Systematic Literature Review to Identify Cost and Resource Use Data in Patients with Early-Stage Non-small Cell Lung Cancer (NSCLC).

BACKGROUND: Approximately 2 million new cases and 1.76 million deaths occur annually due to lung cancer, with the main histological subtype being non-small cell lung cancer (NSCLC). The costs and resource use associated with NSCLC are important considerations to understand the economic impact imposed by the disease on patients, caregivers and healthcare services. OBJECTIVE: The objective of this systematic literature review (SLR) is to provide a comprehensive overview of the available direct medical costs, direct non-medical costs, indirect costs, cost drivers and resource use data available for patients with early-stage NSCLC. METHODS: Electronic searches were conducted via the Ovid platform in March 2021 and June 2022 and were supplemented by grey literature searches. Eligible patients had early-stage (stage I-III) resectable NSCLC and received treatment in the neoadjuvant or adjuvant setting. There was no restriction on intervention or comparators. Publication date was restricted to 2011 onwards, and English language publications or non-English language publications with an English abstract were of primary interest. Due to the anticipation of many studies meeting the inclusion criteria, analyses were restricted to full publications from countries of primary interest (Australia, Brazil, Canada, China, France, Germany, Italy, Japan, South Korea, Spain, UK and the US) and those with > 200 patients. The Molinier checklist was applied to conduct quality assessment. RESULTS: Forty-two full publications met the eligibility criteria and were included in this SLR. Early-stage NSCLC was associated with significant direct medical costs and healthcare utilisation, and the economic burden of the disease increased with its progression. Surgery was the primary cost driver in stage I patients, but as patients progressed to stage II and III, treatments such as chemotherapy and radiotherapy, and inpatient care became the main cost drivers. There was no significant difference in resource use between patients with early-stage disease. However, these data were heavily US-centric and there was a paucity of data relating to direct non-medical and indirect costs associated with early-stage NSCLC. CONCLUSIONS: Preventing disease progression for patients with NSCLC could reduce the economic burden of NSCLC on patients, caregivers and healthcare systems. This review provides a comprehensive overview of the available cost and resource use data in this indication, which is important in guiding the decisions of policy makers regarding the allocation of resources. However, it also indicates a need for more studies comparing the economic impact of NSCLC in markets in addition to the US.

Health State Utility Values in Early-Stage Non-small Cell Lung Cancer: A Systematic Literature Review.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the predominant histological subtype of lung cancer and is the leading cause of cancer-related deaths globally. Quality of life is an important consideration for patients and current treatments can adversely affect health-related quality of life (HRQoL). OBJECTIVE: The objectives of this systematic literature review (SLR) were to identify and provide a comprehensive catalogue of published health state utility values (HSUVs) in patients with early-stage NSCLC and to understand the factors impacting on HSUVs in this indication. METHODS: Electronic searches of Embase, MEDLINE and Evidence-Based Medicine Reviews were conducted via the Ovid platform in March 2021 and June 2022 and were supplemented by grey literature searches of conference proceedings, reference lists, health technology assessment bodies, and other relevant sources. Eligibility criteria were based on patients with early-stage (stage I-III) resectable NSCLC receiving treatment in the adjuvant or neoadjuvant setting. No restriction was placed on interventions or comparators, geography, or publication date. English language publications or non-English language publications with an English abstract were of primary interest. A validated checklist was applied to conduct quality assessment of the full publications. RESULTS: Twenty-nine publications (27 full publications and two conference abstracts) met all eligibility criteria and reported 217 HSUVs and seven disutilities associated with patients with early NSCLC. The data showed that increasing disease stage is associated with decreasing HRQoL. It was also indicated that utility values vary by treatment approach; however, the choice of treatment may be influenced by the patients' disease stage at presentation. Few studies aligned with the requirements of health technology assessment (HTA) bodies, indicating a need for future studies to conform to these preferences, making them suitable for use in economic evaluations. CONCLUSIONS: This SLR found that disease stage and treatment approach were two of several factors that can impact patient-reported HRQoL. Additional studies are warranted to confirm these findings and to investigate emerging therapies for early NSCLC. In collecting a catalogue of HSUV data, this SLR has begun to identify the challenges associated with identifying reliable utility value estimates suitable for use in economic evaluations of early NSCLC.

Cost-effectiveness analysis of adjuvant atezolizumab in stage II-IIIA non-small cell lung cancer expressing ≥50% PD-L1: A United Kingdom health care perspective.

OBJECTIVES: Atezolizumab monotherapy has marketing authorisation by the Medicines and Healthcare products Regulatory Agency as adjuvant treatment following complete resection for adults with stage II-IIIA non-small cell lung cancer (NSCLC) whose tumours have PD-L1 expression on ≥ 50% of tumour cells and whose disease has not progressed following adjuvant platinum-based chemotherapy. This study evaluated the cost-effectiveness of atezolizumab vs best supportive care (BSC) in the licensed patient population from a UK perspective. MATERIALS AND METHODS: Patient characteristics and clinical inputs were derived from the global, randomised, open-label, phaseIII IMpower010 trial. A Markov model with the following health states was developed: disease-free survival (DFS), locoregional recurrence, first-line metastatic recurrence, second-line metastatic recurrence, and death (all partitioned based on receipt of treatment, excluding death). The base case model used a lifetime time horizon (40 years) and 3.5% discounting annually after the first year. DFS from IMpower010 was analysed with parametric survival models to extrapolate outcomes for time points beyond trial follow-up. The models were adjusted to avoid overestimating results for patients with recurrences in the longer term. Grade ≥ 3 treatment-related adverse events with incidences ≥ 2% were included. Health state utility values were derived from the literature and past NICE appraisals. Sensitivity and scenario analyses assessed uncertainty around assumptions and parameter estimates. RESULTS: In the base case analysis, atezolizumab therapy resulted in an expected gain of 1.87 quality-adjusted life-years (QALYs) corresponding to an incremental cost-effectiveness ratio of £20,392/QALY for atezolizumab vs BSC, demonstrating cost-effectiveness. Results were most influenced by discount effects and utility in the on-treatment DFS state. Scenario analyses were consistent with the base case results. CONCLUSION: Atezolizumab after adjuvant chemotherapy is cost-effective for adults with NSCLC in the UK.

The clinical and economic burden of peripheral T-cell lymphoma: a systematic literature review.

Aim: To understand the burden of treatment-naive peripheral T-cell lymphoma (PTCL). Methods: A systematic literature review was conducted in November 2020 following best practice methodology. Results: Fifty-five clinical studies were included, mostly investigating cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or 'CHOP-like' regimens, with combination regimens showing similar effectiveness to CHOP alone. Aside from the combination of brentuximab vedotin + cyclophosphamide, doxorubicin and prednisone (A+CHP), other available treatments showed no statistically significant benefit over CHOP in terms of overall or progression-free survival in overall PTCL patients. The mean monthly cost per patient in the USA ranged from 6328 to US$9356 based on six studies. One economic evaluation demonstrated A+CHP to be a more cost-effective treatment option than CHOP. Conclusion: Further research is needed to understand the humanistic and cost impact of frontline treatment for PTCL and its specific subtypes.

Plain language summary Peripheral T-cell lymphoma (PTCL) is an aggressive cancer that develops from white blood cells called T cells, which are an important part of the immune system. There is limited knowledge on the impact PTCL has on patients and their families. This systematic review of 55 clinical studies was conducted to further understand how safe and effective current treatments are for patients with newly diagnosed PTCL, how these treatments and disease impact their quality of life, and the economic impact of treatment and disease. Chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone [CHOP]) was the most commonly studied regimen, but had limited effectiveness and a notable side effect profile. A newer treatment option, brentuximab vedotin + cyclophosphamide, doxorubicin and prednisone (A+CHP) was the only treatment to show a significant added benefit over CHOP for patients, with side effects that were comparable to those of CHOP. Six studies assessed the economic impact of PTCL, the majority of which were focused on the USA, and found the mean monthly cost per patient to be 6328­US$9356. No studies were identified that assessed the impact of PTCL or its treatment on quality of life. Further research is needed to understand the impact of frontline PTCL treatment on patients and their families.

Patient-Reported Outcomes and Economic Burden of Adults with Sickle Cell Disease in the United States: A Systematic Review.

PURPOSE: To systematically estimate the patient-reported outcomes (PROs) and economic burden of sickle cell disease (SCD) among adults in the United States (US). PATIENTS AND METHODS: Two systematic literature reviews (SLRs), one each for the PROs and economic topics, were performed using MEDLINE and Embase to identify observational studies of adults with SCD. Included studies were published between 2007 and 2018 and evaluated health-related quality of life (HRQL), function, healthcare resource utilization (HCRU), or costs. Given the high degree of clinical and methodological heterogeneity, findings were summarized qualitatively. RESULTS: The SLRs identified 7 studies evaluating the PROs and 15 studies evaluating the economic burden meeting the pre-specified selection criteria. The PRO evidence showed the prevalence of depression and anxiety to be 21-33% and 7-36%, respectively, in adults with SCD. The mean SF-36 physical summary scores ranged from 33.6 to 59.0 and from 46.3 to 61.5 for the mental summary scores. Overall HRQL for adults with SCD was poor and significantly worse in those with opioid use. Adult SCD patients were found to have varying rates of emergency department (ED) utilization (0.3-3.5 annual ED visits), hospitalizations (0.5-27.9 per patient per year), and/or readmission (12-41%). Key factors associated with significant HCRU were age, dental infection, and SCD-related complications. SCD specialized care settings and SCD intensive management strategy were reported to significantly decrease the number of hospitalizations. CONCLUSION: This systematic evidence synthesis found that disease burden measured by PROs and economic burden of SCD on adults in the US are substantial despite the availability of approved SCD treatments during 2007-2018. The use of hydroxyurea, optimal management with opioids, and employing intensive treatment strategies may help decrease the overall burden to patients and healthcare systems. Published data on costs associated with SCD are limited and highlight the need for more economic studies to characterize the full burden of the disease.

Systematic literature review and assessment of patient-reported outcome instruments in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a chronic condition associated with high mortality and morbidity. It is characterized by acute clinical symptoms such as painful vaso-occlusive crises, which can impair health-related quality of life (HRQL). This study was conducted to identify validated patient-reported outcome (PRO) instruments for use in future trials of potential treatments for SCD. METHODS: A systematic literature review (SLR) was performed using MEDLINE and EMBASE to identify United States (US)-based studies published in English between 1997 and 2017 that reported on validated PRO instruments used in randomized controlled trials and real-world settings. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the quality of PRO instruments. RESULTS: The SLR included 21 studies assessing the psychometric properties of 24 PRO instruments. Fifteen of those instruments were developed and validated for adults and 10 for children (one instrument was used in both children and young adults aged up to 21 years). Only five of the 15 adult instruments and three of the 10 pediatric instruments were developed specifically for SCD. For most instruments, there were few or no data on validation conducted in SCD development cohorts. Of the 24 PRO instruments identified, 16 had strong internal reliability (Cronbach's α ≥0.80). There was often insufficient information to assess the content validity, construct validity, responsiveness, or test-retest reliability of the instruments identified for both child and adult populations. No validated PRO instruments measuring caregiver burden in SCD were identified. CONCLUSIONS: The evidence on the psychometric properties of PRO instruments was limited. However, the results of this SLR provide key information on such tools to help inform the design of future clinical trials for patients with SCD in the US.

Cost-effectiveness analysis of abobotulinumtoxinA for the treatment of cervical dystonia in the United Kingdom.

BACKGROUND: Cervical dystonia (CD) involves painful involuntary contraction of the neck and shoulder muscles and abnormal posture in middle-aged adults. Botulinum neurotoxin type A (BoNT-A) is effective in treating CD but little is known about its associated cost-effectiveness. OBJECTIVE: To evaluate the cost-effectiveness of abobotulinumtoxinA for treating CD from the UK payer perspective. METHODS: A Markov model was developed to evaluate the cost-effectiveness of abobotulinum-toxinA versus best supportive care (BSC) in CD, with a lifetime horizon and health states for response, nonresponse, secondary nonresponse, and BSC in patients with CD (mean age: 53 years; 37% male). Clinical improvement measured using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was mapped to utility using data from a randomized trial of abobotulinumtoxinA. Health care resource use, costs, and other inputs were from the British National Formulary, Personal Social Services Research Unit, published literature, or expert opinion. Costs and outcomes were discounted at 3.5% per annum. RESULTS: In the base case, the incremental lifetime quality-adjusted life-years (QALYs) gained from abobotulinumtoxinA arm versus BSC was 0.253 per patient, whereas the incremental cost was £7,160, leading to an incremental cost-effectiveness ratio (ICER) of £30,468 per QALY. One-way sensitivity analyses showed that these results were sensitive to the proportion of responders to abobotulinumtoxinA at first injection, duration between injections, the number of reinjections allowed among primary nonresponders, and any difference in baseline TWSTRS value between the BSC and abobotulinumtoxinA arms. Probabilistic sensitivity analysis showed that abobotulinumtoxinA was cost-effective 46% and 49% of times at thresholds of £20,000 and £30,000 per QALY, respectively. Scenarios are considered including vial-sharing, productivity losses, secondary response/nonresponse at subsequent injections, 5-year time horizon, and alternative reinjection intervals for BoNT-As produced ICERs ranging from cost-saving to £40,777 per QALY, versus BSC. CONCLUSION: AbobotulinumtoxinA was found to be cost-effective in treating adults with CD, at acceptable willingness-to-pay thresholds in the UK.

AbobotulinumtoxinA in the management of cervical dystonia in the United Kingdom: a budget impact analysis.

BACKGROUND: Cervical dystonia (CD) can be effectively managed by a combination of botulinum neurotoxin A (BoNT-A) and conventional therapy (skeletal muscle relaxants and rehabilitative therapy), but the costs of different interventions in the UK vary. METHODS: A budget impact model was developed from the UK payer perspective with a 5-year time horizon to evaluate the effects of changing market shares of abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA, and best supportive care from the UK payer perspective. Epidemiological and resource use data were retrieved from the published literature and clinical expert opinion. Deterministic sensitivity analyses were performed to determine the parameters most influential on the budgetary findings under base case assumptions. RESULTS: Under base case assumptions, an increased uptake of abobotulinumtoxinA showed an accumulated savings of £2,250,992 by year 5. Treatment per patient per year with onabotulinumtoxinA and incobotulinumtoxinA costs more when compared to treatment with abobotulinumtoxinA. One-way sensitivity analyses showed that the prevalence of CD, dose per injection of each of the BoNT-As, and time to reinjection of incobotulinumtoxinA and abobotulinumtoxinA influenced the base case findings most. CONCLUSION: There is potential for cost savings associated with the greater use of abobotulinumtoxinA rather than other BoNT-A treatments, permitting more patients to benefit more from effective BoNT-A treatment with a fixed budget.

Cost-effectiveness and public health benefit of secondary cardiovascular disease prevention from improved adherence using a polypill in the UK.

OBJECTIVE: To evaluate the public health and economic benefits of adherence to a fixed-dose combination polypill for the secondary prevention of cardiovascular (CV) events in adults with a history of myocardial infarction (MI) in the UK. DESIGN: Markov-model-based cost-effectiveness analysis, informed by systematic reviews, which identified efficacy, utilities and adherence data inputs. SETTING: General practice in the UK. PARTICIPANTS: Patients with a mean age of 64.7 years, most of whom are men with a recent or non-recent diagnosis of MI and for whom secondary preventive medication is indicated and well tolerated. INTERVENTION: Fixed-dose combination polypill (100 mg aspirin, 20 mg atorvastatin and 2.5, 5, or 10 mg ramipril) compared with multiple monotherapy. PRIMARY AND SECONDARY OUTCOME MEASURES: CV events prevented per 1000 patients; cost per life-year gained; and cost per quality-adjusted life-year (QALY) gained. RESULTS: The model estimates that for each 10% increase in adherence, an additional 6.7% fatal and non-fatal CV events can be prevented. In the base case, over 10 years, the polypill would improve adherence by ∼20% and thereby prevent 47 of 323 (15%) fatal and non-fatal CV events per 1000 patients compared with multiple monotherapy, with an incremental cost-effectiveness ratio (ICER) of £8200 per QALY gained. Probabilistic sensitivity analyses for the base-case assumptions showed an 81.5% chance of the polypill being cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained compared with multiple monotherapy. In scenario analyses that varied structural assumptions, ICERs ranged between cost saving and £21,430 per QALY gained. CONCLUSIONS: Assuming that some 450,000 adults are at risk of MI, a 10 percentage point uptake of the polypill could prevent 3260 CV events and 590 CV deaths over a decade.The polypill appears to be a cost-effective strategy to prevent fatal and non-fatal CV events in the UK.

Budget impact analysis of botulinum toxin A therapy for upper limb spasticity in the United Kingdom.

BACKGROUND: Botulinum toxin A (BoNT-A) is an effective treatment for patients with upper limb spasticity (ULS), which is a debilitating feature of upper motor neuron lesions. BoNT-A preparations available in the UK are associated with different costs. METHODS: We developed a budget impact model to assess the effect of changing market shares of different BoNT-A formulations - abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA - and best supportive care, from the UK payer perspective, over a 5-year time horizon. Epidemiological and resource use data were derived from published literature and clinical expert opinion. One-way sensitivity analyses were performed to determine parameters most influential on budget impact. RESULTS: Base-case assumptions showed that an increased uptake of abobotulinumtoxinA resulted in a 5-year savings of £6,283,829. Treatment with BoNT-A costs less than best supportive care per patient per year, although treating a patient with onabotulinumtoxinA (£20,861) and incobotulinumtoxinA (£20,717) cost more per patient annually than with abobotulinumtoxinA (£19,800). Sensitivity analyses showed that the most influential parameters on budget were percentage of cerebral palsy and stroke patients developing ULS, and the prevalence of stroke. CONCLUSION: Study findings suggest that increased use of abobotulinumtoxinA for ULS in the UK could potentially reduce total ULS cost for the health system and society.

Epidemiological, humanistic, and economic burden of illness of lower limb spasticity in adults: a systematic review.

BACKGROUND: The purpose of this study was to investigate the epidemiological, humanistic, and economic burden of illness associated with adult lower limb spasticity (LLS) and its complications. METHODS: A systematic search of MEDLINE and EMBASE identified 23 studies published between January 2002 and October 2012 that assessed the epidemiology, impact, and resource use associated with LLS. A hand-search of four neurology conferences identified abstracts published between 2010 and 2012. RESULTS: LLS was found to occur in one third of adults after stroke, half to two thirds with multiple sclerosis, and three quarters with cerebral palsy. LLS limits mobility and reduces quality of life. No clear association was found between LLS and occurrence of pain, development of contractures, or risk of falls. CONCLUSION: The evidence on the burden of LLS and its complications is surprisingly limited given the condition's high prevalence among adults with common disorders, such as stroke. Further research is needed to clarify the impact of LLS, including the likelihood of thrombosis in spastic lower limbs. The dearth of high-quality evidence for LLS suggests a lack of awareness of, and interest in, the problem, and therefore, the unmet need among patients and their carers.