Radiographic Progression-Free Survival and Clinical Progression-Free Survival as Potential Surrogates for Overall Survival in Men With Metastatic Hormone-Sensitive Prostate Cancer.

Purpose: Despite major increases in the longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC), most men still die of prostate cancer. Phase III trials assessing new therapies in mHSPC with overall survival (OS) as the primary end point will take approximately a decade to complete. We investigated whether radiographic progression-free survival (rPFS) and clinical PFS (cPFS) are valid surrogates for OS in men with mHSPC and could potentially be used to expedite future phase III clinical trials.

Effects of oral anticoagulation in people with atrial fibrillation after spontaneous intracranial haemorrhage (COCROACH): prospective, individual participant data meta-analysis of randomised trials.

Background: The safety and efficacy of oral anticoagulation for prevention of major adverse cardiovascular events in people with atrial fibrillation and spontaneous intracranial haemorrhage are uncertain. We planned to estimate the effects of starting versus avoiding oral anticoagulation in people with spontaneous intracranial haemorrhage and atrial fibrillation.

Methods: In this prospective meta-analysis, we searched bibliographic databases and trial registries using the strategies of a Cochrane systematic review (CD012144) on June 23, 2023.

Use of multiple covariates in assessing treatment-effect modifiers: A methodological review of individual participant data meta-analyses.

Individual participant data (IPD) meta-analyses of randomised trials are considered a reliable way to assess participant-level treatment effect modifiers but may not make the best use of the available data. Traditionally, effect modifiers are explored one covariate at a time, which gives rise to the possibility that evidence of treatment-covariate interaction may be due to confounding from a different, related covariate. We aimed to evaluate current practice when estimating treatment-covariate interactions in IPD meta-analysis, specifically focusing on involvement of additional covariates in the models.

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

Purpose: The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups.

Patients And Methods: All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS).

Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials.

Background: Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours.

Methods: The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data.

Duplicated network meta-analysis in advanced prostate cancer: a case study and recommendations for change.

Background: Research overlap and duplication is a recognised problem in the context of both pairwise and network systematic reviews and meta-analyses. As a case study, we carried out a scoping review to identify and examine duplicated network meta-analyses (NMAs) in a specific disease setting where several novel therapies have recently emerged: hormone-sensitive metastatic prostate cancer (mHSPC).

Methods: MEDLINE and EMBASE were systematically searched, in January 2020, for indirect or mixed treatment comparisons or network meta-analyses of the systemic treatments docetaxel and abiraterone acetate in the mHSPC setting, with a time-to-event outcome reported on the hazard-ratio scale.

Using individual participant data to improve network meta-analysis projects.

A network meta-analysis combines the evidence from existing randomised trials about the comparative efficacy of multiple treatments. It allows direct and indirect evidence about each comparison to be included in the same analysis, and provides a coherent framework to compare and rank treatments. A traditional network meta-analysis uses aggregate data (eg, treatment effect estimates and standard errors) obtained from publications or trial investigators.

Estimating interactions and subgroup-specific treatment effects in meta-analysis without aggregation bias: A within-trial framework.

Estimation of within-trial interactions in meta-analysis is crucial for reliable assessment of how treatment effects vary across participant subgroups. However, current methods have various limitations. Patients, clinicians and policy-makers need reliable estimates of treatment effects within specific covariate subgroups, on relative and absolute scales, in order to target treatments appropriately-which estimation of an interaction effect does not in itself provide.

Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.

Background: A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality.

Implications of analysing time-to-event outcomes as binary in meta-analysis: empirical evidence from the Cochrane Database of Systematic Reviews.

Background: Systematic reviews and meta-analysis of time-to-event outcomes are frequently published within the Cochrane Database of Systematic Reviews (CDSR). However, these outcomes are handled differently across meta-analyses. They can be analysed on the hazard ratio (HR) scale or can be dichotomized and analysed as binary outcomes using effect measures such as odds ratios (OR) or risk ratios (RR).

Sharing individual participant data: through a systematic reviewer lens.

An increasing prevalence of data-sharing models, aimed at making individual participant data (IPD) from clinical trials widely available, should facilitate the conduct of systematic reviews and meta-analyses based on IPD. We have assessed these different data-sharing approaches, from the perspective of experienced IPD reviewers, to examine their utility for conducting systematic reviews based on IPD, and to highlight any challenges. We present an overview of the range of different models, including the traditional, single question approach, topic-based repositories, and the newer generic data platforms, and show that there are benefits and drawbacks to each.

Coenzyme Q10 to manage chronic heart failure with a reduced ejection fraction: a systematic review and economic evaluation.

Background: Chronic heart failure is a debilitating condition that accounts for an annual NHS spend of £2.3B. Low levels of endogenous coenzyme Q10 may exacerbate chronic heart failure.

Individual patient data meta-analysis of neoadjuvant chemotherapy followed by surgery versus upfront surgery for carcinoma of the oesophagus or the gastro-oesophageal junction.

Introduction: Which neoadjuvant treatment for locally advanced thoracic oesophagus (TE) or gastro-oesophageal junction carcinoma is best remains an open question. Randomised controlled trials variously accrued patients with adenocarcinoma and squamous cell carcinoma, making strong conclusions hard to obtain. The primary objective of this individual participant data meta-analysis was to investigate the effect of neoadjuvant chemotherapy on overall survival (OS).

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.

Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.

Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021.

A framework for prospective, adaptive meta-analysis (FAME) of aggregate data from randomised trials.

Background: The vast majority of systematic reviews are planned retrospectively, once most eligible trials have completed and reported, and are based on aggregate data that can be extracted from publications. Prior knowledge of trial results can introduce bias into both review and meta-analysis methods, and the omission of unpublished data can lead to reporting biases. We present a collaborative framework for prospective, adaptive meta-analysis (FAME) of aggregate data to provide results that are less prone to bias.

Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data.

Background: It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced prostate cancer. We aimed to prospectively plan a systematic review of randomised controlled trials (RCTs) comparing these radiotherapy approaches.

Methods: We used a prospective framework for adaptive meta-analysis (FAME), starting the review process while eligible trials were ongoing.

Comparison of aggregate and individual participant data approaches to meta-analysis of randomised trials: An observational study.

Background: It remains unclear when standard systematic reviews and meta-analyses that rely on published aggregate data (AD) can provide robust clinical conclusions. We aimed to compare the results from a large cohort of systematic reviews and meta-analyses based on individual participant data (IPD) with meta-analyses of published AD, to establish when the latter are most likely to be reliable and when the IPD approach might be required.

Methods And Findings: We used 18 cancer systematic reviews that included IPD meta-analyses: all of those completed and published by the Meta-analysis Group of the MRC Clinical Trials Unit from 1991 to 2010.

A Systematic Review and Recommendation for Reporting of Surrogate Endpoint Evaluation Using Meta-analyses.

Background: Meta-analysis of randomized controlled trials (RCTs) has been widely conducted for the evaluation of surrogate endpoints in oncology, but little attention has been given to the adequacy of reporting and interpretation. This review evaluated the reporting quality of published meta-analyses on surrogacy evaluation and developed recommendations for future reporting.

Methods: We searched PubMed through August 2017 to identify studies that evaluated surrogate endpoints using the meta-analyses of RCTs in oncology.

Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysis.

Background: Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC).

Objective: To systematically review trials of prostate radiotherapy.

Design, Setting, And Participants: Using a prospective framework (framework for adaptive meta-analysis [FAME]), we prespecified methods before any trial results were known.

Evidence Synthesis to Accelerate and Improve the Evaluation of Therapies for Metastatic Hormone-sensitive Prostate Cancer.

There are many ongoing randomised trials of promising therapies for metastatic hormone-sensitive prostate cancer (mHSPC), but standard systematic reviews may not synthesise these in a timely or reliable way. We demonstrate how a novel approach to evidence synthesis is being used to speed up and improve treatment evaluations for mHSPC. This more prospective, dynamic, and collaborative approach to systematic reviews of both trial results and individual participant data (IPD) is helping in establishing quickly and reliably which treatments are most effective and for which men.

The Accuracy of Clinical Staging of Stage I-IIIa Non-Small Cell Lung Cancer: An Analysis Based on Individual Participant Data.

Background: Clinical staging of non-small cell lung cancer (NSCLC) helps determine the prognosis and treatment of patients; few data exist on the accuracy of clinical staging and the impact on treatment and survival of patients. We assessed whether participant or trial characteristics were associated with clinical staging accuracy as well as impact on survival.

Methods: We used individual participant data from randomized controlled trials (RCTs), supplied for a meta-analysis of preoperative chemotherapy (± radiotherapy) vs surgery alone (± radiotherapy) in NSCLC.