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Purpose Health state utility values are commonly used to inform economic evaluations and determine the cost-effectiveness of an intervention. The aim of this systematic review is to summarise the utility values available to represent the health-related quality of life (HRQoL) of patients with thyroid cancer. Methods Eight electronic databases were searched from January 1999 to April 2019 for studies which included assessment of HRQoL for patients with thyroid cancer. Utility estimates derived from multiple sources (EuroQol questionnaire 5-dimension (EQ-5D), time trade-off [TTO] and standard gamble [SG] methods) were extracted. In addition, utility estimates were generated by mapping from SF-36 and EORTC QLQ-30 to the EQ-5D-3L UK value set using published mapping algorithms. Results Searches identified 33 eligible studies. Twenty-six studies reported HRQoL for patients with differentiated thyroid cancer and seven studies for patients with general thyroid cancer. We identified studies which used different methods and tools to quantify the HRQoL in patients with thyroid cancer, such as the EQ-5D-3L, SF-36, EORTC QLQ-30 and SG and TTO techniques to estimate utility values. Utility estimates range from 0.205 (patients with low-risk differentiated thyroid cancer) to utility values approximate to the average UK population (following successful thyroidectomy surgery and radioiodine treatment). Utility estimates for different health states, across thyroid cancer sub-types and interventions are presented. Conclusion A catalogue of utility values is provided for use when carrying out economic modelling of thyroid cancer; by including mapped values, this approach broadens the scope of health states that can be considered within cost-effectiveness modelling.

Globally, approximately 3 billion primarily cook using inefficient and poorly vented combustion devices, leading to unsafe levels of household air pollution (HAP) in and around the home. Such exposures contribute to nearly 4 million deaths annually (WHO 2018a, 2018b ). Characterizing the effectiveness of interventions for reducing HAP concentration and exposure is critical for informing policy and programmatic decision-making on which cooking solutions yield the greatest health benefits. This review synthesizes evidence of in-field measurements from four cleaner cooking technologies and three clean fuels, using field studies aimed at reducing HAP concentration and personal exposure to health damaging pollutants (particulate matter (PM 2.5 ) and carbon monoxide (CO)). Fifty studies from Africa, Asia, South and Latin America, provided 168 estimates synthesized through meta-analysis. For PM 2.5 kitchen concentrations, burning biomass more cleanly through improved combustion stoves (ICS) with ( n = 29; 63% reduction) or without ( n = 12; 52%) venting (through flue or chimney) and through forced-draft combustion ( n = 9; 50%) was less effective than cooking with clean fuels including ethanol ( n = 4; 83%), liquefied petroleum gas (LPG) ( n = 11; 83%) and electricity ( n = 6; 86%). Only studies of clean fuels consistently achieved post-intervention kitchen PM 2.5 levels at or below the health-based WHO interim target level 1 (WHO-IT1) of 35 μ g m −3 . None of the advanced combustion stoves (gasifiers) achieved WHO-IT1, although no evidence was available for pellet fuelled stoves. For personal exposure to PM 2.5, none of the ICS ( n = 11) were close to WHO-IT1 whereas 75% ( n = 6 of 8) of LPG interventions were at or below WHO-IT1. Similar patterns were observed for CO, although most post-intervention levels achieved the WHO 24 h guideline level. While clean cooking fuel interventions (LPG, electric) significantly reduce kitchen concentrations and personal exposure to PM 2.5 in household settings, stove stacking and background levels of ambient air pollution, have likely prevented most clean fuel interventions from approaching WHO-IT1. In order to maximize health gains, a wholistic approach jointly targeting ambient and HAP should be followed in lower-and-middle income countries.

Background Treatment with radioactive iodine is effective for many patients with progressive, locally advanced or metastatic, differentiated thyroid cancer. However, some patients become refractory to treatment. These types of patients are considered to have radioactive iodine refractory differentiated thyroid cancer (RR-DTC). Methods We searched Embase, MEDLINE, PubMed and the Cochrane Library from January 1999 through January 2017. Reference lists of included studies and ongoing trial registries were also searched. Reports of randomized controlled trials (RCTs), prospective observational studies, and systematic reviews/indirect comparisons were eligible for inclusion. In the absence of direct clinical trial evidence comparing lenvatinib versus sorafenib, we assessed the feasibility of conducting an indirect comparison to obtain estimates of the relative efficacy and safety of these two treatments. Results Of 2364 citations, in total, 93 papers reporting on 2 RCTs (primary evidence), 9 observational studies and 13 evidence reviews (supporting evidence) were identified. Compared to placebo, RCT evidence demonstrated improvements with lenvatinib or sorafenib in median progression-free survival (PFS) and objective tumour response rate (ORR). Overall survival (OS) was confounded by high treatment crossover (≥75%) in both trials. Adverse events (AEs) were more common with lenvatinib or sorafenib than with placebo but the most common AEs associated with each drug differed. Primarily due to differences in the survival risk profiles of patients in the placebo arms of the RCTs, we considered it inappropriate to indirectly compare the effectiveness of lenvatinib versus sorafenib. ORR and AE findings for lenvatinib and sorafenib from the supporting evidence were broadly in line with RCT evidence. Health-related quality of life (HRQoL) data were limited. Conclusions Lenvatinib and sorafenib are more efficacious than placebo (a proxy for best supportive care) for treating RR-DTC. Uncertainty surrounds the extent of the impact on OS and HRQoL. Lenvatinib could not reliably be compared with sorafenib. Choice of treatment is therefore likely to depend on an individual patient’s circumstances.

Personalized medicine, with the aim of safely, effectively, and cost-effectively targeting treatment to a prespecified patient population, has always been a long-time goal within health care. It is often argued that personalizing treatment will inevitably improve clinical outcomes for patients and help achieve more effective use of health care resources. Demand is increasing for demonstrable evidence of clinical and cost-effectiveness to support the use of personalized medicine in health care. This paper begins with an overview of the existing challenges in conducting economic evaluations of genetics- and genomics-targeted technologies, as an example of personalized medicine. Our paper illustrates the complexity of the challenges faced by these technologies by highlighting the variations in the issues faced by diagnostic tests for somatic variations, generally referring to genetic variation in a tumor, and germline variations, generally referring to inherited genetic variation in enzymes involved in drug metabolic pathways. These tests are typically aimed at stratifying patient populations into subgroups on the basis of clinical effectiveness (response) or safety (avoidance of adverse events). The paper summarizes the data requirements for economic evaluations of genetics and genomics-based technologies while outlining that the main challenges relating to data requirements revolve around the availability and quality of existing data. We conclude by discussing current developments aimed to address the challenges of assessing the cost-effectiveness of genetics and genomics-based technologies, which revolve around two central issues that are interlinked: the need to adapt available evaluation methods and identifying who is responsible for generating evidence for these technologies.

Exposure to household air pollution results in a substantial global health burden. The World Health Organization (WHO) Guidelines for Indoor Air Quality: Household Fuel Combustion stipulate emission rates for household energy devices should meet air quality guidelines and protect health. Liquefied petroleum gas (LPG), biogas, natural gas (NG), and alcohol fuels are considered clean for health due to their low emissions at the point of use. In light of the ongoing energy transition and increasing emphasis on these fuels, it is imperative to provide an updated synthesis of the impacts of these fuels on health. A systematic review was completed on the health effects of liquid and gaseous fuels for household energy use for cooking, heating, and lighting across high-, middle- and low-income countries. Comprehensive searches were undertaken in 12 international databases and selected studies were compiled into a new publicly available WHO Health Effects of Household Liquid & Gaseous Fuels Database, containing key study characteristics including pollutants and/or health outcomes measured. This database was then mapped to understand the breadth of evidence and potential gaps. From 48 130 search results, 587 studies were extracted for inclusion in the database on completion of the full-text review. Studies represented low-, middle- and high-income countries (HICs) over several decades - there has been a substantial increase in evidence from low- and middle-income countries (LMICs) published in the last decade, particularly in Asia. Most evidence focused on LPG for cooking in LMICs or NG used in HICs for cooking and heating. Women were the most studied demographic, with self-reported health outcomes and symptoms being the most common assessment method. Particulate matter and nitrogen oxides were the most monitored pollutants. A wide array of health symptoms and disease and injury outcomes were assessed, and most concerned respiratory health. This is the first time that evidence on the health effects of liquid and gaseous fuels for household energy use has been systematically catalogued and mapped. Most evidence concerned cooking and heating, with a paucity of information on the health effects from lighting. Limited evidence was available on the health effects of liquid fuels (such as alcohol fuels), with most studies concerning gaseous fuels. The WHO Health Effects of Household Liquid & Gaseous Fuels Database represents a valuable resource to enable the examination of the positive and negative health effects from these fuels.

This review assessed evidence of disparities in benefits of pharmacogenomics related to 'model performance' in subgroups of patients and studies which reported impact on health inequalities. 'Model performance' refers to the ability of algorithms including clinical, environmental and genetic information to guide treatment. A total of 4978 abstracts were screened by one reviewer and 30% (1494) were double screened by a second independent reviewer, after which data extraction was performed. Additional forward and backward citation searching of reference lists was conducted. Investigators independently double rated study quality and applicability of included studies. Only five individual studies were identified which met our inclusion criteria, but were contradictory in their conclusions. While three studies of genotype-guided dosing of warfarin reported that ethnic disparities in healthcare may widen, two other studies (one reporting on warfarin and reporting on clopidogrel) suggested that disparities in healthcare may reduce. There is a paucity of studies which evaluates the impact of pharmacogenomics on health disparities. Further work is required not only to evaluate health disparities between ethnic groups and countries but also within ethnic groups in the same country and solutions need to be identified to overcome these disparities.

As part of the National Institute for Health and Care Excellence (NICE) highly specialised technology (HST) evaluation programme, Novartis submitted evidence to support the use of onasemnogene abeparvovec as a treatment option for patients with pre-symptomatic 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the survival of motor neuron (SMN) 1 gene and up to three copies of the SMN2 gene. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the External Assessment Group (EAG). This article summarises the EAG’s review of the evidence submitted by the company and provides an overview of the NICE Evaluation Committee’s final decision, published in April 2023. The primary source of evidence for this evaluation was the SPR1NT trial, a single-arm trial including 29 babies. The EAG and committee considered that the SPR1NT trial results suggested that onasemnogene abeparvovec is effective in treating pre-symptomatic SMA; however, long-term efficacy data were unavailable and efficacy in babies aged over 6 weeks remained uncertain. Cost-effectiveness analyses conducted by the company and the EAG (using a discounted price for onasemnogene abeparvovec) explored various assumptions; all analyses generated incremental cost-effectiveness ratios (ICERs) that were less than £100,000 per quality-adjusted life-year (QALY) gained. The committee recommended onasemnogene abeparvovec as an option for treating pre-symptomatic 5q SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene in babies aged ≤ 12 months only if the company provides it according to the commercial arrangement (i.e. simple discount patient access scheme).

Heated humidified high-flow nasal cannula (HHHFNC) is gaining popularity as a mode of respiratory support. We updated a systematic review and meta-analyses examining the efficacy and safety of HHHFNC compared with standard treatments for preterm infants. The primary outcome was the need for reintubation for preterm infants following mechanical ventilation (post-extubation analysis) or need for intubation for preterm infants not previously intubated (analysis of primary respiratory support). We searched PubMed, MEDLINE, Embase, and the Cochrane Library for randomized controlled trials (RCTs) of HHHFNC versus standard treatments. Meta-analysis was conducted using Review Manager 5.3. The post-extubation analysis included ten RCTs (n = 1,201), and the analysis of primary respiratory support included ten RCTs (n = 1,676). There were no statistically significant differences for outcomes measuring efficacy, including the primary outcome. There were statistically significant differences favoring HHHFNC versus nasal cannula positive airway pressure (NCPAP) for air leak (post-extubation, risk ratio [RR] 0.29, 95 percent confidence interval [CI] 0.11 to 0.76, I2 = 0) and nasal trauma (post-extubation: 0.35, 95 percent CI 0.27 to 0.46, I2 = 5 percent; primary respiratory support: RR 0.52, 95 percent CI 0.37 to 0.74; I2 = 27 percent). Studies, particularly those of primary respiratory support, included very few preterm infants with gestational age (GA) <28 weeks. HHHFNC may offer an efficacious and safe alternative to NCPAP for some infants but evidence is lacking for preterm infants with GA ≤28 weeks.

As part of the Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of cenegermin (OXERVATE ® , Dompé) to submit evidence for the clinical and cost effectiveness of cenegermin for neurotrophic keratitis (NK). The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarises the ERG’s review of the evidence submitted by the company and provides a summary of the Appraisal Committee’s (AC) final decision. Clinical-effectiveness evidence from two phase II randomised controlled trials (RCTs) of cenegermin found cenegermin to improve corneal healing after 8 weeks compared with vehicle, considered a proxy for artificial tears. Longer-term data and comparisons with other relevant comparators were insufficient to draw conclusions. The company developed a de novo economic model that found cenegermin to be dominant when compared with artificial tears, except in one of seven scenarios. However, the ERG considered that the model had a major structural flaw in that it failed to allow patients to enter a ‘sustained healing’ state from ‘standard of care (SoC) non-healing’ and ‘SoC deteriorating’ states, or to move into an ‘SoC deteriorating’ state from an ‘SoC non-healing’ state. Following the first AC meeting, the company submitted a revised model with a revised model structure that removed the ‘SoC deteriorating’ state and introduced an ‘SoC healed’ state to sit alongside the existing ‘sustained healing’ and ‘SoC non-healing’ states from the original model. However, the ERG continued to express concerns, which included (1) extrapolation of the treatment effect of cenegermin over a patient’s lifetime; (2) the assumption that patients had two specialist visits a month; (3) the assumption that artificial tears, autologous serum eye drops and contact lenses continued for a lifetime after healing; (4) the simplified modelling of costs and utilities; and (5) the underlying uncertainty in the utility values. The ERG therefore considered the company’s model could not produce a robust incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. The ERG did however present an alternative ICER by amending the use and cost of autologous serum eye drops, contact lenses and artificial tears in the ‘healed’ and ‘non-healed’ states. Applying these changes produced an ICER of £302,717 per QALY gained. Because of uncertainties with the clinical- and cost-effectiveness evidence, the AC concluded that cenegermin cannot be recommended within its marketing authorisation for NK.