Integration of non-randomized studies with randomized controlled trials in meta-analyses of clinical studies: a meta-epidemiological study on effect estimation of interventions

Backgrounds Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associa...

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Vydáno v:BMC medicine Ročník 22; číslo 1; s. 571 - 17
Hlavní autoři: Mei, Fan, Yao, Minghong, Wang, Yuning, Huan, Jiayidaer, Ma, Yu, Li, Guowei, Zou, Kang, Li, Ling, Sun, Xin
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 02.12.2024
BioMed Central Ltd
Springer Nature B.V
BMC
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ISSN:1741-7015, 1741-7015
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Abstract Backgrounds Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associated with combining NRSIs and RCTs. Methods We searched PubMed to identify clinical systematic reviews published between 9 December 2017 and 9 December 2022, randomly sampling reviews in a 1:1 ratio of Core and non-Core clinical journals. We included systematic reviews with RCTs and NRSIs for the same clinical question. Clinical scenarios for considering the inclusion of NRSIs in eligible studies were classified. We extracted the methodological characteristics of the included studies, assessed the concordance of estimates between RCTs and NRSIs, calculated the ratio of the relative effect estimate from NRSIs to that from RCTs, and evaluated the impact on the estimates of pooled estimates when NRSIs are included. Results Two hundred twenty systematic reviews were included in the analysis. The clinical scenarios for including NRSIs were grouped into four main justifications: adverse outcomes ( n  = 140, 63.6%), long-term outcomes ( n  = 36, 16.4%), the applicability of RCT results to broader populations ( n  = 11, 5.0%), and other ( n  = 33, 15.0%). When conducting a meta-analysis, none of these reviews assessed the compatibility of the different types of evidence prior, 203 (92.3%) combined estimates from RCTs and NRSIs in the same meta-analysis. Of the 203 studies, 169 (76.8%) used crude estimates of NRSIs, and 28 (13.8%) combined RCTs and multiple types of NRSIs. Seventy-seven studies (35.5%) showed “qualitative disagree” between estimates from RCTs and NRSIs, and 101 studies (46.5%) found “important difference”. The integration of NRSIs changed the qualitative direction of estimates from RCTs in 72 out of 200 studies (36.0%). Conclusions Systematic reviews typically include NRSIs in the context of assessing adverse or long-term outcomes. The inclusion of NRSIs in a meta-analysis of RCTs has a substantial impact on effect estimates, but discrepancies between RCTs and NRSIs are often ignored. Our proposed recommendations will help researchers to consider carefully when and how to synthesis evidence from RCTs and NRSIs.
AbstractList Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associated with combining NRSIs and RCTs.BACKGROUNDSSyntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associated with combining NRSIs and RCTs.We searched PubMed to identify clinical systematic reviews published between 9 December 2017 and 9 December 2022, randomly sampling reviews in a 1:1 ratio of Core and non-Core clinical journals. We included systematic reviews with RCTs and NRSIs for the same clinical question. Clinical scenarios for considering the inclusion of NRSIs in eligible studies were classified. We extracted the methodological characteristics of the included studies, assessed the concordance of estimates between RCTs and NRSIs, calculated the ratio of the relative effect estimate from NRSIs to that from RCTs, and evaluated the impact on the estimates of pooled estimates when NRSIs are included.METHODSWe searched PubMed to identify clinical systematic reviews published between 9 December 2017 and 9 December 2022, randomly sampling reviews in a 1:1 ratio of Core and non-Core clinical journals. We included systematic reviews with RCTs and NRSIs for the same clinical question. Clinical scenarios for considering the inclusion of NRSIs in eligible studies were classified. We extracted the methodological characteristics of the included studies, assessed the concordance of estimates between RCTs and NRSIs, calculated the ratio of the relative effect estimate from NRSIs to that from RCTs, and evaluated the impact on the estimates of pooled estimates when NRSIs are included.Two hundred twenty systematic reviews were included in the analysis. The clinical scenarios for including NRSIs were grouped into four main justifications: adverse outcomes (n = 140, 63.6%), long-term outcomes (n = 36, 16.4%), the applicability of RCT results to broader populations (n = 11, 5.0%), and other (n = 33, 15.0%). When conducting a meta-analysis, none of these reviews assessed the compatibility of the different types of evidence prior, 203 (92.3%) combined estimates from RCTs and NRSIs in the same meta-analysis. Of the 203 studies, 169 (76.8%) used crude estimates of NRSIs, and 28 (13.8%) combined RCTs and multiple types of NRSIs. Seventy-seven studies (35.5%) showed "qualitative disagree" between estimates from RCTs and NRSIs, and 101 studies (46.5%) found "important difference". The integration of NRSIs changed the qualitative direction of estimates from RCTs in 72 out of 200 studies (36.0%).RESULTSTwo hundred twenty systematic reviews were included in the analysis. The clinical scenarios for including NRSIs were grouped into four main justifications: adverse outcomes (n = 140, 63.6%), long-term outcomes (n = 36, 16.4%), the applicability of RCT results to broader populations (n = 11, 5.0%), and other (n = 33, 15.0%). When conducting a meta-analysis, none of these reviews assessed the compatibility of the different types of evidence prior, 203 (92.3%) combined estimates from RCTs and NRSIs in the same meta-analysis. Of the 203 studies, 169 (76.8%) used crude estimates of NRSIs, and 28 (13.8%) combined RCTs and multiple types of NRSIs. Seventy-seven studies (35.5%) showed "qualitative disagree" between estimates from RCTs and NRSIs, and 101 studies (46.5%) found "important difference". The integration of NRSIs changed the qualitative direction of estimates from RCTs in 72 out of 200 studies (36.0%).Systematic reviews typically include NRSIs in the context of assessing adverse or long-term outcomes. The inclusion of NRSIs in a meta-analysis of RCTs has a substantial impact on effect estimates, but discrepancies between RCTs and NRSIs are often ignored. Our proposed recommendations will help researchers to consider carefully when and how to synthesis evidence from RCTs and NRSIs.CONCLUSIONSSystematic reviews typically include NRSIs in the context of assessing adverse or long-term outcomes. The inclusion of NRSIs in a meta-analysis of RCTs has a substantial impact on effect estimates, but discrepancies between RCTs and NRSIs are often ignored. Our proposed recommendations will help researchers to consider carefully when and how to synthesis evidence from RCTs and NRSIs.
Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associated with combining NRSIs and RCTs. We searched PubMed to identify clinical systematic reviews published between 9 December 2017 and 9 December 2022, randomly sampling reviews in a 1:1 ratio of Core and non-Core clinical journals. We included systematic reviews with RCTs and NRSIs for the same clinical question. Clinical scenarios for considering the inclusion of NRSIs in eligible studies were classified. We extracted the methodological characteristics of the included studies, assessed the concordance of estimates between RCTs and NRSIs, calculated the ratio of the relative effect estimate from NRSIs to that from RCTs, and evaluated the impact on the estimates of pooled estimates when NRSIs are included. Two hundred twenty systematic reviews were included in the analysis. The clinical scenarios for including NRSIs were grouped into four main justifications: adverse outcomes (n = 140, 63.6%), long-term outcomes (n = 36, 16.4%), the applicability of RCT results to broader populations (n = 11, 5.0%), and other (n = 33, 15.0%). When conducting a meta-analysis, none of these reviews assessed the compatibility of the different types of evidence prior, 203 (92.3%) combined estimates from RCTs and NRSIs in the same meta-analysis. Of the 203 studies, 169 (76.8%) used crude estimates of NRSIs, and 28 (13.8%) combined RCTs and multiple types of NRSIs. Seventy-seven studies (35.5%) showed "qualitative disagree" between estimates from RCTs and NRSIs, and 101 studies (46.5%) found "important difference". The integration of NRSIs changed the qualitative direction of estimates from RCTs in 72 out of 200 studies (36.0%).
Abstract Backgrounds Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associated with combining NRSIs and RCTs. Methods We searched PubMed to identify clinical systematic reviews published between 9 December 2017 and 9 December 2022, randomly sampling reviews in a 1:1 ratio of Core and non-Core clinical journals. We included systematic reviews with RCTs and NRSIs for the same clinical question. Clinical scenarios for considering the inclusion of NRSIs in eligible studies were classified. We extracted the methodological characteristics of the included studies, assessed the concordance of estimates between RCTs and NRSIs, calculated the ratio of the relative effect estimate from NRSIs to that from RCTs, and evaluated the impact on the estimates of pooled estimates when NRSIs are included. Results Two hundred twenty systematic reviews were included in the analysis. The clinical scenarios for including NRSIs were grouped into four main justifications: adverse outcomes (n = 140, 63.6%), long-term outcomes (n = 36, 16.4%), the applicability of RCT results to broader populations (n = 11, 5.0%), and other (n = 33, 15.0%). When conducting a meta-analysis, none of these reviews assessed the compatibility of the different types of evidence prior, 203 (92.3%) combined estimates from RCTs and NRSIs in the same meta-analysis. Of the 203 studies, 169 (76.8%) used crude estimates of NRSIs, and 28 (13.8%) combined RCTs and multiple types of NRSIs. Seventy-seven studies (35.5%) showed “qualitative disagree” between estimates from RCTs and NRSIs, and 101 studies (46.5%) found “important difference”. The integration of NRSIs changed the qualitative direction of estimates from RCTs in 72 out of 200 studies (36.0%). Conclusions Systematic reviews typically include NRSIs in the context of assessing adverse or long-term outcomes. The inclusion of NRSIs in a meta-analysis of RCTs has a substantial impact on effect estimates, but discrepancies between RCTs and NRSIs are often ignored. Our proposed recommendations will help researchers to consider carefully when and how to synthesis evidence from RCTs and NRSIs.
Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associated with combining NRSIs and RCTs. We searched PubMed to identify clinical systematic reviews published between 9 December 2017 and 9 December 2022, randomly sampling reviews in a 1:1 ratio of Core and non-Core clinical journals. We included systematic reviews with RCTs and NRSIs for the same clinical question. Clinical scenarios for considering the inclusion of NRSIs in eligible studies were classified. We extracted the methodological characteristics of the included studies, assessed the concordance of estimates between RCTs and NRSIs, calculated the ratio of the relative effect estimate from NRSIs to that from RCTs, and evaluated the impact on the estimates of pooled estimates when NRSIs are included. Two hundred twenty systematic reviews were included in the analysis. The clinical scenarios for including NRSIs were grouped into four main justifications: adverse outcomes (n = 140, 63.6%), long-term outcomes (n = 36, 16.4%), the applicability of RCT results to broader populations (n = 11, 5.0%), and other (n = 33, 15.0%). When conducting a meta-analysis, none of these reviews assessed the compatibility of the different types of evidence prior, 203 (92.3%) combined estimates from RCTs and NRSIs in the same meta-analysis. Of the 203 studies, 169 (76.8%) used crude estimates of NRSIs, and 28 (13.8%) combined RCTs and multiple types of NRSIs. Seventy-seven studies (35.5%) showed "qualitative disagree" between estimates from RCTs and NRSIs, and 101 studies (46.5%) found "important difference". The integration of NRSIs changed the qualitative direction of estimates from RCTs in 72 out of 200 studies (36.0%). Systematic reviews typically include NRSIs in the context of assessing adverse or long-term outcomes. The inclusion of NRSIs in a meta-analysis of RCTs has a substantial impact on effect estimates, but discrepancies between RCTs and NRSIs are often ignored. Our proposed recommendations will help researchers to consider carefully when and how to synthesis evidence from RCTs and NRSIs.
BackgroundsSyntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associated with combining NRSIs and RCTs.MethodsWe searched PubMed to identify clinical systematic reviews published between 9 December 2017 and 9 December 2022, randomly sampling reviews in a 1:1 ratio of Core and non-Core clinical journals. We included systematic reviews with RCTs and NRSIs for the same clinical question. Clinical scenarios for considering the inclusion of NRSIs in eligible studies were classified. We extracted the methodological characteristics of the included studies, assessed the concordance of estimates between RCTs and NRSIs, calculated the ratio of the relative effect estimate from NRSIs to that from RCTs, and evaluated the impact on the estimates of pooled estimates when NRSIs are included.ResultsTwo hundred twenty systematic reviews were included in the analysis. The clinical scenarios for including NRSIs were grouped into four main justifications: adverse outcomes (n = 140, 63.6%), long-term outcomes (n = 36, 16.4%), the applicability of RCT results to broader populations (n = 11, 5.0%), and other (n = 33, 15.0%). When conducting a meta-analysis, none of these reviews assessed the compatibility of the different types of evidence prior, 203 (92.3%) combined estimates from RCTs and NRSIs in the same meta-analysis. Of the 203 studies, 169 (76.8%) used crude estimates of NRSIs, and 28 (13.8%) combined RCTs and multiple types of NRSIs. Seventy-seven studies (35.5%) showed “qualitative disagree” between estimates from RCTs and NRSIs, and 101 studies (46.5%) found “important difference”. The integration of NRSIs changed the qualitative direction of estimates from RCTs in 72 out of 200 studies (36.0%).ConclusionsSystematic reviews typically include NRSIs in the context of assessing adverse or long-term outcomes. The inclusion of NRSIs in a meta-analysis of RCTs has a substantial impact on effect estimates, but discrepancies between RCTs and NRSIs are often ignored. Our proposed recommendations will help researchers to consider carefully when and how to synthesis evidence from RCTs and NRSIs.
Backgrounds Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associated with combining NRSIs and RCTs. Methods We searched PubMed to identify clinical systematic reviews published between 9 December 2017 and 9 December 2022, randomly sampling reviews in a 1:1 ratio of Core and non-Core clinical journals. We included systematic reviews with RCTs and NRSIs for the same clinical question. Clinical scenarios for considering the inclusion of NRSIs in eligible studies were classified. We extracted the methodological characteristics of the included studies, assessed the concordance of estimates between RCTs and NRSIs, calculated the ratio of the relative effect estimate from NRSIs to that from RCTs, and evaluated the impact on the estimates of pooled estimates when NRSIs are included. Results Two hundred twenty systematic reviews were included in the analysis. The clinical scenarios for including NRSIs were grouped into four main justifications: adverse outcomes (n = 140, 63.6%), long-term outcomes (n = 36, 16.4%), the applicability of RCT results to broader populations (n = 11, 5.0%), and other (n = 33, 15.0%). When conducting a meta-analysis, none of these reviews assessed the compatibility of the different types of evidence prior, 203 (92.3%) combined estimates from RCTs and NRSIs in the same meta-analysis. Of the 203 studies, 169 (76.8%) used crude estimates of NRSIs, and 28 (13.8%) combined RCTs and multiple types of NRSIs. Seventy-seven studies (35.5%) showed "qualitative disagree" between estimates from RCTs and NRSIs, and 101 studies (46.5%) found "important difference". The integration of NRSIs changed the qualitative direction of estimates from RCTs in 72 out of 200 studies (36.0%). Conclusions Systematic reviews typically include NRSIs in the context of assessing adverse or long-term outcomes. The inclusion of NRSIs in a meta-analysis of RCTs has a substantial impact on effect estimates, but discrepancies between RCTs and NRSIs are often ignored. Our proposed recommendations will help researchers to consider carefully when and how to synthesis evidence from RCTs and NRSIs. Keywords: Randomized controlled trials, Non-randomized studies of interventions, Systematic review, Meta-analysis, Meta-epidemiology
Backgrounds Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed to summarize when NRSIs are included in evidence syntheses of RCTs, with a particular focus on the methodological issues associated with combining NRSIs and RCTs. Methods We searched PubMed to identify clinical systematic reviews published between 9 December 2017 and 9 December 2022, randomly sampling reviews in a 1:1 ratio of Core and non-Core clinical journals. We included systematic reviews with RCTs and NRSIs for the same clinical question. Clinical scenarios for considering the inclusion of NRSIs in eligible studies were classified. We extracted the methodological characteristics of the included studies, assessed the concordance of estimates between RCTs and NRSIs, calculated the ratio of the relative effect estimate from NRSIs to that from RCTs, and evaluated the impact on the estimates of pooled estimates when NRSIs are included. Results Two hundred twenty systematic reviews were included in the analysis. The clinical scenarios for including NRSIs were grouped into four main justifications: adverse outcomes ( n  = 140, 63.6%), long-term outcomes ( n  = 36, 16.4%), the applicability of RCT results to broader populations ( n  = 11, 5.0%), and other ( n  = 33, 15.0%). When conducting a meta-analysis, none of these reviews assessed the compatibility of the different types of evidence prior, 203 (92.3%) combined estimates from RCTs and NRSIs in the same meta-analysis. Of the 203 studies, 169 (76.8%) used crude estimates of NRSIs, and 28 (13.8%) combined RCTs and multiple types of NRSIs. Seventy-seven studies (35.5%) showed “qualitative disagree” between estimates from RCTs and NRSIs, and 101 studies (46.5%) found “important difference”. The integration of NRSIs changed the qualitative direction of estimates from RCTs in 72 out of 200 studies (36.0%). Conclusions Systematic reviews typically include NRSIs in the context of assessing adverse or long-term outcomes. The inclusion of NRSIs in a meta-analysis of RCTs has a substantial impact on effect estimates, but discrepancies between RCTs and NRSIs are often ignored. Our proposed recommendations will help researchers to consider carefully when and how to synthesis evidence from RCTs and NRSIs.
ArticleNumber 571
Audience Academic
Author Ma, Yu
Li, Ling
Huan, Jiayidaer
Zou, Kang
Mei, Fan
Sun, Xin
Wang, Yuning
Li, Guowei
Yao, Minghong
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  givenname: Fan
  surname: Mei
  fullname: Mei, Fan
  organization: Institute of Integrated Traditional Chinese and Western Medicine, Chinese Evidence-Based Medicine Center, Cochrane China and MAGIC China Center, West China Hospital, Sichuan University, NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Sichuan Center of Technology Innovation for Real World Data
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  givenname: Minghong
  surname: Yao
  fullname: Yao, Minghong
  organization: Institute of Integrated Traditional Chinese and Western Medicine, Chinese Evidence-Based Medicine Center, Cochrane China and MAGIC China Center, West China Hospital, Sichuan University, NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Sichuan Center of Technology Innovation for Real World Data
– sequence: 3
  givenname: Yuning
  surname: Wang
  fullname: Wang, Yuning
  organization: Institute of Integrated Traditional Chinese and Western Medicine, Chinese Evidence-Based Medicine Center, Cochrane China and MAGIC China Center, West China Hospital, Sichuan University, NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Sichuan Center of Technology Innovation for Real World Data
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  givenname: Yu
  surname: Ma
  fullname: Ma, Yu
  organization: Institute of Integrated Traditional Chinese and Western Medicine, Chinese Evidence-Based Medicine Center, Cochrane China and MAGIC China Center, West China Hospital, Sichuan University, NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Sichuan Center of Technology Innovation for Real World Data
– sequence: 6
  givenname: Guowei
  surname: Li
  fullname: Li, Guowei
  organization: Department of Health Research Methods, Evidence and Impact, McMaster University, Center for Clinical Epidemiology and Methodology, Guangdong Second Provincial General Hospital, Biostatistics Unit, Research Institute at St. Joseph’s Healthcare Hamilton
– sequence: 7
  givenname: Kang
  surname: Zou
  fullname: Zou, Kang
  organization: Institute of Integrated Traditional Chinese and Western Medicine, Chinese Evidence-Based Medicine Center, Cochrane China and MAGIC China Center, West China Hospital, Sichuan University, NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Sichuan Center of Technology Innovation for Real World Data
– sequence: 8
  givenname: Ling
  surname: Li
  fullname: Li, Ling
  email: liling@wchscu.cn
  organization: Institute of Integrated Traditional Chinese and Western Medicine, Chinese Evidence-Based Medicine Center, Cochrane China and MAGIC China Center, West China Hospital, Sichuan University, NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Sichuan Center of Technology Innovation for Real World Data
– sequence: 9
  givenname: Xin
  surname: Sun
  fullname: Sun, Xin
  email: sunxin@wchscu.cn
  organization: Institute of Integrated Traditional Chinese and Western Medicine, Chinese Evidence-Based Medicine Center, Cochrane China and MAGIC China Center, West China Hospital, Sichuan University, NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Sichuan Center of Technology Innovation for Real World Data, Department of Epidemiology and Biostatistics, School of Public Health and West China Fourth Hospital, Sichuan University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/39623370$$D View this record in MEDLINE/PubMed
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CitedBy_id crossref_primary_10_1080_15614263_2025_2506647
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Keywords Systematic review
Meta-epidemiology
Non-randomized studies of interventions
Randomized controlled trials
Meta-analysis
Language English
License 2024. The Author(s).
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Snippet Backgrounds Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This...
Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This study aimed...
Backgrounds Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This...
BackgroundsSyntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in decision-making. This...
Abstract Backgrounds Syntheses of non-randomized studies of interventions (NRSIs) and randomized controlled trials (RCTs) are increasingly used in...
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SubjectTerms Biomedicine
Clinical decision making
Clinical trials
Decision making
Epidemiologic Studies
Epidemiology
Estimates
Evidence-based medicine
Humans
Impact analysis
Intervention
Medical research
Medicine
Medicine & Public Health
Medicine, Experimental
Meta-analysis
Meta-Analysis as Topic
Meta-epidemiology
Methods
Non-Randomized Controlled Trials as Topic - methods
Non-randomized studies of interventions
Qualitative analysis
Randomized controlled trials
Randomized Controlled Trials as Topic - methods
Randomized Controlled Trials as Topic - standards
Reviews
Systematic review
Systematic Reviews as Topic - methods
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Title Integration of non-randomized studies with randomized controlled trials in meta-analyses of clinical studies: a meta-epidemiological study on effect estimation of interventions
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