Measuring the Performance of Survival Models to Personalize Treatment Choices.

Various statistical and machine learning algorithms can be used to predict treatment effects at the patient level using data from randomized clinical trials (RCTs). Such predictions can facilitate individualized treatment decisions. Recently, a range of methods and metrics were developed for assessing the accuracy of such predictions.

Effectiveness and safety of shortened intensive treatment for children with tuberculous meningitis (SURE): a protocol for a phase 3 randomised controlled trial evaluating 6 months of antituberculosis therapy and 8 weeks of aspirin in Asian and African children with tuberculous meningitis.

Introduction: Childhood tuberculous meningitis (TBM) is a devastating disease. The long-standing WHO recommendation for treatment is 2 months of intensive phase with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), followed by 10 months of isoniazid and rifampicin. In 2022, WHO released a conditional recommendation that 6 months of intensified antituberculosis therapy (ATT) could be used as an alternative for drug-susceptible TBM.

Treatment outcomes in people with diabetes and multidrug-resistant tuberculosis (MDR TB) enrolled in the STREAM clinical trial.

There is limited evidence on the effect of DM co-morbidity in those undergoing treatment for MDR-TB. We report post-hoc analyses of participants from the STREAM Clinical Trial (Stage 1 and 2 combined). Participants who self-reported diabetes, had random blood glucose ≥200mg/dl at baseline, or reported taking concomitant medication for diabetes were classified as the DM group.

SARS-Cov-2 vaccination strategies in hospitalized recovered COVID-19 patients: a randomized clinical trial (VATICO Trial).

The impact on immunogenicity and efficacy of SARS-CoV-2 vaccination in people with prior COVID-19 could differ depending on timing of vaccination and number of doses. The VATICO study randomized 66 hospitalized recovered COVID-19 individuals to receive either immediate or deferred vaccination, with one or two doses of mRNA SARS-CoV-2 vaccines. We measured binding and neutralizing antibodies against SARS-CoV-2 at enrollment and longitudinally.

Risk of Bias in Network Meta-Analysis (RoB NMA) tool.

Systematic reviews with network meta-analysis (NMA) have potential biases in their conduct, analysis, and interpretation. If the results or conclusions of an NMA are integrated into policy or practice without any consideration of risks of bias, decisions could unknowingly be based on incorrect results, which could translate to poor patient outcomes. The RoB NMA (Risk of Bias in Network Meta-Analysis) tool answers a clearly defined need for a rigorously developed tool to assess risk of bias in NMAs of healthcare interventions.

Reproducibility of the Unaided Subjective Assessment of Orbital Computed X-Ray Tomographic Features in Thyroid Eye Disease.

Purpose: To assess the reproducibility of subjective interpretation of computed x-ray tomography for 8 features associated with thyroid eye disease.

Methods: Patients with confirmed thyroid eye disease had 3 distinct orbital computed x-ray tomography sections presented as anonymized montages to 3 masked observers (#1 orbital radiologist, #2 general radiologist, and #3 orbital surgeon). Eight features were graded: superior orbital fissure clarity, degree of orbital fat prolapse through the superior orbital fissure, loss of fat space at the apex, muscle enlargement, increase in orbital fat volume, vascular congestion, superior ophthalmic vein size, and lamina papyracea bowing.

A Spline-Based Approach to Smoothly Constrain Hazard Ratios With a View to Apply Treatment Effect Waning.

Objectives: To describe and assess, via simulation, a constraint-based spline approach to implement smooth hazard ratio (HR) waning in time-to-event analyses.

Methods: A common consideration when extrapolating survival functions to evaluate the long-term performance of a novel intervention is scenarios where the beneficial effect of an intervention eventually disappears (treatment effect waning). One approach to relaxing the proportional hazards assumption for a treatment effect is to model it as a function of the timescale, with a spline function offering a flexible approach.

Modelling the potential clinical and economic impact of universal antenatal hepatitis C (HCV) screening and providing treatment for pregnant women with HCV and their infants in Egypt: a cost-effectiveness study.

Backgrounds And Aims: Pregnant women and children are not included in Egypt's hepatitis C virus (HCV) elimination programmes. This study assesses the cost-effectiveness of several screening and treatment strategies for pregnant women and infants in Egypt.

Design: A Markov model was developed to simulate the cascade of care and HCV disease progression among pregnant women and their infants according to different screening and treatment strategies, which included: targeted versus universal antenatal screening; treatment of women in pregnancy or deferred till after breast feeding; treatment of infected children at 3 years vs 12 years.

Guidelines for the content of statistical analysis plans in clinical trials: protocol for an extension to cluster randomized trials.

Background: Guidance exists to inform the content of statistical analysis plans in clinical trials. Though not explicitly stated, this guidance is generally focused on clinical trials in which the randomization units are individual patients and not groups of patients. There are critical considerations for the analysis of cluster randomized trials, such as accounting for clustering, the risk of imbalances between the arms due to post-randomization recruitment, and the need to use small sample corrections when the number of clusters is small.

Mixed-methods study to develop extensions to the SPIRIT and CONSORT statements for factorial randomised trials: the Reporting Factorial Trials (RAFT) study.

Background: Extensions to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) reporting recommendations specifically for factorial trials have been developed by the Reporting Factorial Trials (RAFT) study group. This article describes the processes and methods used to develop the extensions.

Objective: To develop SPIRIT and CONSORT extensions for factorial trials.

Long-term non-progression in children with HIV: estimates from international cohort data.

Objectives: To estimate the probability of long-term nonprogression (LTNP) in the absence of antiretroviral treatment (ART) in children with perinatally acquired HIV, and the impact of LTNP definitions on these estimates.

Design: Analysis of longitudinal routine care data (follow-up to 2016) collected through a collaboration of cohorts of children in routine HIV care across Europe and Thailand.

Methods: LTNP was defined as reaching age 8 years without disease progression (defined as an AIDS diagnosis or immunosuppression based on WHO immunosuppression-for-age thresholds, age-adjusted CD4 +z -scores or CD4 + counts).

New Methods for Two-Stage Treatment Switching Estimation.

Treatment switching is common in randomized trials of oncology treatments. For example, control group patients may receive the experimental treatment as a subsequent therapy. One possible estimand is the effect of trial treatment if this type of switching had instead not occurred.

Guidance for protocol content and reporting of factorial randomised trials: explanation and elaboration of the CONSORT 2010 and SPIRIT 2013 extensions.

This report presents the explanation and elaboration paper for the CONSORT (Consolidated Standards of Reporting Trials) 2010 and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 extensions for factorial trials. Factorial trials involve randomising participants to more than one intervention, often with the aim of evaluating multiple interventions in one study or assessing whether treatments interact. The CONSORT and SPIRIT statements have been extended to allow for the unique features of the factorial design.

Comparison of standard-dose and reduced-dose treatment of metastatic prostate cancer with enzalutamide, apalutamide or darolutamide: a rapid review.

Objective: To review the efficacy and safety of low-dose versus standard-dose enzalutamide, apalutamide or darolutamide treatment for metastatic prostate cancer.

Methods And Analysis: Keyword searches in MEDLINE and EMBASE up to 1 June 2023, with forward and backward citation searches of potentially relevant studies. Studies were included if primary outcome data were reported for patients with metastatic prostate cancer who had received reduced doses of enzalutamide, apalutamide or darolutamide.

Reference-Based Multiple Imputation for Longitudinal Binary Data.

Introduction: In clinical trials, a treatment policy strategy is often used to handle treatment nonadherence. However, estimation in this context is complicated when data are missing after treatment deviation. Reference-based multiple imputation has been developed for the analysis of a longitudinal continuous outcome in this setting.

Intra-patient comparison of microarchitecture of tumour negative lymph nodes from oesophageal cancer patients - Results from the MRC Oe02 trial.

Background: Regional lymph node (LN) status is a key prognostic factor in oesophageal cancer (OeC). Tumour-derived antigens can activate immune reactions in LNs, potentially reflecting the host's anti-tumour immune response. It remains unclear whether this response is homogeneous across all tumour negative LNs (LNneg) within individual OeC patients.

Adjusting for switches to multiple treatments: Should switches be handled separately or combined?

Treatment switching is common in randomised controlled trials (RCTs). Participants may switch onto a variety of different treatments, all of which may have different treatment effects. Adjustment analyses that target hypothetical estimands - estimating outcomes that would have been observed in the absence of treatment switching - have focused primarily on a single type of switch.

Assessing Whether Providing Regular, Free HIV Self-Testing Kits Reduces the Time to HIV Diagnosis: An Internet-Based, Randomized Controlled Trial in Men Who Have Sex With Men.

Background: The risk of onward HIV transmission is strongly influenced by the interval between HIV infection and its diagnosis. The SELPHI trial examined whether this interval could be reduced by offering free HIV self-testing kits to men who have sex with men (MSM).

Setting: Internet-based RCT of MSM aged ≥16 years, resident in England/Wales, recruited through sexual and social networking sites.

Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS.

Background: The ovarian cancer (OC) preclinical detectable phase (PCDP), defined as the interval during which cancer is detectable prior to clinical diagnosis, remains poorly characterised. We report exploratory analyses from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Methods: In UKCTOCS between Apr-2001 and Sep-2005, 101,314 postmenopausal women were randomised to no screening (NS) and 50,625 to annual multimodal screening (MMS) (until Dec-2011) using serum CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA).

Prioritizing attributes of approaches to analyzing patient-centered outcomes that are truncated due to death in critical care clinical trials: a Delphi study.

Background: A key challenge for many critical care clinical trials is that some patients will die before their outcome is fully measured. This is referred to as "truncation due to death" and must be accounted for in both the treatment effect definition (i.e.

Developing a knowledge transfer and exchange strategy for a clinical trials unit.

Need For A Strategic Approach To Knowledge Transfer And Exchange: Late-phase clinical trials and systematic reviews find results that have the potential to improve health outcomes for people. However, there are often delays in these results influencing clinical practice. We developed a knowledge transfer and exchange strategy to support research teams, aiming to identify activities along the research process to maximise and accelerate the research impact.

Central statistical monitoring in clinical trial management: A scoping review.

Background: Clinical trials handle a huge amount of data which can be used during the trial to improve the ongoing study conduct. It is suggested by regulators to implement the remote approach to evaluate clinical trials by analysing collected data. Central statistical monitoring helps to achieve that by employing quantitative methods, the results of which are a basis for decision-making on quality issues.

Re-analysis of data from cluster randomised trials to explore the impact of model choice on estimates of odds ratios: study protocol.

Background: There are numerous approaches available to analyse data from cluster randomised trials. These include cluster-level summary methods and individual-level methods accounting for clustering, such as generalised estimating equations and generalised linear mixed models. There has been much methodological work showing that estimates of treatment effects can vary depending on the choice of approach, particularly when estimating odds ratios, essentially because the different approaches target different estimands.