Cost-Effectiveness of Lovotibeglogene Autotemcel (Lovo-Cel) Gene Therapy for Patients with Sickle Cell Disease and Recurrent Vaso-Occlusive Events in the United States.

BACKGROUND AND OBJECTIVE: Gene therapies for sickle cell disease (SCD) may offer meaningful benefits for patients and society. This study evaluated the cost-effectiveness of lovotibeglogene autotemcel (lovo-cel), a one-time gene therapy administered via autologous hematopoietic stem cell transplantation, compared with common care for patients in the United States (US) with SCD aged ≥ 12 years with ≥ 4 vaso-occlusive events (VOEs) in the past 24 months. METHODS: We developed a patient-level simulation model accounting for lovo-cel and SCD-related events, complications, and mortality over a lifetime time horizon. The pivotal phase 1/2 HGB-206 clinical trial (NCT02140554) served as the basis for lovo-cel efficacy and safety. Cost, quality-of-life, and other clinical data were sourced from HGB-206 data and the literature. Analyses were conducted from US societal and third-party payer perspectives. Uncertainty was assessed through probabilistic sensitivity analysis and extensive scenario analyses. RESULTS: Patients treated with lovo-cel were predicted to survive 23.84 years longer on average (standard deviation [SD], 12.80) versus common care (life expectancy, 62.24 versus 38.40 years), with associated discounted patient quality-adjusted life-year (QALY) gains of 10.20 (SD, 4.10) and direct costs avoided of $1,329,201 (SD, $1,346,446) per patient. Predicted societal benefits included discounted caregiver QALY losses avoided of 1.19 (SD, 1.38) and indirect costs avoided of $540,416 (SD, $262,353) per patient. Including lovo-cel costs ($3,282,009 [SD, $29,690] per patient) resulted in incremental cost-effectiveness ratios of $191,519 and $124,051 per QALY gained from third-party payer and societal perspectives, respectively. In scenario analyses, the predicted cost-effectiveness of lovo-cel also was sensitive to baseline age and VOE frequency and to the proportion of patients achieving and maintaining complete resolution of VOEs. CONCLUSIONS: Our analysis of lovo-cel gene therapy compared with common care for patients in the US with SCD with recurrent VOEs estimated meaningful improvements in survival, quality of life, and other clinical outcomes accompanied by increased overall costs for the health care system and for broader society. The predicted economic value of lovo-cel gene therapy was influenced by uncertainty in long-term clinical effects and by positive spillover effects on patient productivity and caregiver burden.

Heterogeneity of the long-term economic burden of severe sickle cell disease: a 5-year longitudinal analysis.

BACKGROUND: Sickle cell disease (SCD) is a lifelong burdensome disorder of heterogenic expression. This study investigated the longer-term economic burden of severe presentation of SCD. As SCD treatment landscapes evolve toward curative intent gene therapies, understanding how SCD-associated costs may change over the patient lifetime will be important for medical decision-making. METHODS: Patients with severe presentation of SCD (presence of acute vaso-occlusive events [VOEs] or history of stroke and/or other disease-related sequelae), were identified within the MarketScan Commercial and Medicare Supplemental and Multi-state Medicaid Databases from 1/1/2010 to 12/31/2018. The first SCD claim served as the index date and patients were followed over a 5-year post-period. Clinical characteristics and healthcare resource utilization and costs were assessed over follow-up for eligible cohorts of commercial and Medicaid patients with severe SCD presentation and age-based subgroups (<18, 18-30, and ≥31). RESULTS: A total of 4,487 patients, primarily insured via Medicaid (79.2%), qualified for the analysis. Patients evidenced persistent VOEs over follow-up; prevalence of most comorbidities increased with age. Mean total healthcare costs over the 5-year follow-up were $275,143 (SD± $406,770) and $362,728 (SD± $620,189) in the commercial and Medicaid samples, respectively. Disease severity, assessed by the number of VOEs and utilization of inpatient and emergency services, peaked in the 18-30 year group in both samples. These groups also evidenced the highest mean healthcare costs over the 5-year follow-up at $344,776 (SD± $434,521) and $671,321 (SD± $938,764) in the commercial and Medicaid samples respectively. CONCLUSION: Results indicate high clinical need and economic burden among patients with severe presentation of SCD. These findings not only highlight the need for improved therapeutic options to limit or prevent disease progression, but also start to provide insight on lifetime costs of SCD that will be needed in the evaluation of emerging curative intent therapies.

Evaluating the mental health of Jordanian women in relationships with intimate partner abuse.

This study evaluated the mental health consequences of abuse among Jordanian women and tested the effectiveness of using cognitive behavioral interventions to change the level of depression and level of stress among Jordanian women experiencing intimate partner abuse (IPA). A mixed methods design using phenomenology and quasi-experimental research data collection and analysis was implemented. The most commonly reported form of abuse was psychological abuse. Prior to cognitive behavioral intervention, participants demonstrated moderate to severe levels of depression, low levels of perceived social support, moderate to high levels of self-efficacy, and used approach coping skills more frequently than avoidance coping. Cognitive behavioral interventions resulted in decreased depression (p = .003) and decreased stress levels, although this finding did not reach significance (p > .05). Cognitive behavioral interventions are effective interventions when working with women experiencing IPA.

A review of instruments assessing public health preparedness.

OBJECTIVES: The purpose of this study was to review instruments that assess the level of preparedness of state and local public health departments to respond to health threats such as bioterrorism. METHODS: The authors examined 27 published population-based instruments for planning or evaluating preparedness that were mostly unavailable in the peer-reviewed literature. Using the Essential Public Health Services framework, the instruments were evaluated for (1) clarity of measurement parameters, (2) balance between structural and process measures, (3) evidence of effectiveness, and (4) specification of an accountable entity. RESULTS: There was a great deal of overlap but little consistency in what constitutes "preparedness" or how it should be measured. Most instruments relied excessively on subjective or structural measures, lacked scientific evidence for measures assessed, and failed to clearly define what entity was accountable for accomplishing the task or function. CONCLUSION: Strategies for improvement include measure standardization, better interagency communication, and investment in public health practice research to develop the underlying evidence base required for developing quality measures and assessments.