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Hepatitis C screening and treatment versus liver transplantation: a financial option appraisal and commissioning model for purchasers |
Batra N |
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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 use of screening and treatment strategies for hepatitis C virus (HCV) infection in different settings.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised patients with recognised exposure to HCV infections and those at risk of HCV infection. The 'HCV-exposed' group consisted of patients such as health care, emergency medical and public safety workers after needle sticks, sharps, or mucosal exposures to HCV-positive blood. It also included children born to HCV-positive women. The 'at risk' group consisted of the following:
individuals who had ever injected illegal drugs;
individuals with selected medical conditions, including those who had received clotting factor concentrates produced before 1987;
individuals who had ever received long-term haemodialysis;
individuals with persistently abnormal alanine aminotransferase levels; and
prior recipients of transfusions or organ transplant, including those who had been notified that they had received blood from a donor who later tested positive for HCV infection, and those who had received a transfusion of blood or blood components before July 1992.
Setting The setting of the study was unclear but appears to have been that of a community. The economic study was carried out in West Kent (UK).
Dates to which data relate The effectiveness data were gathered from studies published between 1997 and 1999. The resource use data were collected during 1998 to 1999. The price year was 1999.
Source of effectiveness data The effectiveness evidence was derived from published studies, the authors' assumptions, and activity data from West Kent.
Modelling A care pathway model was used to define the clinical pathways for the tests and treatments for HCV infection, according to four different models.
Model 1 followed NICE guidelines and used actual data from West Kent on the prevalence of high risk individuals, those accepting the anti-HCV test and those testing positive.
Model 2 assumed a lower loss to follow-up and used data from a NICE guideline publication which indicated default values of 50% for several of the parameters.
Model 3 was as for model 1, but it assumed a high rate of HCV positives and lower loss to follow-up.
Model 4 followed international guidelines (no quantitative RNA or biopsy) with the lower loss to follow-up, and higher rate of anti-HCV positives.
Outcomes assessed in the review The primary outcomes assessed in the review were:
the percentage of the population at high risk of HCV infection;
the rate of anti-HCV antibody positive tests that were also positive for HCV ribonucleic acid (RNA);
the proportion of patients with HCV who recover with a benign outcome;
the proportion of patients who develop cirrhosis in "10 or 20 years", and who may die of complications of cirrhosis in the absence of liver transplantation;
the rate of newly diagnosed chronically HCV RNA-positive patients who do not want further investigations;
the percentage of HCV RNA-positive patients who have moderate or severe hepatic fibrosis (Knodell > 6) on liver biopsy, and the percentage of these who do not want treatment;
the rate of moderate or severe hepatic fibrosis due to genotype 1, or other genotypes;
the efficacy of the combined ribavirin and interferon treatment for genotypes 1, 2 and 3; and
the number of patients who dropped out or were lost to follow-up.
Study designs and other criteria for inclusion in the review Audits and cohort studies were included in the review.
Sources searched to identify primary studies The primary studies were mainly identified from Internet websites. The websites searched included PubMed, the Department of Health (UK), the Public Health Laboratory Service (UK), the Centers for Disease Control (Atlanta, USA), the National Institutes of Health (USA), the New Zealand Ministry of Health Committee, and the World Health Organisation.
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 Eight studies were the main source of the inputs for the model.
Methods of combining primary studies Investigation of differences between primary studies Results of the review 12.5% of the population were at high risk of HCV infection.
The rate of anti-HCV antibody positive tests, which were also positive for HCV RNA, was 80%.
40% of the patients with HCV recovered with a benign outcome.
The proportion of patients who developed cirrhosis in "10 or 20 years", and who may have died of complications of cirrhosis in the absence of liver transplantation, was 20%.
39% of newly diagnosed chronically HCV RNA-positive patients did not want further investigation.
44% of HCV RNA-positive patients had moderate or severe hepatic fibrosis (Knodell > 6) on liver biopsy, of which 42% did not want treatment.
The rate of moderate or severe hepatic fibrosis was 70% for genotype 1 and 30% for genotypes other than 1.
The efficacy of the combined ribavirin and interferon treatment was 40 to 50% for genotypes 2 and 3, and 28% for genotype 1. This equates to a weighted average of 33%.
66% of patients dropped out or were lost to follow-up.
Methods used to derive estimates of effectiveness The authors made an assumption about the effectiveness. The data were collected from the West Kent NHS Trusts.
Estimates of effectiveness and key assumptions The assumption was that all the reported probabilities were independent. The number of individuals at high risk was 120,375. Of these, 1,870 (1.55%) underwent anti-HCV antibody testing and 78 (4.17%) were found to be positive during 1998 to 1999.
Measure of benefits used in the economic analysis The measures of benefits used were the percentage of cirrhosis cases prevented from those at high risk of HCV (community effectiveness), and the NNS to prevent one patient developing cirrhosis. This was calculated by multiplying the probabilities taken from the results of the review by the data from West Kent. NNS was incorrectly calculated by starting with the total number at high risk rather than those actually screened.
Direct costs Discounting was carried out at 6%. The quantities of resources used were reported in terms of the numbers of procedures. The cost analysis included the market prices for the following: the anti-HCV antibody test, the qualitative HCV RNA test (presence or absence of HCV), the liver biopsy, the genotype and quantitative HCV RNA test (quantifies the viral load), and the treatment (interferon-alpha and ribavirin). The unit costs were reported. Only variable costs were considered and fixed costs, such as staff, capital charges, and overheads, were excluded because it was stated that they were unlikely to change from usual baseline care in the short term. The costs (prices) and the quantities (volume of activity) were mainly estimated from the actual data derived from the microbiology departments and pharmacies of local providers in the period 1998 to 1999. The cost of monitoring liver transplantation was unavailable in the UK, and US data were therefore used. The price year was 1999.
Statistical analysis of costs No statistical analysis of costs was reported.
Indirect Costs No indirect costs were reported.
Currency UK pounds sterling (). These were converted into US dollars ($). The exchange rate was $1.6 = 1.
Sensitivity analysis Sensitivity analyses were conducted to assess the effect of a 50% value for the following variables (model 2):
the proportion of high-risk individuals accepting the anti-HCV antibody test;
the proportion of patients who subsequently received a qualitative HCV RNA test;
the proportion of patients who underwent liver biopsy;
the proportion of patients who were Knodell greater than 6; and
the proportion of patients who accepted treatment requiring genotyping.
The authors also assumed a greater prevalence rate of high-risk individuals positive to the HCV antibody (8%) than that used in the base case. This constituted model 3.
Model 4 was the "international model". This used a combination of the above assumptions.
Models 2, 3 and 4 also assumed a lower drop-out of 0.2 as opposed to 0.33 in the base-case (model 1).
Finally, a break-even analysis was also performed because of the lack of UK data on such cost items. This was conducted to determine the changes required to the international model variables to breach two specific thresholds (25,540 and 18,475), corresponding to the present values of the NHS Trust maximum and 50% NHS Trust maximum of liver transplantation and monitoring.
Estimated benefits used in the economic analysis All community effectiveness results were based on the number of cases of cirrhosis prevented as a percentage of the total high-risk population, The number of anti-HCV antibody tests performed during the period 1998 to 1999 in West Kent was 1,870 out of a possible 120,375 (1.55%). Of these, 78 (4.17%) were positive.
According to the NICE recommendations (model 1), the average current screening community effectiveness was 0.00088%. This means that, on average, 113,479 high-risk patients need to be screened and treated to prevent one patient developing cirrhosis.
According to model 2, the NNS was 3,776 and the community effectiveness was 0.02648%.
According to model 3, the NNS was 758 and the community effectiveness was 0.13191%.
According to model 4, the NNS was 118 and the community effectiveness was 0.847%.
Cost results According to model 1, the total cost was 54,043.
According to model 2, the total cost was 1,433,257.
According to model 3, the total cost was 5,118,054.
According to model 4, the total cost was 25,454,642.
Finally, the costs (present value) for one liver transplant ranged from 11,610 (50% NHS Trust maximum) to 16,049 (NHS Trust maximum). The costs (present value) for monitoring (for 10 years) varied between 6,864 and 9,489.
The discount rate was 6%.
Synthesis of costs and benefits According to model 1, the cost to prevent one patient developing cirrhosis was 50,947.
According to model 2, the cost to prevent one cirrhosis case was 44,965.
According to model 3, the cost to prevent one cirrhosis case was 32,232.
According to model 4, the cost to prevent one cirrhosis case was 24,955.
The net present value (NPV) of screening and combined treatment, compared with liver transplantation, was calculated as the cost to prevent one case of cirrhosis minus the cost of transplantation and monitoring. The NPV ranged from -25,407 to -32,471 for model 1.
If the West Kent Health Authority funded need, potential demand or actual use, the variable cost would be 16.3 million (need), 1.7 million (potential demand), and 54,043 (actual use), respectively.
The adoption of international guidelines would result in the NPV of HCV screening and combined treatment ranging from 584 to -6,479. The variable costs would be 63 million to fund need, 25 million to fund potential demand, and 74,904 to fund actual use.
Authors' conclusions The first analysis indicated that the community effectiveness of combined treatment, even at its best (i.e. following international guidelines), was 33 to 53 time less than its efficacy. In terms of the second analysis, screening and drug treatments for hepatitis C virus (HCV) proved to be more expensive in preventing one patient developing cirrhosis than liver transplantation. The international model appeared to be a more technically efficient pathway for delivering care for HCV than that recommended by the National Institute of Clinical Excellence (NICE). This is because it produced a more effective result, in terms of community effectiveness, with a potential saving when compared to no screening (liver transplant plus monitoring). However, it should be remembered that there are substantial differences between the international and UK data. Caution is therefore necessary when applying these results to UK purchasing authorities, since the international model led to very high costs and a very high volume. This might not be a feasible pathway for a publicly funded health care system such as the UK NHS.
CRD COMMENTARY - Selection of comparators The reason for the selection of liver transplantation as the comparator was clear. However, some of the assumptions used to define the comparators were unclear. For models 2 to 4, a higher percentage left after drop-out was assumed (0.8), compared with model 1 (0.33). It was also assumed that half the high-risk population would enter the screening programme, i.e. 60,188 versus 1,870 in model 1. In correspondence with the author, these were stated to be part of the NICE assumptions. Finally, although it was explicitly assumed that the rate of HCV positives in model 3 (0.08) would be twice that in model 1 (0.04), the same higher figure was also used in model 4 without any explanation.
Validity of estimate of measure of effectiveness The effectiveness analysis used the probability estimates from published literature, mainly international guidelines and audit reports, and the West Kent NHS trusts. However, the conduct of the review was not reported clearly and some estimates produced in the USA were then applied to the UK, even though the authors recognised substantial differences in the two systems. Also, as the author states, model 1 focused on individuals who were at high risk of HCV infection, but who could potentially benefit from the health intervention. This meant that numerous individuals at very high risk for HCV, such as drug users continuing to share needles, were excluded from the analysis, thus limiting the sample to those who actually presented to the health service for treatment.
The calculation of NNS was inaccurate in that it was based on the total high-risk population, despite the fact that not all were screened, at most (in models 2 to 4), only a half. The NNS would therefore be much lower if only those who entered the programme were used. Also, as already highlighted, by combining several assumptions (explicit and implicit), the differences between models 2 to 4 and model 1 have increased. Finally, it was unclear why the following of international guidelines (model 4), which avoid certain tests such as biopsy and quantitative immunology, does not alter the efficacy of the treatment.
Validity of estimate of measure of benefit The benefit measures were the NNS to prevent one case of cirrhosis and the percentage screening effectiveness. The authors stated that they did not perform an analysis based on quality of life measures because it had already been conducted.
Validity of estimate of costs The costs were estimated from actual data. However, as for the effectiveness measure, some categories of cost data (in particular monitoring after liver transplantation) were unavailable in the UK literature, and therefore US estimates were used. To reduce the impact of differences in the source of data, a plausible range of data were used, thus enhancing the external validity of the study at the same time. In addition, the unit costs and the quantities were reported separately, and appropriate currency conversions were conducted. The fixed costs were not included because they were not deemed to be relevant for purchasing authorities in the short term. The monitoring costs for blood tests were also excluded since existing block contracts covered them.
Other issues The authors made several comparisons of their findings with those from other studies. However, they found that their results were in contrast with some of the published literature. The issue of generalisability of the results to other settings was not explicitly addressed, because the analysis was only intended to be valid for the UK district health authorities.
Implications of the study The authors recommended that further research should focus on qualitative studies that explain the low volume of activity around HCV in England, to elicit attitudes with regards to the referral, testing and treatment by professionals and patients. The authors emphasise that the community effectiveness was very low in comparison with the efficacy of the treatment. They also focused on the relative costs of screening and treatment versus transplant and monitoring, in particular comparing the greater cost-effectiveness of the international model with its much higher costs. As already stated, the study could have benefited from greater clarity in the reporting of the assumptions.
Bibliographic details Batra N. Hepatitis C screening and treatment versus liver transplantation: a financial option appraisal and commissioning model for purchasers. Disease Management and Health Outcomes 2001; 9(7): 371-384 Indexing Status Subject indexing assigned by CRD MeSH Cost-Benefit Analysis; Hepatitis C /diagnosis /economics /prevention & Interferon-alpha /therapeutic use; Liver Cirrhosis /prevention & Liver Transplantation /economics; Mass Screening /economics; Ribavirin /therapeutic use; Risk Factors; control; control AccessionNumber 22001001505 Date bibliographic record published 31/07/2002 Date abstract record published 31/07/2002 |
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