Individual patient data meta-analysis of time-to-event outcomes: one-stage versus two-stage approaches for estimating the hazard ratio under a random effects model

Background: Exercise referral schemes (ERSs) within clinical populations offer inactive individuals the opportunity to increase physical activity levels over the length of scheme. Schemes are also intended to support the treatment of specific health conditions of medically referred individuals through increased physical activity behaviours. The extant literature concerning the impact of exercise referral on physical activity levels is inconsistent. It is of interest researchers, policy makers, commissioners and practitioners to to consider broadly whether meaningful change in physical activity levels are observed in people who undergo exercise referral, to identify potential effective policy actions in supporting active living. Purpose: To examine if ERSs increase physical activity levels in a large cohort of individuals throughout England, Scotland and Wales from The National Referral Database. Method: Data were obtained from 5246 participants from 12 different referral schemes. Average age was 53±15 years and, 68% of participants were female. Participants self-reported International Physical Activity Questionnaire (IPAQ) scores pre- and post- scheme, to determine if exercise referral had any impact on change in physical activity levels. Two stage individual patient data meta-analysis was performed on the both pre-ERS, and change scores, (i.e. post- minus pre-ERS scores) for MET-minutes/week calculated from IPAQ. Analyses were conducted on the continuous data collected using the IPAQ. Results: For pre-ERS MET-minutes/week the estimate and 95%CI from random effects model was 676 MET-minutes/week [539 to 812 minutes]. For change in MET-minutes/week the estimate and 95%CI from random effects model for was an increase of 540 MET-minutes/week [396 to 684 minutes]. Significant heterogeneity was evident among the schemes (I2 > 80%). Changes in total PA levels occurred as a result of increases in vigorous activity of 17 minutes [95%CI 9 to 24 minutes], increases in moderate activity of 29 minutes [95%CI 22 to 36 minutes], and reductions in sitting of -61 minutes [95%CI -78 to -43 minutes], though little change in walking (-5 minutes [95%CI -14 to 5 minutes]). Conclusion: Observation of participants undergoing ERSs suggests that most are already ‘moderately active’ upon entering an ERS. Changes in physical activity behaviour associated with ERS participation were varied and primarily facilitated by increased moderate-to-vigorous physical activity and reduced sitting. However, this was not sufficient to result in IPAQ categorical change and participants where thus on average still classed as ‘moderately active’. Further work is required to ensure ERSs are implemented to targeting the appropriate populations where they may result in the greatest benefit.

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Weniger Erwerbsminderungsrenten nach der kardiologischen Rehabilitation durch intensivierte Nachsorge?

Die Rehabilitation ◽

10.1055/a-1338-0613 ◽

2021 ◽

Author(s):

Sarah Schröer ◽

Wolfgang Mayer-Berger ◽

Claudia Pieper

Keyword(s):

Fixed Effects ◽

Individual Patient Data ◽

Meta Analysis ◽

Patient Data ◽

Odds Ratios ◽

Two Stage ◽

Kardiologische Rehabilitation ◽

One Stage

Zusammenfassung Ziel Ziel war es die Daten aus 3 randomisierten kontrollierten Studien, in denen Nachsorgekonzepte im Rahmen der kardiologischen Rehabilitation evaluiert wurden, in Form einer Pooling-Studie zusammenzufassen, um stärker belastbare Erkenntnisse über den nachsorgeassoziierten weiteren Verlauf der Patienten und Patientinnen im Anschluss an die Rehabilitation zu gewinnen. Nachfolgend werden die Auswirkungen von poststationärer Nachsorge auf das Erwerbsminderungsrisiko kardiologischer Rehabilitanden und Rehabilitandinnen vorgestellt. Methodik Aus 3 randomisierten kontrollierten Primärstudien (SeKoNa, Sinko, OptiHyp), in denen als Intervention jeweils ein intensiviertes (telefongestütztes) poststationäres Nachsorgekonzept mit einer unbehandelten Kontrollgruppe verglichen wurde, stehen umfangreiche Daten zu soziodemografischen, klinischen und diagnostischen Charakteristika auf Individualebene zur Verfügung. Mittels einer im August 2019 durchgeführten Sekundärdatenanalyse von Routinedaten der Deutschen Rentenversicherung Rheinland wurden als primäre Outcomeparameter Mortalität (alle Ursachen), bewilligte Erwerbsminderungsrenten sowie bewilligte Anträge auf eine erneute kardiologische Rehabilitation zum individuellen Stichtag 3 Jahre nach Rehabilitationsende als Endpunkte erhoben. Die Daten wurden als Meta-Analyse für individuelle Patientendaten (Individual Patient Data Meta-Analysis IPD-MA) unter Verwendung klassischer meta-analytischer Techniken (One-Stage Approach mittels gemischter Modelle und Two-Stage Approach mit inverser Varianzschätzung als Fixed Effects Modell) gepoolt und über Risiko-Odds-Ratios vergleichend ausgewertet. Ergebnisse Das Gesamtkollektiv besteht aus insgesamt 1058 kardiologischen Rehabilitanden und Rehabilitandinnen, die im Zeitraum zwischen 2004 und 2015 stationäre rehabilitative Leistungen der Deutschen Rentenversicherung Rheinland in der kardiologischen Rehabilitationseinrichtung Klinik Roderbirken in Leichlingen in Anspruch genommen haben. Die gepoolte Interventionsgruppe (poststationäre Nachsorge) und die gepoolte Kontrollgruppe (Standardbehandlung) unterschieden sich zum Ausgangspunkt (Entlassung nach 3-wöchiger Rehabilitation) nicht. Hinweise auf statistische Heterogenität liegt nicht vor. Drei Jahre nach Rehabilitationsende betrug die inzidente Erwerbsminderungsrentenquote 11,8% der Gesamtstichprobe. Bei Teilnahme an einem poststationären Nachsorgekonzept war das Erwerbsminderungsrisiko gegenüber der Kontrollgruppe um rund 60% reduziert (OR: 0,43; 95% CI: 0,36–0,51). Schlussfolgerung Rehabilitation und Wiedereingliederung gewinnen weiter an Bedeutung, um die Gefahr von gesundheitlich bedingten vorzeitigen Erwerbsausstiegen mit erheblichen sozioökonomischen Folgen für Betroffene und das Sozialversicherungssystem zu vermeiden. Nachsorgeaktivitäten, die Rehabilitationserfolge über Dauer einer mehrwöchigen Rehabilitation hinaus erhalten, unterstützen die Prävention von gesundheitlich bedingten vorzeitigen Erwerbsminderungsrenten effektiv und nachhaltig und sollten das bestehende Rehabilitationsangebot komplettieren. Aus unseren Ergebnissen folgern wir, dass Nachsorge lange genug (mindestens ein Jahr) und im persönlichen Kontakt erfolgen muss.

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Transcatheter versus surgical aortic valve replacement in the digital era: Meta‐analysis based on the reconstruction of time‐to‐event individual patient data

Catheterization and Cardiovascular Interventions ◽

10.1002/ccd.29079 ◽

2020 ◽

Vol 96 (1) ◽

pp. 167-168

Author(s):

Giuseppe Tarantini ◽

Daniele Giacoppo

Keyword(s):

Aortic Valve ◽

Aortic Valve Replacement ◽

Valve Replacement ◽

Individual Patient Data ◽

Meta Analysis ◽

Patient Data ◽

Time To Event ◽

Surgical Aortic Valve Replacement ◽

Digital Era

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Mortality in trials on transcatheter aortic valve implantation versus surgical aortic valve replacement: a pooled meta-analysis of Kaplan–Meier-derived individual patient data

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezaa087 ◽

2020 ◽

Vol 58 (2) ◽

pp. 221-229 ◽

Cited By ~ 6

Author(s):

Fabio Barili ◽

Nicholas Freemantle ◽

Alberto Pilozzi Casado ◽

Mauro Rinaldi ◽

Thierry Folliguet ◽

...

Keyword(s):

Aortic Valve ◽

Individual Patient Data ◽

Meta Analysis ◽

Patient Data ◽

Time Varying ◽

Time To Event ◽

Surgical Aortic Valve Replacement ◽

Transcatheter Aortic Valve ◽

Kaplan Meier ◽

Valve Implantation

Abstract OBJECTIVES This meta-analysis of Kaplan–Meier-estimated individual patient data was designed to evaluate the effects of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) on the long-term all-cause mortality rate, to examine the potential time-varying effect and to model their hazard ratios (HRs) over time. Moreover, we sought to compare traditional meta-analytic tools and estimated individual patient data meta-analyses. METHODS Trials comparing TAVI versus SAVR were identified through Medline, Embase, Cochrane databases and specialist websites. The primary outcome was death from any cause at follow-up. Enhanced secondary analyses of survival curves were performed estimating individual patient time-to-event data from published Kaplan–Meier curves. Treatments were compared with the random effect Cox model in a landmark framework and fully parametric models. RESULTS We identified 6 eligible trials that included 6367 participants, randomly assigned to undergo TAVI (3252) or SAVR (3115). According to the landmark analysis, the incidence of death in the first year after implantation was significantly lower in the TAVI group [risk-profile stratified HR 0.85, 95% confidence interval (CI) 0.73–0.99; P = 0.04], whereas there was a reversal of the HR after 40 months (risk-profile stratified HR 1.31, 95% CI 1.01–1.68; P = 0.04) favouring SAVR over TAVI. This time-varying trend of HRs was also confirmed by a fully parametric time-to-event model. Traditional meta-analytic tools were shown to be biased because they did not intercept heterogeneity and the time-varying effect. CONCLUSIONS The mortality rates in trials of TAVI versus SAVR are affected by treatments with a time-varying effect. TAVI is related to better survival in the first months after implantation whereas, after 40 months, it is a risk factor for all-cause mortality.

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Empirical comparison of subgroup effects in conventional and individual patient data meta-analyses

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462308080471 ◽

2008 ◽

Vol 24 (03) ◽

pp. 358-361 ◽

Cited By ~ 30

Author(s):

Laura Koopman ◽

Geert J. M. G. van der Heijden ◽

Arno W. Hoes ◽

Diederick E. Grobbee ◽

Maroeska M. Rovers

Keyword(s):

Individual Patient Data ◽

Meta Analysis ◽

Acute Otitis Media ◽

Patient Data ◽

Published Data ◽

Summary Statistics ◽

Two Stage ◽

Data Set ◽

Meta Analyses ◽

Subgroup Effects

Objectives:Individual patient data (IPD) meta-analyses have been proposed as a major improvement in meta-analytic methods to study subgroup effects. Subgroup effects of conventional and IPD meta-analyses using identical data have not been compared. Our objective is to compare such subgroup effects using the data of six trials (n= 1,643) on the effectiveness of antibiotics in children with acute otitis media (AOM).Methods:Effects (relative risks, risk differences [RD], and their confidence intervals [CI]) of antibiotics in subgroups of children with AOM resulting from (i) conventional meta-analysis using summary statistics derived from published data (CMA), (ii) two-stage approach to IPD meta-analysis using summary statistics derived from IPD (IPDMA-2), and (iii) one-stage approach to IPD meta-analysis where IPD is pooled into a single data set (IPDMA-1) were compared.Results:In the conventional meta-analysis, only two of the six studies were included, because only these reported on relevant subgroup effects. The conventional meta-analysis showed larger (age < 2 years) or smaller (age ≥ 2 years) subgroup effects and wider CIs than both IPD meta-analyses (age < 2 years: RDCMA-21 percent, RDIPDMA-1-16 percent, RDIPDMA-2-15 percent; age ≥2 years: RDCMA-5 percent, RDIPDMA-1-11 percent, RDIPDMA-2-11 percent). The most important reason for these discrepant results is that the two studies included in the conventional meta-analysis reported outcomes that were different both from each other and from the IPD meta-analyses.Conclusions:This empirical example shows that conventional meta-analyses do not allow proper subgroup analyses, whereas IPD meta-analyses produce more accurate subgroup effects. We also found no differences between the one- and two-stage meta-analytic approaches.

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The “Central Vein Sign” on T2*-weighted Images as a Diagnostic Tool in Multiple Sclerosis: A Systematic Review and Meta-analysis using Individual Patient Data

Scientific Reports ◽

10.1038/s41598-019-54583-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Chong Hyun Suh ◽

Sang Joon Kim ◽

Seung Chai Jung ◽

Choong Gon Choi ◽

Ho Sung Kim

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Random Effects ◽

Diagnostic Performance ◽

Individual Patient Data ◽

White Matter Lesions ◽

Patient Data ◽

Central Vein ◽

Random Effects Model ◽

T2 Weighted Images

AbstractWe aimed to evaluate the pooled incidence of central vein sign on T2*-weighted images from patients with multiple sclerosis (MS), and to determine the diagnostic performance of this central vein sign for differentiating MS from other white matter lesions and provide an optimal cut-off value. A computerized systematic search of the literature in PUBMED and EMBASE was conducted up to December 14, 2018. Original articles investigating central vein sign on T2*-weighted images of patients with MS were selected. The pooled incidence was obtained using random-effects model. The pooled sensitivity and specificity were obtained using a bivariate random-effects model. An optimal cut-off value for the proportion of lesions with a central vein sign was calculated from those studies providing individual patient data. Twenty-one eligible articles covering 501 patients with MS were included. The pooled incidence of central vein sign at the level of individual lesion in patients with MS was 74% (95% CI, 65–82%). The pooled sensitivity and pooled specificity for the diagnostic performance of the central vein sign were 98% (95% CI, 92–100%) and 97% (95% CI, 91–99%), respectively. The area under the HSROC curve was 1.00 (95% CI, 0.99–1.00). The optimal cut-off value for the proportion of lesions with a central vein sign was found to be 45%. Although various T2*-weighted images have been used across studies, the current evidence supports the use of the central vein sign on T2*-weighted images to differentiate MS from other white matter lesions.

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