Cost-Effectiveness Of Arsenic Trioxide In The Treatment Of Relapsed/Refractory Acute Promyelocytic Leukemia In Canada
Bibliographic record
Abstract
Abstract Acute promyelocytic leukemia (APL) is a distinct and rare morphological, clinical and pathological variant of acute myeloid leukemia (AML). It represents approximately 10% to 15% of AML. APL is characterized by a high incidence of coagulopathy caused by disseminated intravascular coagulation and/or excessive fibrinolysis and is associated with a high early mortality. Current first-line treatments consist of all-trans retinoic acid (ATRA), anthracyclines and conventional chemotherapy (CT). Although considerable progress has been made in the first-line treatment of APL, about 20 to 30% of patients who achieved complete remission (CR) still relapse Trisenox® is a sterile injectable solution of arsenic trioxide (ATO) and has been approved in several countries, including Canada, for the induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy. At this time, ATO is recognized as the standard treatment for relapsed or refractory APL. However, it is not reimbursed yet by provincial public health care systems and was available through a special access program in Canada until product availability. The objective of this study was to assess, from a Canadian perspective, the economic impact of ATO in the treatment of patients with relapsed or refractory APL. A time-dependent Markov model was constructed to assess the cost-effectiveness of ATO compared to ATRA+CT in the treatment of relapsed/refractory APL. Because there was no head-to-head clinical trial available, data from the ATO treatment arm were taken from Soignet, 2001, while data for ATRA+CT were taken from Thomas, 2000. The comparative treatment was composed of ATRA + sequential CT including cytarabine, mitoxantrone or etoposide, followed by autologous hematopoietic stem cell transplantation (HSCT) in consolidation as described in Thomas, 2000. The Markov model comprises five health states: induction, second remission, treatment failure/relapse, post-failure, and death. The length of each Markov cycle was one month for the first 24-month study period then of one year. The model continued to run until all patients reached the absorbing state of death. All patients started in the induction state and could move to other health states thereafter. In case of treatment relapse/failure, patients were subsequently assigned to receive an allogeneic HSCT. The model also takes into account the incidence of treatment-induced grade 3-4 toxicity reported in both clinical trials (Soignet, 2001 and Thomas, 2000). Analyses were conducted from both a Canadian Ministry of Health (MoH) and a societal perspective over a lifetime horizon. In the treatment of relapsed/refractory APL, ATO is a cost-effective strategy over ATRA+CT, from both a health care system and a societal perspective. In fact, compared with ATRA+CT, ATO is associated with an incremental cost-effectiveness ratios (ICERs) of $20,443 per QALY and $22,219 per QALY, from a MoH and societal perspective respectively. Moreover, the results of the exhaustive sensitivity analysis confirm the robustness of the base-case results. In fact, according to the deterministic analysis results, ATO remained a cost-effective strategy compared with ATRA+CT from both perspectives. The ICERs vary between $9,785 and $40,732 / QALY from a MoH perspective and between $11,561 and $44,271 / QALY from a societal perspective. Results of the probabilistic sensitivity analysis indicated that, according to a willingness to pay of $50,000, ATO remains a cost-effective strategy in 99.37% and 98.98% of the simulations, from a MoH and a societal perspective respectively. In conclusion, this economic evaluation demonstrates that ATO+ATRA is a cost-effective strategy in the treatment of relapsed/refractory APL. Disclosures: Lachaine: Lundbeck Canada: Research Funding. Barakat:Lundbeck Canada: Employment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".