of life and resource use would seem to be the next step if the information is available as evidenced by a systematic review. Following this, or instead of this, a larger prospective trial would seem reasonable.
Bibliographic details Taal M W, van Zyl-Smit R. Cost-effectiveness of hepatitis B vaccination in haemodialysis patients. South African Medical Journal 2001; 91(4): 340-344 Indexing Status Subject indexing assigned by NLM MeSH Adult; Cost-Benefit Analysis; Female; Hepatitis B /economics /prevention & Hepatitis B Vaccines /administration & Humans; Kidney Failure, Chronic /economics /therapy; Male; Middle Aged; Renal Dialysis /economics; South Africa; control; dosage /economics AccessionNumber 22001001089 Date bibliographic record published 31/05/2002 Date abstract record published 31/05/2002 |
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