Shifting from Equality toward Equity: Addressing Disparities in Research Participation for Clinical Cancer Research.

AbstractThere is societal consensus that cancer clinical trial participation is unjust because some sociodemographic groups have been systematically underrepresented. Despite this, neither a definition nor an ethical explication for the justice norm of equity has been clearly articulated in this setting, leading to confusion over its application and goals. Herein we define equity as acknowledging sociodemographic circumstances and apportioning resource and opportunity allocation to eliminate disparities in outcomes, and we explore the issues and tensions this norm generates through practical examples. We assess how equality-based enrollment structures in clinical cancer research have perpetuated historical disparities and what equity-based alternatives are necessary to achieve representativeness and an expansive conception of participatory justice in clinical cancer research. This framework addresses the breadth from normative to applied by defining the justice norm of equity and translating it into practical strategies for addressing participation disparities in clinical cancer research.

Second-Line Chimeric Antigen Receptor T-Cell Therapy in Diffuse Large B-Cell Lymphoma : A Cost-Effectiveness Analysis.

BACKGROUND: First-line treatment of diffuse large B-cell lymphoma (DLBCL) achieves durable remission in approximately 60% of patients. In relapsed or refractory disease, only about 20% achieve durable remission with salvage chemoimmunotherapy and consolidative autologous stem cell transplantation (ASCT). The ZUMA-7 (axicabtagene ciloleucel [axi-cel]) and TRANSFORM (lisocabtagene maraleucel [liso-cel]) trials demonstrated superior event-free survival (and, in ZUMA-7, overall survival) in primary-refractory or early-relapsed (high-risk) DLBCL with chimeric antigen receptor T-cell therapy (CAR-T) compared with salvage chemoimmunotherapy and consolidative ASCT; however, list prices for CAR-T exceed $400 000 per infusion. OBJECTIVE: To determine the cost-effectiveness of second-line CAR-T versus salvage chemoimmunotherapy and consolidative ASCT. DESIGN: State-transition microsimulation model. DATA SOURCES: ZUMA-7, TRANSFORM, other trials, and observational data. TARGET POPULATION: "High-risk" patients with DLBCL. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: Axi-cel or liso-cel versus ASCT. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (iNMB) in 2022 U.S. dollars per quality-adjusted life-year (QALY) for a willingness-to-pay (WTP) threshold of $200 000 per QALY. RESULTS OF BASE-CASE ANALYSIS: The increase in median overall survival was 4 months for axi-cel and 1 month for liso-cel. For axi-cel, the ICER was $684 225 per QALY and the iNMB was -$107 642. For liso-cel, the ICER was $1 171 909 per QALY and the iNMB was -$102 477. RESULTS OF SENSITIVITY ANALYSIS: To be cost-effective with a WTP of $200 000, the cost of CAR-T would have to be reduced to $321 123 for axi-cel and $313 730 for liso-cel. Implementation in high-risk patients would increase U.S. health care spending by approximately $6.8 billion over a 5-year period. LIMITATION: Differences in preinfusion bridging therapies precluded cross-trial comparisons. CONCLUSION: Neither second-line axi-cel nor liso-cel was cost-effective at a WTP of $200 000 per QALY. Clinical outcomes improved incrementally, but costs of CAR-T must be lowered substantially to enable cost-effectiveness. PRIMARY FUNDING SOURCE: No research-specific funding.

Mental health disorders and survival among older patients with diffuse large B-cell lymphoma in the USA: a population-based study.

BACKGROUND: Mental health disorders can potentially decrease quality of life and survival in patients with cancer. Little is known about the survival implications of mental health disorders in patients with diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the effect of pre-existing depression, anxiety, or both on survival in a US cohort of older patients with DLBCL. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients aged 67 years or older, diagnosed with DLBCL in the USA between Jan 1, 2001, and Dec 31, 2013. We used billing claims to identify patients with pre-existing depression, anxiety, or both before their DLBCL diagnosis. We compared 5-year overall survival and lymphoma-specific survival between these patients and those without pre-existing depression, anxiety, or both using Cox proportional analyses, adjusting for sociodemographic and clinical characteristics, including DLBCL stage, extranodal disease, and B symptoms. FINDINGS: Among 13 244 patients with DLBCL, 2094 (15·8%) had depression, anxiety, or both disorders; 6988 (52·8%) were female, and 12 468 (94·1%) were White. The median follow-up for the cohort was 2·0 years (IQR 0·4-6·9 years). 5-year overall survival was 27·0% (95% CI 25·1-28·9) for patients with these mental health disorders versus 37·4% (36·5-38·3) for those with no mental health disorder (hazard ratio [HR] 1·37, 95% CI 1·29-1·44). Although survival differences between mental health disorders were modest, those with depression alone had the worst survival compared with no mental health disorder (HR 1·37, 95% CI 1·28-1·47), followed by those with depression and anxiety (1·23, 1·08-1·41), and then anxiety alone (1·17, 1·06-1·29). Individuals with these pre-existing mental health disorders also had lower 5-year lymphoma-specific survival, with depression conferring the greatest effect (1·37, 1·26-1·49) followed by those with depression and anxiety (1·25, 1·07-1·47) and then anxiety alone (1·16, 1·03-1·31). INTERPRETATION: Pre-existing depression, anxiety, or both disorders present within 24 months before DLBCL diagnosis, worsens prognosis for patients with DLBCL. Our data underscore the need for universal and systematic mental health screening for this population, as mental health disorders are manageable, and improvements in this prevalent comorbidity might affect lymphoma-specific survival and overall survival. FUNDING: American Society of Hematology, National Cancer Institute, Alan J Hirschfield Award.

Benefits and Barriers of Technology for Home Function and Mobility Assessment: Perspectives of Older Patients With Blood Cancers, Caregivers, and Clinicians.

PURPOSE: Advances in digital health technology can overcome barriers to measurement of function and mobility for older adults with blood cancers, but little is known about how older adults perceive such technology for use in their homes. METHODS: To characterize potential benefits and barriers associated with using technology for home functional assessment, we conducted three semistructured focus groups (FGs) in January 2022. Eligible patients came from the Older Adult Hematologic Malignancies Program at Dana-Farber Cancer Institute (DFCI), which includes adults 73 years and older enrolled during their initial consult with their oncologist. Eligible caregivers were 18 years and older and identified by enrolled patients as their primary caregiver. Eligible clinicians were practicing DFCI hematologic oncologists, nurse practitioners, or physician assistants with ≥2 years of clinical experience. A qualitative researcher led thematic analysis of FG transcripts to identify key themes. RESULTS: Twenty-three participants attended the three FGs: eight patients, seven caregivers, and eight oncology clinicians. All participants valued function and mobility assessments and felt that technology could overcome barriers to their measurement. We identified three themes related to potential benefits: making it easier for oncology teams to consider function and mobility; providing standardized, objective data; and facilitating longitudinal data. We also identified four themes related to barriers to home functional assessment: concerns related to privacy and confidentiality, burden of measuring additional patient data, challenges in operating new technology, and concerns related to data improving care. CONCLUSION: These data suggest that specific concerns raised by older patients, caregivers, and oncology clinicians must be addressed to improve acceptability and uptake of technology used to measure function and mobility in the home.

Precancer and cancer-associated depression and anxiety among older adults with blood cancers in the United States.

For patients with blood cancers, comorbid mental health disorders at diagnosis likely affect the entire disease trajectory, as they can interfere with disease information processing, lead to poor coping, and even cause delays in care. We aimed to characterize the prevalence of depression and anxiety in patients with blood cancers. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients ≥67 years old diagnosed with lymphoma, myeloma, leukemia, or myelodysplastic syndromes between 2000 and 2015. We determined the prevalence of precancer depression and anxiety and cancer-associated (CA) depression and anxiety using claims data. We identified factors associated with CA-depression and CA-anxiety in multivariate analyses. Among 75 691 patients, 18.6% had at least 1 diagnosis of depression or anxiety. Of the total cohort, 13.7% had precancer depression and/or precancer anxiety, while 4.9% had CA-depression or CA-anxiety. Compared with patients without precancer anxiety, those with precancer anxiety were more likely to have subsequent claims for CA-depression (odds ratio [OR] 2.98; 95% CI 2.61-3.41). Other factors associated with a higher risk of CA- depression included female sex, nonmarried status, higher comorbidity, and myeloma diagnosis. Patients with precancer depression were significantly more likely to have subsequent claims for CA-anxiety compared with patients without precancer depression (OR 3.01; 95% CI 2.63-3.44). Female sex and myeloma diagnosis were also associated with CA-anxiety. In this large cohort of older patients with newly diagnosed blood cancers, almost 1 in 5 suffered from depression or anxiety, highlighting a critical need for systematic mental health screening and management for this population.

Peri-transfusion quality-of-life assessment for patients with myelodysplastic syndromes.

BACKGROUND: Many patients with myelodysplastic syndromes (MDS) receive red cell transfusions to relieve symptoms associated with anemia, with transfusions triggered by hemoglobin level. It is not known if patients' quality of life (QOL) improves after transfusion, nor if peri-transfusion QOL assessment (PTQA) can guide future transfusion decisions. STUDY DESIGN AND METHODS: We conducted a prospective pilot study of adults with MDS at three centers. Participants, who had to have hemoglobin ≥7.5, completed an MDS-specific measure of QOL (the Quality of Life in Myelodysplasia Scale, [QUALMS]) 1 day before and 7 days after red cell transfusion. A report was sent to each patient and provider before the next transfusion opportunity, indicating whether there were clinically significant changes in QOL. We assessed the proportion of patients experiencing changes in QOL, and with a follow-up questionnaire, whether they perceived their PTQA data were used for future transfusion decisions. RESULTS: From 2018 to 2020, 62 patients enrolled (mean age 73 years) and 37 completed both pre- and post-transfusion QOL assessments. Of these, 35% experienced a clinically significant increase in QUALMS score 7 days after transfusion; 46% no change; and 19% a decrease. Among those completing the follow-up questionnaire, 23% reported that PTQA results were discussed by their provider when considering repeat transfusion. CONCLUSIONS: These data suggest PTQA is feasible for patients with MDS. Moreover, while helpful for some, for many others, red cell transfusion may not achieve its intended goal of improving QOL. PTQA offers a strategy to inform shared decision-making regarding red cell transfusion.

US State Government Crisis Standards of Care Guidelines: Implications for Patients With Cancer.

Importance: State crisis standards of care (CSC) guidelines in the US allocate scarce health care resources among patients. Anecdotal reports suggest that guidelines may disproportionately allocate resources away from patients with cancer, but no comprehensive evaluation has been performed. Objective: To examine the implications of US state CSC guidelines for patients with cancer, including allocation methods, cancer-related categorical exclusions and deprioritizations, and provisions for blood products and palliative care. Design, Setting, and Participants: This cross-sectional population-based analysis examined state-endorsed CSC guidelines published before May 20, 2020, that included health care resource allocation recommendations. Main Outcomes and Measures: Guideline publication before or within 120 days after the first documented US case of coronavirus disease 2019 (COVID-19), inclusion of cancer-related categorical exclusions and/or deprioritizations, provisions for blood products and/or palliative care, and associations between these outcomes and state-based cancer demographics. Results: Thirty-one states had health care resource allocation guidelines that met inclusion criteria, of which 17 had been published or updated since the first US case of COVID-19. States whose available hospital bed capacity was predicted to exceed 100% at 6 months (χ2 = 3.82; P = .05) or that had a National Cancer Institute-designated Comprehensive Cancer Center (CCC; χ2 = 6.21; P = .01) were more likely to have publicly available guidelines. The most frequent primary methods of prioritization were the Sequential Organ Failure Assessment score (27 states [87%]) and deprioritizing persons with worse long-term prognoses (22 states [71%]). Seventeen states' (55%) allocation methods included cancer-related deprioritizations, and 8 states (26%) included cancer-related categorical exclusions. The presence of an in-state CCC was associated with lower likelihood of cancer-related categorical exclusions (multivariable odds ratio, 0.06 [95% CI, 0.004-0.87]). Guidelines with disability rights statements were associated with specific provisions to allocate blood products (multivariable odds ratio, 7.44 [95% CI, 1.28-43.24). Both the presence of an in-state CCC and having an oncologist and/or palliative care specialist on the state CSC task force were associated with the inclusion of palliative care provisions. Conclusions and Relevance: Among states with CSC guidelines, most deprioritized some patients with cancer during resource allocation, and one-fourth categorically excluded them. The presence of an in-state CCC was associated with guideline availability, palliative care provisions, and lower odds of cancer-related exclusions. These data suggest that equitable state-level CSC considerations for patients with cancer benefit from the input of oncology stakeholders.

Practical allocation system for the distribution of specialised care during cellular therapy access scarcity.

Novel cellular therapy techniques promise to cure many haematology patients refractory to other treatment modalities. These therapies are intensive and require referral to and care from specialised providers. In the USA, this pool of providers is not expanding at a rate necessary to meet expected demand; therefore, access scarcity appears forthcoming and is likely to be widespread. To maintain fair access to these scarce and curative therapies, we must prospectively create a just and practical system to distribute care. In this article, we first review previously implemented medical product and personnel allocation systems, examining their applicability to cellular therapy provider shortages to demonstrate that this problem requires a novel approach. We then present an innovative system for allocating cellular therapy access, which accounts for the constraints of distribution during real-world oncology practice by using a combination of the following principles: (1) maximising life-years per personnel time, (2) youngest and robust first, (3) sickest first, (4) first come/first served and (5) instrumental value. We conclude with justifications for the incorporation of these principles and the omission of others, discuss how access can be distributed using this combination, consider cost and review fundamental factors necessary for the practical implementation and maintenance of this system.

The National MDS Natural History Study: design of an integrated data and sample biorepository to promote research studies in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS), a spectrum of heterogeneous hematopoietic stem cell diseases, vary in clinical severity, response to therapy, and propensity toward progression to acute myeloid leukemia. These are acquired clonal disorders resulting from somatic mutations within the hematopoietic stem or progenitor cell population. Understanding the natural history and the risk of developing leukemia and other adverse outcomes is dependent on access to well-annotated biospecimens linked to robust clinical and molecular data. To facilitate the acquisition and distribution of MDS biospecimens to the wider scientific community and support scientific discovery in this disease, the National MDS Natural History study was initiated by the National Heart, Lung, and Blood Institute (NHLBI) and is being conducted in collaboration with community hospitals and academic medical centers supported by the National Cancer Institute (NCI). The study will recruit up to 2000 MDS patients or overlapping myeloproliferative neoplasms (MDS/MPN) and up to 500 cases of idiopathic cytopenia of undetermined significance (ICUS). The National MDS Natural History Study (NCT02775383) will offer the world's largest disease-focused tissue biobank linked to longitudinal clinical and molecular data in MDS. Here, we report on the study design features and describe the vanguard phase of 200 cases. The study assembles a comprehensive clinical database, quality of life results, laboratory data, histopathology slides and images, genetic information, hematopoietic and germline tissues representing high-quality biospecimens and data from diverse centers across the United States. These resources will be available to the scientific community for investigator-initiated research.

Relationship between paid leave, financial burden, and patient-reported outcomes among employed patients who have undergone bone marrow transplantation.

PURPOSE: The US does not have universal paid family and medical leave. We examine the direct effects of access to paid leave on patient-reported health, quality of life (QOL), and perceived stress of employed patients who underwent bone marrow transplantation (BMT) to treat advanced blood cancer as well as the indirect effects through reductions in the financial burden (FB) that patients face. METHODS: Our cross-sectional observational study took place at three US transplantation centers in 2014 and 2015. All English-speaking cancer patients 6-month post-BMT were mailed a 43-item survey assessing financial situation, employer benefits, and patient-reported health outcomes. The sample includes the 171 respondents who were employed at the time of BMT. RESULTS: Seemingly unrelated regression analysis confirms that patient access to paid leave was associated with reductions in all three measures of FB, and lower levels of financial hardship were related with improved health, QOL, and perceived stress outcomes. For self-reported health and perceived stress outcomes, all of the effects of patient paid leave operate indirectly through reductions in FB. For QOL outcomes, there is both a direct effect (over 80%) of paid leave and an indirect effect through reduction of FB. CONCLUSION: We found that paid leave affected health outcomes for BMT patients mostly through alleviating FB. These findings suggest universal paid leave policies in the US might alleviate financial hardship and have positive effects on the self-reported QOL of employed patients facing intensive medical treatments.

Employment, Insurance, and Financial Experiences of Patients with Chronic Graft-versus-Host Disease in North America.

Understanding the socioeconomic impact of chronic graft-versus-host disease (GVHD) on affected patients is essential to help improve their overall well-being. Using data from the Chronic GVHD Consortium, we describe the insurance, employment, and financial challenges faced by these patients and the factors associated with the ability to work/attend school and associated financial burdens. A 15-item cross-sectional questionnaire designed to measure financial concerns, income, employment, and insurance was completed by 190 patients (response rate, 68%; 10 centers) enrolled on a multicenter Chronic GVHD Consortium Response Measures Validation Study. Multivariable logistic regression models examined the factors associated with financial burden and ability to work/attend school. The median age of respondents was 56years, and 87% of the patients were white. A higher proportion of nonrespondents had lower income before hematopoietic cell transplantation and less than a college degree. All but 1 patient had insurance, 34% had faced delayed/denied insurance coverage for chronic GVHD treatments, and 66% reported a financial burden. Patients with a financial burden had greater depression/anxiety and difficulty sleeping. Nonwhite race, lower mental functioning, and lower activity score were associated with a greater likelihood of financial burden. Younger age, early risk disease, and higher mental functioning were associated with a greater likelihood of being able to work/attend school. In this multicenter cohort of patients with chronic GVHD, significant negative effects on finances were observed even with health insurance coverage. Future research should investigate potential interventions to provide optimal and affordable care to at-risk patients and prevent long-term adverse financial outcomes in this vulnerable group.

Meaningful changes in end-of-life care among patients with myeloma.

Patients with advanced myeloma experience a high symptom burden particularly near the end of life, making timely hospice use crucial. Little is known about the quality and determinants of end-of-life care for this population, including whether potential increases in hospice use are also accompanied by "late" enrollment (≤ 3 days before death). Using the Surveillance, Epidemiology, and End-Results-Medicare database, we identified patients ≥ 65 years diagnosed with myeloma between 2000 and 2013 who died by December 31, 2013. We assessed prevalence and trends in hospice use, including late enrollment. We also examined six established measures of potentially aggressive medical care at the end of life. Independent predictors of late hospice enrollment and aggressive end-of-life care were assessed using multivariable logistic regression analyses. Of 12,686 myeloma decedents, 48.2% enrolled in hospice. Among the 6111 who enrolled, 17.2% spent ≤ 3 days there. There was a significant trend in increasing hospice use, from 28.5% in 2000 to 56.5% by 2013 (Ptrend <0.001), no significant rise in late enrollment (12.2% in 2000 to 16.3% in 2013, Ptrend =0.19), and a slight decrease in aggressive end-of-life care (59.2% in 2000 to 56.7% in 2013, Ptrend =0.01). Patients who were transfusion-dependent, on dialysis, or survived for less than one year were more likely to enroll late in hospice and experience aggressive medical care at the end of life. Gains in hospice use for myeloma decedents were not accompanied by increases in late enrollment or aggressive medical care. These findings suggest meaningful improvements in end-of-life care for this population.

Cancer drug shortages: Awareness and perspectives from a representative sample of the US population.

BACKGROUND: Although cancer drug shortages are a persistent problem in oncology, little is known about the awareness and perspectives of the US population with respect to shortages. METHODS: In 2016, we administered a 13-item cross-sectional survey to 420 respondents who were randomly selected from an online, probability-based sample demographically representative of the adult US population with respect to sex, age, race/ethnicity, education, geography, and income. Analyses applied poststratification sampling weights to draw national inferences. RESULTS: Overall, 16% of respondents reported being aware of drug shortages. Those with a personal history of cancer were more likely to be aware (31% vs 14% [P = .03]). In the overall cohort, most reported wanting to be informed about a substitution due to shortage: 87% and 82% for major or minor differences in efficacy, and 87% and 83% for major or minor differences in side effects. Most also reported they would transfer care to avoid a substitution: 72% for major differences in efficacy, and 61% for major differences in side effects. Black respondents, the uninsured, the unemployed, those with lower income, and the less well-educated were all less likely to report that they would transfer care to avoid major differences in efficacy (all P < .05). CONCLUSION: These data suggest that the US population is largely unaware of cancer drug shortages. Moreover, if being treated for cancer, most people would want to know about drug substitutions, even if it were to result in only minor differences in efficacy or side effects. With more significant differences, many would transfer care. Cancer 2018;124:2205-11. © 2018 American Cancer Society.

Financial Hardship after Hematopoietic Cell Transplantation: Lack of Impact on Survival.

Background: Financial hardship is a growing challenge for patients with blood cancer who undergo hematopoietic cell transplantation (HCT), and it is associated with poor patient-reported outcomes. In contrast, little is known about the potential impact of patient-reported financial hardship on post-HCT survival.Methods: We sought to describe the association of financial hardship with survival after HCT in a prospectively assembled cohort of patients from three large transplant centers (n = 325).Results: There was no association between financial hardship measures assessed at 6 months post-HCT and 1- or 2-year survival after HCT.Conclusions: Patient-reported financial distress after HCT does not seem to adversely affect post-HCT survival.Impact: When assessing the effectiveness of interventions to ameliorate familial financial burden among HCT, the focus should be on patient-reported outcomes rather than survival. Cancer Epidemiol Biomarkers Prev; 27(3); 345-7. ©2018 AACR.

Low-molecular weight heparin versus vitamin K antagonists for the treatment of cancer-associated thrombosis: A cost-effectiveness analysis.

INTRODUCTION: Cancer-associated venous thromboembolism (VTE) is primarily treated with low-molecular weight heparin (LMWH), a strategy based on studies showing it to be superior to the vitamin K antagonist (VKA) warfarin for preventing VTE recurrence. Subsequent analyses suggest that the magnitude of this benefit might be less than previously determined. Neither patient-focused measures of utility nor the costs of each strategy have been evaluated in the current treatment era. METHODS: This is a cost-effectiveness analysis of VKA and LMWH for the treatment of cancer-associated thrombosis through use of a microsimulation model of outcomes for competing anticoagulation management strategies from a 2014 United States societal perspective. RESULTS: LMWH therapy added 0.27 QALYs relative to VKA treatment with an ICER of $217,007. One-way sensitivity analysis evaluating the utility of LMWH revealed that VKA was always the preferred strategy at a willingness to pay (WTP) threshold of $100,000 per QALY. Limitations include that the model incorporates a low VKA time in therapeutic range (TTR) and that the TTR in some centers may be higher thereby increasing the cost-effectiveness of the VKA strategy. Utilities for anticoagulation strategies were not derived from cancer patients, and preference is known to vary depending on how anticoagulation method is integrated with cancer treatment. CONCLUSIONS: Our findings suggest that compared to LMWH, warfarin is a more cost-effective strategy to treat cancer-associated VTE. Although LMWH is associated with a modest increase in life expectancy, this increase comes at significant cost.

Assessing Quality of Care for the Myelodysplastic Syndromes.

Measuring the quality of care for patients with chronic cancers is difficult, especially for heterogeneous malignancies such as the myelodysplastic syndromes (MDS). Recent work suggests that improvements may be needed in the quality of diagnostic, treatment, and end-of-life care for patients with these syndromes. Moreover, rigorous assessment of factors that are necessary to deliver high-quality care such as preferred method of decision-making and pre-treatment quality of life are often overlooked. Finally, a key component of quality care is that it is received equitably across different patient populations, yet several recent studies suggest that there are financial, educational, race-ethnic, and age-related barriers to equitable MDS care.