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.

Systematic Literature Review to Assess Economic Evaluations in Spinal Muscular Atrophy (SMA).

BACKGROUND: Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease that affects individuals with a broad age range. SMA is typically characterised by symmetrical muscle weakness but is also associated with cardiac defects, life-limiting impairments in respiratory function and bulbar function defects that affect swallowing and speech. Despite the advent of three innovative disease-modifying therapies (DMTs) for SMA, the cost of DMTs in addition to the costs of standard of care can be a barrier to treatment access for patients. Health Technology Assessment (HTA) decision makers evaluate the cost effectiveness of a new treatment before making a reimbursement decision. OBJECTIVE: The primary objective was to conduct a systematic literature review (SLR) to identify the modelling approaches used in economic evaluations that assess current approved treatments in SMA, with a secondary objective to widen the scope and identify economic evaluations assessing other (non-SMA) neuromuscular disorders. METHODS: An SLR was performed to identify available economic evaluations associated with any type of SMA (Type 1, 2, 3 and/or 4). Economic evaluations associated with other (non-SMA) neuromuscular disorders were identified but not further analysed. Electronic searches were conducted in Embase, MEDLINE, Evidence-Based Medicine Reviews and EconLit via the Ovid platform in August 2019, and were supplemented by searches of the grey literature (reference lists, conference proceedings, global HTA body websites and other relevant sources). Eligibility criteria were based on the population, interventions, comparators and outcomes (PICO) framework. Quality assessment of full publications was conducted with reference to a published checklist. RESULTS: Nine publications covering eight unique studies met all eligibility criteria for inclusion in the SLR, including four conference abstracts, two peer-reviewed original research articles and three HTA submissions (conducted in Canada, the US and the UK). Evaluations considered patients with early infantile-onset (most likely to develop Type 1 or Type 2 SMA), later-onset SMA and both infantile- and later-onset SMA. Data for the identified economic models were collected from literature reviews and relatively short-term clinical trials. Several intent-to-treat clinical trial populations were used in the studies, which resulted in variation in cycle length and different outcome measures to determine clinical efficacy. The results of the quality assessment on the five full-text, peer-reviewed publications found that they generally provided clear descriptions of objectives, modelling methods and results. However, key decisions, such as choice of economic evaluation, model type and choice of variables for sensitivity analysis, were often not adequately justified. CONCLUSIONS: This SLR highlights the need for economic evaluations in SMA to better align in modelling approaches with respect to (i) consistency in model structure and use of motor function milestones as health states; (ii) consensus on measuring quality of life to estimate utilities; (iii) consistency in data collection by registries; and (iv) consensus on SMA-type classification and endpoints that determine intervention efficacy. Future economic evaluations should also incorporate the review group critiques of previous HTA submissions relating to data inputs and approaches to modelling and should include patient data reflective of the SMA population being modelled. Economic evaluations would also be improved with inclusion of long-term efficacy and safety data from clinical trials and valid patient and caregiver utility data.

Systematic Literature Review to Assess the Cost and Resource Use Associated with Spinal Muscular Atrophy Management.

BACKGROUND: Spinal muscular atrophy (SMA) is a severe neuromuscular disease that is inherited in an autosomal recessive manner with an estimated incidence of 1 in 10,000 live births. The traditional classification of SMA includes five types (Types 0-4 SMA) based on patient age at disease onset and the highest motor milestone achieved. Spinal muscular atrophy leads to progressive muscle denervation, skeletal muscle atrophy and loss of motor function and ambulation, though phenotypes vary along a disease continuum. Regardless of disease severity, or access to treatment, a multidisciplinary approach to care is required to ease the burden of disease. To date, limited global data exist regarding the cost and resource use associated with SMA management. OBJECTIVE: We planned to perform a systematic literature review to identify studies on cost and healthcare resource use associated with SMA. METHODS: A comprehensive search was conducted in 2019 using several electronic databases in addition to supplementary sources and updated in 2021 in order to capture recently published studies. Electronic searches performed in Embase, MEDLINE, Evidence-Based Medicine Reviews and EconLit via the Ovid platform were supplemented by searches of the grey literature (reference lists, conference proceedings, global Health Technology Assessment body websites and other relevant sources). Study eligibility criteria were based on the population, interventions, comparators and outcomes (PICO) framework. Quality assessment of full-text publications was evaluated with reference to a published checklist. To accommodate heterogeneity across studies including countries, currencies, populations, time units and methods of reporting used, costs were reported in Euros in 2019. RESULTS: A total of 51 publications, comprising 49 unique studies of patients with SMA that met all eligibility criteria were included in the final selection. The publications comprised data from 14 countries and seven additional studies that reported multi-national data. Because of the heterogeneity between the different types of SMA, data were frequently reported separately for individuals with Type 1 or early-onset SMA and for Types 2, 3, and 4 SMA or later-onset SMA. Generally, direct medical costs and resource use were reported to be highest for patients with Type 1 SMA, decreasing incrementally for patients with Type 2 and Type 3 disease. Where cost categories were similar, direct costs were much lower in Europe than in the USA. Indirect costs were primarily associated with informal care, which was a substantial burden on patients and families in terms of both cost and time. Cost drivers were generally found to be dependent on SMA type. CONCLUSIONS: Long-term robust studies are required to fully elucidate the economic burden of SMA. Considering that motor function can vary broadly, especially in Type 2 SMA, it would be beneficial to understand how costs and resource use are affected by different degrees of ambulation. Reporting data in terms of achieved motor function could also mitigate the challenges of comparing global data studies of small populations. Global, regional, and/or local data collection platforms and disease registry networks could play an important role in helping to address current data gaps.

Adherence to and persistence with antidiabetic medications and associations with clinical and economic outcomes in people with type 2 diabetes mellitus: A systematic literature review.

We designed a systematic literature review to identify available evidence on adherence to and persistence with antidiabetic medication in people with type 2 diabetes (T2D). Electronic screening and congress searches identified real-world noninterventional studies (published between 2010 and October 2020) reporting estimates of adherence to and persistence with antidiabetic medication in adults with T2D, and associations with glycaemic control, microvascular and/or macrovascular complications, hospitalizations and healthcare costs. Ninety-two relevant studies were identified, the majority of which were retrospective and reported US data. The proportions of patients considered adherent (median [range] 51.2% [9.4%-84.3%]) or persistent (median [range] 47.7% [16.9%-94.0%]) varied widely across studies. Multiple studies reported an association between greater adherence/persistence and greater reductions in glycated haemoglobin levels. Better adherence/persistence was associated with fewer microvascular and/or macrovascular outcomes, although there was little consistency across studies in terms of which outcomes were improved. More adherent and more persistent patients were typically less likely to be hospitalized or to have emergency department visits/admissions and spent fewer days in hospital annually than less adherent/persistent patients. Greater adherence and persistence were generally associated with lower hospitalization costs, higher pharmacy costs and lower or budget-neutral total healthcare costs compared with lower adherence/persistence. In conclusion, better adherence and persistence in people with T2D is associated with lower rates of microvascular and/or macrovascular outcomes and inpatient hospitalization, and lower or budget-neutral total healthcare expenditure. Education and treatment strategies to address suboptimal adherence and persistence are needed to improve clinical and economic outcomes.

Systematic Literature Review to Identify Utility Values in Patients with Spinal Muscular Atrophy (SMA) and Their Caregivers.

BACKGROUND: Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder that has a substantial impact on health-related quality of life for patients with SMA and their caregivers. Utility values ('utilities') are used in health economic analyses to incorporate individual or societal perspectives regarding the desirability of health outcomes such as a certain health state or change in health states over time. OBJECTIVES: The primary objective of this systematic literature review (SLR) was to identify published utilities associated with patients with SMA and their caregivers and to determine the extent to which Health Technology Assessment (HTA) requirements of methods used to generate utilities are met. A secondary objective was to broaden the scope to identify utilities associated with other (non-SMA) neuromuscular disorders. METHODS: A comprehensive search to capture published utilities associated with patients with SMA and their caregivers was performed in 2019 and updated in 2021 using several electronic databases in addition to supplementary sources. As we anticipated that few published utilities associated with SMA would be identified, the search also captured utilities for other (non-SMA) neuromuscular disorders that may serve as useful surrogate values for studies of SMA and other rare diseases. Electronic searches were performed in Embase, MEDLINE, Evidence-Based Medicine Reviews, and EconLit via the Ovid platform and were supplemented by searches of the grey literature (reference lists, conference proceedings, global HTA body websites, and other relevant sources). Study eligibility criteria were based on the population, interventions, comparators, and outcomes (PICO) framework. The quality of the full-text publications was assessed using a checklist based on UK National Institute for Health and Care Excellence technical support documents. RESULTS: In total, 14 publications that reported SMA-related patient or caregiver utilities or disutilities met the eligibility criteria to be included in the SLR; the included studies demonstrate the substantial health-related quality-of-life burden of SMA on both patients with SMA and their caregivers. A variety of preference-based measures were used to derive utilities for patients with SMA and their caregivers. Different methods for collecting utility data included patient and proxy assessment of health states using questionnaires, vignette methodologies, structured forms of expert elicitation, and mapped data from results of clinical trials. A range of utilities was reported from both patient- and proxy-reported data, which reflects the degree of disability associated with early- and later-onset SMA. Methods for deriving utilities were assessed with respect to three reference cases from HTA bodies in the UK, the USA, and Canada. None of the 14 publications met the requirements of all three HTA bodies because of differing tariff requirements between countries; one study met the requirements of HTA bodies in Canada and the UK. Also, six studies did not report the method of valuation, which precluded analysis with respect to the HTA reference cases. CONCLUSIONS: This SLR provides a comprehensive repository of the currently available utilities relevant to patients with SMA and their caregivers. This SLR provides recommendations for establishing consensus on the approach to generating utility values for the SMA patient population and their caregivers for health economic decisions.

Burden of selected infectious diseases covered by UK childhood vaccinations: systematic literature review.

Aim: An overview of recent epidemiology and disease burden, independent of patient age, of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Hemophilus influenzae invasive disease in the UK. Materials & methods: A systematic review was undertaken. Outcomes included incidence, prevalence, risk factors and cost burden. Results: 39 publications were included. Hepatitis B prevalence is high among certain risk groups. A small pertussis risk remains in pregnancy and for infants, which led to the introduction of maternal vaccination. H. influenzae invasive disease cases are limited to rare serotypes. Polio, tetanus and diphtheria are well controlled. Conclusion: The evaluated diseases are currently well controlled, thanks to a comprehensive vaccination program, with a generally low clinical and cost burden.

Review of the Reporting of Survival Analyses within Randomised Controlled Trials and the Implications for Meta-Analysis.

BACKGROUND: Meta-analysis is a growing approach to evidence synthesis and network meta-analysis in particular represents an important and developing method within Health Technology Assessment (HTA). Meta-analysis of survival data is usually performed using the individual summary statistic-the hazard ratio (HR) from each randomised controlled trial (RCT). OBJECTIVES: The objectives of this study are to: (i) review the methods and reporting of survival analyses in oncology RCTs; and (ii) assess the suitability and relevance of survival data reported in RCTs for inclusion into meta-analysis. METHODS: Five oncology journals were searched to identify Phase III RCTs published between April and July 2015. Eligible studies included those that analysed a survival outcome. RESULTS: Thirty-two RCTs reporting survival outcomes in cancer populations were identified. None of the publications reported details relating to a strategy for statistical model building, the goodness of fit of the final model, or final model validation for the analysis of survival outcomes. The majority of studies (88%) reported the use of Cox proportional hazards (PH) regression to analyse survival endpoints. However, most publications failed to report the validation of the statistical models in terms of the PH assumption. CONCLUSIONS: This review highlights deficiencies in terms of reporting the methods and validity of survival analyses within oncology RCTs. We support previous recommendations to encourage authors to improve the reporting of survival analyses in journal publications. We also recommend that the final choice of a statistical model for survival should be informed by goodness of model fit to a given dataset, and that model assumptions are validated. The failure of trial investigators and statisticians to investigate the PH for RCT survival data is likely to result in clinical decisions based on inappropriate methods. The development of alternative approaches for the meta-analysis of survival outcomes when the PH assumption is implausible is required if valid clinical decisions are to be made.