Descripciones abreviadas de los casos de uso del sistema

The results of the economic evaluation are given in Table 8. The average costs are determined from 100 simulations, each with 100 patients given a set of costs derived from the gamma distribution of each cost variable. The simulations were run in Matlab 7.8 (The MathWorks, Inc., Natick, MA). Table 8 gives the average cost of a specific treatment (TACE with basic chemotherapy, TACE with DC beads, sorafenib and palliative care) and the life years gained from treatment, including pre-treatment, treatment and post-treatment costs. The mean number of treatments is listed in Table 7.a., and is incorporated into the

cost. All the treatments listed above are compared with the proposed new treatment, TARE. The incremental changes (in costs and life years gained) from using TARE compared to the current specific treatment are given with incremental costs divided by incremental life years gained. This results in a cost per life year gained estimate. This is the cost effectiveness measure of using TARE compared to the current, standard treatment.

For the average course of therapy (2.5 treatments of TACE⁶², 1.5 of TARE¹⁰⁰, 5.5 months of sorafenib⁶⁴, and 6 months of palliative treatment), the healthcare system costs are

$41,720 for TACE with chemotherapy, $41,633 for TACE with DC beads, $55,330 for TARE, $38,207 for sorafenib, and $5,221 for palliative treatment. TARE resulted in a gain in life expectancy of .116 years compared to TACE for BCLC stage B patients, while sorafenib resulted in a gain in life expectancy of .284 years compared to TARE for BCLC stage C patients. For CRCLM, TARE resulted in an increase of .296 years of life expectancy.

By calculating the differences in both cost and life years gained (effectiveness) between the standard treatment and TARE, incremental cost-effectiveness estimates can be calculated. Cost-effectiveness ratios represent system costs required, on average, to extend life by one year. These estimates show that moving from TACE with chemotherapy to TARE resulted in a cost per life year gained of $117,328 for BCLC stage B patients. TACE with DC beads to TARE resulted in a cost per life year of $118,078 for BCLC stage B patients. Sorafenib is less costly and more effective than TARE for BCLC stage C patients.

For CRCLM, moving from palliative treatment to TARE resulted in a cost per life year gained of $169,287. These estimates do not meet the range of $50,000 to $100,000 that is generally accepted as a cost effective switch in treatments¹⁰².

Several sensitivity estimates were calculated. These sensitivity analyses help to emphasize which costs are directly related to the treatment, as opposed to the course of the disease. This is accounted for in a sensitivity analysis that eliminates the possibility of death.

This, especially in BCLC stage C patients, would not be a side-effect of treatment, but caused directly by the disease. Assuming all patients complete their treatment in full, the revised costs are given in Table 9. Overall results do not vary significantly from the baseline results in Table 8, as the incremental costs decrease only slightly. The cost per life years gained for moving to TARE from current standard treatments remained above $100,000 per year gained, with the lowest estimate occurring if TARE was used instead of TACE with basic chemotherapy, which has an additional cost per life year gained of $107,319. An additional sensitivity analysis was done on the life years gained assumption for TARE in BCLC stage C patients compared to sorafenib. Assumption 1 uses .608 life years gained, which was based off a small-sample study³³. Assumption 2 uses a higher estimate of life years gained of .916 and is an Alberta specific estimate that was obtained from an EAG member that performs the treatment in the province. Using the original analysis in Table 8, however, the cost-effectiveness ratio is well above $100,000 – a gain of approximately 1.2 weeks when using TARE compared to sorafenib came at an additional cost of approximately

$17,000. This resulted in a cost per life years gained of approximately $713,000 when switching to TARE (with the increased life expectancy assumption) compared to sorafenib.

Another simulation completed was to omit the post-treatment nuclear scan for patients whom received TARE. This simulation was added after an EAG member commented that post-treatment nuclear scans were not always competed. Although REBOC

recommendations, as noted in previous sections, state that post-nuclear scans should be included incorporated into best practice⁷⁸. In this case, the average cost was reduced to

$53,688. This did not change the incremental cost-effectiveness results between TARE and the other treatments for both BCLC stage B and C patients, as all ratios remained above

$100,000, which is above the generally accepted threshold.

The overall budget impact is given in Table 10. These costs are the additional costs of receiving TARE compared to the previous treatments for a set number of patients noted in each row. Sensitivity results here include different estimates of patient populations. The AHW total estimates are assumed to be an overestimate, since they include all BCLC stage patients, not specifically those in BCLC B and C stages. Hence, comparisons are made given a patient population of 10, 20 and 30 per year. As a conservative baseline, the CADTH estimates for Alberta (with 82 patients per year) are also given for HCC patients. The estimates allow for budget impact estimates to be calculated, with varying percentages of the yearly estimated patient population switching to TARE from standard of care (i.e from TACE or sorafenib for HCC, and palliative care for CRCLM). These show that, using the CADTH estimates for patient population, the budget impact of shifting to TARE from current standards of care for HCC would range from approximately $1,100,000 to

$1,400,000 (from using TACE and sorafenib, respectively, to using TARE). Assuming a lower estimate of ten HCC patients switching to TARE treatment, the range for budget impact decreases to $136,000 to $171,000 per year. When comparing palliative care to TARE, additional cost estimates range from $501,000 if ten new patients use TARE, to

$1,500,000 if thirty new patients use TARE for CRCLM. At this point determining the actual

level of demand is not appropriate, but after consultation with clinical experts and an

member of the EAG it is unlikely that demand would be higher than 20-30 per year total for treatment with TARE (i.e. both HCC and CRCLM patients).

Overall, the additional life years gained from using TARE compared to current standard treatments is relatively small – ranging from .024 years (approximately 9 days) to .116 years (42 days) for HCC, and .296 years (108 days) for CRCLM treatment. These small changes result in high incremental cost effectiveness estimates for switching to TARE.

These estimates are above the generally accepted threshold of $50,000 per life year gained, and are in fact above $100,000, which is the upper bound in most cost-effectiveness acceptability ranges¹⁰².

Future technologies and changes in the patient population will have an impact on the analysis, and are not included in this analysis. Survival data, especially when looking at BCLC stage C patients with TARE is highly preliminary, as few patients with this extent of disease have received the treatment, and subject to change. Data on CRCLM and the use of TARE with concomitant chemotherapy is also extremely preliminary, as newer agents are just beginning to be investigated in conjunction with TARE, and could potentially change the results of the analysis. If the life years gained estimate increases, this will increase the chance of TARE with concomitant chemotherapy becoming cost-effective. The quality of life of patients suffering from these inoperable tumours is also a factor not accounted for in the present analysis and deserves consideration. By focusing on system costs in the analysis, societal costs, such as lost caregiver wages, and the living standards of patients, are not considered.