Reading, Conducting, and Developing Systematic Review and Individual Patient Data Meta-Analyses in Psychiatry for Treatment Issues

Introduction: Individual participant data meta-analyses (IPD-MAs) include the raw data from relevant randomised clinical trials (RCTs) and involve secondary analyses of the data. Performed since the late 1990s, ~50 such meta-analyses have been carried out in psychiatry, mostly in the field of treatment. IPD-MAs are particularly relevant for three objectives: (1) evaluation of the average effect of an intervention by combining effects from all included trials, (2) evaluation of the heterogeneity of an intervention effect and sub-group analyses to approach personalised psychiatry, (3) mediation analysis or surrogacy evaluation to replace a clinical (final) endpoint for the evaluation of new treatments with intermediate or surrogate endpoints. The objective is to describe the interest and the steps of an IPD-MA method applied to the field of psychiatric therapeutic research.Method: The method is described in three steps. First, the identification of the relevant trials with an explicit description of the inclusion/exclusion criteria for the RCT to be incorporated in the IPD-MA and a definition of the intervention, the population, the context and the relevant points (outcomes or moderators). Second, the data management with the standardisation of collected variables and the evaluation and the assessment of the risk-of-bias for each included trial and of the global risk. Third, the statistical analyses and their interpretations, depending on the objective of the meta-analysis. All steps are illustrated with examples in psychiatry for treatment issues, excluding study protocols.Conclusion: The meta-analysis of individual patient data is challenging. Only strong collaborations between all stakeholders can make such a process efficient. An “ecosystem” that includes all stakeholders (questions of interest prioritised by the community, funders, trialists, journal editors, institutions, …) is required. International medical societies can play a central role in favouring the emergence of such communities.

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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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Individual patient data meta-analysis of delayed gastric emptying after pylorus-preserving versus pylorus-resecting pancreatoduodenectomy

British Journal of Surgery ◽

10.1093/bjs/znab202.030 ◽

2021 ◽

Vol 108 (Supplement_4) ◽

Author(s):

P Probst ◽

U Klaiber ◽

S Seide ◽

M Kawai ◽

I Matsumoto ◽

...

Keyword(s):

Gastric Emptying ◽

Delayed Gastric Emptying ◽

Individual Patient Data ◽

Meta Analysis ◽

International Study ◽

Postoperative Outcome ◽

Patient Data ◽

Individual Patient Level ◽

Quantitative Synthesis ◽

Meta Analyses

Abstract Objective Some studies have indicated that resecting the pylorus during partial pancreatoduodenectomy (PD) may lead to reduced delayed gastric emptying (DGE). Randomized controlled trials (RCTs) showed conflicting results regarding superiority of pylorus-resecting PD (prPD) compared to the pylorus-preserving procedure (ppPD). The aim of this individual patient data meta-analysis was to investigate risk factors on an individual patient level which may explain the observed differences between the existing RCTs. Methods RCTs comparing ppPD and prPD were searched systematically in MEDLINE, Web of Science and CENTRAL. Individual patient data (IPD) from existing RCTs were included. The primary endpoint was DGE according to the International Study Group of Pancreatic Surgery (ISGPS) adjusted for age, sex and body-mass-index (BMI). The meta-regression model was applied to the IPD of the RCTs. Mixed effects models were applied to perform meta-analyses. Results IPD from 418 patients (three RCTs) were used for quantitative synthesis. There was no significant statistical difference between ppPD and prPD regarding DGE adjusted for age, sex and BMI (OR 0.72; 95%-CI: 0.41 to 1.22) and DGE grade (RR 1.01; 95%-CI: 0.64 to 1.57). Regarding other relevant perioperative and postoperative outcome parameters, there were also no significant differences among the two techniques. Conclusion This IPD meta-analysis comparing preservation and resection of the pylorus during PD confirmed that the resection of the pylorus is not superior to the pylorus-preserving procedure regarding DGE. The pylorus should therefore be preserved whenever possible. Further RCT are futile, because their results are unlikely to change the pooled estimate for DGE.

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Presenting a meta-analysis

10.1093/med/9780198779100.003.0013 ◽

2017 ◽

Author(s):

Janet L. Peacock ◽

Sally M. Kerry ◽

Raymond R. Balise

Keyword(s):

Systematic Reviews ◽

Individual Patient Data ◽

Meta Analysis ◽

Patient Data ◽

Meta Analyses

Chapter 13 introduces systematic reviews and meta-analyses, describing the use of aggregate or individual patient data. It describes how bias can arise in meta-analyses. It describes and demonstrates the use of the PRISMA guidelines statement.

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IS THERE BIAS IN THE PUBLICATION OF INDIVIDUAL PATIENT DATA META-ANALYSES?

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462300101217 ◽

2000 ◽

Vol 16 (2) ◽

pp. 657-667 ◽

Cited By ~ 18

Author(s):

Jayne F. Tierney ◽

Mike Clarke ◽

Lesley A. Stewart

Keyword(s):

Clinical Research ◽

Individual Patient Data ◽

Meta Analysis ◽

Strong Association ◽

Patient Data ◽

Good Evidence ◽

Current Data ◽

Current Evidence ◽

Publication History ◽

Meta Analyses

Objective: There is increasing empirical evidence for the existence of bias in the publication of primary clinical research, with statistically significant results being published more readily, more quickly, and in higher impact journals. Meta-analysis of individual patient data (IPD) may represent a gold standard of “secondary” clinical research, giving the best possible summary of current evidence for a particular question, but publication of these may also be subject to bias. This study aimed to explore which factors might be associated with publication of IPD meta-analyses and to identify potential sources of bias.Methods: For all known IPD meta-analysis projects in cancer, the responsible investigator was surveyed by means of a questionnaire to determine descriptive characteristics of the meta-analysis, the nature of the results, and details of the publication history.Results: There is no good evidence that overall publication status of meta-analyses in cancer is dependent on the statistical or clinical significance of the results. However, those meta-analyses with nonsignificant results did seem to take longer to publish and were published in lower impact journals compared with those with more striking results.Conclusions: Based on the current data, there seems to be no strong association between the results of IPD meta-analyses in cancer and publication.

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Meta-analysis when only the median survival times are known: A comparison with individual patient data results

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462305050154 ◽

2005 ◽

Vol 21 (1) ◽

pp. 119-125 ◽

Cited By ~ 92

Author(s):

Stefan Michiels ◽

Pascal Piedbois ◽

Sarah Burdett ◽

Nathalie Syz ◽

Lesley Stewart ◽

...

Keyword(s):

Median Survival ◽

Individual Patient Data ◽

Meta Analysis ◽

Survival Rates ◽

Patient Data ◽

Survival Times ◽

Time To Event ◽

Sufficient Detail ◽

Meta Analyses ◽

Surrogate Measures

Background:The hazard ratio (HR) is the most appropriate measure for time to event outcomes such as survival. In systematic reviews, HRs can be calculated either from the raw trial data obtained as part of an individual patient data (IPD) meta-analysis or from the appropriate trial-level summary statistics. However, the information required for the latter are seldom reported in sufficient detail to allow reviewers to calculate HRs. In contrast, the median survival and survival rates at specific time points are frequently presented. We aimed to evaluate retrospectively the performance of meta-analyses using median survival times and survival rates by comparing them with meta-analyses using IPD to calculate HRs.Methods:IPD from thirteen published meta-analyses (MAs) in cancers with high mortality rates were used. Median survival and survival rates were calculated from the IPD rather than taken from publications so that the same trials, patients, and extended follow-up are used in each analysis.Results and Conclusions:We show that using median survival times or survival rates at a particular point in time are not reasonable surrogate measures for meta-analyses of survival outcomes and that, wherever possible, HRs should be calculated. Individual trial publications reporting on time to event outcomes, therefore, should provide more detailed statistical information, preferably logHRs and their variances, or their estimators.

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Recombinant Human Erythropoiesis Stimulating Agents in Cancer Patients: Individual Patient Data Meta-Analysis on Behalf of the EPO IPD Meta-Analysis Collaborative Group

Blood ◽

10.1182/blood.v112.11.4675.4675 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4675-4675 ◽

Cited By ~ 1

Author(s):

Julia Bohlius ◽

Corinne Brillant ◽

Michael Clarke ◽

Sabine Kluge ◽

Maryann Napoli ◽

...

Keyword(s):

Cancer Patients ◽

Individual Patient Data ◽

Meta Analysis ◽

Patient Data ◽

Red Blood Cell Transfusion ◽

Collaborative Group ◽

Study Phase ◽

Erythropoiesis Stimulating Agents ◽

Meta Analyses ◽

The Impact

Abstract Background: Erythropoiesis stimulating agents (ESAs) consistently have been shown to decrease transfusions in anemic oncology patients. However, whether they increase mortality in cancer patients is under debate. Results from individual studies conflict, and results from literature based meta-analyses are inconclusive. We conducted a meta-analysis based on individual patient data (IPD) from all available randomized controlled trials (RCTs). Meta-analyses with individual patient data offer several advantages over study-level analysis, including the ability to gain statistical power and increase validity using time-to-event analyses, to adjust for prognostic variables that may have confounded the original treatment comparisons and to investigate subgroups in which treatment may be either more or less effective or harmful. Methods: An international collaboration conducted an individual patent data meta-analysis of ESA effects on mortality in cancer patients. With guidance from an independent steering committee of international experts in hematology, oncology, radiotherapy, epidemiology, medical statistics and a consumer representative, we developed a detailed protocol and statistical analysis plan. Independent RCT investigators and representatives from pharmaceutical companies who submitted data provided additional input through the project’s advisory board. IPD from RCTs of ESA plus red blood cell transfusion (RBCT) (as needed) versus placebo or no ESA plus RBCT (as needed), for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy, were included. Hazard ratios and 95% confidence intervals (CIs) were calculated per study and meta-analyzed with fixed-effects and random-effects models. Primary endpoints were overall survival (during active study phase and for the longest follow-up available) for patients receiving chemotherapy, and for all cancer patients regardless of anticancer treatment. Stratified multivariable Cox-regression analyses were conducted to assess the impact of baseline imbalances and to identify potential effect modifiers. Duplicate main statistical analyses were conducted independently at two academic statistical departments. Results: Data on 13933 patients enrolled in 53 studies were included in the analysis. Data were provided by the companies Amgen Inc., Johnson & Johnson Pharmaceutical Research & Development, L.L.C., and F. Hoffmann-La Roche Ltd.; and by five independent investigators. Results are currently undergoing internal verification and final evaluation and will be presented at the meeting. Conclusion: Final conclusions will be presented at the meeting. Future analyses using IPD will be conducted to estimate the risks (clots, tumor progression) and potential benefits (transfusion needs and quality of life/fatigue) from other outcomes.

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