Table 2.
Summary of results of published cost-effectiveness analyses
| Study (reference) | QHES score | Country setting | Population | Clinical results | Cost results | Cost-effectiveness and key drivers |
|---|---|---|---|---|---|---|
| Oncotype DX® cost-effectiveness evaluations | ||||||
| Hornberger et al. [21] | 89 | USA | LN−, ER+ | 8.6 QALYs gained per 100 patients | USD 202,828 decrease in cost per 100 patients | Versus NCCN guidelines: Oncotype DX® dominates |
| Test increases costs if <50 % of patients receiving chemotherapy under NCCN guidelines are spared treatment | ||||||
| Cost-effectiveness increases when chemotherapy costs are higher | ||||||
| Lyman et al. [22] | 68 | USA | LN−, ER+ | Versus tamoxifen: 0.97 QALYs gained | Versus tamoxifen: USD 4,272 increase in direct costs | Versus tamoxifen: USD 4,432 per QALY gained |
| Versus tamoxifen plus chemotherapy: 1.71 QALYs gained | Versus tamoxifen plus chemotherapy: USD 2,256 decrease in direct costs | Versus tamoxifen plus chemotherapy: Oncotype DX® dominates | ||||
| Benefit over tamoxifen driven by additional life years saved as a result of prescribing chemotherapy to those will benefit | ||||||
| Benefit over tamoxifen plus chemotherapy driven by cost savings as a result of avoided chemotherapy. This benefit increases as more costly chemotherapy regimens are used | ||||||
| Kondo et al. [23] | 92 | Japan | LN−, ER+ | Versus NCCN: 0.097 QALYs gained | Versus NCCN: JPY 289,355 increase in direct cost | Versus NCCN: JPY 2,997,495 per QALY gained |
| Versus St. Gallen: 0.237 QALYs gained | Versus St. Gallen: JPY 293,211 increase in direct cost | Versus St. Gallen: JPY 1,239,055 per QALY gained | ||||
| Budget impact: JPY 2,638 million to JPY 3,225 million increase in direct costs | ||||||
| Results most sensitive to changes in the price of the assay and frequency of chemotherapy prescription in standard care | ||||||
| Greater cost-effectiveness versus St. Gallen, compared to NCCN, is due to improved outcomes in terms of recurrence, not avoided chemotherapy | ||||||
| Cosler and Lyman [24] | 68 | USA | LN−, ER+ | Versus tamoxifen: 2.2 life years gained | Versus tamoxifen: USD 4,272 increase in direct costs | Versus tamoxifen: USD 1,944 per life year gained |
| Versus tamoxifen plus chemotherapy: Oncotype DX® dominates | ||||||
| Versus tamoxifen plus chemotherapy: No significant difference | Versus tamoxifen plus chemotherapy: USD 2,256 decrease in direct costs | Benefit over tamoxifen driven by additional life years saved as a result of prescribing chemotherapy to those will benefit | ||||
| Benefit over tamoxifen plus chemotherapy driven by cost savings as a result of avoided chemotherapy. This benefit increases as more costly chemotherapy regimens are used | ||||||
| de Lima Lopes et al. [25] | N/A | Singapore | LN−, ER+ | – | Direct cost saving of SGD 2,942, SGD 1,077, SGD 169 and SGD 1,340 due to reduced chemotherapy, supportive care, management of adverse events, and administration, respectively | Versus current practice: Oncotype DX® cost saving |
| Indirect cost savings of SGD 468 | Cost saving driven chiefly by reduced chemotherapy drug costs | |||||
| Klang et al. [26] | 86 | Israel | LN−, ER+ | 0.170 QALYs gained | USD 1,828 per patient increase in direct costs | Versus traditional treatment: USD 10,770 per QALY gained |
| Patients receiving chemotherapy reduced from 56 to 28 % | Cost savings were driven chiefly by reduced expenditure on chemotherapy | |||||
| Clinical benefits were driven by avoided quality of life decrement associated with chemotherapy in patients previously prescribed chemotherapy who were spared, and lower risk of recurrence in patients previously not receiving chemotherapy who were treated | ||||||
| O’Leary et al. [27] | N/A | Australia | LN− and LN+ | 0.098 QALYs gained | AUD 974 increase in direct costs | Versus conventional treatment: AUD 9,986 per QALY gained |
| Cost savings were driven chiefly by avoided chemotherapy costs | ||||||
| Quality of life benefit was driven by avoiding chemotherapy in patients who would show no benefit, and avoidance of recurrence in patients switching to chemotherapy | ||||||
| Tsoi et al. [28] | 90 | Canada | LN−, ER+, HER2− | 0.065 QALYs gained | CAD 4,102 increase in direct costs | Versus Adjuvant!: CAD 63,064 per QALY gained |
| Assay more cost-effective in younger patients | ||||||
| Cost difference was largely driven by the cost of the assay | ||||||
| de Lima Lopes et al. [29] | N/A | Singapore | LN−, ER+ | 0.12 QALYs gained through avoidance of chemotherapy | Direct cost saving of SGD 2,735, SGD 1,001, SGD 157 and SGD 1,245 due to reduced chemotherapy, supportive care, management of adverse events, and administration, respectively | Versus current practice: Oncotype DX® cost saving and improves clinical outcomes |
| 0.15 QALYs gained by prevention of future recurrence | Indirect cost savings of SGD 468 | Cost savings driven by reduced expenditure on chemotherapy drugs | ||||
| Clinical benefits driven by avoided recurrence and avoided reduced quality of life during chemotherapy | ||||||
| Hall et al. [30] | 96 | UK | LN+, ER+ | 0.16 QALYs gained | GBP 860 increase in direct cost | Versus current practice: GBP 5,529 per QALY gained |
| 61 % probability of cost-effectiveness at willingness to pay threshold of GBP 30,000 | ||||||
| Oncotype DX® becomes more cost-effective when more costly chemotherapy regimens are used | ||||||
| Oncotype DX® is dominated when the recurrence score cut off for chemotherapy increases | ||||||
| Oncotype DX® is cost saving to the NHS provided that the proportion of patients classified as low risk (and therefore avoid chemotherapy) is >40 % | ||||||
| Holt et al. [31] | N/A | UK | LN 0–3, ER+ | 0.14 QALYs gained | GBP 888 increase in direct cost | Versus current clinical practice: GBP 6,232 per QALY gained |
| 99.6 % probability of being cost-effective at a willingness to pay threshold of GBP 20,000 per QALY gained | ||||||
| More cost-effective in younger patients | ||||||
| More cost-effective as chemotherapy use in standard care increases | ||||||
| Hornberger et al. [32] | 92 | USA | LN−, ER+ | 0.162 QALYs gained | USD 1,103,874 decrease in cost to insurer over 2 million plans | Versus NCCN guidelines: Oncotype DX® dominates |
| 81 % probability of being cost saving | ||||||
| Cost savings were driven chiefly by reduced supportive care costs | ||||||
| Cost savings increase as chemotherapy use in standard care increases | ||||||
| Quality of life increase was driven by avoided chemotherapy in low risk patients | ||||||
| Kondo et al. [33] | 93 | Japan | LN−, ER+ | LN−: 0.63 QALYs gained | LN−: JPY 240,683 increase in direct cost | LN−, versus St. Gallen: JPY 384,828 per QALY gained |
| LN− and LN+, ER+ | All patients: 0.47 QALYs gained | All patients: JPY 270,035 increase in direct cost | All patients, versus St. Gallen: JPY 568,533 per QALY gained | |||
| Increased ICER in LN+ patients due to the higher rate of recurrence | ||||||
| Clinical benefit of the assay driven by identifying patients who would have missed adjuvant therapy, despite being at high risk of recurrence | ||||||
| Lacey et al. [34] | N/A | Ireland | LN−, ER+ | 0.12 QALYs gained | EUR 1,139 increase in direct costs | Versus current practice: EUR 9,462 per QALY gained |
| 74.2 % probability of being cost-effective at a willingness to pay threshold of EUR 20,000 per QALY gained | ||||||
| Results most sensitive to changes in price of the assay | ||||||
| Paulden et al. [35] | N/A | Canada | LN−, ER+ | Not stated | Not stated | Low Adjuvant! risk: CAD 29,000 per QALY gained |
| High Adjuvant! risk: Oncotype DX® dominates | ||||||
| Oncotype DX® is cost-effective in all early-stage breast cancer patients, irrespective of risk of recurrence as determined by Adjuvant! | ||||||
| Vanderlaan et al. [36] | 85 | USA | LN1–3, ER+ | 0.127 QALYs gained | USD 384 decrease in direct costs | Versus current practice: Oncotype DX® dominates |
| Cost savings driven by reduced chemotherapy expenditure | ||||||
| Cost only increased when chemotherapy costs were 25 % lower than in the base case and when the assay reduced chemotherapy by only 15 %, but QALE remained increased in these two scenarios | ||||||
| Lamond et al. [37] (also reported in Lamond et al. 2011) | 94 | Canada | LN− | LN−: 0.27 QALYs gained | LN−: CAD 2,585 increase in direct costs | LN− versus current practice: CAD 9,591 per QALY gained |
| LN+ | LN+: 0.06 QALYS gained | LN+: CAD 864 increase in direct costs | LN+: CAD 14,844 per QALY gained | |||
| Mixed cohort (40 % LN+) | Mixed cohort: 0.18 QALYs gained | Mixed: CAD 1,852 increase in direct costs | Mixed: CAD 10,316 per QALY gained | |||
| Results most sensitive to chemotherapy utilization following the assay | ||||||
| Madaras et al. [38] | N/A | Hungary | LN−, ER+ | Not stated | Not stated | Versus current practice: EUR 6,871 per QALY gained |
| Cost-effectiveness increases when more aggressive treatment is used | ||||||
| Oncotype DX® budget impact studies | ||||||
| Wilson et al. [39] | N/A | Ireland | LN−, ER+, HER2− | – | EUR 666,844 cost saving if chemotherapy only given to high-risk patients, over the 140 patients included in this analysis | Versus current practice: Oncotype DX® will result in cost savings in European health systems |
| Only the cost of chemotherapy and the assay were included in this analysis | ||||||
| Hassan et al. [40] | N/A | Canada | LN−, ER+, HER2− | – | Cost saving of CAD 34.5 million |
Oncotype DX® is cost saving Cost savings driven by reduced chemotherapy drug costs |
| Lacey and Hornberger [41] | N/A | Ireland | LN− | – | 0.4 % increase in direct cost | Versus current practice: adoption of Oncotype DX®is approximately cost neutral |
| 47 % probability of being cost saving | ||||||
| Main driver was reduction in chemotherapy expenditure | ||||||
| Ragaz et al. [42] | N/A | Canada and USA | LN− and LN+, ER+ | – | Cost saving of USD 330.8 million in USA | Oncotype DX® is cost saving in both USA and Canada |
| Cost saving of USD 46.2 million in Canada | Cost savings are driven by reduced expenditure on chemotherapy | |||||
| MammaPrint cost-effectiveness evaluations | ||||||
| Oestreicher et al. [43] | 95 | Netherlands | LN− and LN+ (approximately equal proportion), ER+ | 0.21 decrease in QALYs | USD 2,882 fall in direct and indirect costs | Versus NIH guidelines: reduced cost and reduced quality-adjusted life expectancy |
| NIH guidelines identified 96 % of patients as high risk, while MammaPrint identified 61 % as high risk, lowering the expenditure on adjuvant chemotherapy | ||||||
| Since MammaPrint was assumed to have a sensitivity of 84 %, distant recurrence rates increased, driving a reduction in QALE | ||||||
| Sensitivity of 95 % (with specificity of 51 % kept constant) to increase QALE over NIH | ||||||
| Chen et al. [44] | 91 | USA | LN−, ER+, HER2− | Overall population: 0.15 QALYs gained | Overall population: USD 1,440 per patient increase in direct cost | Versus St. Gallen, overall population: USD 9,428 per QALY gained |
| LN−, ER−, HER2− | ER+: 0.23 QALYs gained | ER+: USD 1,332 per patient increase in direct cost | Versus St. Gallen, ER+: USD 6,167 per QALY gained | |||
| Mixed population | ER−: 0.098 QALYs lost | ER−: USD 1,811 per patient increase in direct cost | Versus St. Gallen, ER−: MammaPrint dominated | |||
| SEER registry population | SEER registry patients: 0.571 QALYs gained | SEER registry patients: USD 401 per patient increase in direct cost | Versus St. Gallen, SEER registry patients: USD 716 per QALY gained | |||
| Results were highly sensitive to the proportion of patients the assay classed as high risk, with an increase in high-risk patients reducing cost-effectiveness | ||||||
| Retèl et al. [45] | 75 | Netherlands | LN−, ER+ | Versus St. Gallen: 1.20 QALYs gained | Versus St. Gallen: EUR 7,430 decrease in direct costs | Versus St. Gallen: MammaPrint dominates |
| Versus Adjuvant!: 0.24 QALYs gained | Versus Adjuvant!: EUR 1,130 increase in direct costs | Versus Adjuvant!: EUR 4,614 per QALY gained | ||||
| Cost savings driven by avoided chemotherapy, which was greater versus St. Gallen and resulted in dominance | ||||||
| Kondo et al. [46] | 85 | Japan | LN−, ER+, HER2− | 0.048 years gained versus St. Gallen | Societal costs were JPY 231,385 per patient higher with MammaPrint than with St. Gallen | JPY 4,820,813 per life year gained versus St. Gallen |
| 55-year-old patients from a Japanese cancer registry | 0.060 QALYs gained versus St. Gallen | JPY 3,873,922 per QALY gained versus St. Gallen (willingness to pay threshold from a societal perspective is JPY 5,000,000 (approx. USD 55,000) per QALY gained) | ||||
| Results were sensitive to changes in assumptions on risk classification (low versus high) and distant recurrence rates | ||||||
| MammaPrint budget impact studies | ||||||
| Zarca et al. [47] | N/A | France | LN 1–2 | – | Cost savings of EUR 9,043 per 100 patients per year | Versus current practice: MammaPrint is cost saving |
| Cost saving driven by reduced chemotherapy expenditure | ||||||
| Results are sensitive to the relative use of St. Gallen and Adjuvant! | ||||||
| MammaPrint versus Oncotype DX® cost-effectiveness studies | ||||||
| Retèl et al. [48] | 66 | Netherlands | Two populations evaluated based on data previously collected by Thomassen et al. and Fan et al. | Thomassen: MammaPrint increased QALYs by 0.08 over Oncotype DX® | Thomassen: Oncotype DX® increased direct cost by EUR 1,475 | Thomassen: MammaPrint dominates Oncotype DX® |
| Fan: MammaPrint increased QALYs by 0.31 over Oncotype DX® | Fan: Oncotype DX® increased direct cost by EUR 3,941 | Fan: MammaPrint dominates Oncotype DX® Uncertainty around these outcomes is high | ||||
| Yang et al. [49] | 72 | USA | LN−, ER+ | MammaPrint increased QALYs by 0.097 over Oncotype DX® | Oncotype DX® increased direct cost by USD 6,284 | MammaPrint dominates Oncotype DX® |
| Drivers of outcomes are not stated | ||||||
ER− estrogen receptor negative, ER+ estrogen receptor positive, HER2− human epidermal growth factor receptor 2 negative, LN− lymph node negative, LN+ lymph node positive, N/A not applicable, NCCN National Comprehensive Cancer Network, NICE National Institute for Health and Clinical Excellence, NIH National Institute for Health, QALE quality-adjusted life expectancy, QALY quality-adjusted life year, QHES Quality of Health Economic Studies, AUD Australian dollars, CAD Canadian dollars, EUR Euros, GBP Pounds, JPY Japanese Yen, SGD Singapore dollars, USD US dollars