Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature

Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be “all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty”. The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios

CN3 – Early Stage Cost-Effectiveness Analysis of a Brca1-Like Test to Detect Triple Negative Breast Cancers Responsive to High Dose Alkylating Chemotherapy

Objectives: Triple negative breast cancers (TNBC) with a BRCA1-like profile may benefit from high dose alkylating chemotherapy (HDAC). This study examines whether treating TNBC with personalized HDAC based on BRCA1-like testing can be more cost-effective than current clinical practice. Additionally we estimated the minimum required prevalence of BRCA1-likeness and the required positive predictive value (PPV) for a BRCA1-like test to render this strategy cost-effective. Methods: Our markov model compared the outcomes of treating TNBC women with personalized HDAC based on BRCA1-like testing vs. current clinical practice from a societal Dutch perspective and a 20-year time horizon. From our base-case model we assessed: 1) the incremental number of respondents; 2) the incremental number of Quality Adjusted Life Years, 3) the incremental costs, and 4) the incremental cost-effectiveness ratio (ICER). We performed one-way sensitivity analysis (SA) of all model parameters, and two-way SA of prevalence and PPV. Data were obtained from a current trial (NCT01057069), published literature and expert opinions where necessary. Results: Based on our base-case analysis with 68% BRCA1-like prevalence, 100% PPV, and costs of € 164 / test, treating TNBC according to BRCA1-like testing would be cost-effective (€16.192/QALY). One-way SA on the prevalence and PPV demonstrated that only the PPV drives the ICER changes. In two-way SA, the lower bound for the two parameters was: prevalence 39.6% and PPV 46.4%. Regardless of prevalence, at PPVs > 46.4% BRCA1-like testing was always cost-effective. Conclusions: Treating TNBC with personalized HDAC based on BRCA1-like testing is expected to be cost-effective at a minimum PPV of 46%. This information can help test developers in decisions on further research and developmen

Cost-effectiveness of physical activity in the management of COPD patients in the UK

Mafalda Ramos,1 Mark Lamotte,1 Laetitia Gerlier,1 Per Svangren,2 Anna Miquel-Cases,3 John Haughney4 1Real World Evidence Solutions, IQVIA, 1930 Zaventem, Belgium; 2Core Respiratory, Global Product and Portfolio Strategy – Global Payer Evidence and Pricing, AstraZeneca Gothenburg R&D, SE-431 83 Mölndal, Sweden; 3Global Price and Reimbursement, Global Payer Evidence and Pricing, AstraZeneca Gothenburg R&D, Cambridge CB2 8PA, UK; 4Academic Primary Care Division of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK Background: While the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines advise exercise to reduce disease progression, little investment in promoting physical activity (PA) is made by health care authorities. The purpose of this study was to estimate the cost-effectiveness of regular PA vs sedentary lifestyle in people with COPD in the UK.Methods: Efficacy, quality of life, and economic evidence on the PA effects in COPD patients were retrieved from literature to serve as input for a Markov microsimulation model comparing a COPD population performing PA vs a COPD population with sedentary lifestyle. The GOLD classification defined the model health states. For the base case, the cost of PA was estimated at zero, a lifetime horizon was used, and costs and effects were discounted at 3.5%. Analyses were performed from the UK National Health Service (NHS) perspective. Uncertainty around inputs and assumptions were explored via scenario and sensitivity analyses, including a cost threshold analysis. Outcomes were cost/quality-adjusted life year (QALY) gained and cost/year gained.Results: Based on our model, the effects of PA in the UK COPD population would be lower mortality (-6%), fewer hospitalizations (-2%), gains in years (+0.82) and QALYs (+0.66), and total cost savings of £2,568. The cost/QALY and cost/year gained were dominant. PA was cost-saving at costs <£35/month and cost-effective at cost <£202/month. The main model drivers were age and PA impact on death and hospital-treated exacerbations.Conclusion: Including PA in the management of COPD leads to long-term clinical benefits. If the NHS promotes only exercise via medical advice, this would lead to health care cost savings. If the NHS chose to fund PA, it would still likely be cost-effective. Keywords: cost-effectiveness, physical activity, exercise, COPD, microsimulation, Markov&nbsp

Cost-Effectiveness of 18f-Fdg Pet/Ct for Screening Distant Metastasis in Stage Ii/Iii Breast Cancer Patients of the UK, the United States and the Netherlands

Objectives:\ud 18F-FDG-PET/CT is accurate in detecting distant metastases (DM) in breast cancer patients scheduled for neoadjuvant chemotherapy. If DMs are screen-detected in an early phase, morbidity and mortality may be reduced. Because 18F-FDG-PET/CT comes at a significant cost, we compared its expected cost-effectiveness in stage II/III breast cancer patients of the UK, the US and the Netherlands (NL) vs. the gold-standard (X-thorax/liver sonography/bone scan (UK/NL) and CT-thorax-abdomen/bone scan (US)).\ud \ud Methods:\ud A time-dependent Markov model compared expected Life Year (LY) and cost/Quality-adjusted Life Year (QALY) gained in four breast cancer subtypes (ER-/HER2+;ER+/HER2+;ER-/HER2-;ER+/HER2-) over a 5-year time horizon from a hospital perspective. Sensitivity and specificity of imaging and type of systemic and local treatments were derived from the Netherlands Cancer Institute. Epidemiological, survival and utility data were estimated from literature or informed by expert assumptions. Costs (2013) were derived from national tariffs (UK and NL), and from the Centres for Medicaid and Medicare Services (US).\ud \ud Results:\ud 18F-FDG-PET/CT is more sensitive (53% vs. 15%) and specific (97% vs. 94%) than the gold-standard. LYs and QALYs gained were similar across subtypes, ranging from 0.025 to 0.027 and 0.0037 to 0.0044 respectively. In all countries, ER+HER2+ was the least and ER+HER2- the most costly group. 18F-FDG-PET/CT is expected to be cost-effective in the NL and the US (with highest ICERs of €165/QALY in ER+/HER2+ and $750 in ER-HER2+), with probabilities of cost-effectiveness ranging from 46-52% and 62-72% respectively, but not in the UK, with a 66-75% probability, depending on tumor subtype.\ud \ud Conclusions:\ud Using 18F-FDG-PET/CT for DM screening in stage II/III breast cancer is expected to result in incremental QALY gains in all subtypes and countries. Due to costs differences between countries, 18F-FDG-PET/CT is expected to be cost-effective in the US and the NL, but not in the UK

Imaging performance in guiding response to neoadjuvant therapy according to breast cancer subtypes: A systematic literature review

Monitoring therapeutic response to neoadjuvant chemotherapy(NAC) is likely to improve NAC effectiveness in breast cancer(BC). Imaging performance seems to vary per tumour subtype(by ER and HER2 status), therefore we performed a systematic review on subtype specific imaging performance in monitoring NAC in BC. Studies examining imaging performance in predicting pathologic complete response(pCR) during NAC in BC subtypes were selected. Per study, negative- and positive predictive value, sensitivity(se) and specificity(sp), AUC and accuracy were derived. Fifteen/106 articles were included. Inter-study variability was revealed in: monitoring interval, response and pCR definitions. In ER-positive/HER2-negative BC, 181F FDG-PET/CT showed se/sp of 38%–89%/74%–100%, MRI showed se/sp of 35%–37%/87%–89%. In triple negative BC, 181F FDG-PET/CT showed se/sp of 0%–79%/95%–100%. 181F FDG-PET/CT showed in ER-positive/HER2-positive BC se/sp of 59%/80% and in ER-negative/HER2-positive 27%/88%. Evidence on imaging performance in monitoring NAC according BC subtypes is lacking. Consensus should be reached in: definitions of pCR, response and monitoring interval before starting well-designed studies

Age-dependent neuromelanin accumulation in a novel humanized transgenic mouse model for Parkinson's disease and brain aging

Trabajo presentado en Neuroscience, celebrado en Chicago (Estados Unidos), del 19 al 23 de octubre de 2019Parkinson's disease (PD) is characterized by a selective and progressive loss of neurons that contain the dark brown pigment neuromelanin (NM), especially neurons from the substantia nigra (SN) and the locus coeruleus (LC), as well as, to a lesser extent, neurons from the ventral tegmental area (VTA) and the dorsal motor nucleus of the vagus nerve (DMNV). In humans, NM accumulates with age, the latter being the main risk factor for PD. The contribution of NM to PD pathogenesis remained unknown because, unlike humans, common laboratory animals lack NM. To overcome this major limitation, we have recently generated a new humanized rodent model based on the overexpression of human tyrosinase in the SN (AAV-hTyr). These animals show an age-dependent production of human-like NM, up to levels reached in elderly humans, and an age-dependent parkinsonian phenotype. We have now generated a humanized transgenic mouse model (Tg-TH-hTyr) that represents the first model that recapitulates the age-dependent accumulation and distribution of NM in all catecholaminergic neuronal cell groups in the brain, including SN, VTA, LC, and DNV. Using this unique animal model, we have assessed the functional, morphological and molecular implications of progressive NM accumulation in cellular functions. Our results show that NM accumulation affects neuronal function and viability in different catecholaminergic neuronal groups, which is relevant to PD pathogenesis and to the manifestation of both motor and non-motor symptoms of the disease