Economic evaluations of medical devices in paediatrics: a systematic review and a quality appraisal of the literature.

BACKGROUND: Although economic evaluations (EEs) have been increasingly applied to medical devices, little discussion has been conducted on how the different health realities of specific populations may impact the application of methods and the ensuing results. This is particularly relevant for pediatric populations, as most EEs on devices are conducted in adults, with specific aspects related to the uniqueness of child health often being overlooked. This study provides a review of the published EEs on devices used in paediatrics, assessing the quality of reporting, and summarising methodological challenges. METHODS: A systematic literature search was performed to identify peer-reviewed publications on the economic value of devices used in paediatrics in the form of full EEs (comparing both costs and consequences of two or more devices). After the removal of duplicates, article titles and abstracts were screened. The remaining full-text articles were retrieved and assessed for inclusion. In-vitro diagnostic devices were not considered in this review. Study descriptive and methodological characteristics were extracted using a structured template. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist was used to assess the quality of reporting. A narrative synthesis of the results was conducted followed by a critical discussion on the main challenges found in the literature. RESULTS: 39 full EEs were eligible for review. Most studies were conducted in high-income countries (67%) and focused on high-risk therapeutic devices (72%). Studies comprised 25 cost-utility analyses, 13 cost-effectiveness analyses and 1 cost-benefit analysis. Most of the studies considered a lifetime horizon (41%) and a health system perspective (36%). Compliance with the CHEERS 2022 items varied among the studies. CONCLUSIONS: Despite the scant body of evidence on EEs focusing on devices in paediatrics results highlight the need to improve the quality of reporting and advance methods that can explicitly incorporate the multiple impacts related to the use of devices with distinct characteristics, as well as consider specific child health realities. The design of innovative participatory approaches and instruments for measuring outcomes meaningful to children and their families should be sought in future research.

Cost Effectiveness of Pembrolizumab for Advanced Melanoma Treatment in Portugal.

BACKGROUND: The aim of this study was to assess the cost-effectiveness of pembrolizumab in treating patients with ipilimumab-naïve advanced melanoma in Portugal. METHODS: A cost-effectiveness model was developed to analyze the costs and consequences of treatment with pembrolizumab compared to treatment with ipilimumab in patients with advanced melanoma not previously treated with ipilimumab. The model was parameterized by using data from a head-to-head phase III randomized clinical trial, KEYNOTE-006. Extrapolation of long-term outcomes was based on approaches previously applied, combining ipilimumab data and melanoma patients' registry data. The analysis was conducted from the perspective of the Portuguese National Health Service, and a lifetime horizon (40 years) was used. Portugal-specific disease management costs were estimated by convening a panel of six clinical experts to derive health state resource use and multiplying the results by national unit costs. To test for the robustness of the conclusions, we conducted deterministic and probabilistic sensitivity analyses. RESULTS: Pembrolizumab increases life expectancy in 1.57 undiscounted life-years (LYs) and is associated with an increase in costs versus that of ipilimumab. The estimated incremental cost-effectiveness ratio is €47,221 per quality-adjusted life-year (QALY) and €42,956 per LY. Deterministic sensitivity analysis showed that the results were robust to the change of most input values or assumptions and were sensitive to time on treatment scenarios. According to the probabilistic sensitivity analysis performed, pembrolizumab is associated with a cost per QALY gained inferior to €50,000 in 75% of the cases. CONCLUSIONS: Considering the usually accepted thresholds in oncology, pembrolizumab is a cost-effective alternative for treating patients with advanced melanoma in Portugal.

Cost-effectiveness of cladribine tablets versus fingolimod in patients with highly active relapsing multiple sclerosis in Portugal.

Aims: To assess the cost-utility of cladribine tablets versus fingolimod in patients with highly active relapsing-remitting multiple sclerosis (RRMS) in Portugal.Methods: A 1-year cycle cohort-based Markov state transition model was developed to simulate disease progression, measured by Kurtzke Expanded Disability Status Scale (EDSS), relapses, and conversion to secondary-progressive MS (SPMS). Patients were assumed to remain on treatment until progression to EDSS level 7, conversion to SPMS, or complete loss of efficacy due to waning effect. Natural history was based on British Columbia Multiple Sclerosis registry, London Ontario database, UK MS Trust, and cladribine tablets clinical trial (CLARITY). Portuguese all-cause mortality was adjusted for the MS associated increased mortality. Clinical inputs for active treatments (disability progression and relapse rate) were estimated on a network meta-analysis. Utility weights were derived from UK-MS Survey and published literature. Resource consumption by EDSS and due to relapses was based on published literature, National DRG microdata and expert opinion. Unit costs were obtained from official sources. The analysis was conducted from payers' perspective, time horizon of 50 years and discount rate of 5%, for both costs and benefits. Uncertainty was assessed via probabilistic and deterministic sensitivity analyses.Results: Compared to fingolimod, cladribine tablets were associated with a delay in progression, resulting in a gain of 0.85 quality adjusted life years (QALYs) and a cost decrease of 25,935 €. Probabilistic sensitivity analysis resulted in a mean ICER of -31,781 € per QALY and was dominant in 98.7% of the simulations. Cladribine tablets were dominant across the scenario analyses tested.Conclusions: Treatment of highly active RRMS with cladribine tablets was less costly and more effective than treatment with fingolimod. Hence, it is a dominant strategy in the Portuguese setting. No conclusions can be drawn from the present study regarding other treatment options, in particular natalizumab and alemtuzumab.

Sociedade Portuguesa de Cuidados Intensivos guidelines for stress ulcer prophylaxis in the intensive care unit. / Diretrizes da Sociedade Portuguesa de Cuidados Intensivos para profilaxia da úlcera de estresse na unidade de terapia intensiva.

Critically ill patients are at risk of developing stress ulcers in the upper digestive tract. Agents that suppress gastric acid are commonly prescribed to reduce the incidence of clinically important stress ulcer-related gastrointestinal bleeding. However, the indiscriminate use of stress ulcer prophylaxis in all patients admitted to the intensive care unit is not warranted and can have potential adverse clinical effects and cost implications. The present guidelines from the Sociedade Portuguesa de Cuidados Intensivos summarizes the current evidence and gives six clinical statements and an algorithm aiming to provide a standardized prescribing policy for the use of stress ulcer prophylaxis in the intensive care unit.

O paciente crítico corre risco de desenvolver úlceras de estresse do trato gastrintestinal. Antiácidos e antiulcerosos de diferentes classes são frequentemente prescritos para reduzir a incidência de hemorragia gastrintestinal clinicamente significativa associada à úlcera de estresse. No entanto, o uso indiscriminado deste tipo de profilaxia em todos os pacientes admitidos a unidades de terapia intensiva não só não se justifica, como tem potenciais efeitos adversos e implicações de custo. As presentes diretrizes da Sociedade Portuguesa de Cuidados Intensivos resume a evidência atual e fornece seis afirmações clínicas e um algoritmo com o objetivo de fornecer uma política padronizada para prescrição de profilaxia da úlcera estresse em unidades de terapia intensiva.

Cost-effectiveness of rosuvastatin in the prevention of ischemic heart disease in Portugal.

OBJECTIVE: To assess the cost-effectiveness of rosuvastatin in the treatment of hypercholesterolemia and the prevention of ischemic heart disease (IHD) in Portugal. METHODS: A probabilistic Markov model was constructed to analyze the costs and consequences of lifetime treatment with rosuvastatin, atorvastatin, pravastatin, and simvastatin. For this purpose, the results from randomized head-to-head trials evaluating low-density lipoprotein (LDL) changes were combined with the results from a meta-analysis defining the relationship between LDL levels and fatal and nonfatal IHD events. The incidence of myocardial infarction (MI) was derived from a 9-year Portuguese observational study. The eligible population was defined as untreated individuals aged more than 35 years with LDL levels above 115 mg/dl. Death rates due to IHD and other causes were obtained from official data. Resource use in the treatment of MI was estimated by a Delphi panel of eight Portuguese cardiologists with at least 15 years of clinical practice. Costs were calculated from the payers' perspective. RESULTS: Rosuvastatin increases life expectancy between 5.5 and 12.1 days per patient. It is cost-saving when compared to atorvastatin, but it increases costs when assessed against pravastatin and simvastatin (euro1,004 and euro684 per patient, respectively). Therefore, rosuvastatin is a dominant alternative compared to atorvastatin, having an incremental cost-effectiveness ratio of euro30,350 to pravastatin and euro39,340 to simvastatin. In the probabilistic sensitivity analysis, performed rosuvastatin always dominates atorvastatin and is associated with a cost per life-year gained inferior to euro50,000 in 95.7% of the cases when compared to pravastatin and in 67.0% simulations when assessed against simvastatin. CONCLUSIONS: Rosuvastatin is a cost-effective alternative in the prevention of IHD in Portugal.

Cost-Effectiveness Analysis of Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukaemia in Portuguese Patients who are Unsuitable for Full-Dose Fludarabine-Based Therapy.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) mostly affects patients with comorbidities and limited therapeutic options. Obinutuzumab in combination with chlorambucil (GClb) is a new therapeutic option for previously untreated CLL patients who are unsuitable for full-dose fludarabine-based therapy. This combination delays disease progression but incurs additional costs; thus, an assessment of its value for money is relevant. OBJECTIVE: To estimate the incremental cost-utility ratio of GClb in comparison with (i) rituximab in combination with chlorambucil (RClb), and (ii) chlorambucil alone (Clb) from the perspective of the Portuguese National Health Service (NHS). METHODS: A Markov model was used to predict disease progression. Pre-progression clinical data were based on the latest CLL11 trial data, and post-progression clinical data were obtained from CLL5 trial data. Utility values are from Kosmas et al. (Leuk Lymphoma 56:1320-1326, 14). Only direct medical costs were included. The resource consumption was estimated by a panel of Portuguese experts, and the unit costs were obtained from official sources. A discount rate of 5% was applied to costs and consequences. RESULTS: GClb and RClb were associated with an increase of 1.06 and 0.39 quality-adjusted life-years (QALY) at an additional cost of €21,720 and €9836 when compared to Clb, respectively. The cost-utility ratio of GClb versus Clb was €20,397/QALY, while RClb was extendedly dominated. CONCLUSIONS: The use of GClb for previously untreated CLL patients who are unsuitable for full-dose fludarabine-based therapy incurs an incremental cost per QALY that is generally accepted in Portugal. Therefore, although there is some uncertainty, obinutuzumab is probably a cost-effective therapy in the Portuguese setting.

Procedural justice in public health care resource allocation.

INTRODUCTION: The legal studies literature on procedural justice identifies six key characteristics of procedural justice: accuracy, consistency, impartiality, reversibility, transparency and voice. However, the relative importance of these in the context of public health care resource allocation is unclear, as is whether they are valuable instrumentally (because it contributes to better outcomes) or inherently (for its own sake). METHODS: A survey of 80-odd members of the UK public determined the following: the ranking of all the six characteristics; the pairwise comparisons of the characteristics; and whether each characteristic was important for instrumental reasons, for intrinsic reasons or for both. RESULTS: Respondents ranked the procedures in the order of accuracy, consistency, impartiality, reversibility and transparency. Procedural justice was valued for both instrumental and inherent reasons. DISCUSSION/CONCLUSION: A robust ranking of five of the six procedural characteristics was found. The ranking for voice was sensitive to the question format, which has methodological implications. Around a quarter to a third of respondents regarded a procedural characteristic to have entirely intrinsic value.

Diretrizes da Sociedade Portuguesa de Cuidados Intensivos para profilaxia da úlcera de estresse na unidade de terapia intensiva / Sociedade Portuguesa de Cuidados Intensivos guidelines for stress ulcer prophylaxis in the intensive care unit

RESUMO O paciente crítico corre risco de desenvolver úlceras de estresse do trato gastrintestinal. Antiácidos e antiulcerosos de diferentes classes são frequentemente prescritos para reduzir a incidência de hemorragia gastrintestinal clinicamente significativa associada à úlcera de estresse. No entanto, o uso indiscriminado deste tipo de profilaxia em todos os pacientes admitidos a unidades de terapia intensiva não só não se justifica, como tem potenciais efeitos adversos e implicações de custo. As presentes diretrizes da Sociedade Portuguesa de Cuidados Intensivos resume a evidência atual e fornece seis afirmações clínicas e um algoritmo com o objetivo de fornecer uma política padronizada para prescrição de profilaxia da úlcera estresse em unidades de terapia intensiva.

ABSTRACT Critically ill patients are at risk of developing stress ulcers in the upper digestive tract. Agents that suppress gastric acid are commonly prescribed to reduce the incidence of clinically important stress ulcer-related gastrointestinal bleeding. However, the indiscriminate use of stress ulcer prophylaxis in all patients admitted to the intensive care unit is not warranted and can have potential adverse clinical effects and cost implications. The present guidelines from the Sociedade Portuguesa de Cuidados Intensivos summarizes the current evidence and gives six clinical statements and an algorithm aiming to provide a standardized prescribing policy for the use of stress ulcer prophylaxis in the intensive care unit.