Recommendations for studying the association of the cancer diagnosis to treatment interval with overall survival: a modified Delphi process.

Background: The duration from diagnosis to primary treatment initiation (DTI) is an important interval for patients with cancer, as delayed treatment has been found to be associated with heightened recurrence rates and worsened survival. Studying the association between DTI duration and overall survival (OS) is biased and confounded by clinical triaging, heterogeneous definitions, and variation in analytic approaches.

Objective: To develop consensus-based guidance for conducting studies investigating the association of DTI duration and OS.

Instrumental variable approaches for estimating time-varying treatment effects in comparative effectiveness research.

Background: The increased availability of large-scale longitudinal data offers important opportunities to assess the causal effects of health interventions. In this setting, Instrumental Variable (IV) approaches have the potential to reduce the risk of bias from confounding due to unmeasured variables. However, there has been a lack of attention given to the development of IV approaches in settings when both the instrument and the potential confounders vary over time.

An Assessment of the Maturity of Cancer Survival Data Used in Economic Models for the National Institute for Health and Care Excellence's Single Technology Appraisals.

Objectives: This study examines the maturity of survival data used in cancer drug appraisals by the National Institute for Health and Care Excellence (NICE) and the implications for decision making.

Methods: We assessed the maturity of survival data used in economic models within NICE single technology appraisals published between January 1, 2011 and December 31, 2023 (n = 301). We categorized these survival data according to whether they were "highly immature" (<20% of events), "immature" (20%-50%), or "mature" (>50%).

Surgery or radiotherapy for early-stage cancer study (SORT) target trial protocol: stereotactic ablative radiotherapy (SABR) with curative intent versus surgical resection for early-stage non-small cell lung cancer (NSCLC).

Introduction: Randomised controlled trials have aimed to assess the effectiveness of stereotactic ablative radiotherapy (SABR) with curative intent versus surgical resection for individuals diagnosed with early-stage non-small cell lung cancer (NSCLC) but have failed to recruit sufficient numbers of patients. Non-randomised studies for early-stage NSCLC have reported mixed outcomes following curative SABR versus surgical resection, but did not fully address confounding by indication. The Surgery Or RadioTherapy for early-stage cancer study (SORT) will assess the comparative effectiveness of SABR with curative intent versus surgical resection for NSCLC with a target trial emulation approach, as this can reduce biases in observational studies that aim to estimate the causal effect of interventions.

Comparative effectiveness of alternative second-line oral glucose-lowering therapies for type 2 diabetes: a precision medicine approach applied to routine data.

Aims/hypothesis: National clinical guidelines recommend that second-line treatment for type 2 diabetes mellitus is chosen according to individuals' characteristics but there is limited evidence available to inform this choice. This paper's aim is to compare the effects on HbA of sulfonylureas (SU), dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose cotransporter-2 inhibitors (SGLT2i) added to metformin as second-line oral glucose-lowering treatments according to an individual's age, baseline HbA and presence of multiple long-term conditions (MLTCs).

Methods: We accessed primary care-hospital linked data for 41,790 individuals from the Clinical Practice Research Datalink (CPRD) in England who initiated second-line treatment after metformin between 2015 and 2021.

Long-term outcomes following alternative second-line oral glucose-lowering treatments: Results from the real-world progression in type 2 diabetes mellitus United Kingdom (RAPIDS-UK) model.

Aims: To compare long-term complications for people with type 2 diabetes mellitus (T2DM) following second-line treatment in routine practice with sulphonylureas (SU), dipeptidyl peptidase-4 inhibitors (DPP4i), or sodium-glucose co-transporter-2 inhibitors (SGLT2i) added to metformin.

Materials And Methods: We used the RAPIDS microsimulation model to predict diabetes complications over 5 years after second-line treatment initiation. We combined information on 'real-world' treatment duration in England from the Clinical Practice Research Datalink with evidence on treatment effectiveness from Randomised Controlled Trials (RCTs).

Variation in acute myocardial infarction management by kidney function across hospitals in England: a cross-sectional study using the Myocardial Ischaemia National Audit Project (MINAP).

Objectives: We hypothesised that there is substantial variation in acute myocardial infarction (AMI) treatment across English hospitals, particularly for people hospitalised for non-ST-elevation myocardial infarction (NSTEMI) and with reduced kidney function. This study aimed to describe this variation at the hospital and the individual level to understand treatment variation and potential disparities in AMI management among people with reduced kidney function.

Design: Cross-sectional study.

High-flow nasal cannula therapy versus continuous positive airway pressure for non-invasive respiratory support in paediatric critical care: the FIRST-ABC RCTs.

Background: Despite the increasing use of non-invasive respiratory support in paediatric intensive care units, there are no large randomised controlled trials comparing two commonly used non-invasive respiratory support modes, continuous positive airway pressure and high-flow nasal cannula therapy.

Objective: To evaluate the non-inferiority of high-flow nasal cannula, compared with continuous positive airway pressure, when used as the first-line mode of non-invasive respiratory support in acutely ill children and following extubation, on time to liberation from respiratory support, defined as the start of a 48-hour period during which the child was free of respiratory support (non-invasive and invasive).

Design: A master protocol comprising two pragmatic, multicentre, parallel-group, non-inferiority randomised controlled trials (step-up and step-down) with shared infrastructure, including internal pilot and integrated health economic evaluation.

So Many Choices: A Guide to Selecting Among Methods to Adjust for Observed Confounders.

Non-randomised studies (NRS) typically assume that there are no differences in unobserved baseline characteristics between the treatment groups under comparison. Traditionally regression models have been deployed to estimate treatment effects adjusting for observed confounders but can lead to biased estimates if the model is missspecified, by making incorrect functional form assumptions. A multitude of alternative methods have been developed which can reduce the risk of bias due to model misspecification.

Study protocol: Comparison of different risk prediction modelling approaches for COVID-19 related death using the OpenSAFELY platform.

On March 11th 2020, the World Health Organization characterised COVID-19 as a pandemic. Responses to containing the spread of the virus have relied heavily on policies involving restricting contact between people. Evolving policies regarding shielding and individual choices about restricting social contact will rely heavily on perceived risk of poor outcomes from COVID-19.

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.