Exploring Heterogeneity in Cost-Effectiveness Using Machine Learning Methods: A Case Study Using the FIRST-ABC Trial.

OBJECTIVE: The aim of this study was to explore heterogeneity in the cost-effectiveness of high-flow nasal cannula (HFNC) therapy compared with continuous positive airway pressure (CPAP) in children following extubation. DESIGN: Using data from the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) trial, we explore heterogeneity at the individual and subgroup levels using a causal forest approach, alongside a seemingly unrelated regression (SUR) approach for comparison. SETTINGS: FIRST-ABC is a noninferiority randomized controlled trial (ISRCTN60048867) including children in UK paediatric intensive care units, which compared HFNC with CPAP as the first-line mode of noninvasive respiratory support. PATIENTS: In the step-down FIRST-ABC, 600 children clinically assessed to require noninvasive respiratory support were randomly assigned to HFNC and CPAP groups with 1:1 treatment allocation ratio. In this analysis, 118 patients were excluded because they did not consent to accessing their medical records, did not consent to follow-up questionnaire or did not receive respiratory support. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study is the incremental net monetary benefit (INB) of HFNC compared with CPAP using a willingness-to-pay threshold of £20,000 per QALY gain. INB is calculated based on total costs and quality adjusted life years (QALYs) at 6 months. The findings suggest modest heterogeneity in cost-effectiveness of HFNC compared with CPAP at the subgroup level, while greater heterogeneity is detected at the individual level. CONCLUSIONS: The estimated overall INB of HFNC is smaller than the INB for patients with better baseline status suggesting that HFNC can be more cost-effective among less severely ill patients.

Cost-effectiveness of nasal high-flow in children with acute hypoxaemic respiratory failure.

AIM: A pilot randomised controlled trial assessed the early application of nasal high-flow (NHF) therapy compared with standard oxygen therapy (SOT), in children aged 0 to 16 years presenting to paediatric emergency departments with acute hypoxaemic respiratory failure (AHRF). The study estimated the need to escalate therapy and hospital length of stay in the NHF group compared with SOT. This sub-study then assessed the subsequent cost-effectiveness. METHODS: A decision tree-based model was developed, alongside the clinical study, to estimate cost-effectiveness, from the healthcare sector perspective. The primary health economics outcome is measured as incremental cost per length of hospital stay avoided. Incremental cost effectiveness ratios (ICER) measuring change in cost per change in length of stay, were obtained for four samples, depending on responder status and obstructive airways disease. These were (1) obstructive and responder, (2) non-obstructive and responder, (3) obstructive and non-responder and (4) non obstructive and non-responder. Bootstrapping of parameters accounted for uncertainty in estimates of cost and outcome. RESULTS: The ICER for patients randomised to NHF, indicated an additional A$367.20 for a lower hospital length of stay (in days) in the non-obstructive/non-responder sample. In the bootstrap sample, this was found to be cost effective above a willingness to pay threshold of A$10 000. The ICER was A$440.86 in the obstructive/responder sample and A$469.56 in the non-obstructive/responder sample - but both resulted in a longer length of stay. The ICER in the obstructive/non-responder sample was A$52 167.76, also with a longer length of stay, mainly impacted by a small sample of severe cases. CONCLUSION: As first-line treatment, NHF is unlikely to be cost-effective compared with SOT, but for non-obstructive patients who required escalation in care (non-obstructive non-responder), NHF is likely to be cost-effective if willingness-to-pay per reduced hospital length of stay is more than A$10 000 per patient.

Oxigenoterapia domiciliar prolongada em crianças e adolescentes: uma análise do uso clínico e de custos de um programa assistencial / Long-term home oxygen therapy in children and adolescents: analysis of clinical use and costs of a home care program

OBJETIVOS: Descrever as características clínicas e laboratoriais dos pacientes em oxigenoterapia domiciliar prolongada acompanhados pelo programa de atendimento domiciliar do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, durante um período de 8 anos, e comparar os grupos com e sem hipertensão pulmonar secundária. Estimar o custo do programa utilizando concentradores versus cilindros de oxigênio arcados pela instituição. MÉTODOS: Estudo descritivo retrospectivo e de coorte dos pacientes em oxigenoterapia domiciliar prolongada, em seguimento no período de 2002 a 2009, na Unidade de Pneumologia do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTADOS: Foram estudados 165 pacientes, 53 por cento do sexo masculino, com as medianas: idade de início da oxigenoterapia - 3,6 anos; tempo de oxigenoterapia - 7 anos; e tempo de sobrevida após início da oxigenoterapia - 3,4 anos. Os principais diagnósticos foram: fibrose cística (22 por cento), displasia broncopulmonar (19 por cento) e bronquiolite obliterante (15 por cento). Dos 33 pacientes que realizaram espirometria, 70 por cento apresentavam distúrbio ventilatório obstrutivo grave. O exame ecocardiográfico foi executado em 134 pacientes; 51 por cento deles tinham hipertensão pulmonar secundária. Houve associação estatisticamente significante entre: presença de hipertensão pulmonar e necessidade de maiores fluxos de oxigênio (qui-quadrado, p = 0,011); e presença de hipertensão pulmonar e maior tempo de oxigenoterapia (Logrank, p = 0,0001). Não houve diferença estatisticamente significante entre tempo de sobrevida após início da oxigenoterapia e presença de hipertensão pulmonar. Os custos médios mensais do programa foram: US$ 7.392,93 para os concentradores e US$ 16.630,92 para cilindros. CONCLUSÕES: A oxigenoterapia domiciliar prolongada foi empregada em distintas doenças crônicas, predominantemente em lactentes e pré-escolares. Houve alta frequência de hipertensão pulmonar associada a maiores períodos de uso e fluxos de oxigênio, sem associação à sobrevida. A substituição dos cilindros por concentradores poderá reduzir custos significativamente.

OBJECTIVES: To describe the clinical and laboratory characteristics of patients on long-term home oxygen therapy followed up by the home care program of Hospital das Clínicas, School of Medicine, Universidade de São Paulo, during a period of 8 years; to compare groups with and without secondary pulmonary hypertension; and to estimate the cost of the program using oxygen concentrators versus oxygen cylinders provided by the hospital. METHODS: A descriptive, retrospective cohort study of patients on long-term home oxygen therapy followed up from 2002 to 2009 at the Unit of Pulmonology, Children's Institute, Hospital das Clínicas, School of Medicine, Universidade de São Paulo. RESULTS: We studied 165 patients, of whom 53 percent were male, with the following medians: age at the beginning of oxygen therapy - 3.6 years; duration of oxygen therapy - 7 years; and survival time after beginning of oxygen therapy - 3.4 years. The main diagnoses were: cystic fibrosis (22 percent), bronchopulmonary dysplasia (19 percent), and bronchiolitis obliterans (15 percent). Of the 33 patients who underwent spirometry, 70 percent had severe obstructive lung disease. Echocardiogram was performed in 134 patients; 51 percent of them had secondary pulmonary hypertension. There was a statistically significant association between pulmonary hypertension and need of higher oxygen flows (chi-square, p = 0.011), and between pulmonary hypertension and longer duration of oxygen therapy (Logrank, p = 0.0001). There was no statistically significant difference between survival time after the beginning of oxygen therapy and pulmonary hypertension. The average monthly costs of the program were US$ 7,392.93 for concentrators and US$ 16,630.92 for cylinders. CONCLUSIONS: Long-term home oxygen therapy was used to treat different chronic diseases, predominantly in infants and preschool children. There was a high frequency of pulmonary hypertension associated with longer periods of oxygen use and greater oxygen flow, without association with survival rate. The use of concentrators instead of cylinders may reduce costs significantly.

Oxigenoterapia en vuelos nacionales e internacionales en la Argentina / Oxygen therapy during Argentine-based national and international flights

No existe estudio que evalúe el estado de la oxigenoterapia en vuelo (OV) en nuestro país. El objetivo de este estudio fue evaluar los requisitos, dificultades, sistemas y costos de la OV de las companías aéreas nacionales (N) e internacionales (I) que operan desde Buenos Aires. Se utilizó la misma encuesta telefónica y metodología que el estudio de Stoller y col.12. Los autores se comunicaron telefónicamente con 25 aerolíneas que operaban en los dos aeropuertos de Buenos Aires en julio de 2007, y se interrogó sobre los requisitos necesarios para viajar, sistemas y costos. Se usaron técnicas estadísticas convencionales siendo significativa p<0.05. De 25 aerolíneas, se descartaron seis (24%) por falta de información (60% de las N y 16% de las I). El 100% de las N permitían la OV vs. 80% de las I (p<0.05). El 100% de las N y 94% de las I exigían certificado médico (p=NS). El 71% de las N requerían de aviso previo vs. 100% de las I (p<0.05). El 50% de las N proveían interfases de administración de oxígeno vs. 87% de las I (p=NS). El 100% de las N disponían del oxígeno sin cargo, vs. 50% de las I (p=NS). El costo oscilaba entre 70 a 300 dólares por escala. En conclusión, se observó una marcada dificultad en la provisión de información de las compañías aéreas, y restricciones de su uso. El costo es muy variable y se da principalmente en las compañías aéreas I. Consideramos necesario implementar acciones que faciliten el acceso de los pacientes y médicos a la información pertinente de cada compañía aérea sobre OV.

There are no data about supplemental oxygen in flight in our country. The objective of our study was to evaluate arranging in-flight-oxygen required by a simulated traveler, system of administration and costs, and to compare the results between Argentine-based (A) and international (I) airlines. The questionnaire used was similar to that of Stoller et al12. Data collection consisted of telephone calls placed by one of the authors to all commercial air carriers listed in our two Buenos Aires City airports during July 2007. A structured interview with questions was addressed on issues that an oxygen-using air traveler would need to arrange in-flight oxygen. Of the 25 airlines, 6 were discarded because of lack of information (24%, three A -60%-and one I-16%-). All A allowed in-flightoxygen vs. 80% of I (p<0.05), 100% of A and 94% of I required a medical certificate (p=NS); 71% of A and 100% of I required previous notification (p<0.05); 50% of A and 87% of I provided patient interphases of oxygen administration (p=NS). Free of charge oxygen could be provided by 100% of A and 50% of I, with airline charge between 70 to 300 dollars. In conclusion, we observed different policies, rules, availability, and a pronounced lack of standardization of airline information. The cost of oxygen was very different between airlines and it was superior on I. It will be necessary to carry out actions to facilitate patient access to oxygentherapy and to standardize medical information among airlines in our country.

Estudio comparativo de costos anuales en salud entre usuarios de oxígeno domiciliario y pacientes en lista de espera / Comparative study of health care costs for patients using home oxygen therapy or those in waiting lists

Background: Home oxygen therapy is the only intervention that significantly prolongs survival of patients with chronic obstructive pulmonary disease. Since this therapy is expensive, it is imperative to calculate its cost-benefit ratio. Aim: To compare health care costs for patients in a home oxygen therapy program, with those of a similar group of patients in a waiting list for this therapy. Material and methods: A retrospective analysis of 21 patients on home oxygen therapy for 36 months or less and a group of 13 patients in the waiting list during a similar lapse. Medical consultations, drugs delivered and the cost of oxygen therapy were considered among ambulatory costs. Hospitalization costs included the number of days on regular or intermediary care beds, laboratory tests and drugs delivered. Results: The annual health care costs for patients on home oxygen therapy were 709,656 Chilean pesos and the costs for patients in the waiting list were 797,320 Chilean pesos. Conclusions: The overall health care costs of home oxygen therapy are similar to the costs required by patients with chronic obstructive pulmonary disease remaining in waiting lists

Oxigenoterapia domiciliaria en niños con insuficiencia respiratoria crónica / Home oxygen therapy in children with chronic respiratory failure

Background: Home oxygen therapy improves survival and quality of the life in adults with chronic obstructive airwais disease. The few studies about home oxigen therapy in children show improvements in weight gain, school performance and decreasesin hospitalization expenses. Aim: To report our experience in home oxygen therapy in children followed for six month to four years. Patients and methods: Fifty five children, less than 15 years old, discharged from a University hospital with the diagnosis of chronic respiratory failure, were followed for up at their homes. Results: Dicharge diagnoses were bronchopulmonary dysplasia in 36 percent of children, postinfectious pulmonary damage in 22 percent, neonatal distress in 13 percent, chronic aspiration in 9 percent, cystic fibrosis in 7 percent and miscellaneous in 13 percent. Forty six completed at least 6 months of follow up, five moved to other hospitals, three required ventilatory support and one died. Oxygen was discontinued in 33 patients, and this occurred before the ninth month of follow up in 88percent of those children. Neonatal distress and bronchopulmonary dysplasia had the best prognoses, and oxygen was discontinued at 4ñ1 and 5.7ñ3 months respectively. Patients with postinfectious pulmonary disease had a higher incidence of bronchoneumoniae, and those with bronchopulmonary dysplasia a higher incidence of acute bronchiolitis, that motivated hospital admissions. Expenses due to home oxygen were lower than hospitalization costs. No adverse effects were detected. Conclusions: Infants and newborns on home oxygen therapy have a good prognosis, specially those with reversible diseases. this type of therapy allows an earlier hospital discharge with considerable cost reductions

Doença pulmonar obstrutiva crônica: estudo de 50 casos internados, com ênfase no custo / Chronic obstructive pulmonary disease: study of fifty inpatient cases, with emphasis in the cost

Os autores estudaram 50 pacientes com doença pulmonar obstrutiva crônica, internados com insuficiência respiratória no Hospital dos Servidores do Estado - RJ. A idade média foi de 63,9 anos (38 a 96 anos), sendo 32 homens (64 por cento) e 18 mulheres (36 por cento). Os sintomas mais freqüentes foram dispnéia (96 por cento), tosse e expectoraçao (92 por cento) e dor torácica (32 por cento). As causas mais freqüentes de descompensaçao foram infecçao respiratória, insuficiência ventricular esquerda e trombembolismo pulmonar. Os autores ressaltam o alto custo representado pela internaçao, já que estes pacientes ficam em média 20 dias na enfermaria. No CTI sao internados 18,3 por cento dos pacientes, com permanência média de 12 dias.