How to Effectively Decrease Patient Co-Payments of High-Cost Drugs Through Innovation: Lessons From the Karmanos Specialty Pharmacy.

PURPOSE: High-cost drugs impose a financial burden on patients with cancer. Karmanos Specialty Pharmacy (KSP) developed a process to automate financial assistance (FA) applications to decrease patient drug cost. We evaluate the outcomes of this program on cost to patients and payers. METHODS: This is an observational, retrospective study of the KSP claims data set from January to December 2019, accessed by 13 statewide cancer centers within Michigan. Drug cost of patients, payers, FA (funds to lower patient drug cost), and types of FA were obtained. A subset analysis was performed to determine drug delivery times. RESULTS: In 2019, 869 prescriptions and 1,722 prescription fills were provided to 463 patients through KSP. The total cost of drug claims was approximately $10 million US dollars (USD) among Medicare patients (58%), approximately $3.4 million USD for privately insured patients (20%), and approximately $3.7 million USD for Medicaid patients (22%). Twenty-seven percent of patients (22% of all prescription fills) required additional FA with initial total co-payment claims of $335,216 USD. $280,988 USD of FA was obtained, which substantially lowered total patient costs by 81%. $250,818 USD of FA obtained was from foundation grants (327 fills), and $21,441 USD from manufacturer co-pay cards (47 fills). An additional $12,260 USD (12 fills) from a Karmanos Patient Assistance Fund was used. There was high dependence on foundation grant assistance among Medicare patients (33% of claims). In a subset analysis, the median time from prescription written to delivery to the patient was < 7 days (0-56 days). CONCLUSION: Twenty-seven percent of patients (22% of prescriptions fills) in 2019 required additional FA for high-cost drugs. KSP substantially reduced patient cost by implementing an efficient process using additional pharmacy assistants to obtain FA.

The costs of treating and not treating patients with chronic myeloid leukemia with tyrosine kinase inhibitors among Medicare patients in the United States.

BACKGROUND: Patients with high cost-sharing of tyrosine kinase inhibitors (TKIs) experience delays in treatment for chronic myeloid leukemia (CML). To the authors' knowledge, the clinical outcomes among and costs for patients not receiving TKIs are not well defined. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors evaluated differences in TKI initiation, health care use, cost, and survival among patients with CML with continuous Medicare Parts A and B and Part D coverage who were diagnosed between 2007 and 2015. RESULTS: A total of 941 patients were included. Approximately 29% of all patients did not initiate treatment with TKIs within 6 months (non-TKI users), and had lower rates of BCR-ABL testing and more hospitalizations compared with TKI users. Approximately 21% were not found to have any TKI claims at any time. TKI initiation rates within 6 months of diagnosis increased for all patients over time (61% to 85%), with greater improvements observed in patients receiving subsidies (55% to 90%). Total Medicare costs were greater in patients treated with TKIs, with approximately 50% because of TKI costs. Non-TKI users had more inpatient costs compared with TKI users. Trends in cost remained significant when adjusting for age and comorbidities. The median overall survival was 40 months (95% confidence interval [95% CI], 34-48 months) compared with 86 months (95% CI, 73 months to not reached), respectively, for non-TKI users versus TKI users, a finding that remained consistent when adjusting for age, comorbidities, and subsidy status (hazard ratio, 2.23; 95% CI, 1.77-2.81). CONCLUSIONS: Approximately 21% of all patients with CML did not receive TKIs at any time. Cost-sharing subsidies consistently are found to be associated with higher initiation rates. Non-TKI users had higher inpatient costs and poorer survival outcomes. Interventions to lower TKI costs for all patients are desirable.

Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial.

IMPORTANCE: Tyrosine kinase inhibitors (TKIs) have been associated with improved survival of patients with chronic myeloid leukemia (CML) but are also associated with adverse effects, especially fatigue and diarrhea. Discontinuation of TKIs is safe and is associated with the successful achievement of treatment-free remission (TFR) for some patients. OBJECTIVE: To evaluate molecular recurrence (MRec) and patient-reported outcomes (PROs) after TKI discontinuation for US patients with CML. DESIGN, SETTING, AND PARTICIPANTS: The Life After Stopping TKIs (LAST) study was a prospective single-group nonrandomized clinical trial that enrolled 172 patients from 14 US academic medical centers from December 18, 2014, to December 12, 2016, with a minimum follow-up of 3 years. Participants were adults with chronic-phase CML whose disease was well controlled with imatinib, dasatinib, nilotinib, or bosutinib. Statistical analysis was performed from August 13, 2019, to March 23, 2020. INTERVENTION: Discontinuation of TKIs. MAIN OUTCOMES AND MEASURES: Molecular recurrence, defined as loss of major molecular response (BCR-ABL1 International Scale ratio >0.1%) by central laboratory testing, and PROs (Patient-Reported Outcomes Measurement Information System computerized adaptive tests) were monitored. Droplet digital polymerase chain reaction (ddPCR) was performed on samples with undetectable BCR-ABL1 by standard real-time quantitative polymerase chain reaction (RQ-PCR). RESULTS: Of 172 patients, 89 were women (51.7%), and the median age was 60 years (range, 21-86 years). Of 171 patients evaluable for molecular analysis, 112 (65.5%) stayed in major molecular response, and 104 (60.8%) achieved TFR. Undetectable BCR-ABL1 by either ddPCR or RQ-PCR at the time of TKI discontinuation (hazard ratio, 3.60; 95% CI, 1.99-6.50; P < .001) and at 3 months (hazard ratio, 5.86; 95% CI, 3.07-11.1; P < .001) was independently associated with MRec. Molecular recurrence for patients with detectable BCR-ABL1 by RQ-PCR was 50.0% (14 of 28), undetectable BCR-ABL1 by RQ-PCR but detectable by ddPCR was 64.3% (36 of 56), and undetectable BCR-ABL1 by both ddPCR and RQ-PCR was 10.3% (9 of 87) (P ≤ .001). Of the 112 patients in TFR at 12 months, 90 (80.4%) had a clinically meaningful improvement in fatigue, 39 (34.8%) had a clinically meaningful improvement in depression, 98 (87.5%) had a clinically meaningful improvement in diarrhea, 24 (21.4%) had a clinically meaningful improvement in sleep disturbance, and 5 (4.5%) had a clinically meaningful improvement in pain interference. Restarting a TKI resulted in worsening of PROs. CONCLUSIONS AND RELEVANCE: In this study, TKI discontinuation was safe, and 60.8% of patients remained in TFR. Discontinuation of TKIs was associated with improvements in PROs. These findings should assist patients and physicians in their decision-making regarding discontinuation of TKIs. Detectable BCR-ABL1 by RQ-PCR or ddPCR at the time of TKI discontinuation was associated with higher risk of MRec; clinical application of this finding should be confirmed in other studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02269267.

Challenges in the Clinical Application of the American Society of Clinical Oncology Value Framework: A Medicare Cost-Benefit Analysis in Chronic Lymphocytic Leukemia.

PURPOSE: The ASCO Value Framework calculates the value of cancer therapies. Given costly novel therapeutics for chronic lymphocytic leukemia, we used the framework to compare net health benefit (NHB) and cost within Medicare of all regimens listed in the National Comprehensive Cancer Network (NCCN) guidelines. METHODS: The current NCCN guidelines for chronic lymphocytic leukemia were reviewed. All referenced studies were screened, and only randomized controlled prospective trials were included. The revised ASCO Value Framework was used to calculate NHB. Medicare drug pricing was used to calculate the cost of therapies. RESULTS: Forty-nine studies were screened. The following observations were made: only 10 studies (20%) could be evaluated; when comparing regimens studied against the same control arm, ranking NHB scores were comparable to their preference in guidelines; NHB scores varied depending on which variables were used, and there were no clinically validated thresholds for low or high values; treatment-related deaths were not weighted in the toxicity scores; and six of the 10 studies used less potent control arms, ranked as the least-preferred NCCN-recommended regimens. CONCLUSION: The ASCO Value Framework is an important initial step to quantify value of therapies. Essential limitations include the lack of clinically relevant validated thresholds for NHB scores and lack of incorporation of grade 5 toxicities/treatment-related mortality into its methodology. To optimize its application for clinical practice, we urge investigators/sponsors to incorporate and report the required variables to calculate the NHB of regimens and encourage trials with stronger comparator arms to properly quantify the relative value of therapies.

Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States.

BACKGROUND: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib's price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness ("imatinib-first") would be cost-effective compared with the current standard of care: "physicians' choice" of initiating treatment with any one of the three TKIs. METHODS: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician's choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models' clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven's MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study's conduct. RESULTS: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician's choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. CONCLUSION: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP.

Pattern of Duplicate Presentations at National Hematology-Oncology Meetings: Influence of the Pharmaceutical Industry.

PURPOSE: The major large US hematology-oncology meetings sponsored by the American Society of Hematology (ASH) and American Society of Clinical Oncology (ASCO) have specific guidelines in place discouraging submission of scientific information presented previously at other meetings. Nonetheless, duplicate submissions are frequent. The incidence and motivations for duplicate hematologic presentations and the influence of the pharmaceutical industry on this process have not been thoroughly analyzed. Therefore, were viewed four consecutive ASH and ASCO meetings to assess the frequency of duplicate abstract presentations. METHODS: All abstracts presented at ASCO2010 in the area of malignant hematology were compared with abstracts from ASCO and ASH 2009 and ASH 2010, and funding sources were reviewed. RESULTS: More than half (54%) of all abstracts submitted to ASCO 2010 acknowledged pharmaceutical company support. Almost one third (31%) of ASCO 2010 abstracts were resubmitted in the 2-year time period, and it was notable that a high fraction (75%) of these duplicate abstracts had pharmaceutical industry sponsorship, compared with 42% of the abstracts that were submitted only once. CONCLUSION: Despite current guidelines prohibiting duplicate abstract presentation, a substantial proportion (31%) of abstracts at large international hematology-oncology meetings are duplicative, with potential negative consequences. In addition, a disproportionate percentage of the duplicate abstracts rely on pharmaceutical industry support (75%), suggesting that marketing strategies may be a motivation for some of these repetitive submissions.

Prospective assessment of effects on iron-overload parameters of deferasirox therapy in patients with myelodysplastic syndromes.

We report the first prospective study evaluating the effects of deferasirox on liver iron concentration (LIC), labile plasma iron (LPI) and pharmacokinetics (PK) along with serum ferritin values in patients with IPSS Low- and Intermediate-1 risk myelodysplastic syndromes (MDS) and evidence of iron overload. Twenty-four heavily transfused MDS patients were enrolled in a planned 52 weeks of therapy. PK studies showed dose-proportional total drug exposure. Data demonstrated that deferasirox was well tolerated and effectively reduced LIC, LPI and serum ferritin in the iron-overloaded patients with MDS who completed 24 and 52 weeks of therapy despite ongoing receipt of red blood cell transfusions.