Spondylectomy in the treatment of neoplastic spinal lesions – A retrospective outcome analysis of 582 patients using a patient-level meta-analysis

Objective: We developed and evaluated a privacy-preserving One-shot Distributed Algorithm for Cox model to analyze multi-center time-to-event data without sharing patient-level information across sites, while accounting for heterogeneity across sites by allowing site-specific baseline hazard functions and feature distributions. Materials and Methods: We constructed a surrogate likelihood function to approximate the Cox log partial likelihood function which is stratified by site, using patient-level data from a single site and aggregated information from other sites. The ODAC estimator was obtained by maximizing the surrogate likelihood function. We evaluated and compare the performance of ODACH with meta-analysis by extensive numerical studies. Results: The simulation study showed that ODACH provided estimates close to the pooled estimator, which is obtained by directly analyzing patient-level data from all sites via a stratified Cox model. The relative bias was <1% across all scenarios. As a comparison, the meta-analysis estimator, which was obtained by the inverse variance weighted average of the site-specific estimates, had substantial bias when the event rate is <5%, with the relative bias reaching 12% when the event rate is 1%. Conclusions: ODACH is a privacy-preserving and communication-efficient method for analyzing multi-center time-to-event data, which allows the baseline hazard functions as well as the distribution of covariate variables to vary across sites. It provides estimates that is close to the pooled estimator and substantially outperforms the meta-analysis estimator when the event is rare. It is thus extremely suitable for studying rare events with heterogeneous baseline hazards across sites in a distributed manner.

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Abstract 17059: Re-Use of Clinical Trial Data From the NHLBI Data Repository (BioLINCC) for Patient-Level Meta-Analyses of Cardiovascular Outcomes: Challenges and Opportunities

Circulation ◽

10.1161/circ.138.suppl_1.17059 ◽

2018 ◽

Vol 138 (Suppl_1) ◽

Author(s):

Helena Sviglin ◽

Gauri Dandi ◽

Eileen Navarro Almario ◽

Tejas Patel ◽

Colin O Wu ◽

...

Keyword(s):

Risk Factors ◽

Meta Analysis ◽

Cardiovascular Outcomes ◽

Data Repository ◽

Common Data Elements ◽

Patient Level Data ◽

Patient Level ◽

Level Data ◽

Data Elements ◽

Meta Analyses

Introduction: An objective of the Meta-AnalyTical Interagency Group (MATIG) is to conduct patient-level meta-analyses of cardiovascular outcomes using data from publicly available repositories. We describe challenges with data re-use from a seminal trial, provide a systematic approach to identify and curate data elements for hypothesis generation, and establish stackable trials to support these analyses. Methods: We used data from the ACCORD trial to assess risk factors and their gender specific differences for the event of hospitalization or death due to heart failure (hdHF), in patients with type 2 diabetes*. We identified the data elements needed to answer the research questions, reviewed the trial protocol to verify definitions, extracted patient-level data, performed quality assessment and statistical analysis. The results showed a gender difference in the effect of intensive vs. standard glucose-lowering therapy on hdHF. To validate the findings, we sought additional trials in BioLINCC to develop a compendium for meta-analysis, and repeated these steps for each trial. Results: Challenges for reusing the ACCORD trial included access to complete patient-level data and metadata. The compendium, developed to evaluate the stackability** of data across trials, identified differences in trial designs, patient populations, study interventions, and data elements that may impact the feasibility and interpretation of meta-analysis. An example of compendium components is shown in Table 1. Conclusion: High-quality metadata facilitate re-use of trial repository data. This compendium standardizes common data elements for gender, racial and age-group specific outcome assessment in major clinical trials. It provides the framework to assess the fitness of trials for patient-level meta-analyses. Efforts are underway by MATIG to expand the compendium to include risk factors and major cardiovascular outcomes across multiple large trials for meta-analysis.

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Nivolumab plus Ipilimumab versus Existing Immunotherapies in Patients with PD-L1-Positive Advanced Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

Cancers ◽

10.3390/cancers12071905 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1905 ◽

Cited By ~ 3

Author(s):

Koichi Ando ◽

Yasunari Kishino ◽

Tetsuya Homma ◽

Sojiro Kusumoto ◽

Toshimitsu Yamaoka ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Meta Analysis ◽

Small Cell ◽

Outcome Analysis ◽

Efficacy And Safety ◽

Small Cell Lung ◽

Platinum Based Chemotherapy

No head-to-head trials have compared the efficacy and safety of nivolumab (Niv) plus ipilimumab (Ipi) combination therapy (Niv+Ipi) and existing regimens with immunotherapies approved as first-line treatment in patients with programmed cell death ligand 1 (PD-L1)-positive previously untreated advanced non-small cell lung cancer (NSCLC). We conducted a network meta-analysis of four relevant Phase Ⅲ trials to compare the efficacy and safety of Niv+Ipi, pembrolizumab (Pem) plus platinum-based chemotherapy (PBC) (Pem+PBC), Pem, Niv, or PBC using Bayesian analysis. The primary efficacy endpoint was progression-free survival (PFS) in patients with advanced NSCLC with PD-L1 expression ≥1%. The primary safety endpoint was the incidence of Grade 3–5 drug-related adverse events (G3–5AEs). Efficacy and safety were ranked using surface under the cumulative ranking curve (SUCRA). With regard to PFS, Niv+Ipi was inferior to Pem+PBC, and superior to Pem, Niv, or PBC alone. SUCRA ranking showed Pem+PBC had the highest efficacy for PFS, followed by Niv+Ipi, Niv, PBC, and Pem. The safety outcome analysis revealed Niv+Ipi was generally well tolerated compared to existing immunotherapy regimens. These results provide clinical information regarding the efficacy and safety of Niv+Ipi and indicate the possibility of the Niv+Ipi combination as a new therapeutic option in PD-L1-positive advanced NSCLC.

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Guided or self-guided internet-based cognitive–behavioural therapy (iCBT) for depression? Study protocol of an individual participant data network meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-026820 ◽

2019 ◽

Vol 9 (6) ◽

pp. e026820 ◽

Cited By ~ 2

Author(s):

Eirini Karyotaki ◽

Toshi A Furukawa ◽

Orestis Efthimiou ◽

Heleen Riper ◽

Pim Cuijpers

Keyword(s):

Cognitive Behavioural Therapy ◽

Meta Analysis ◽

Substantial Reduction ◽

Behavioural Therapy ◽

Cochrane Library ◽

Individual Participant Data ◽

Relative Efficacy ◽

Patient Level ◽

Cognitive Behavioural ◽

Individual Participant

IntroductionAlthough guided forms of internet-based cognitive–behavioural therapy (iCBT) result in a substantial reduction in depression, it seems that the most scalable way to deliver iCBT is without guidance. However, direct evidence on the comparison between guided and self-guided iCBT is scarce. Moreover, it is unclear which types of patients may benefit more from each of these two forms of iCBT. Network meta-analysis (NMA) using individual participant data (IPD) offers a way to assess the relative efficacy of multiple (>2) interventions. Moreover, it maximises our power to detect patient-level characteristics (covariates) that have an important effect on the efficacy of interventions. This protocol describes the procedures of an IPD-NMA, which aims at examining the relative efficacy of guided compared with self-guided iCBT and at identifying predictors and moderators of treatment outcome.Methods and analysisWe will use an existing database on psychotherapies for adult depression to identify eligible studies. This database has been updated up to 1 January 2018, through literature searches in PubMed, Embase, PsycINFO and Cochrane Library. The outcome of this IPD-NMA is reduction in depressive symptoms severity. We will fit the model in a Bayesian setting. After fitting the model, we will report the relative treatment effects for different types of patients, and we will discuss the clinical implications of our findings. Based on the results from the IPD-NMA model, we will develop and validate a personalised prediction model, aiming to provide patient-level predictions about the effects of the interventions.Ethics and disseminationAn ethical approval is not required for this study. The results will be published in a peer-review journal. These results will guide clinical decisions about the most efficient way to allocate iCBT resources, thereby increasing the scalability of this innovative therapeutic approach.

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