The DiSC assay: a cost-effective guide to treatment for chronic lymphocytic leukemia? Mason J M, Drummond M F, Bosanquet A G, Sheldon T A

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1 The DiSC assay: a cost-effective guide to treatment for chronic lymphocytic leukemia? Mason J M, Drummond M F, Bosanquet A G, Sheldon T A 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 Differential staining cytotoxicity (DiSC) assay to identify optimal therapy for chronic lymphocytic leukemia. DiSC assay assessment involves a standardised test, which finds the lowest concentration of drug at which 90% of tumour cells are eradicated in vitro. Type of intervention Diagnosis and treatment. Economic study type Cost-effectiveness analysis. Study population Patients with a primary diagnosis of CLL. Setting Hospital. The economic study was performed in the United Kingdom. Dates to which data relate Effectiveness data corresponded to patients examined and treated between 1988 and Resource use data and their corresponding dates were not reported prices were used. Source of effectiveness data Effectiveness data were derived from a single study. Link between effectiveness and cost data Costing was undertaken retrospectively based on the typical cost of a DiSC assay at the time of the study. Study sample Power calculations were not used to determine the sample size. Assays were conducted for 178 CLL patients: 94 as they entered into a Medical Research Council CLL trial, 37 as they entered into other trials and 47 at the commencement of nontrial treatment. The mean age at the start of treatment was 65 years. Patients were categorised as: sensitive to drugs in vitro and receiving a sensitive drug in vivo (70%) (exploited sensitivity group) with a mean (SD) age of 65.3 (10.21) years, sensitive in vitro but not treated with a sensitive drug (23%)(unexploited sensitivity group) with a mean (SD) age of Page: 1 / 5

2 62.7 (9.03) years, having disease resistant to all drugs tested in vitro (7%) with a mean (SD) age of 69.1 (6.19) years. Study design Prospective cohort study, carried out in a single centre. This mixed cohort study had a maximum follow-up from the time of commencing treatment of 5.9 years with a median of 1.3 years. The median duration of treatment was 4.9 months and continued beyond 12 months for only 2% of patients. Loss to follow-up was not reported. Analysis of effectiveness The analysis of the clinical study was based on intention to treat. The primary outcomes recorded were remission (after a minimum of two monthly courses of therapy) and survival time from the date of the assay. Adjustments were made, using regression analysis, for the effects of known confounding variables. Stochastic simulation was used to generate confidence intervals (CI) for the estimates of survival. Effectiveness results The rate of remission was more than 70% in patients with exploited sensitivity but only 30% in patients with unexploited sensitivity. Only 2 of the 12 patients with no drug sensitivity experienced remission after treatment (16.7%); the odds ratio for the comparison of exploited sensitivity group versus unexploited sensitivity group was 6.5 (95% CI: ). The rate of dying was reduced to less than a third in patients with exploited sensitivity (95% CI: ) compared with the base category. Patients with no drug sensitivity experienced a rate of death twice that of base case patients (95% CI: ). Clinical conclusions Analysis shows that the odds of remission among CLL patients is increased by about 6 times for patients with exploited drug sensitivity indicated by the DiSC assay, compared with those with unexploited sensitivity. Patients whose drug sensitivity is exploited by receiving treatment with a drug indicated by the assay results have markedly better survival than those whose drug sensitivity is not exploited. There is a notably poorer survival for those patients with no sensitivity to any drugs tested. Measure of benefits used in the economic analysis Years of life gained was the benefit measure used in the economic analysis. Survival gains were estimated for 3.3 years following treatment and for various patient age and disease categories. Survival curves were generated, and gains in life expectancy were estimated, from the baseline cumulative hazard function and prognostic index. Direct costs No cost discounting was reported. Quantities were not reported separately from the costs. The cost analysis covered the cost of a DiSC assay with the assumption of no net change in other costs. The perspective adopted in the cost analysis was not explicitly specified price data were used. The authors assumed that, as it was not possible to estimate what combination of chemotherapy a clinician would give, the cost of treatment before and after the assay result would not change. They also stated that although no adequate data were available to estimate savings in blood transfusions or optimisation of therapy, the value of these could considerably offset the cost of the DiSC assay. Indirect Costs Page: 2 / 5

3 Not included. Currency UK pounds sterling (). Sensitivity analysis Quantitative one-way sensitivity analysis was performed only on discount rate for future benefits. The authors descriptively identified a number of other important parameters: extrapolating the emerging survival pattern, taking account of unmeasured systematic differences between the 2 groups, and the fact that the patient sample may not have been representative of all patients with CLL. Estimated benefits used in the economic analysis A 50-year old male, stage A,B patient would gain life-years (95% CI: ) or life-years gained A 70-year old male, stage A,B patient would gain life-years (95% CI: ) or life-years gained A 50-year old male, stage C patient would gain life-years (95% CI: ) or life-years gained A 70-year old male, stage C patient would gain life-years (95% CI: ) or life-years gained per DiSC assay. A 50-year old female, stage A,B patient would gain life-years (95% CI: ) or life-years gained A 70-year old female, stage A,B patient would gain life-years (95% CI: ) or life-years gained A 50-year old female, stage C patient would gain life-years (95% CI: ) or life-years gained A 70-year old female, stage C patient would gain life-years (95% CI: ) or life-years gained Cost results The cost of a DiSC assay was stated to be 380 with the assumption of no net change in other costs. Synthesis of costs and benefits The cost per life-year gained with DiSC assay guided treatment ranged from 790 for male patients aged 50 with stage C disease to 6,410 for female patients aged 70 with stage A or B disease. The influence of discounting future benefits at 5% per annum is predictably small, since survival is truncated to 3.3 years; the range became 860 to 7,040 per life-year gained. Weighted by the study cohort's particular mix of age, sex and stage of disease, the estimated average incremental cost-effectiveness of DiSC assay assessment was 1,470 per life-year gained (undiscounted). The authors stated that if the emerging survival pattern was extrapolated then the cost-effectiveness ratios would become more attractive, assuming benefits were sustained, particularly in younger patients. Authors' conclusions The authors concluded that the available evidence suggests that the DiSC assay may be a cost-effective technology for Page: 3 / 5

4 improving patient outcomes and should be more widely evaluated. CRD COMMENTARY - Selection of comparators The reason for the choice of the comparator (not exploiting the results of DiSC assay to tailor therapy) is clear. Validity of estimate of measure of benefit As the authors indicated, the estimate of the measure of benefit used in the economic analysis was based upon a number of assumptions relating to the likely gain in survival amongst a possibly non-representative sample of CLL patients, and lacked a long-term follow-up period. Validity of estimate of costs Resource quantities were not reported separately from prices and the authors acknowledged that important cost items (chemotherapy, blood transfusions) were omitted from the cost analysis. Other issues The issue of generalisability to other settings or countries was not addressed and appropriate comparisons were not made with other studies. Implications of the study The data justify the investment in a well-designed randomised controlled trial to establish more reliably and precisely the benefits and costs of using the DiSC assay to tailor drug treatment for CLL. Source of funding Funded by a grant from World in Need. Bibliographic details Mason J M, Drummond M F, Bosanquet A G, Sheldon T A. The DiSC assay: a cost-effective guide to treatment for chronic lymphocytic leukemia? International Journal of Technology Assessment in Health Care 1999; 15(1): PubMedID Indexing Status Subject indexing assigned by NLM MeSH Aged; Cohort Studies; Cost-Benefit Analysis; Drug Screening Assays, Antitumor /economics /statistics & numerical data; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell /economics /mortality /therapy; Male; Proportional Hazards Models; Prospective Studies; Sensitivity and Specificity AccessionNumber Date bibliographic record published 31/07/2000 Date abstract record published 31/07/2000 Page: 4 / 5

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