Cost-effectiveness of high flow nasal cannula therapy versus continuous positive airway pressure for non-invasive respiratory support in paediatric critical care.

Background: High flow nasal cannula therapy (HFNC) and continuous positive airway pressure (CPAP) are two widely used modes of non-invasive respiratory support in paediatric critical care units. The FIRST-ABC randomised controlled trials (RCTs) evaluated the clinical and cost-effectiveness of HFNC compared with CPAP in two distinct critical care populations: acutely ill children ('step-up' RCT) and extubated children ('step-down' RCT). Clinical effectiveness findings (time to liberation from all forms of respiratory support) showed that HFNC was non-inferior to CPAP in the step-up RCT, but failed to meet non-inferiority criteria in the step-down RCT.

Going beyond randomised controlled trials to assess treatment effect heterogeneity across target populations.

Methods have been developed for transporting evidence from randomised controlled trials (RCTs) to target populations. However, these approaches allow only for differences in characteristics observed in the RCT and real-world data (overt heterogeneity). These approaches do not recognise heterogeneity of treatment effects (HTE) according to unmeasured characteristics (essential heterogeneity).

Persistence and heterogeneity of the effects of educating mothers to improve child immunisation uptake: Experimental evidence from Uttar Pradesh in India.

Childhood vaccinations are among the most cost-effective health interventions. Yet, in India, where immunisation services are widely available free of charge, a substantial proportion of children remain unvaccinated. We revisit households 30 months after a randomised experiment of a health information intervention designed to educate mothers on the benefits of child vaccination in Uttar Pradesh, India.

Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data.

Objective: To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice.

Design: Cohort study emulating a comparative effectiveness trial (target trial).

Setting: Linked primary care, hospital, and death data in England, 2015-21.

Improving transportability of randomized controlled trial inference using robust prediction methods.

Randomized trials have been the gold standard for assessing causal effects since their introduction by Fisher in the 1920s, since they can eliminate both observed and unobserved confounding. Estimates of causal effects at the population level from randomized controlled trials can still be biased if there are both effect modification and systematic differences between the trial sample and the ultimate population of inference with respect to these modifiers. Recent advances in the survey statistics literature to improve inference in nonprobability samples by using information from probability samples can provide an avenue for improving population causal inference in randomized controlled trials when relevant probability samples of the patient population are available.

How does a local instrumental variable method perform across settings with instruments of differing strengths? A simulation study and an evaluation of emergency surgery.

Local instrumental variable (LIV) approaches use continuous/multi-valued instrumental variables (IV) to generate consistent estimates of average treatment effects (ATEs) and Conditional Average Treatment Effects (CATEs). There is little evidence on how LIV approaches perform according to the strength of the IV or with different sample sizes. Our simulation study examined the performance of an LIV method, and a two-stage least squares (2SLS) approach across different sample sizes and IV strengths.

The Evolving Nature of Health Technology Assessment: A Critical Appraisal of NICE's New Methods Manual.

Objectives: The National Institute for Health and Care Excellence (NICE) recently completed a review of its methods for health technology assessment, involving a 2-stage public consultation. We appraise proposed methodological changes and analyze key decisions.

Methods: We categorize all changes proposed in the first consultation as "critical," "moderate" or "limited" updates, considering the importance of the topic and the degree of change or the level of reinforcement.

Emulating Target Trials With Real-World Data to Inform Health Technology Assessment: Findings and Lessons From an Application to Emergency Surgery.

Objectives: International health technology assessment (HTA) agencies recommend that real-world data (RWD) are used in some circumstances to add to the evidence base about the effectiveness and cost-effectiveness of health interventions. The target trial framework applies the design principles of randomized-controlled trials to RWD and can help alleviate inevitable concerns about bias and design flaws with nonrandomized studies. This article aimed to tackle the lack of guidance and exemplar applications on how this methodology can be applied to RWD to inform HTA decision making.

Adapting Patient and Public Involvement processes in response to the Covid-19 pandemic.

Background: The COVID-19 pandemic brought rapid and major changes to research, and those wishing to carry out Patient and Public Involvement (PPI) activities faced challenges, such as restrictions on movement and contact, illness, bereavement and risks to potential participants. Some researchers moved PPI to online settings during this time but remote consultations raise, as well as address, a number of challenges. It is important to learn from PPI undertaken in this period as face-to-face consultation may no longer be the dominant method for PPI.

A Comparison of Ordered Categorical versus Discrete Choices within a Stated Preference Survey of Whole-Blood Donors.

This article compares the relative preferences from stated preference (SP) questions requiring ordered categorical versus discrete choice responses. The approaches were contrasted for blood donation service characteristics that offer opportunities to donate blood.The estimates of relative preferences for alternative blood donation service characteristics were similar between the 2 forms of SP approach.

Ethnic and socioeconomic disparities in initiation of second-line antidiabetic treatment for people with type 2 diabetes in England: A cross-sectional study.

Aims: To assess any disparities in the initiation of second-line antidiabetic treatments prescribed among people with type 2 diabetes mellitus (T2DM) in England according to ethnicity and social deprivation level.

Materials And Methods: This cross-sectional study used linked primary (Clinical Practice Research Datalink) and secondary care data (Hospital Episode Statistics), and the Index of Multiple Deprivation (IMD). We included people aged 18 years or older with T2DM who intensified to second-line oral antidiabetic medication between 2014 and 2020 to investigate disparities in second-line antidiabetic treatment prescribing (one of sulphonylureas [SUs], dipeptidyl peptidase-4 [DPP-4] inhibitors, or sodium-glucose cotransporter-2 [SGLT2] inhibitors, in combination with metformin) by ethnicity (White, South Asian, Black, mixed/other) and deprivation level (IMD quintiles).

Cost-effectiveness of alternative minimum recall intervals between whole blood donations.

Background: The INTERVAL trial showed shorter inter-donation intervals could safely increase the frequency of whole-blood donation. We extended the INTERVAL trial to consider the relative cost-effectiveness of reduced inter-donation intervals.

Methods: Our within-trial cost-effectiveness analysis (CEA) used data from 44,863 whole-blood donors randomly assigned to 12, 10 or 8 week (males), and 16, 14 or 12 week inter-donation intervals (females).

Impact of the first wave of COVID-19 on outcomes following emergency admissions for common acute surgical conditions: analysis of a national database in England.

Background: This study assessed the impact of the first COVID-19 wave in England on outcomes for acute appendicitis, gallstone disease, intestinal obstruction, diverticular disease, and abdominal wall hernia.

Methods: Emergency surgical admissions for patients aged 18 years and older to 124 NHS Trust hospitals between January and June in 2019 and 2020 were extracted from Hospital Episode Statistics. The risk of 90-day mortality after admission during weeks 11-19 in 2020 (national lockdown) and 2019 (pre-COVID-19) was estimated using multilevel logistic regression with case-mix adjustment.

Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Therapy on Liberation From Respiratory Support in Acutely Ill Children Admitted to Pediatric Critical Care Units: A Randomized Clinical Trial.

Importance: The optimal first-line mode of noninvasive respiratory support for acutely ill children is not known.

Objective: To evaluate the noninferiority of high-flow nasal cannula therapy (HFNC) as the first-line mode of noninvasive respiratory support for acute illness, compared with continuous positive airway pressure (CPAP), for time to liberation from all forms of respiratory support.

Design, Setting, And Participants: Pragmatic, multicenter, randomized noninferiority clinical trial conducted in 24 pediatric critical care units in the United Kingdom among 600 acutely ill children aged 0 to 15 years who were clinically assessed to require noninvasive respiratory support, recruited between August 2019 and November 2021, with last follow-up completed in March 2022.

Application of quantitative bias analysis for unmeasured confounding in cost-effectiveness modelling.

Due to uncertainty regarding the potential impact of unmeasured confounding, health technology assessment (HTA) agencies often disregard evidence from nonrandomized studies when considering new technologies. Quantitative bias analysis (QBA) methods provide a means to quantify this uncertainty but have not been widely used in the HTA setting, particularly in the context of cost-effectiveness modelling (CEM). This study demonstrated the application of an aggregate and patient-level QBA approach to quantify and adjust for unmeasured confounding in a simulated nonrandomized comparison of survival outcomes.

Unmeasured confounding in nonrandomized studies: quantitative bias analysis in health technology assessment.

Evidence generated from nonrandomized studies (NRS) is increasingly submitted to health technology assessment (HTA) agencies. Unmeasured confounding is a primary concern with this type of evidence, as it may result in biased treatment effect estimates, which has led to much criticism of NRS by HTA agencies. Quantitative bias analyses are a group of methods that have been developed in the epidemiological literature to quantify the impact of unmeasured confounding and adjust effect estimates from NRS.

Local Instrumental Variable Methods to Address Confounding and Heterogeneity when Using Electronic Health Records: An Application to Emergency Surgery.

Background: Electronic health records (EHRs) offer opportunities for comparative effectiveness research to inform decision making. However, to provide useful evidence, these studies must address confounding and treatment effect heterogeneity according to unmeasured prognostic factors. Local instrumental variable (LIV) methods can help studies address these challenges, but have yet to be applied to EHR data.

A Machine-Learning Approach for Estimating Subgroup- and Individual-Level Treatment Effects: An Illustration Using the 65 Trial.

This article examines a causal machine-learning approach, causal forests (CF), for exploring the heterogeneity of treatment effects, without prespecifying a specific functional form.The CF approach is considered in the reanalysis of the 65 Trial and was found to provide similar estimates of subgroup effects to using a fixed parametric model.The CF approach also provides estimates of individual-level treatment effects that suggest that for most patients in the 65 Trial, the intervention is expected to reduce 90-d mortality but with wide levels of statistical uncertainty.

Effect of High-Flow Nasal Cannula Therapy vs Continuous Positive Airway Pressure Following Extubation on Liberation From Respiratory Support in Critically Ill Children: A Randomized Clinical Trial.

Importance: The optimal first-line mode of noninvasive respiratory support following extubation of critically ill children is not known.

Objective: To evaluate the noninferiority of high-flow nasal cannula (HFNC) therapy as the first-line mode of noninvasive respiratory support following extubation, compared with continuous positive airway pressure (CPAP), on time to liberation from respiratory support.

Design, Setting, And Participants: This was a pragmatic, multicenter, randomized, noninferiority trial conducted at 22 pediatric intensive care units in the United Kingdom.

Target Trial Emulation for Transparent and Robust Estimation of Treatment Effects for Health Technology Assessment Using Real-World Data: Opportunities and Challenges.

Evidence about the relative effects of new treatments is typically collected in randomised controlled trials (RCTs). In many instances, evidence from RCTs falls short of the needs of health technology assessment (HTA). For example, RCTs may not be able to capture longer-term treatment effects, or include all relevant comparators and outcomes required for HTA purposes.