Real-World Survival, Healthcare Resource Utilization, and Costs Among U.S. Elderly Patients With Diffuse Large B-Cell Lymphoma (DLBCL) Treated With R-GemOx in the Relapsed/Refractory Setting.

BACKGROUND: Little recent real-world evidence exists on overall survival, healthcare resource utilization (HCRU), and costs among R/R DLBCL patients treated with the combination of rituximab, gemcitabine, and oxaliplatin (R-GemOx), a widely-used regimen for patients ineligible for stem cell transplant due to age or comorbidities. PATIENTS AND METHODS: This retrospective analysis used 2014 to 2019 U.S. Medicare claims. Individuals aged ≥66 years with a new DLBCL diagnosis between October 1, 2015 and December 31, 2018 and continuous fee-for-service Medicare Part A, B, and D coverage in the 12 months pre- and postindex were followed to identify the sample of patients with evidence of R-GemOx treatment in the second-line (2L) or third-line (3L) setting. Outcomes included overall survival, all-cause and DLBCL-related HCRU, and costs after R-GemOx initiation. RESULTS: The final sample included 157 patients who received treatment with R-GemOx in the R/R settings (mean (SD) age 77.5 (6.0) years, 39.5% age>80 years; 66.9% male; 91.1% White). Of these, 126 received R-GemOx in the 2L setting and 31 received R-GemOx in the 3L setting. Median overall survival from R-GemOx initiation was 6.9 months and 6.8 months in the 2L and 3L setting, respectively. Rates of all-cause hospitalization (68.1% [2L] and >90% [3L]) and hospice use (42.9% [2L] and 51.7% [3L]) were high in the 12 months after R-GemOx initiation. All-cause total costs were substantial ($144,653 [2L] and $142,812 [3L]) and approximately 80% of costs were DLBCL-related within 12 months of R-GemOx initiation. CONCLUSION: Elderly U.S. Medicare beneficiaries diagnosed with DLBCL who initiated R-GemOx treatment in the R/R setting have poor overall survival, high rates of HCRU, and substantial costs.

Real-world analysis of adverse event rates after initiation of ibrutinib among Medicare beneficiaries with chronic lymphocytic leukemia.

BACKGROUND: The first-generation BTK inhibitor ibrutinib is a standard-of-care therapy in the treatment of chronic lymphocytic leukemia (CLL) despite potential side effects that often lead to discontinuation. METHODS: This study used 2013-2019 claims data to describe the incidence rate of adverse events (AEs) among elderly Medicare beneficiaries newly initiating ibrutinib for CLL. RESULTS: The final sample contained 11,870 Medicare beneficiaries with CLL (mean age 77.2) newly initiating ibrutinib, of whom 65.2% discontinued over mean follow-up of 2.3 years. The overall incidence rate of AEs was 62.5 per 1000 patient-months for all discontinuers and 32.9 per 1000 patient-months for non-discontinuers. Discontinuers had a higher incidence rate of AEs per 1000 patient-months compared with non-discontinuers for all AEs examined, including infection (22.8 vs. 14.5), atrial fibrillation (15.1 vs. 7.0), anemia (21.9 vs. 14.5), and arthralgia/myalgia (19.5 vs. 13.6). CONCLUSION: In this first real-world study of a national sample of elderly US patients treated with ibrutinib, we found a clear unmet need for improved management of ibrutinib-related AEs and/or new treatments to improve real-world outcomes in patients with CLL.

Real-world treatment patterns, survival, health resource use and costs among Medicare beneficiaries with diffuse large B-cell lymphoma.

Aim: To examine real-world treatment patterns, survival, healthcare resource use and costs in elderly Medicare beneficiaries with diffuse large B-cell lymphoma (DLBCL). Methods: 11,880 Medicare patients aged ≥66 years with DLBCL between 1 October 2015 and 31 December 2018 were followed for ≥12 months after initiating front-line treatment. Results: Two-thirds (61.2%) of the patients received standard-of-care R-CHOP as first-line treatment. Hospitalization was common (57%) in the 12-months after initiation of 1L treatment; the mean DLCBL-related total costs were US$84,416 during the same period. Over a median follow-up of 2.1 years, 17.8% received at least 2L treatment. Overall survival was lower among later lines of treatment (median overall survival from initiation of 1L: not reached; 2L: 19.9 months; 3L: 9.8 months; 4L: 5.5 months). Conclusion: A large unmet need exists for more efficacious and well-tolerated therapies for older adults with DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of Non-Hodgkin lymphoma, and it becomes more common with age. While researchers continue to develop newer, more effective treatments for DLBCL, it is important to understand how patients use existing treatments and the associated costs, particularly among the elderly. In our real-world analysis of nearly 12,000 older patients with DLBCL, we found high rates of hospitalization and hospice use, short length of life in later lines of therapy and substantial healthcare costs. Our findings suggest a large current unmet need for more effective and well-tolerated therapies for older adults with DLBCL in both the front-line and relapse/refractory settings.

Ibrutinib discontinuation and associated factors in a real-world national sample of elderly Medicare beneficiaries with chronic lymphocytic leukemia.

Prior studies evaluating ibrutinib discontinuation are limited to clinical trials and selected medical centers and hence may not reflect real-world practice. This study used Medicare claims (2013-2019) to examine ibrutinib discontinuation and associated factors among elderly patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Over a median follow-up of 2.1 years, two-thirds (65.2%) of the 11,870 new ibrutinib initiators were discontinued, with half (45.1%) of patients discontinuing within 12 months of initiation. Factors such as advanced age, lack of Part D low-income subsidy, evidence of prior CLL/SLL treatment, and cardiovascular comorbidities (e.g. atrial fibrillation) were associated with higher risk of discontinuation. Over a median of 1.2 years from discontinuation, 40% of discontinuers initiated another CLL/SLL treatment after ibrutinib discontinuation; 25% of patients restarted ibrutinib treatment at some point over follow-up. Our findings point to a large unmet need with the widely used BTKi ibrutinib and underscore the importance of ongoing development of efficacious and well-tolerated CLL/SLL therapies.

Real-world adherence and discontinuation among Medicare beneficiaries initiating venetoclax vs. BTKis in relapsed/refractory chronic lymphocytic leukemia.

The treatment landscape for chronic lymphocytic leukemia (CLL) has been transformed by the availability of Bruton's tyrosine kinase inhibitors (BTKis) and the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Despite clinical trial data supporting these novel oral agents, evidence evaluating real-world adherence is limited. This study used 2015-2019 Medicare claims data for elderly patients with relapsed/refractory CLL to assess differences in real-world adherence and discontinuation in the 12 months after treatment initiation. In the final sample of 711 venetoclax patients and 1,566 BTKi patients, we found that those initiating venetoclax tended to be younger (mean age 75.6 [SD 6.0] vs 77.6 [SD 6.9] years, p < .001) but had poorer clinical characteristics. After risk-adjustment, the venetoclax group had higher adherence (61.9% vs. 45.4%, p < .0001) and lower discontinuation when compared to the BTKi group (28.5% vs. 47.4%, p < .001). These favorable real-world findings underscore the importance of developing well-tolerated novel combinations for older adults.

Assessing unmet need among elderly Medicare Beneficiaries with Mantle cell lymphoma: an analysis of treatment patterns, survival, healthcare resource utilization, and costs.

Studies evaluating real-world outcomes and health care utilization for mantle cell lymphoma are limited. We utilized national Medicare claims (2009-2019) to examine treatment patterns, healthcare resource utilization, costs, and survival in 3664 elderly patients receiving 1 L treatment for MCL. Over a median follow-up of 2.8 years, 40.3% received at least 2 L treatment. The most common 1 L regimen was bendamustine-rituximab (50.1%), with increased use of BTKi-based regimens observed in 2 L (39.4%). Half (51.8%) of patients had an all-cause hospitalization within 12 months of initiating 1 L; hospitalization rates were higher in later lines. Healthcare costs were substantial and most costs (>80%) were MCL-related. Overall survival was poorer among later lines of treatment (median OS from initiation of 1 L: 53.5 months; 2 L: 22.0 months; 3 L: 11.8 months; 4 L: 7.8 months). These results suggest a large unmet need and future work should evaluate whether novel therapies have improved outcomes among elderly patients with MCL.

Impact of Updated Clinical Practice Guidelines on Outpatient Treatment for Clostridioides difficile Infection and Associated Clinical Outcomes.

Background: The 2017 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) Clostridium (Clostridioides) difficile infection (CDI) guideline update recommended treatment with fidaxomicin or vancomycin for CDI. We aimed to examine outpatient CDI treatment utilization before and after the guideline update and compare clinical outcomes associated with fidaxomicin versus vancomycin use. Methods: A pre-post study design was employed using Medicare data. CDI treatment utilization and clinical outcomes (4- and 8-week sustained response, CDI recurrence) were compared between patients indexed from April-September 2017 (preguideline period) and those indexed from April-September 2018 (postguideline period). Clinical outcomes associated with fidaxomicin versus vancomycin were compared using propensity score-matched analyses. Results: From the pre- to postguideline period, metronidazole use decreased (initial CDI: 81.2% to 53.5%; recurrent CDI: 49.7% to 27.6%) while vancomycin (initial CDI: 17.9% to 44.9%; recurrent CDI: 48.1% to 66.4%) and fidaxomicin (initial CDI: 0.87% to 1.63%; recurrent CDI: 2.2% to 6.0%) use increased significantly (P < .001 for all). However, clinical outcomes did not improve. In propensity score-matched analyses, fidaxomicin versus vancomycin users had 4-week sustained response rates that were higher by 13.5% (95% confidence interval [CI], 4.0%-22.9%; P = .0058) and 30.0% (95% CI, 16.8%-44.3%; P = .0002) in initial and recurrent CDI cohorts, respectively. Recurrence rates were numerically lower for fidaxomicin in both cohorts. Conclusions: Vancomycin use increased and metronidazole use decreased after the 2017 guideline update. Fidaxomicin use increased but remained low. Improved outcomes associated with fidaxomicin relative to vancomycin suggest benefits from its greater use in Medicare patients.

Financial incentives tied to Medicare star ratings: impact on influenza vaccination uptake in Medicare beneficiaries.

OBJECTIVES: To evaluate the impact of the star rating bonus payment policy on annual influenza vaccination rates before and after the policy was adopted for Medicare Advantage (MA) plans in 2012. STUDY DESIGN: Observational study using data from the Medicare Current Beneficiary Survey from 2007 to 2015 to test whether the bonus payment policy led to higher flu vaccination rates in MA prescription drug (MAPD) plans vs fee-for-service prescription drug plans (PDPs), which were ineligible for bonus payments. METHODS: Mean preperiod (2007-2011) and postperiod (2012-2015) influenza vaccination rates were compared for enrollees in both types of plans using descriptive and multivariate difference-in-difference (DID) equations. The experimental effect of the MA bonus payment policy was estimated as the interaction between plan type (MAPD plan vs PDP) and period (pre- vs post period) controlling for the main effects of plan type (MAPD vs PDP), timing of the observation (pre- vs post period), and other potential confounders. RESULTS: The study sample included 40,369 person-years of data in the preperiod and 27,703 person-years of data in the post period. Vaccination rates increased by 3.8% in MAPD plans compared with 2.7% in PDPs, leading to a relative MAPD-favored difference that was nonsignificant (P = .31). However, the effect was statistically significant (odds ratio [OR], 1.12; P = .03) in the main multivariate DID model. A larger relative difference was observed among beneficiaries 75 years and older (OR, 1.18; P = .03). CONCLUSIONS: The Medicare bonus payment policy led to a small increase in beneficiaries' flu vaccination rates, suggesting that expanding the star measure set could be an effective way to increase uptake for other recommended adult vaccines.

Barriers and solutions to improve access for chimeric antigen receptor therapies.

Chimeric antigen receptor T cells are a potentially curative new therapeutic option, but access challenges remain. The limited number of certified treatment centers and the need to travel to these centers, the expenses of travel and lodging and the out-of-pocket costs associated with treatment pose a challenge for patients. Further, the logistics of follow-up coupled with an ad hoc reimbursement environment make chimeric antigen receptor T-cell treatment an unattractive proposition for many providers. The patient-specific nature of these gene therapies has made scaling up production difficult for manufacturers. Providing expanded financial assistance for patients and education for community oncologists, and addressing reimbursement challenges, can alleviate some of these access barriers.

Chimeric antigen receptor T cells are a new type of cancer treatment where the cells from a patient's own blood are changed in the laboratory and injected back into the patient so they attack cancer cells. While these drugs offer a possible cure for some cancers, patients have had problems getting these treatments because there are not many approved treatment centers. Patients have to travel to these centers, and there can be high out-of-pocket costs for travel, a place to stay and the treatment itself. The paper discusses several ways to make it easier to get these treatments, such as helping patients pay for lodging and travel and changing insurance payment policies for chimeric antigen receptor T cell treatment.

Valuing treatment in oncology: embracing a broader notion of value.

Over the past decade, we have witnessed unprecedented, groundbreaking innovation in pharmaceuticals. This has been particularly true in oncology, where new therapies have increased survival and at times offered clinical cure. However, the impact of these promising treatments has been attenuated by persistent access and cost challenges that may limit their effect. A narrative has emerged that many of these so-called breakthroughs are not priced according to the value they provide. Traditional cost-effectiveness analyses would appear to support these doubts, often suggesting that innovative therapies do not represent value for money. However, there is a case to be made that innovative therapies require equally innovative value assessments. To explore this emerging viewpoint, this article provides a brief introduction to the current value debate and oncology-specific considerations when assessing elements of value. We offer a brief background on the nature and development of quality-adjusted life-years as a part of cost-effectiveness analyses and some of their key limitations; a primer on "novel" elements of value, which capture specific aspects of patient and societal preferences not included in quality-adjusted life-years; and their applicability to oncology including discussion on areas where further thought and research might be needed. We conclude with a potential checklist of novel elements of value that should be considered. DISCLOSURES: This Viewpoints article was funded by Novartis, Inc., which also provided funding to COVIA Health Solutions for manuscript development. The sponsor was involved in developing the manuscript. Kamal-Bahl and Puckett are employees of COVIA Health Solutions, a consulting firm that provides services to biopharmaceutical clients, trade organizations, and foundations. Kamal-Bahl holds stock in Merck and Pfizer. Singh is an employee of Novartis Pharmaceuticals. Willke received personal fees from COVIA Health Solutions for work on the manuscript.

A practical path forward to more patient-centered value assessment.

To ensure that value assessment accounts for patient needs, we need a better understanding of the outcomes that are most important to patients, write authors from COVIA Health Solutions and the University of Washington School of Pharmacy.

Payer and Pharmaceutical Manufacturer Considerations for Outcomes-Based Agreements in the United States.

BACKGROUND: Considerable interest exists among health care payers and pharmaceutical manufacturers in designing outcomes-based agreements (OBAs) for medications for which evidence on real-world effectiveness is limited at product launch. OBJECTIVES: To build hypothetical OBA models in which both payer and manufacturer can benefit. METHODS: Models were developed for a hypothetical hypercholesterolemia OBA, in which the OBA was assumed to increase market access for a newly marketed medication. Fixed inputs were drug and outcome event costs from the literature over a 1-year OBA period. Model estimates were developed using a range of inputs for medication effectiveness, medical cost offsets, and the treated population size. Positive or negative feedback to the manufacturer was incorporated on the basis of expectations of drug performance through changes in the reimbursement level. Model simulations demonstrated that parameters had the greatest impact on payer cost and manufacturer reimbursement. RESULTS: Models suggested that changes in the size of the population treated and drug effectiveness had the largest influence on reimbursement and costs. Despite sharing risk for potential product underperformance, manufacturer reimbursement increased relative to having no OBA, if the OBA improved market access for the new product. Although reduction in medical costs did not fully offset the cost of the medication, the payer could still save on net costs per patient relative to having no OBA by tying reimbursement to drug effectiveness. CONCLUSIONS: Pharmaceutical manufacturers and health care payers have demonstrated interest in OBAs, and under a certain set of assumptions both may benefit.

A Review of Empirical Analyses of Disinvestment Initiatives.

BACKGROUND: Disinvesting in low-value health care services provides opportunities for investment in higher value care and thus an increase in health care efficiency. OBJECTIVES: To identify international experience with disinvestment initiatives and to review empirical analyses of disinvestment initiatives. METHODS: We performed a literature search using the PubMed database to identify international experience with disinvestment initiatives. We also reviewed empirical analyses of disinvestment initiatives. RESULTS: We identified 26 unique disinvestment initiatives implemented across 11 countries. Nineteen addressed multiple intervention types, six addressed only drugs, and one addressed only devices. We reviewed 18 empirical analyses of disinvestment initiatives: 7 reported that the initiative was successful, 8 reported that the initiative was unsuccessful, and 3 reported that findings were mixed; that is, the study considered multiple services and reported a decrease in the use of some but not others. Thirty-seven low-value services were evaluated across the 18 empirical analyses, for 14 (38%) of which the disinvestment initiative led to a decline in use. Six of the seven studies that reported the disinvestment initiative to be successful included an attempt to promote the disinvestment initiative among participating clinicians. CONCLUSIONS: The success of disinvestment initiatives has been mixed, with fewer than half the identified empirical studies reporting that use of the low-value service was reduced. Our findings suggest that promotion of the disinvestment initiative among clinicians is a key component to the success of the disinvestment initiative.

Toward a Broader Concept of Value: Identifying and Defining Elements for an Expanded Cost-Effectiveness Analysis.

This commentary identifies and defines potentially useful expansions to traditional cost-effectiveness analysis as often used in health technology assessment. Since the seminal 1977 article by Weinstein and Stason, the recommended approach has been the use of the incremental cost-effectiveness ratio based on the metric of the cost per quality-adjusted life-year gained, allowing comparisons across different technologies. An expanded framework, incorporating a wider range of the elements of value, is proposed. In addition to the core value drivers of health gain and other health system cost savings (if any), we propose adding other less recognized elements related to the value of knowing and informational externalities. We describe each of five factors related to the value of knowing: 1) a reduction in uncertainty, reflecting the benefit of a companion diagnostic increasing the certainty of a patient׳s response to a medicine; 2) insurance value related to greater peace of mind due to protection against catastrophic health and financial loss; 3) the value of hope for a "cure," leading individuals to become risk seekers in some circumstances; 4) real option value due to life extension opening possibilities for individuals to benefit from future innovation; and 5) spillovers or externalities arising from benefits of scientific advances that cannot be entirely appropriated by those making the advances. Further thought and research are needed on how best to measure and integrate these elements into an incremental value framework and on coverage and pricing decisions.

Estimating Population Health Benefits Associated with Specialty and Traditional Drugs in the Year Following Product Approval.

OBJECTIVE: Compared to traditional drugs, specialty drugs tend to be indicated for lower prevalence diseases. Our objective was to compare the potential population health benefits associated with specialty and traditional drugs in the year following product approval. METHODS: First, we created a dataset of estimates of incremental quality-adjusted life-year (QALY) gains and incremental life-year (LY) gains for US FDA-approved drugs (1999-2011) compared to standard of care at the time of approval identified from a literature search. Second, we categorized each drug as specialty or traditional. Third, for each drug we identified estimates of US disease prevalence for each pertinent indication. Fourth, in order to conservatively estimate the potential population health gains associated with each new drug in the year following its approval we multiplied the health gain estimate by 10% of the identified prevalence. Fifth, we used Mann-Whitney U tests to compare the population health gains for specialty and traditional drugs. RESULTS: We identified QALY gain estimates for 101 drugs, including 56 specialty drugs, and LY gain estimates for 50 drugs, including 34 specialty drugs. The median estimated population QALY gain in the year following approval for specialty drugs was 4200 (IQR = 27,000) and for traditional drugs was 694 (IQR = 24,400) (p = 0.245). The median estimated population LY gain in the year following approval for specialty drugs was 7250 (IQR = 39,200) and for traditional drugs was 2500 (IQR = 58,200) (p = 0.752). CONCLUSIONS: Despite often being indicated for diseases of lower prevalence, we found a trend towards specialty drugs offering larger potential population health gains than traditional drugs, particularly when measured in terms of QALYs.

Financing a Cure for Diabetes in a Multipayer Environment.

BACKGROUND: Financing medical breakthroughs or cures is becoming increasingly challenging in the current fiscal environment. OBJECTIVES: In this paper, we develop the precise conditions needed for a financing mechanism, HealthCoin, to work between a private payer and Medicare, to incentivize the former to invest in breakthrough therapies or cures in the US. METHODS: We illustrate the valuation of such a currency for a cure of Type 2 diabetes. RESULTS: We show that without a HealthCoin, a private payer does not invest in the cure, a small fraction of the patients live up to age 65, Medicare pays for the full price of the cure at age 65 and incurs net loss in returns over the elderly ages, and the manufacturer only sells cures for those who reach age 65. In contrast, a HealthCoin is feasible in this market, incentivizing the private payer to invest in the cure during the non-elderly ages and leading to Pareto improvements for all three stakeholders. CONCLUSIONS: Discussions around the applicability of HealthCoin for breakthrough therapies on the horizon, such as gene therapies for blindness and hemophilia B, and the feasibility of instituting such payments through new legislations or demonstration projects could be of great value.

CHALLENGES FACED IN TRANSFERRING ECONOMIC EVALUATIONS TO MIDDLE INCOME COUNTRIES.

BACKGROUND: Decision makers in middle-income countries are using economic evaluations (EEs) in pricing and reimbursement decisions for pharmaceuticals. However, whilst many of these jurisdictions have local submission guidelines and local expertise, the studies themselves often use economic models developed elsewhere and elements of data from countries other than the jurisdiction concerned. The objectives of this study were to describe the current situation and to assess the challenges faced by decision makers in transferring data and analyses from other jurisdictions. METHODS: Experienced health service researchers in each region conducted an interview survey of representatives of decision making bodies from jurisdictions in Asia, Central and Eastern Europe, and Latin America that had at least 1 year's experience of using EEs. RESULTS: Representatives of the relevant organizations in twelve countries were interviewed. All twelve jurisdictions had developed official guidelines for the conduct of EEs. All but one of the organizations evaluated studies submitted to them, but 9 also conducted studies and 7 commissioned them. Nine of the organizations stated that, in evaluating EEs submitted to them, they had consulted a study performed in a different jurisdiction. Data on relevant treatment effect was generally considered more transferable than those on prices/unit costs. Views on the transferability of epidemiological data, data on resource use and health state preference values were more mixed. Eight of the respondents stated that analyses submitted to them had used models developed in other jurisdictions. Four of the organizations had a policy requiring models to be adapted to reflect local circumstances. The main obstacles to transferring EEs were the different patterns of care or wealth of the developed countries from which most economic evaluations originate. CONCLUSIONS: In middle-income countries it is commonplace to deal with the issue of transferring analyses or data from other jurisdictions. Decision makers in these countries face several challenges, mainly due to differences in current standard of care, practice patterns, or gross domestic product between the developed countries where the majority of the studies are conducted and their own jurisdiction.