Development of low-cost, compact chiroptical imaging systems.

Circular dichroism spectroscopy is a key probe of the structural and optical properties of chiral materials, however, commercial circular dichroism spectrometers are large, prohibitively expensive and rarely offer environmental control of the sample under test. Using Fresnel rhombs as inexpensive broadband quarter-wave plates, we demonstrate two novel, low-cost (<£2000) and portable imaging systems controlled by our own bespoke open-source control software which are capable of spatially mapping the circular dichroism of chiral solid state films. By coupling these imaging systems with a temperature controlled stage, we show that we can rapidly identify the thermal processing conditions required to maximise circular dichroism in chiral solid state films by measuring circular dichroism in situ during thermal annealing of a sample under test. The accuracy and spatial resolution of these circular dichroism imagers are cross-compared against our previous studies using an existing circular dichroism imaging system at the Diamond Light Source and are shown to be in good agreement, with a sensitivity down to 250 mdeg and a spatial resolution of 100 µm.

Cost-Effectiveness Analysis of Ultra-Hypofractionated Whole Breast Radiation Therapy Alone Versus Hormone Therapy Alone or Combined Treatment for Low-Risk ER-Positive Early Stage Breast Cancer in Women Aged 65 Years and Older.

PURPOSE: The optimal management of early-stage, low-risk, hormone-positive breast cancer in older women remains controversial. Recent trials have shown that 5-fraction ultrahypofractionated whole-breast irradiation (U-WBI) has similar outcomes to longer courses, reducing the cost and inconvenience of treatment. We performed a cost-utility analysis to compare U-WBI to hormone therapy alone or their combination. METHODS AND MATERIALS: We simulated 3 different treatment approaches for women age 65 years or older with pT1-2N0 ER-positive invasive ductal carcinoma treated with lumpectomy with negative margins using a Markov microsimulation model. The strategies were U-WBI performed with a 3-dimensional conformal technique over 5 fractions without a boost ("radiation therapy [RT] alone"), adjuvant hormone therapy (anastrozole for 5 years) without RT ("aromatase-inhibitor [AI] alone"), or the combination of the 2. The combination strategy was calibrated to match trial results, and the relative effectiveness of the RT alone and AI alone strategies were inferred from previous randomized trials. The primary endpoint was the cost-effectiveness of the 3 strategies over a lifetime horizon as measured by the incremental cost-effectiveness ratio (ICER), with a value of $100,000/quality-adjusted life-year deemed "cost-effective." RESULTS: The model results compared with the prespecified target outcomes. On average, RT alone was the least expensive strategy ($14,775), with AI alone slightly more ($14,998), and combination therapy the costliest ($19,802). RT alone dominated AI alone (the incremental cost-effectiveness ratio [ICER] -$5089). Combination therapy, compared with RT alone, was slightly more expensive than our definition of cost-effective (ICER $113,468) but was cost-effective compared with AI alone (ICER $54,451). Probabilistic sensitivity analysis demonstrated RT alone to be cost-effective in 50% of trials, with combination therapy in 36% and AI alone in 14%. CONCLUSIONS: U-WBI alone appears the more cost-effective de-escalation strategy for these low-risk patients, compared with AI alone. Combining U-WBI and AI appears more costly but may be preferred by some patients.

The economic impact of circulating tumor-tissue modified HPV DNA for the post-treatment surveillance of HPV-driven oropharyngeal cancer: A simulation.

PURPOSE: Following treatment of HPV-driven oropharynx cancer, surveillance nasopharyngoscopy and imaging are often performed but are expensive and frequently ineffective. A novel plasma circulating tumor-tissue modified viral HPV DNA (TTMV-HPV-DNA) assay accurately detects recurrences. We modeled the cost of the new assay. METHODS: We designed and validated a partitioned survival model which replicated the results of the RTOG 1016 study and calculated cumulative surveillance costs from the payer's perspective. Two strategies were considered: a standard of routine endoscopy with imaging as needed and an alternative strategy which omitted scopes and imaging but obtained serial TTMV-HPV-DNA samples. No difference in effectiveness (QALY or LY) was assumed in the base case. A 5-year horizon was used, costs were reported in 2020 U.S. dollars discounted by 3%. Seven scenarios tested model assumptions and practice variation. Deterministic and probabilistic sensitivity analyses assessed parameter uncertainty. RESULTS: In the base case, at the list TTMV-HPV-DNA price, the cumulative cost of surveillance was $11,674 for the standard strategy and $20,756 for the TTMV-HPV-DNA strategy (+$9082 over 5 years). Probabilistic sensitivity analysis demonstrated the cost difference ranged from $4917-$12,047. The TTMV-HPV-DNA strategy was most likely to be either cost saving or cost-effective if future data demonstrate small improvements in quality or quantity of life (approximately 33 quality-adjusted life-days), if the assay reduces utilization of imaging, and if the periodicity of TTMV-HPV-DNA draws could be reduced from that on clinical trials. CONCLUSIONS: This data informs providers seeking to design more accurate, accessible, and economical post-treatment surveillance strategies.

Cost-Effectiveness Analysis of No Adjuvant Therapy Versus Partial Breast Irradiation Alone Versus Combined Treatment for Treatment of Low-Risk DCIS: A Microsimulation.

PURPOSE: Adjuvant therapy in patients with ductal carcinoma in situ who undergo partial mastectomy remains controversial, particularly for low-risk patients (60 years or older, estrogen-positive, tumor extent < 2.5 cm, grade 1 or 2, and margins ≥ 3 mm). We performed a cost-effectiveness analysis comparing three strategies: no adjuvant treatment after surgery, a five-fraction course of accelerated partial breast irradiation using intensity-modulated radiation therapy (accelerated partial breast irradiation [APBI]-alone), or APBI plus an aromatase inhibitor for 5 years. MATERIALS AND METHODS: Outcomes including local recurrence, distant metastases, and survival as well as toxicity data were modeled by a patient-level Markov microsimulation model, which were validated against trial data. Costs of treatment and possible adverse events were included from the societal perspective over a lifetime horizon, adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALYs) were calculated based on utilities extracted from the literature. RESULTS: No adjuvant therapy was the least costly approach ($5,744), followed by APBI-alone ($11,070); combined therapy was costliest ($16,052). Adjuvant therapy resulted in slightly higher QALYs (no adjuvant, 11.320; APBI-alone, 11.343; and combination, 11.381). In the base case, no treatment was the cost-effective strategy, with an incremental cost-effectiveness ratio of $239,109/QALY for APBI-alone and $171,718/QALY for combined therapy. The incremental cost-effectiveness ratio for combined therapy compared with APBI-alone was $131,949. Probabilistic sensitivity analyses found that no therapy was cost effective (defined as $100,000/QALY of lower) in 63% of trials, APBI-alone in 19%, and the combination in 18%. CONCLUSION: No adjuvant therapy represents the most cost-effective approach for postmenopausal women 60 years or older who receive partial mastectomy for low-risk ductal carcinoma in situ.

Prehospital continuous positive airway pressure for acute respiratory failure: the ACUTE feasibility RCT.

BACKGROUND: Acute respiratory failure is a life-threatening emergency. Standard prehospital management involves controlled oxygen therapy. Continuous positive airway pressure is a potentially beneficial alternative treatment; however, it is uncertain whether or not this treatment could improve outcomes in NHS ambulance services. OBJECTIVES: To assess the feasibility of a large-scale pragmatic trial and to update an existing economic model to determine cost-effectiveness and the value of further research. DESIGN: (1) An open-label, individual patient randomised controlled external pilot trial. (2) Cost-effectiveness and value-of-information analyses, updating an existing economic model. (3) Ancillary substudies, comprising an acute respiratory failure incidence study, an acute respiratory failure diagnostic agreement study, clinicians perceptions of a continuous positive airway pressure mixed-methods study and an investigation of allocation concealment. SETTING: Four West Midlands Ambulance Service hubs, recruiting between August 2017 and July 2018. PARTICIPANTS: Adults with respiratory distress and peripheral oxygen saturations below the British Thoracic Society's target levels were included. Patients with limited potential to benefit from, or with contraindications to, continuous positive airway pressure were excluded. INTERVENTIONS: Prehospital continuous positive airway pressure (O-Two system, O-Two Medical Technologies Inc., Brampton, ON, Canada) was compared with standard oxygen therapy, titrated to the British Thoracic Society's peripheral oxygen saturation targets. Interventions were provided in identical sealed boxes. MAIN OUTCOME MEASURES: Feasibility objectives estimated the incidence of eligible patients, the proportion recruited and allocated to treatment appropriately, adherence to allocated treatment, and retention and data completeness. The primary clinical end point was 30-day mortality. RESULTS: Seventy-seven patients were enrolled (target 120 patients), including seven patients with a diagnosis for which continuous positive airway pressure could be ineffective or harmful. Continuous positive airway pressure was fully delivered to 74% of participants (target 75%). There were no major protocol violations/non-compliances. Full data were available for all key outcomes (target ≥ 90%). Thirty-day mortality was 27.3%. Of the 21 deceased participants, 14 (68%) either did not have a respiratory condition or had ceiling-of-treatment decision implemented that excluded hospital non-invasive ventilation and critical care. The base-case economic evaluation indicated that standard oxygen therapy was probably cost-effective (incremental cost-effectiveness ratio £5685 per quality-adjusted life-year), but there was considerable uncertainty (population expected value of perfect information of £16.5M). Expected value of partial perfect information analyses indicated that effectiveness of prehospital continuous positive airway pressure was the only important variable. The incidence rate of acute respiratory failure was 17.4 (95% confidence interval 16.3 to 18.5) per 100,000 persons per year. There was moderate agreement between the primary prehospital and final hospital diagnoses (Gwet's AC1 coefficient 0.56, 95% confidence interval 0.43 to 0.69). Lack of hospital awareness of the Ambulance continuous positive airway pressure (CPAP): Use, Treatment Effect and economics (ACUTE) trial, limited time to complete trial training and a desire to provide continuous positive airway pressure treatment were highlighted as key challenges by participating clinicians. LIMITATIONS: During week 10 of recruitment, the continuous positive airway pressure arm equipment boxes developed a 'rattle'. After repackaging and redistribution, no further concerns were noted. A total of 41.4% of ambulance service clinicians not participating in the ACUTE trial indicated a difference between the control and the intervention arm trial boxes (115/278); of these clinician 70.4% correctly identified box contents. CONCLUSIONS: Recruitment rate was below target and feasibility was not demonstrated. The economic evaluation results suggested that a definitive trial could represent value for money. However, limited compliance with continuous positive airway pressure and difficulty in identifying patients who could benefit from continuous positive airway pressure indicate that prehospital continuous positive airway pressure is unlikely to materially reduce mortality. FUTURE WORK: A definitive clinical effectiveness trial of continuous positive airway pressure in the NHS is not recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12048261. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 7. See the NIHR Journals Library website for further project information.

Acute respiratory failure is a life-threatening medical emergency. It occurs when heart or lung disease suddenly develops, or deteriorates, and leads to the patient being unable to maintain oxygen levels in their blood. Continuous positive airway pressure is a potentially useful treatment that could be used by paramedics. It involves delivering oxygen under increased pressure through a tight-fitting face mask. However, it is uncertain whether or not it could work effectively in NHS ambulance services, or if it represents value for money. The Ambulance continuous positive airway pressure (CPAP): Use, Treatment Effect and economics (ACUTE) trial investigated whether or not it is possible and worthwhile to undertake a full-scale study comparing continuous positive airway pressure with normal paramedic treatment. Paramedics identified adults with acute respiratory failure when attending 999 emergency calls. Half were randomly assigned to receive continuous positive airway pressure, whereas the other half were treated normally. Patients were then followed up to see what happened to them. Fewer patients than expected were entered into the trial, but paramedics were able to provide treatment with continuous positive airway pressure, and most patients were successfully followed up. It therefore seems possible to do a full-scale trial. A cost-effectiveness model also showed that it is uncertain whether or not continuous positive airway pressure represents value for money for the NHS, so further research might be worthwhile, if continuous positive airway pressure is thought to be effective. However, examination of patients recruited to the trial uncovered important doubts about whether or not continuous positive airway pressure would help them. One-quarter of patients were not able to tolerate the tight continuous positive airway pressure mask. Some of the patients had conditions that are not usually treated by continuous positive airway pressure, or had severe underlying disease that could not be helped by this treatment. Others had collapsed lungs that could have been made worse by continuous positive airway pressure. This means that, although a full-scale trial may be possible, it is difficult to see how continuous positive airway pressure could save enough lives to make a trial worthwhile.

Cost-effectiveness of out-of-hospital continuous positive airway pressure for acute respiratory failure: decision analytic modelling using data from a feasibility trial.

BACKGROUND: Standard prehospital management for Acute respiratory failure (ARF) involves controlled oxygen therapy. Continuous positive airway pressure (CPAP) is a potentially beneficial alternative treatment, however, it is uncertain whether this could improve outcomes and provide value for money. This study aimed to evaluate the cost-effectiveness of prehospital CPAP in ARF. METHODS: A cost-utility economic evaluation was performed using a probabilistic decision tree model synthesising available evidence. The model consisted of a hypothetical cohort of patients in a representative ambulance service with undifferentiated ARF, receiving standard oxygen therapy or prehospital CPAP. Costs and quality adjusted life years (QALYs) were estimated using methods recommended by NICE. RESULTS: In the base case analysis, using CPAP effectiveness estimates form the ACUTE trial, the mean expected costs of standard care and prehospital CPAP were £15,201 and £14,850 respectively and the corresponding mean expected QALYs were 1.190 and 1.128, respectively. The mean ICER estimated as standard oxygen therapy compared to prehospital CPAP was £5685 per QALY which indicated that standard oxygen therapy strategy was likely to be cost-effective at a threshold of £20,000 per QALY (67% probability). The scenario analysis, using effectiveness estimates from an updated meta-analysis, suggested that prehospital CPAP was more effective (mean incremental QALYs of 0.157), but also more expensive (mean incremental costs of £1522), than standard care. The mean ICER, estimated as prehospital CPAP compared to standard care, was £9712 per QALY. At the £20,000 per QALY prehospital CPAP was highly likely to be the most cost-effective strategy (94%). CONCLUSIONS: Cost-effectiveness of prehospital CPAP depends upon the estimate of effectiveness. When based on a small pragmatic feasibility trial, standard oxygen therapy is cost-effective. When based on meta-analysis of heterogeneous trials, CPAP is cost-effective. Value of information analyses support commissioning of a large pragmatic effectiveness trial, providing feasibility and plausibility conditions are met.

Hürthle Cells on Fine-Needle Aspiration Cytology Are Important for Risk Assessment of Focally PET/CT FDG Avid Thyroid Nodules.

This study assesses the role of [18F] FDG PET/CT, fine needle aspiration (FNA) cytology and ultrasound in the 1-2% of patients with focally positive thyroid nodules on FDG PET/CT. All FDG PET/CT scans with focally increased thyroid FDG PET/CT uptake performed over 37 months in one institution were matched to patients undergoing thyroid FNA. Diffuse FDG PET/CT uptake patients were excluded. A total of 47 patients showed focally increased thyroid uptake. Consistent with previous studies, 18 (38.2%) patients had malignancy-12 primary thyroid carcinoma, 1 parathyroid carcinoma, 3 metastatic carcinoma to the thyroid and 2 lymphoma. A total of 15 (31.9%) lesions categorized as non-malignant contained Hürthle cells/oncocytes. A total of 14 lesions (29.8%) had focally increased FDG PET/CT uptake with no specific cytological or histopathological cause identified. No focally PET avid Hürthle cell/oncocytic lesions were found to be malignant. Exclusion of oncocytic lesions increased the calculated risk of malignancy (ROM) of focally PET avid nodules from 38% to 68%. It may be useful to exclude focally FDG PET/CT avid Hürthle cell/oncocytic lesions, typically reported as follicular neoplasm or suspicious for a follicular neoplasm, Hürthle cell type (Oncocytic) type, RCPath Thy 3F: Bethesda IV or sometimes Thy 3a: Bethesda III FNAs) from ROM calculations. Oncocytic focally PET/CT FDG avid lesions appear of comparatively lower risk of malignancy and require investigation or operation but these lesions should be readily identified by FNA cytology on diagnostic work up of focally PET avid thyroid nodules.

Cost-effectiveness analysis of endocrine therapy alone versus partial-breast irradiation alone versus combined treatment for low-risk hormone-positive early-stage breast cancer in women aged 70 years or older.

PURPOSE: We performed a cost-effectiveness analysis of three strategies for the adjuvant treatment of early breast cancer in women age 70 years or older: an aromatase inhibitor (AI-alone) for 5 years, a 5-fraction course of accelerated partial-breast irradiation using intensity-modulated radiation therapy (APBI-alone), or their combination. METHODS: We constructed a patient-level Markov microsimulation from the societal perspective. Effectiveness data (local recurrence, distant metastases, survival), and toxicity data were obtained from randomized trials when possible. Costs of side effects were included. Costs were adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALY) were calculated using utilities extracted from the literature. RESULTS: The strategy of AI-alone ($12,637) was cheaper than both APBI-alone ($13,799) and combination therapy ($18,012) in the base case. All approaches resulted in similar QALY outcomes (AI-alone 7.775; APBI-alone 7.768; combination 7.807). In the base case, AI-alone was the cost-effective strategy and dominated APBI-alone, while combined therapy was not cost-effective when compared to AI-alone ($171,451/QALY) or APBI-alone ($107,932/QALY). In probabilistic sensitivity analyses, AI-alone was cost-effective at $100,000/QALY in 50% of trials, APBI-alone in 28% and the combination in 22%. Scenario analysis demonstrated that APBI-alone was more effective than AI-alone when AI compliance was lower than 26% at 5 years. CONCLUSIONS: Based on a Markov microsimulation analysis, both AI-alone and APBI-alone are appropriate options for patients 70 years or older with early breast cancer with small cost differences noted. A prospective trial comparing the approaches is warranted.

The diagnostic accuracy of pre-hospital assessment of acute respiratory failure.

INTRODUCTION: Acute respiratory failure (ARF) is a common medical emergency. Pre-hospital management includes controlled oxygen therapy, supplemented by specific management options directed at the underlying disease. The aim of the current study was to characterise the accuracy of paramedic diagnostic assessment in acute respiratory failure. METHODS: A nested diagnostic accuracy and agreement study comparing pre-hospital clinical impression to the final hospital discharge diagnosis was conducted as part of the ACUTE (Ambulance CPAP: Use, Treatment effect and Economics) trial. Adults with suspected ARF were recruited from the UK West Midlands Ambulance Service. The pre-hospital clinical impression of the recruiting ambulance service clinician was prospectively recorded and compared to the final hospital diagnosis at 30 days. Agreement between pre-hospital and hospital diagnostic assessments was evaluated using raw agreement and Gwets AC1 coefficient. RESULTS: 77 participants were included. Chronic obstructive pulmonary disease (32.9%) and lower respiratory tract infection (32.9%) were the most frequently suspected primary pre-hospital diagnoses for ARF, with secondary contributory conditions recorded in 36 patients (46.8%). There was moderate agreement between the primary pre-hospital and hospital diagnoses, with raw agreement of 58.5% and a Gwets AC1 coefficient of 0.56 (95% CI 0.43 to 0.69). In five cases, a non-respiratory final diagnosis was present, including: myocardial infarction, ruptured abdominal aortic aneurysm, liver failure and sepsis. CONCLUSIONS: Pre-hospital assessment of ARF is challenging, with limited accuracy compared to the final hospital diagnosis. A syndromic approach, providing general supportive care, rather than a specifically disease-orientated treatment strategy, is likely to be most appropriate for the pre-hospital environment.

Radiation Therapy Without Hormone Therapy for Women Age 70 or Above with Low-Risk Early Breast Cancer: A Microsimulation.

PURPOSE: Hormone therapy without radiation therapy is considered appropriate for women age 70 or above with low-risk, hormone-positive breast cancer after partial mastectomy. However, some patients may prefer radiation without hormone therapy, for which there is minimal modern data. We modeled the comparative efficacy of aromatase inhibition alone without radiation versus radiation alone without hormone therapy. METHODS AND MATERIALS: We constructed a patient-level Markov model and compared 5 years of anastrozole to a 15-fraction course of radiation without boost or anastrozole. The relative effectiveness between treatments was based on the National Surgical Adjuvant Breast and Bowel Project B-21 trial, which was further adjusted such that the endocrine-alone arm matched the Cancer and Leukemia Group B 9343 and PRIME II trials. Common or severe side effects were considered. Eight survival metrics were assessed and validated against clinical trial data. The cost-efficacy of each strategy was considered using the quality-adjusted life year and incremental cost-effectiveness ratio (ICER). RESULTS: The model's predicted outcomes matched those demonstrated by modern trials. Aromatase inhibitors were superior in preventing contralateral cancers, with a small impact on the risk of distant metastatic disease. Radiation was superior in preventing ipsilateral breast tumor recurrence with a small impact on regional failure. No clinically significant differences were seen in the other 4 oncologic endpoints. Differences in quality-adjusted life years were small, but radiation therapy was $3809 more expensive over the average lifetime. The ICER suggested anastrozole was cost-effective in 62% of probabilistic simulations. However, the ICER was unstable owing to a denominator that approached zero. CONCLUSIONS: Women age 70 or above with low-risk early breast cancer who are reluctant or unable to pursue adjuvant aromatase inhibition can safely pursue adjuvant radiation alone with limited differences in outcome and a modest increase in costs.

Clinical Factors Associated With Cost in Head and Neck Cancer: Implications for a Bundled Payment Model.

PURPOSE: To determine which factors influence cost in head and neck cancer (HNC) to inform the development of a bundled payment model (BPM). METHODS: Patients with stages 0 to IVB (by American Joint Commission on Cancer, 7th edition) HNC of various sites and histology treated definitively at a single tertiary care center during 2013 were included. Clinical variables and direct cost data were obtained, and their associations were investigated using χ2, t, Wilcoxon rank sum, and analysis of variance testing. Results were used to develop a BPM. RESULTS: One hundred fifty patients were included; 87% were white, 74% were men, 48% had oropharyngeal cancer, and 58% had stage IVA disease. Treatment consisted of surgery alone (17%), radiation alone (11%), surgery plus radiation (14%), chemoradiation (45%), and surgery plus chemoradiation (13%). On multivariable analysis, both increasing group stage and number of treatment modalities used were significantly associated with higher cost. Given that stage often dictates treatment, we developed three cost tiers that were based on overall treatment modality. Tier A, the least costly, consisted of single-modality therapy with either surgery alone or radiation alone (median cost divided by the median overall cost of treatment, 0.54; 25th to 75th percentile range, 0.29 to 1.02), followed by tier B, which consisted of bimodality therapy with either chemoradiation or surgery plus radiation (1.03; range, 0.81 to 1.35), followed by tier C, which consisted of trimodality therapy with surgery plus chemoradiation (1.43; range, 1.10 to 1.96). CONCLUSION: The number of treatment modalities required is the primary driver of cost in HNC. These data can simplify development of a comprehensive HNC BPM.

Cost and Cost-Effectiveness of Image Guided Partial Breast Irradiation in Comparison to Hypofractionated Whole Breast Irradiation.

PURPOSE: Hypofractionated whole breast irradiation (HWBI) and accelerated partial breast irradiation (APBI) represent two adjuvant radiation therapy options after breast-conserving surgery. We performed a cost and cost-effectiveness analysis of an external beam image guided APBI technique compared with HWBI. METHODS AND MATERIALS: HWBI was defined as 40 Gy in 15 fractions to the whole breast with or without a 10-Gy/5-fraction boost. APBI was 30 Gy in 5 fractions per Livi et al and was evaluated as both intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy. The decision analytical model measured effectiveness in quality-adjusted life years. Micro-costing was conducted to estimate the true cost of the different treatment regimens, and incremental cost-effectiveness analysis was performed. RESULTS: Based on micro-costing, the cost of HWBI was $4551 with boost and $3666 without boost, compared with $2966 for APBI. Including indirect costs, HWBI with boost cost $6160, HWBI without boost cost $4940, and APBI cost $3569. Cost savings for APBI compared with HWBI with and without boost was $1585 and $700 based on direct costs and $2591 and $1371 including indirect costs. APBI was also more effective, at 0.2300 quality-adjusted life years compared with 0.2289 for HWBI with or without boost. Thus, APBI was both less costly and more effective. Basing cost on Medicare reimbursement (IMRT) leads to APBI again dominating HWBI, but basing cost for APBI on reimbursement billed as stereotactic body radiation therapy leads to HWBI being far more cost-effective. CONCLUSIONS: Image guided partial breast irradiation is less costly to deliver and has slightly improved efficacy compared with HWBI, with or without a boost. IMRT APBI should be considered a standard-of-care option in appropriately selected patients based on efficacy and value.

The ACUTE (Ambulance CPAP: Use, Treatment effect and economics) feasibility study: a pilot randomised controlled trial of prehospital CPAP for acute respiratory failure.

BACKGROUND: Acute respiratory failure (ARF) is a common and life-threatening medical emergency. Standard prehospital management involves controlled oxygen therapy and disease-specific ancillary treatments. Continuous positive airway pressure (CPAP) is a potentially beneficial alternative treatment that could be delivered by emergency medical services. However, it is uncertain whether this treatment could work effectively in United Kingdom National Health Service (NHS) ambulance services and if it represents value for money. METHODS: An individual patient randomised controlled external pilot trial will be conducted comparing prehospital CPAP to standard oxygen therapy for ARF. Adults presenting to ambulance service clinicians will be eligible if they have respiratory distress with peripheral oxygen saturation below British Thoracic Society (BTS) target levels, despite titrated supplemental oxygen. Enrolled patients will be allocated (1:1 simple randomisation) to prehospital CPAP (O_two system) or standard oxygen therapy using identical sealed boxes. Feasibility outcomes will include incidence of recruited eligible patients, number of erroneously recruited patients and proportion of cases adhering to allocation schedule and treatment, followed up at 30 days and with complete data collection. Effectiveness outcomes will comprise survival at 30 days (definitive trial primary end point), endotracheal intubation, admission to critical care, length of hospital stay, visual analogue scale (VAS) dyspnoea score, EQ-5D-5L and health care resource use at 30 days. The cost-effectiveness of CPAP, and of conducting a definitive trial, will be evaluated by updating an existing economic model. The trial aims to recruit 120 patients over 12 months from four regional ambulance hubs within the West Midlands Ambulance Service (WMAS). This sample size will allow estimation of feasibility outcomes with a precision of < 5%. Feasibility and effectiveness outcomes will be reported descriptively for the whole trial population, and each trial arm, together with their 95% confidence intervals. DISCUSSION: This study will determine if it is feasible, acceptable and cost-effective to undertake a full-scale trial comparing CPAP and standard oxygen treatment, delivered by ambulance service clinicians for ARF. This will inform NHS practice and prevent inappropriate prehospital CPAP adoption on the basis of limited evidence and at a potentially substantial cost. TRIAL REGISTRATION: ISRCTN12048261. Registered on 30 August 2017. http://www.isrctn.com/ISRCTN12048261.

Cost-effectiveness of nivolumab for recurrent or metastatic head and neck cancer☆.

OBJECTIVE: Nivolumab is the first drug to demonstrate a survival benefit for platinum-refractory recurrent or metastatic head and neck cancer. We performed a cost-utility analysis to assess the economic value of nivolumab as compared to alternative standard agents in this context. MATERIALS AND METHODS: Using data from the CheckMate 141 trial, we constructed a Markov simulation model from the US payer's perspective to evaluate the cost-effectiveness of nivolumab compared to physician choice of either cetuximab, methotrexate or docetaxel. Alternative strategies considered included: single-agent cetuximab, methotrexate or docetaxel, or first testing for PD-L1 to select for nivolumab. Costs were extracted from Medicare and utilities from the literature and CheckMate. Probabilistic sensitivity analysis (PSA) was used to evaluate parameter uncertainty. $100,000/QALY was the primary threshold for cost-effectiveness. RESULTS: When comparing nivolumab to the standard arm of CheckMate, nivolumab demonstrated an incremental cost-effectiveness ratio (ICER) of $140,672/QALY. When comparing standard therapies, methotrexate was the most cost-effective with similar results for docetaxel. Nivolumab was cost-effective compared to single-agent cetuximab (ICER $89,786/QALY). Treatment selection by PD-L1 immunohistochemistry did not markedly improve the cost-effectiveness of nivolumab. Factors likely to positively impact the cost-effectiveness of nivolumab include better baseline quality-of-life, poor tolerability of standard treatments and/or a lower cost of nivolumab. CONCLUSIONS: Nivolumab is preferred to single-agent cetuximab but requires a willingness-to-pay of at least $150,000/QALY to be considered cost-effective when compared to docetaxel or methotrexate. Selection by PD-L1 does not markedly improve the cost-effectiveness of nivolumab. This informs patient selection and clinical care-path development.

2013-2014 National Health Law Moot Court Competition Best Brief.

This document was judged Best Brief submitted to the 2013­2014 National Health Law Moot Court Competition. The brief was submitted by students Jessica Robinson DeShon, Brandon Jackson, and Matthew Ward on behalf of Faulkner University School of Law in Montgomery, Alabama. Address correspondence to Professor Joe Lester at Jlester@Faulkner.edu.