High cost sharing and specialty drug initiation under Medicare Part D: a case study in patients with newly diagnosed chronic myeloid leukemia.

OBJECTIVES: Specialty drugs often offer medical advances but are frequently subject to high cost sharing. This is particularly true with Medicare Part D, where after meeting a deductible, patients without low-income subsidies (non-LIS) typically face 25% to 33% coinsurance (initial coverage phase with "specialty tier" cost sharing), followed by ~50% coinsurance (coverage gap phase), and then 5% coinsurance (catastrophic phase). Yet, no studies have examined the impact of such high cost sharing on specialty drug initiation under Part D. Oral tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), making it an apt case study. STUDY DESIGN: A retrospective claims-based analysis utilizing 2011 to 2013 100% Medicare claims. METHODS: TKI initiation rates and time to initiation were compared between fee-for-service non-LIS Part D patients newly diagnosed with CML and their LIS counterparts who faced nominal cost sharing of ≤ $5. RESULTS: The first 30-day TKI fill "straddled" benefit phases, for a mean out-of-pocket cost of $2600 or more for non-LIS patients. Non-LIS patients were less likely than LIS patients to have a TKI claim within 6 months of diagnosis (45.3% vs 66.9%; P < .001) and those initiating a TKI took twice as long to fill it (mean = 50.9 vs 23.7 days; P < .001). Cox regressions controlling for sociodemographic, clinical, and plan characteristics confirmed descriptive findings (hazard ratio, 0.59; 95% CI, 0.45-0.76). Extensive sensitivity analyses confirmed the robustness of our findings. CONCLUSIONS: High cost sharing was associated with reduced and/or delayed initiation of TKIs. We discuss policy strategies to reduce current financial barriers that adversely impact access to critical therapies under Medicare Part D.

Cost utility of allogeneic stem cell transplantation with matched unrelated donor versus treatment with imatinib for adult patients with newly diagnosed chronic myeloid leukaemia.

OBJECTIVE: To estimate, from the perspective of the German statutory health insurance, the cost utility of allogeneic stem cell transplantation with matched unrelated donor (MUD-SCT) in newly diagnosed, chronic-phase chronic myeloid leukaemia (CML) patients aged 40 years or younger, relative to the treatment with imatinib. METHODS: The incremental cost-effectiveness ratio (ICER) of the additional cost of imatinib versus MUD-SCT per quality-adjusted life year (QALY) gained was chosen as a target assessment. ICER was quantified using a Markov cohort modelling approach. The evaluation encompassed 5 years of treatment with either approach, and only direct medical costs (in euro, year 2005) were considered. RESULTS: There were incremental costs of euro77,410 for imatinib therapy per QALY gained versus MUD-SCT. No strategy was clearly dominant; on average, during 5 years, cost savings of euro63,433 were obtained and 0.82 QALY lost by SCT compared to treatment with imatinib. QALYs gained in CML patients with either treatment resulted in considerable cost to the third-party payer in Germany. The results were particularly sensitive to the price of imatinib. CONCLUSIONS: The analysis finds that imatinib is more costly but more effective (as measured in QALYs) over a 5-year time horizon. The resulting ICER of euro77,410 per QALY is higher than commonly cited thresholds. The cost utility of MUD-SCT to treat CML in patients with a European Group for Blood and Marrow Transplantation score < or = to 2 compares with that of the imatinib strategy.

Growth factors in leukemia.

The role of myeloid growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, in the management of acute myeloid and acute lymphoblastic leukemias has been evaluated extensively in multiple clinical trials. Growth factors have been given before, concurrently, or sequentially with chemotherapy with the goal of reducing the duration of neutropenia and consequently the incidence and severity of infections, and improving the rate of remissions and overall survival. They also have been studied as chemotherapy-sensitizing agents in an effort to recruit dormant myeloid stem cells into the sensitive phase of the cycle. Additionally, growth factors, shown to stimulate proliferation and differentiation of leukemia cells in vitro, were evaluated as monotherapy in patients with acute leukemia. Most studies show modest improvement in the duration of the neutropenia, which does not consistently correlate with the severity of infection, rate or duration of remissions, or disease-free and overall survival. Attempts to enhance the chemosensitivity of the leukemic cells and decrease drug resistance failed to improve the rate of remission and survival in several large series. However, more recent reports suggested an improved outcome in younger patients with acute myeloid leukemia with normal karyotype. Several anecdotal case reports have shown that growth factor monotherapy can induce a complete remission in patients with acute leukemia. Data from the published clinical trials do not seem to support emergence of drug-resistant leukemia, worsening toxicity, and bone marrow failure with growth factor administration.

[Cost of hospital-based management of acute myeloid leukemia: from analytical to procedure-based tarification]. / Coûts hospitaliers de prise en charge des leucémies aiguës myéloïdes: de la comptabilité analytique à la T2A.

The confrontation of the macro- and micro-economic approaches of hospital costs is a recurrent question, in particular for pathologies where length of stay is highly variable, like acute myeloid leukemias (AML). This monocentric and retrospective study compares direct hospital medical costs of induction and relapse treatment sequences for AML, valued according to four different approaches: the analytic accounting system of our hospital, the French Diagnosis Related Group (DRG) cost databases of hospital discharges (readjusted, or not, to actual hospital stay duration), and official tariffs from the new French DRG prospective payment system. The average cost of hospital AML care valued by the analytic accounting system of our hospital is 61,248 euros for the induction phase and 91,702 euros for the relapse phase. All other national valuation methods result in a two- to four-fold underestimation of these costs. Even though AMLs are now individualized in the 10th version of the French diagnosis related group (DRG) classification, the impact of this issue in other pathologies is going to increase with the gradual implementation of the French DRG prospective payment system. That is why it must be assessed before the progressive extension of this financing system.

Trends in the treatment of acute myeloid leukaemia in the elderly.

INTRODUCTION: Acute myeloid leukaemia (AML) is the most common type of leukaemia among adults in the US. However, data on longitudinal treatment patterns and outcomes associated with AML and its relapse are sparse, particularly among the elderly. This study documents changes in treatment patterns and outcomes among elderly AML patients over the past decade. METHODS: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we retrospectively evaluated trends in mortality, treatment patterns, healthcare resource utilisation and Medicare payments associated with AML and its relapse among Medicare beneficiaries > or =65 years of age who were initially diagnosed with AML in a SEER registry between 1991 and 1999. Chemotherapy was ascertained from examination of inpatient and outpatient bills. AML relapse and retreatment were identified using a validated algorithm. Costs of care were based on total Medicare payments. RESULTS: A total of 3439 elderly patients with AML were identified. Median survival across all study patients was 2.4 months (mean +/- SD 5.6 +/- 6.8 months), with medians of 3.9, 2.2 and 1.4 months for patients 65-74 years of age, 75-84 years of age and > or =85 years of age, respectively. Fewer than 7% of patients were alive at 2 years, and there was very little variation during the decade of our analysis. Costs and overall healthcare utilisation patterns also changed very little, with the exception of those relating to hospice use and chemotherapy. Hospice use more than doubled during the decade (from 12% to 29% among patients diagnosed in 1991 and 1999, respectively; p < 0.0001), mostly among the oldest patients. Administration of chemotherapy also increased from 29% of patients diagnosed in 1991 to 38% of patients diagnosed in 1999 (p = 0.014), with the increase being seen mostly among younger patients and those treated in teaching hospitals. Average total costs (+/- SD) were US$51,888 +/- $54,825 and declined by age as a result of lower survival. A total of 192 patients (16% of treated patients) relapsed and received retreatment with chemotherapy. These patients survived a median 18 months, with a median duration of remission of 8 months, and average total costs three times higher than the overall sample. CONCLUSIONS: The high early mortality and costs associated with AML have not changed significantly over the past decade. However, treatment patterns appear to be changing, with increasing use of chemotherapy and hospice care. The ongoing introduction of new treatments for AML in the elderly is likely to further impact treatment patterns, and may change the economic burden of the disease. Our findings can be used as a baseline against which the benefits of new therapies can be compared.

The outcomes and costs of acute myeloid leukemia among the elderly.

BACKGROUND: The incidence of acute myeloid leukemia (AML) among the elderly can be expected to grow as the population continues to age. However, data on current treatment practices and costs for this form of cancer are sparse. METHODS: We used a retrospective inception cohort design and data from a linkage between 11 Surveillance, Epidemiology, and End Results cancer registries and Medicare administrative claims. We evaluated survival, use of health care resources, use of chemotherapy, and Medicare payments among adults 65 years and older with an initial diagnosis of AML between January 1, 1991, and December 31, 1996. RESULTS: A total of 2657 elderly patients with AML and complete Medicare claims data were identified. The prognosis for these patients was poor, with median survival estimated to be 2 months and a 2-year survival rate of 6%. Mean +/- SE total Medicare payments were $41,594 +/- $870 (in 1998 US dollars), 84% of which was attributed to inpatient payments. In the 2 years after the AML diagnosis, 790 patients (30%) underwent chemotherapy treatment. These patients had costs almost 3 times higher than those of other patients, and their median survival was 6 months longer. The use of hospice care was rare (17% of patients). CONCLUSIONS: Among the elderly, AML is associated with a poor prognosis and substantial costs during the relatively few remaining months of life. Moreover, most patients do not receive active treatment with chemotherapy or hospice services. Further work is needed to characterize this disease and the patient-related factors that influence treatment decisions and associated health outcomes.

Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia.

The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects.

Childhood leukaemia: the medical cost of cure.

More than 1 in every 1,500 individuals in the UK between 16 and 44 years of age has survived childhood cancer. This article describes the medical cost of cure in survivors of acute leukaemia, the most common form of childhood cancer.

Costs of diagnosis, treatment, and follow up of patients with acute myeloid leukemia in the netherlands.

The aim of the study was to calculate the costs in various places of acute myeloid leukemia (AML). Patients less than 65 years old, who were treated for newly diagnosed AML were included. The cost analysis distinguished between diagnosis, treatment, follow-up (maximum of 2 years), and treatment of relapse. The treatment period was divided into remission induction and consolidation treatment, harvest of bone marrow (BM) or peripheral blood stem cells, and transplantation. The costs of diagnosis amounted to $3,167 (1995 US$). Remission-induction treatments cost on average $46,387 and harvest of bone marrow or peripheral blood stem cells costs $6,491. The costs of the transplantation varied between $25,531 and $44,087. Costs of follow-up amounted to $4,167. Relapse treatment, mainly consisting of reinduction therapy, costs on average $24,338. The total average weighted costs of AML patients amounted to $104,386. Treating AML patients is very expensive, and major reductions in costs are not expected in the next future. Considering efficacy and effectiveness, it seemed that choices based on costs could be made between several consolidation techniques and between a specific consolidation technique and/or palliative treatment.

Cost-effectiveness and quality-of-life assessment of GM-CSF as an adjunct to intensive remission induction chemotherapy in elderly patients with acute myeloid leukemia.

We conducted a prospective, randomized, multicentre clinical trial comparing the effects and costs of GM-CSF as an adjunct to intensive chemotherapy in elderly patients with acute myeloid leukaemia (AML). The patients were randomized to either daunomycin-cytosine arabinoside (control arm: n = 161) or daunomycin-cytosine arabinoside with GM-CSF (GM-CSF arm: n = 157). The primary end-point was the effect of GM-CSF on the percentage of complete remissions (CR). Survival duration, disease-free survival, quality of life and costs were evaluated separately. CR after remission induction treatment was achieved in 55% of the patients in the control group and in 56% of the patients in the GM-CSF group (P = NS). The duration of survival and disease-free survival at 2 years after randomization were estimated at 22% and 19% for the control group and 22% and 14% for the GM-CSF group (P = NS). Considering the short-term quality of life, the administration of GM-CSF resulted in more problems with regard to depressed mood, diarrhoea and rash/eczema. With regard to the long-term quality of life there were no significant differences between the two groups. The average costs of the primary treatment were higher in GM-CSF-treated patients than in the control group, i.e. US$40782 and US$34465, respectively (P < 0.01). The costs during the follow-up period did not differ between the two groups. The results of this randomized clinical trial indicate that daunomycin-cytosine arabinoside plus GM-CSF is not a cost-effective treatment strategy when compared with daunomycin-cytosine arabinoside alone.

Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party.

Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and less blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05) and survival (23% v 18%; P < 0.05) were also better with DAT 3 + 10. Post-remission intensification of therapy with MAZE resulted in fewer relapses (66% v 74% at 5 years; P = 0.03) but patients allocated MAZE required considerably more supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths occurred following COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.

Costs over time in conventional treatment of acute myeloid leukaemia. A study exploring changes in treatment strategies over two decades.

OBJECTIVES: The aim was to analyse the consumption of different items in conventional treatment of acute myeloid leukaemia (AML) and their cost, in order to evaluate the economic consequences of new treatment strategies. DESIGN: Data on items of treatment were gathered retrospectively from case notes, including amount and date. Prices were gathered from price lists made up for internal billing/accounting. SETTING: The patients were all treated in a hospital with excellent treatment and service facilities. SUBJECTS: Seventy-three AML patients treated from 1973 to 1980, all since deceased, were compared with 54 patients treated from 1981 to 1988, of whom 14 were alive at the end of the observation period. INTERVENTIONS: The patients were treated according to randomized treatment protocols to achieve complete remission. Maintenance treatment or consolidation courses were given. In relapse, new induction treatment was given. MAIN OUTCOME MEASURES: Complete remission and survival were registered. The costs were divided into basic hospital costs and patient-specific costs. RESULTS: The mean total treatment cost for an AML patient in the 1970s was 211,138 SEK, and in 1980s 356,911 SEK. (UK 1 pound = 10.57 SEK, US$1 = 5.91 SEK 1990). All treatment costs increased between the periods: hospital costs by 20%, and patient-specific costs by 186%. Antibiotics, cytostatics and outpatient department costs had increased the most. The mean survival time almost doubled, and in the 1980s group there were several long-term survivors. CONCLUSIONS: The costs for AML treatment increased considerably from the 1970s to the 1980s. The effectiveness of these treatments increased as well, resulting in increased rate and duration of survival, and several patients were long-term survivors. It was not possible to identify the cost consequences of separate new technologies.

Cost analysis of different phases of acute myeloid leukaemia.

Priority lists have been formulated in several countries and cut-backs can be a threat to leukaemia treatment. We analysed the costs in different phases of disease for 54 conventionally treated patients with acute myeloid leukaemia. Thirty-two patients reached CR 1, seven patients are still alive as of May 1994. We found a cost per week and patient of 17,334 Swedish Crowns (SEK) (U.K. 1 pound = 10.57 and U.S. $1 = 5.91, 1990) in induction phase, 1854 in remission phase and 10,529 SEK in relapse phase. In the terminal phase 10% of the total cost was spent. The quality of life of the patients in relapse is discussed and palliative treatment is emphasized.

The economic costs of acute myeloid leukemia in Sweden.

The direct and indirect costs of acute myeloid leukemia were estimated for Sweden in 1989. The calculated total cost was SEK 460 million. Nearly half of the costs, or 1.7 million per patient diagnosed, were indirect costs due to premature mortality. Direct costs of relapses and indirect costs of mortality represent costs due to the absence of completely curable therapy. They also represent potential cost savings that could be obtained after introduction of new treatment options in the future.

Idarubicin: a pharmacoeconomic evaluation of its use in adult patients with acute myeloid leukaemia.

Idarubicin is an effective agent in the treatment of acute myeloid leukaemia (AML), inducing complete remission in 39 to 80% of newly diagnosed patients. Although it also demonstrates efficacy as monotherapy, and is of use in relapsed or refractory disease, most comparative clinical trials have administered idarubicin intravenously in combination with cytarabine in newly diagnosed patients. These trials indicate that improved survival and response rates, and rapid achievement of remission, are more likely with idarubicin than with daunorubicin, when both agents are given in combination with cytarabine. In elderly patients, however, response rates are lower than in younger patients, and there is less disparity in efficacy between idarubicin and daunorubicin induction therapy. Although AML is an expensive disease to treat, the majority of costs are associated with the length of hospitalisation, with the acquisition cost of the chemotherapy agents contributing less than 10% to overall expenditure. Idarubicin combined with cytarabine therapy achieved higher response rates with the first cycle of therapy than daunorubicin, thereby reducing the requirements for a second cycle of therapy and further hospitalisation. Compared with daunorubicin plus cytarabine induction treatment, idarubicin plus cytarabine reduced the costs of achieving a complete response by between 22 and 39% in patients with a median age less than 60 years. In patients with a median age of 62 years, who are more representative of the AML population, costs of achieving a complete response were reduced by 3 to 6%. Thus, idarubicin is more cost effective than daunorubicin as induction therapy in combination with cytarabine, in adult patients with AML. The pharmacoeconomic position of idarubicin in postinduction therapy remains to be established.