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Quality of systematic reviews of observational nontherapeutic studies.
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PMID:  20950540     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: High-quality epidemiologic research is essential in reducing chronic diseases. We analyzed the quality of systematic reviews of observational nontherapeutic studies.
METHODS: We searched several databases for systematic reviews of observational nontherapeutic studies that examined the prevalence of or risk factors for chronic diseases and were published in core clinical journals from 1966 through June 2008. We analyzed the quality of such reviews by using prespecified criteria and internal quality evaluation of the included studies.
RESULTS: Of the 145 systematic reviews we found, fewer than half met each quality criterion; 49% reported study flow, 27% assessed gray literature, 2% abstracted sponsorship of individual studies, and none abstracted the disclosure of conflict of interest by the authors of individual studies. Planned, formal internal quality evaluation of included studies was reported in 37% of systematic reviews. The journal of publication, topic of review, sponsorship, and conflict of interest were not associated with better quality. Odds of formal internal quality evaluation (odds ratio [OR], 1.10 per year; 95% confidence interval [CI], 1.02-1.19) and either planned, formal internal quality evaluation or abstraction of quality criteria of included studies (OR, 1.17 per year; 95% CI, 1.08-1.26) increased over time, without positive trends in other quality criteria from 1990 through June 2008. Systematic reviews with internal quality evaluation did not meet other quality criteria more often than those that ignored the quality of included studies.
CONCLUSION: Collaborative efforts from investigators and journal editors are needed to improve the quality of systematic reviews.
Authors:
Tatyana Shamliyan; Robert L Kane; Stacy Jansen
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2010-10-15
Journal Detail:
Title:  Preventing chronic disease     Volume:  7     ISSN:  1545-1151     ISO Abbreviation:  Prev Chronic Dis     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2011-04-12     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101205018     Medline TA:  Prev Chronic Dis     Country:  United States    
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Languages:  eng     Pagination:  A133     Citation Subset:  IM    
Affiliation:
Minnesota Evidence-based Practice Center, University of Minnesota School of Public Health, D351 Mayo (MMC 197), 420 Delaware St SE, Minneapolis, MN 55455, USA. shaml005@umn.edu
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Chronic Disease / epidemiology*
Conflict of Interest
Epidemiologic Studies*
Periodicals as Topic
Publishing / standards
Research / economics,  standards*
Review Literature as Topic*
Risk Factors
Grant Support
ID/Acronym/Agency:
290-02-0009//PHS HHS
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Journal ID (nlm-ta): Prev Chronic Dis
ISSN: 1545-1151
Publisher: Centers for Disease Control and Prevention
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collection publication date: Month: 11 Year: 2010
Electronic publication date: Day: 15 Month: 10 Year: 2010
Volume: 7 Issue: 6
E-location ID: A133
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PubMed Id: 20950540
Publisher Id: PCDv76_09_0195

Quality of Systematic Reviews of Observational Nontherapeutic Studies
Tatyana Shamliyan, MD, MS Affiliation: Minnesota Evidence-based Practice Center, University of Minnesota School of Public Health
Address: D351 Mayo (MMC 197), 420 Delaware St SE, Minneapolis, MN 55455 612-624-1185 shaml005@umn.edu
Robert L. Kane, MD Affiliation: University of Minnesota School of Public Health, Minneapolis, Minnesota
Stacy Jansen, MPH Affiliation: University of Minnesota School of Public Health, Minneapolis, Minnesota

Introduction

Valid epidemiologic research is essential in preventing chronic diseases (1-3). Assessing the quality of observational studies is an important part of evidence synthesis (4). Systematic reviews have become key tools in evidence synthesis from a growing number of epidemiologic studies (5). Producing high-quality systematic reviews is essential to developing generalizable and actionable conclusions (6,7). Quality criteria for systematic reviews have been proposed by working groups that developed the Meta-analysis of Observational Studies in Epidemiology (MOOSE), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and a measurement tool for assessment of multiple systematic reviews (AMSTAR) (8-12). The working groups and the Cochrane handbook (13) addressed those criteria for systematic reviews that more likely result in biased results, including bias in selection of the studies or the information within studies by the reviewers (14-18) or bias in the publication of positive significant results (6,15,19,20).

Previous research and guidelines (13,21-23) focus on systematic reviews of interventional therapeutic studies. Validity of observational nontherapeutic studies of prevalence of chronic diseases or risk factors for diseases is essential for effective preventive public health actions (24,25). Our aim was to evaluate the quality of systematic reviews of observational nontherapeutic studies that examined the incidence and prevalence of chronic conditions and risk factors for diseases. The criteria we used to determine the reporting and methodologic quality in systematic reviews were from published standards (8-12). We hypothesized that the quality of systematic reviews differs by the time when the study was published, the country in which the study was conducted, the journal of publication, the sponsorship of the study, and whether a conflict of interest was disclosed. We hypothesized also that systematic reviews with internal quality evaluation of the included studies would have better quality, demonstrating commitment to quality of evidence.


Methods
Data sources

We searched MEDLINE via PubMed and via Ovid MEDLINE, the Cochrane Library (26) and working groups, WorldCat (27), and Scirus (28) to find systematic reviews of observational nontherapeutic studies published in English from 1966 through June 2008 in core clinical journals (exact search string is listed in Appendix Table 1). We used the definitions of core clinical journals from the Abridged Index Medicus (119 indexed titles). We defined observational nontherapeutic studies as observations of patient outcomes that did not examine procedures concerned with the remedial treatment or prevention of diseases (29).

Study selection

Three investigators independently decided on the eligibility of the studies according to recommendations from the Cochrane Handbook for Systematic Reviews of Interventions (13). We reviewed abstracts to exclude comments, expert opinions, letters, case reports, systematic reviews of interventional studies, and systematic reviews of studies of diagnostic accuracy of tests.

Data extraction

Evaluations of the studies and data extraction were performed independently by 2 researchers. Predefined categorical responses to the checklist items were abstracted into our spreadsheet. Errors in data extraction were assessed by a comparison of the data charts with the original articles (13,30). Any discrepancies were discussed and resolved. The quality criteria that we abstracted were based on guidelines for determining the reporting and methodologic quality of systematic reviews (8-12).

To evaluate selection bias, we abstracted whether the authors of systematic reviews described the search strategy (yes, no, or partially); yes indicated that the authors reported time periods of searches, searched databases, and exact search string. We abstracted whether the authors of systematic reviews described study flow (yes, no, or partially); yes indicated that the authors reported the list of retrieved citations, the list of excluded studies, and justification for exclusion.

We abstracted as dichotomous variables whether the authors of systematic reviews did any of the following:

  • Stated the aim of the review and the primary and secondary hypotheses of the review.
  • Included or justified exclusion of articles published in languages other than English.
  • Searched for gray literature, including abstracts and unpublished studies, to evaluate publication bias (21).
  • Described any contact with authors of the included studies.
  • Analyzed sponsorship of and conflict of interest in the included studies.

We abstracted how the authors of systematic reviews described obtained statistical methods with justification and models for pooling with fixed or random effects models in sufficient detail to be replicated (no pooling, random, or fixed). We abstracted whether the authors of pooling analyses reported statistical tests for heterogeneity and whether heterogeneity was statistically significant (not reported, not significant, or significant).

We used 3 categories to classify whether the authors of systematic reviews had evaluated the quality of included studies by using developed or previously published checklists or scales (31): 1) the authors stated planned, formal internal quality evaluations; 2) the authors abstracted selected criteria of external or internal validity without using a planned, formal, and comprehensive internal quality evaluation; and 3) the authors did not conduct internal quality evaluations. We further categorized the studies that evaluated quality criteria to compare studies with no mention of internal quality evaluation of the included studies. We also compared studies with and without planned formal internal quality evaluation. We abstracted with dichotomous responses blinding and reliability testing (reported or not reported) of internal quality evaluations.

We abstracted several explanatory variables that could be related to the quality of systematic reviews:

  • The year of publication, defined as a continuous variable. We created categories of 4- or 5-year periods: 1990 to 1994, 1995 to 1999, 2000 to 2004, and 2005 through June 2008.
  • The journals of publication.
  • The country where the systematic reviews were performed.
  • The sponsorship of the reviews. Those that had either governmental or foundational support or were fellowships were defined as having nonprofit support.
  • The disclosure of conflict of interest by authors of reviews (either not disclosed, disclosed as no conflict of interest, or disclosed conflict of interest).
  • The number of disclosed relationships with industry, defined as a continuous variable.
  • The sponsor's participation in data collection, analysis, and interpretation of the results of the review.
  • The review outcomes as risk factors for prevalence or incidence of chronic conditions or diseases.
Data synthesis

We summarized the results in evidence tables. We used prespecified categories of dependent and independent variables and did not force the data into binary categories for definitive tests of significance. We used univariate logistic regression to examine the association between internal quality evaluation and the year of the publication by using the Wald test. Odds ratios (ORs) were calculated with binary logit models and Fisher's scoring method technique. We computed the fractions of systematic reviews meeting various quality criteria in each of the 4 time periods considered. The proportions of systematic reviews that met different levels of each quality criterion were evaluated by using χ2 tests and Fisher's exact tests in cases of small numbers. All calculations were performed at 95% confidence intervals (CIs) by using 2-sided P values with SAS version 9.1.3 (SAS Institute Inc, Cary, North Carolina).


Results

We found 145 eligible systematic reviews of observational nontherapeutic studies (study flow in the Appendix Figure) (32-176). The number of published systematic reviews increased from 17 during 1990-1994 to 56 during 2005-2008. Most of the studies were conducted in the United States (55 publications) or in the United Kingdom (28 publications) (Appendix Table 2). Half of the systematic reviews (73 publications) were funded by nonprofit organizations; 56 (39%) reviews did not publish their funding sources, 4 reviews received industry support, and 10 were sponsored jointly by industry and nonprofit organizations. Almost three-fourths (106) of the authors of systematic reviews did not disclose conflict of interest; 35 publications stated that the authors do not have any conflict of interest; and 4 studies were conducted by authors who reported conflict of interest. The studies were published in 49 journals. Most systematic reviews (122 studies) assessed risk factors for chronic diseases, 19 summarized estimates of prevalence or incidence, 2 studies reported prevalence and associations with risk factors, and 2 studies examined levels of risk factors. Most studies reported incidence and risk factors for cardiovascular diseases (46 studies) or cancer (26 studies).

Quality of systematic reviews

Less than half of the studies reported study flow (49%), assessed gray literature (27%), or addressed language bias (29%) (Table 1). Only 2% of reviews abstracted sponsorship of individual studies and none abstracted the disclosure of conflict of interest by the authors of individual studies that were eligible for the reviews. Pooling was performed in 137 studies; of these, 62% used a random effects model; 57% reported detecting significant heterogeneity across the studies; and 19% did not provide any information about statistical heterogeneity in pooled estimates. The proportion of systematic reviews that met quality criteria including study flow, assessment of gray literature, or the abstraction of funding sources of included studies did not show significant trends from 1990 through 2008. The proportion of systematic reviews that assessed language bias increased from 8% during 1995-1999 to 41% during 2005-2008. In later years, more studies reported using random effects models (79% during 2005-2008 vs 39% during 1995-1999) and tests for statistical heterogeneity (89% during 2005-2008 vs 65% during 1995-1999).

Internal quality evaluation

Planned and detailed quality assessment of included studies was reported in 37% of systematic reviews, and 18% abstracted more than 1 criterion of external or internal quality; significant positive trends were reported during the evaluated time (Table 1). Quality assessment was masked in 3 studies. Development of the appraisals, including references to previously published tools, was reported in 32 studies, but only 6 tested interobserver agreement for quality assessment.

Quality of systematic review by explanatory factors

The quality of systematic reviews did not differ much by study location or by the journal of publication. Systematic reviews of prevalence or incidence or risk factors of the diseases did not differ in their quality measures. Sponsorship was not associated with quality of the reviews. The role of conflict of interest was impossible to establish because the authors of 56 reviews did not disclose funding and authors of 106 reviews did not disclose conflict of interest.

Explanatory factors of internal quality evaluation of included studies

The journal of publication, topic of the review, and continent where the review was conducted were not associated with the likelihood of internal quality evaluation. Systematic reviews of risk factors tended to conduct internal quality evaluation of the included studies more often than reviews of incidence or prevalence or of levels of risk factors. Systematic reviews sponsored by nonprofit organizations conducted internal quality evaluations of individual studies more often than reviews that received corporate funding. Systematic reviews that disclosed conflict of interest conducted internal quality evaluation of individual studies less frequently (10 of 39 studies; 26%) than reviews with no disclosure (44 of 106 studies; 42%). Odds of formal internal quality evaluation (OR, 1.10 per year; 95% CI, 1.02-1.19) and either planned, formal internal quality evaluation or abstraction of quality criteria (OR, 1.17 per year; 95% CI, 1.08-1.26) increased over time. Disclosure of conflict of interest by the authors of systematic reviews was not associated with greater odds of internal quality evaluation.

Quality of systematic reviews by internal quality evaluation

Complete documentation of the literature search including time period, databases searched, and exact literature search strings was less common among reviews with planned, formal internal quality evaluation (48 studies, 35%) than among reviews without it (90 studies, 65%) (Table 2). However, reviews that either abstracted selected quality criteria or planned, formal internal quality evaluation reported partial (6 studies) or complete (74 studies) information about the literature search more often than studies that did not evaluate quality of included studies (64 studies). Reviews that did not justify exclusion of non-English studies ignored quality of individual studies more often (72 studies) than reviews with planned, formal internal quality evaluation (31 studies). The same pattern was present for publication bias: the reviews that did not mention gray literature also ignored the quality of individual studies. The reviews reporting attempts to contact the authors of included studies either performed planned, formal internal quality evaluation or abstracted selected quality criteria more often than reviews without such attempts (OR, 2.3; 95% CI, 1.1-4.7). Reviews with complete reporting of study flow performed planned, formal internal quality evaluation or abstracted quality criteria more often (51 studies) than reviews without study flows (20 studies). More than half of systematic reviews without planned, formal internal quality evaluation (44 studies) also did not report study flow.

The association between quality of systematic reviews and sponsor participation in the data collection, analyses, and interpretation was difficult to analyze because this information was either omitted or reported in various ways. Less than 10% of systematic reviews contained a clear statement that the sponsors did not play any role in gathering the studies or analyzing or interpreting the results and did not influence the content of the manuscript. Other reviews omitted mention of the role of the sponsor in approval of the manuscript or provided a general statement that sponsors did not influence the conclusions or the content of the paper. Two reviews included statements of unconditional or unrestricted sponsorship of the meta-analyses.


Discussion

Our analyses showed that less than half of the systematic reviews of nontherapeutic observational studies that were published in core clinical journals met each quality criterion. Quality of systematic reviews did not improve over time. Planned, formal internal quality evaluations of the included studies was reported in less than half of systematic reviews, but the prevalence of internal quality evaluations has increased during the last decade. Our findings are in concordance with previously published methodologic analyses of systematic reviews that also found inconsistent quality and incomplete internal quality evaluation of individual studies (6). Methodologic analyses of systematic reviews that focused on particular diseases or conditions demonstrated that half of the publications had major flaws in design and reporting. For instance, systematic reviews of therapies for renal diseases failed to assess the methodologic quality of included studies (177). Methodologic analyses of systematic reviews of interventions showed that 69% of those randomly selected in MEDLINE meta-analyses did not analyze quality of trials (22). Most (68%) systematic reviews of diagnostic tests for cancer did not provide formal assessments of study quality (178). We also found that the quality of reviews did not differ among types of studies (incidence or risk factors for diseases), types of diseases, or journal of publication.

Journal commitment to high-quality research, however, was associated with improved reporting quality of the publications. For example, adoption by journals of the Consolidated Standards of Reporting Trials (CONSORT) improved the quality of the publications of interventional studies (179,180). An endorsement of the developed standards for observational studies including MOOSE and STROBE checklists may also improve quality of the publications. We did not analyze how many core clinical journals adopted these standards and how quality of the publications changed depending on this adaptation. Peer review of submitted manuscripts should include quality assessment using validated tools (12).

We could not identify the factors that can explain differences in quality of systematic reviews. The role of sponsorship and conflict of interest could not be estimated because of poor reporting of this information. The quality and reliability of quality evaluation of the included studies is unclear because development of the appraisals was described in a small proportion of systematic reviews (32 of 80 studies), and only 6 of 80 studies tested interobserver agreement for quality assessment. We did not evaluate all reviews of observational studies that were published in epidemiologic journals. However, it is unlikely that the quality of reviews published in other journals would be better than those in core clinical journals. Future research should investigate the factors that can explain differences in the quality of systematic reviews.

Peer reviewed publications of high-quality systematic reviews can provide the best available research evidence for evidence-based public health (24). Evidence-based decisions can improve public health practice in preventing incidence and progression of chronic diseases (25). In our analysis, less than half of the systematic reviews of observational nontherapeutic studies met quality criteria established in the MOOSE, STROBE, and AMSTAR statements. Internal quality evaluation of included studies should be an essential part of evidence synthesis, but only half of the reviews reported such evaluation. Collaborative efforts from investigators and journal editors are needed to improve quality of systematic reviews.


Notes

The opinions expressed by authors contributing to this journal do not necessarily reflect the opinions of the US Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above. URLs for nonfederal organizations are provided solely as a service to our users. URLs do not constitute an endorsement of any organization by CDC or the federal government, and none should be inferred. CDC is not responsible for the content of Web pages found at these URLs.

Suggested citation for this article: Shamliyan T, Kane RL, Jansen S. Quality of systematic reviews of observational nontherapeutic studies. Prev Chronic Dis 2010;7(6) http://www.cdc.gov/pcd/issues/2010/nov/09_0195.htm. Accessed [date].

This article is based on research conducted by the Minnesota Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, Maryland (contract no. 290-02-0009).

We thank our reviewers David Atkins, MD, John Hoey, MD, and Christine Laine, MD, for reviewing and commenting on the draft; our collaborating experts, Mohammed Ansari, MBBS, Ethan Balk, MD, Nancy Berkman, PhD, Chantelle Garritty, Mark Grant, MD, Gail Janes, PhD, Margaret Maglione, MPP, David Moher, PhD, Mona Nasser, DDS, Gowri Raman, MD, Karen Robinson, MD, Jodi Segal, MD, and Thomas Trikalinos, PhD, for their scientific input throughout this project; and Carmen Kelly, PharmD, our task order officer, and Stephanie Chang, MD, medical officer, at AHRQ for their guidance throughout the project. We also thank librarian Judith Stanke for her contributions to the literature search; research assistants Emily Zabor, candidate for the master of science degree (MS) in biostatistics, and Akweley Ablorh, candidate for MS in biostatistics, for the data abstraction, quality control, and synthesis of evidence; Zhihua Bian, candidate for MS in biostatistics, for her statistical help; Zhiyuan Xu, candidate for MS in applied economics, for his work creating the ACCESS database; Dean McWilliams for his assistance in database development; Qi Wang, research fellow, for her statistical expertise in reliability testing; Susan Duval, PhD, for her help estimating sample size; Marilyn Eells for editing and formatting the report; and Nancy Russell, MLS, and Rebecca Schultz for their assistance gathering data from the experts and formatting the tables, and Christa Prodzinski for quality control of the data.


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Appendix

Figures

[Figure ID: AF1]
Figure 1 

Study flow to identify systematic reviews of observational studies, scales, and checklists for planned formal internal quality evaluation, and studies about bias in observational research, 1990 through June 2008.


Alternate Text: Flow chart.

Tables
[TableWrap ID: TA1] Table 1 

Search Strategy and Exact Search Strings Used to Identify Systematic Reviews of Observational Studies, Scales and Checklists for Internal Quality Evaluation, and Studies About Bias in Observational Research, 1966 Through June 2008


Search Method No. of Articles Identified
Search strategy for Ovid MEDLINE
1. exp Research Design/st [Standards] 4,303
2. exp Chronic Disease/ep [Epidemiology] 1,619
3. exp Urinary Incontinence/ep [Epidemiology] 1,155
4. exp Fecal Incontinence/ep [Epidemiology] 328
5. exp "Sleep Initiation and Maintenance Disorders"/ep [Epidemiology] 565
6. exp Depression/ep [Epidemiology] 4,700
7. exp Depressive Disorder/ep [Epidemiology] 6,816
8. exp Myocardial Infarction/ 43,531
9. 6 or 7 11,214
10. 8 and 9 105
11. 2 or 3 or 4 or 5 or 10 3,636
12. 1 and 11 9
13. exp Data Collection/mt, st [Methods, Standards] 36,173
14. exp "Bias (Epidemiology)"/ 25,369
15. exp Questionnaires/st [Standards] 3,879
16. exp Evidence-Based Medicine/ 27,487
17. 13 or 14 or 15 or 16 86,857
18. 11 and 17 127
19. 12 or 18 133
20. limit 19 to english language 124
21. exp "Predictive Value of Tests"/ 62,290
22. exp "Reproducibility of Results"/ 126,475
23. 21 or 22 182,941
24. 11 and 23 126
25. limit 24 to english language 121
26. 20 or 25 224
27. exp randomized controlled trial/ 151,027
28. 11 and 27 74
29. exp research design/ 134,468
30. 28 and 29 15
31. 1 and 16 547
32. ep.fs. 434,923
33. exp epidemiology/ 6,500
34. 32 or 33 437,784
35. 31 and 34 29
36. exp incidence/ 81,260
37. exp prevalence/ 83,713
38. 36 or 37 157,239
39. 31 and 38 14
40. 26 or 30 or 35 or 39 268
41. limit 40 to english language 267
42. limit 41 to journal article 251
43. from 42 keep 1-251 251
MEDLINE search via PubMed
("Biomedical Research/methods"[MeSH] OR "Biomedical Research/organization and administration"[MeSH] OR "Biomedical Research/standards"[MeSH] OR "Biomedical Research/statistics and numerical data"[MeSH] OR "Biomedical Research/trends"[MeSH]) Limits: Humans, Journal Article, English 3,703
"Epidemiologic Studies"[MeSH] AND "Research Design/standards"[MeSH] AND ("Evaluation Studies as Topic/classification"[MeSH] OR "Evaluation Studies as Topic/methods"[MeSH] OR "Evaluation Studies as Topic/standards"[MeSH]) Limits: Humans, Journal Article, English 59
"Publishing/standards"[MeSH] AND "Epidemiologic Methods"[MeSH] AND "Research Design/standards"[MeSH] Limits: Humans, Journal Article, English 65
"STROBE Initiative"[Corporate Author] 10
"Bias (Epidemiology)"[MeSH] AND "Epidemiologic Studies"[MeSH] AND "Epidemiologic Methods"[MeSH] AND "Research Design/standards"[MeSH] Limits: Humans, Journal Article, English 97
"Evidence-Based Medicine"[MeSH] AND "Epidemiologic Studies"[MeSH] AND "Epidemiologic Methods"[MeSH] AND "Research Design/standards"[MeSH] Limits: Humans, Journal Article, English 25
"Research Design/standards"[MeSH] AND "Epidemiologic Studies"[MeSH] AND "Epidemiologic Measurements"[MeSH] AND "Bias (Epidemiology)"[MeSH] Limits: Humans, Journal Article, English AND "Incidence"[MeSH] Limits: Humans, Journal Article, English 8
"Research Design/standards"[MeSH] AND "Epidemiologic Studies"[MeSH] AND "Epidemiologic Measurements"[MeSH] AND "Bias (Epidemiology)"[MeSH] Limits: Humans, Journal Article, English AND "Prevalence"[MeSH] Limits: Humans, Journal Article, English 7
("Prevalence"[MeSH]) AND systematic[sb] "Working group" Limits: English 15
[CN] Limits: Humans, Meta-Analysis, English, Core clinical journals 2
("Prevalence"[MeSH]) AND systematic[sb] Limits: Humans, Meta-Analysis, English, Core clinical journals 83
Moher D[author] 198
"Epidemiologic Studies"[MeSH] Limits: Humans, Meta-Analysis, English AND "Incidence"[MeSH] Limits: Humans, Meta-Analysis, English Limits: Humans, Meta-Analysis, English, Core clinical journals 57
"Epidemiologic Studies"[MeSH] AND "Incidence"[MeSH] Limits: Humans, Meta-Analysis, English 236
"Epidemiologic Studies"[MeSH] AND "Incidence"[MeSH] AND Evidence Limits: Humans, Meta-Analysis, English 52
"Incidence"[MeSH] Limits: Humans, Meta-Analysis, English 635
"Risk"[MeSH] AND "Epidemiologic Studies"[MeSH] Limits: Humans, Meta-Analysis, English, Core clinical journals 273
"Prevalence"[MeSH] Limits: Humans, Meta-Analysis, English, Core clinical journals 84
Altman DG[author] 7
Higgins J[author] 3
"Review Literature as Topic"[MeSH] AND "Research Design/standards"[MeSH] AND "Epidemiologic Studies"[MeSH] Limits: Humans, English, Core clinical journals 0
"Review Literature as Topic"[MeSH] AND "Epidemiologic Studies"[MeSH] AND "Quality control"[MeSH] 1
"Incidence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Peer Review, Research"[MeSH] AND "Research Design/standards"[MeSH] 0
"Incidence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Peer Review, Research"[MeSH] 0
"Incidence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Research Design/standards"[MeSH] 0
"Incidence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND ("Data Collection/methods"[MeSH] OR "Data Collection/standards"[MeSH]) 5
"Incidence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Bias (Epidemiology)"[MeSH] 1
"Incidence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND ("Questionnaires/methods"[MeSH] OR "Questionnaires/standards"[MeSH]) 0
"Incidence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Evidence-Based Medicine"[MeSH] 2
"Incidence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Reproducibility of Results"[MeSH] 3
"Prevalence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Peer Review, Research"[MeSH] AND "Research Design/standards"[MeSH] 0
"Prevalence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Peer Review, Research"[MeSH] 0
"Prevalence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Research Design/standards"[MeSH] 0
"Prevalence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND ("Data Collection/methods"[MeSH] OR "Data Collection/standards"[MeSH]) 16
"Prevalence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Bias (Epidemiology)"[MeSH] 6
"Prevalence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND ("Questionnaires/methods"[MeSH] OR "Questionnaires/standards"[MeSH]) 1
"Prevalence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Evidence-Based Medicine"[MeSH] 0
"Prevalence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Reproducibility of Results"[MeSH] 12
"Risk Factors"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Peer Review, Research"[MeSH] AND "Research Design/standards"[MeSH] 0
"Risk Factors"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Peer Review, Research"[MeSH] 0
"Risk Factors"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Research Design/standards"[MeSH] 1
"Risk Factors"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND ("Data Collection/methods"[MeSH] OR "Data Collection/standards"[MeSH]) 18
"Risk Factors"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Bias (Epidemiology)"[MeSH] 7
"Risk Factors"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND ("Questionnaires/methods"[MeSH] OR "Questionnaires/standards"[MeSH]) 1
"Risk Factors"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Evidence-Based Medicine"[MeSH] 4
"Risk Factors"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Reproducibility of Results"[MeSH] 10
"Health Care Quality, Access, and Evaluation"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Peer Review, Research"[MeSH] AND "Research Design/standards"[MeSH] 0
"Health Care Quality, Access, and Evaluation"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Peer Review, Research"[MeSH] 0
"Health Care Quality, Access, and Evaluation"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Research Design/standards"[MeSH] 4
"Health Care Quality, Access, and Evaluation"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Evidence-Based Medicine"[MeSH] 8
"Health Care Quality, Access, and Evaluation"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Bias (Epidemiology)"[MeSH] 33
"Models, Statistical"[MeSH] AND "Risk Factors"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Research Design/standards"[MeSH] 0
"Models, Statistical"[MeSH] AND "Incidence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Research Design/standards"[MeSH] 0
"Models, Statistical"[MeSH] AND "Prevalence"[MeSH] AND "Chronic Disease/epidemiology"[MeSH] AND "Research Design/standards"[MeSH] 0
"Epidemiologic Studies"[MeSH] AND "Models, Statistical"[MeSH] AND "Research Design/standards"[MeSH] 47
"Prevalence"[MeSH] AND "Epidemiologic Studies"[MeSH] AND "Models, Statistical"[MeSH] AND "Bias (Epidemiology)"[MeSH] 61
"Incidence"[MeSH] AND "Epidemiologic Studies"[MeSH] AND "Models, Statistical"[MeSH] AND "Bias (Epidemiology)"[MeSH] 66
"Research Design/standards"[MeSH] AND ("Biomedical Research/methods"[MeSH] OR "Biomedical Research/organization and administration"[MeSH] OR "Biomedical Research/standards"[MeSH] OR "Biomedical Research/statistics and numerical data"[MeSH] OR "Biomedical Research/trends"[MeSH]) Limits: Humans, Journal Article, English 62

T1AFN1Abbreviations: MeSH, Medical Subject Heading term; sb, subset; CN, corporate author.


[TableWrap ID: d32e8540]
This flow chart shows 3 boxes. The top box reads
Total references — 1,053
  • Medline via PubMed — 904
  • Related publications — 14
  • WorldCat — 2
  • Scirus — 28
  • Manual search — 70
  • Guidelines, textbooks, consensus statements — 23
  • Published by the authors — 11
  • Cochrane Library — 1
It is connected by a vertical line to 2 additional boxes. The left box reads
Included studies — 397
  • Systematic reviews for the present article — 145
  • Tools (scales and checklists) — 96
  • Working groups — 13
  • Methodologic studies about bias in observational research — 143
The right box reads
Excluded studies — 656
  • Ethical guidelines — 3
  • Reviews — 23
  • Centers for Disease Control and Prevention study — 4
  • Related to interventions — 209
  • Related to diagnostic studies — 54
  • Not relevant to research questions — 363

[TableWrap ID: TA2] Table 2 

Quality of Systematic Review and Meta-Analyses of Nontherapeutic Observational Studies Published in Core Clinical Journals, 1990 through June 2008


Publication Characteristics Outcome Estimate Assessment of Quality of Included Studies
Bracken, 1990 (32)
Country: United States
Journal: Obstet Gynecol
Sponsorship: Not reported
Conflict of interest (COI): Not reported
Sponsor participation in data analyses: Not reported
Congenital malformations in offspring Risk No
Romieu et al, 1990 (33)
Country: United States
Journal: Cancer
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Breast cancer Risk Quality criteria abstracted
Haughey et al, 1992 (34)
Country: United States
Journal: Ann Otol Rhinol Laryngol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Second malignant tumors in head and neck cancer Risk No
Lemon et al, 1992 (35)
Country: United States
Journal: Cancer
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Nonfamilial breast cancer Continuous variable No
McKenna, 1992 (36)
Country: United Kingdom
Journal: Am J Med
Sponsorship: Nonprofit organization, nursing home
COI: Not reported
Sponsor participation in data analyses: Not reported
Differences in vitamin D status Prevalence Quality criteria abstracted
Morris et al, 1992 (37)
Country: United States
Journal: Am J Public Health
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Cancer Risk Yes
Myers and Basinski, 1992 (38)
Country: Canada
Journal: Arch Intern Med
Sponsorship: Nonprofit organization, award
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary heart disease Risk No
Becker et al, 1993 (39)
Country: United States
Journal: Ann Emerg Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Survival of cardiac arrest Risk No
Brownson et al, 1993 (40)
Country: United States
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Adult leukemia Risk Yes
Ernst and Resch, 1993 (41)
Country: Austria
Journal: Ann Intern Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Cardiovascular risk factor Risk No
Katerndahl, 1993 (42)
Country: United States
Journal: J Nerv Ment Dis
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Panic disorder and mitral valve prolapse Risk Yes
Harris and Barraclough, 1994 (43)
Country: United Kingdom
Journal: Medicine
Sponsorship: Industry
COI: Not reported
Sponsor participation in data analyses: Not reported
Suicide Risk No
Kawachi et al, 1994 (44)
Country: United States
Journal: Br Heart J
Sponsorship: Industry, scholarship
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary heart disease Risk No
Law et al, 1994 (45)
Country: United Kingdom
Journal: BMJ
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Hazards of reducing serum cholesterol Risk No
Law et al, 1994 (46)
Country: United Kingdom
Journal: BMJ
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Ischemic heart disease Risk No
Steffen et al, 1994 (47)
Country: Switzerland
Journal: JAMA
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Hepatitis A Risk No
Zhang and Begg, 1994 (48)
Country: United States
Journal: Int J Epidemiol
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Cervical neoplasia Risk No
Everhart and Wright, 1995 (49)
Country: United States
Journal: JAMA
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Pancreatic cancer Risk No
Feinberg et al, 1995 (50)
Country: United States
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Atrial fibrillation Prevalence No
Ritchie and Kildea, 1995 (51)
Country: France
Journal: Lancet
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Senile dementia Prevalence No
Raman-Wilms et al, 1995 (52)
Country: Canada
Journal: Obstet Gynecol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Fetal genital effects Risk No
Hatsukami and Fischman, 1996 (53)
Country: United States
Journal: JAMA
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Use of crack cocaine and cocaine hydrochloride Prevalence No
Hill and Schoener, 1996 (54)
Country: United States
Journal: Am J Psychiatry
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Attention deficit hyperactivity disorder Prevalence No
Hackshaw et al, 1997 (55)
Country: United Kingdom
Journal: BMJ
Sponsorship: Government
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: "The views expressed are those of the authors and not necessarily those of the Department of Health."
Lung cancer Risk No
Kluijtmans et al, 1997 (56)
Country: Netherlands
Journal: Circulation
Sponsorship: Nonprofit organization, industry
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary artery disease Risk No
Law and Hackshaw, 1997 (57)
Country: United Kingdom
Journal: BMJ
Sponsorship: None
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: None
Hip fracture Risk No
Law et al, 1997 (58)
Country: United Kingdom
Journal: BMJ
Sponsorship: Government
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: "The Department of Health (England) supported this work, although the views are our own."
Ischemic heart disease Risk No
Danesh et al, 1998 (59)
Country: United Kingdom
Journal: JAMA
Sponsorship: Scholarship, nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary heart disease Risk Yes
French and Brocklehurst, 1998 (60)
Country: United Kingdom
Journal: Br J Obstet Gynaecol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Survival in women infected with human immunodeficiency virus Risk Yes
Forgie et al, 1998 (61)
Country: Canada
Journal: Arch Intern Med
Sponsorship: Industry, government, fellowships, nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Allogeneic blood transfusion Risk No
Huang et al, 1998 (62)
Country: Canada
Journal: Gastroenterology
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Gastric cancer Risk Yes
Johnston et al, 1998 (63)
Country: United States
Journal: Neurology
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Subarachnoid hemorrhage Risk No
Lazarou et al, 1998 (64)
Country: Canada
Journal: JAMA
Sponsorship: Scholarship, nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Adverse drug reactions in hospitalized patients Prevalence Quality criteria abstracted
Ray, 1998 (65)
Country: Canada
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Venous thromboembolic disease Risk Quality criteria abstracted
Spencer-Green, 1998 (66)
Country: United States
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Secondary diseases from primary Reynaud phenomenon Risk Yes
Stratton et al, 1998 (67)
Country: United Kingdom
Journal: Br J Obstet Gynaecol
Sponsorship: Research fellowship, nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Ovarian cancer Risk No
Zock and Katan, 1998 (68)
Country: Netherlands
Journal: Am J Clin Nutr
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Breast, colorectal, and prostate cancer Risk Quality criteria abstracted
Zondervan et al, 1998 (69)
Country: United Kingdom
Journal: Br J Obstet Gynaecol
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Chronic pelvic pain in women Prevalence No
Angelillo and Villari, 1999 (70)
Country: Italy
Journal: Bull World Health Organ
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Childhood leukemia Risk Yes
He et al, 1999 (71)
Country: United States
Journal: N Engl J Med
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary heart disease Risk No
Shaffer et al, 1999 (72)
Country: United States
Journal: Am J Public Health
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Disordered gambling behavior Prevalence No
Wittrup et al, 1999 (73)
Country: Denmark
Journal: Circulation
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Ischemic heart disease Risk Yes
Yoder et al, 1999 (74)
Country: United States
Journal: Obstet Gynecol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Fetus with isolated choroid plexus cysts Risk No
Christen et al, 2000 (75)
Country: United States
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Cardiovascular disease Risk Yes
Cleophas et al, 2000 (76)
Country: Netherlands
Journal: Am J Cardiol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary artery disease Risk Yes
DiMatteo et al, 2000 (77)
Country: United States
Journal: Arch Intern Med
Sponsorship: Industry, scholarship
COI: Not reported
Sponsor participation in data analyses: Not reported
Noncompliance with medical treatment Risk Quality criteria abstracted
WHO Collaborative Study Team on the Role of Breastfeeding on the Prevention of Infant Mortality, 2000 (78)
Country: Brazil
Journal: Lancet
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Infant and child mortality Risk No
Wilson et al, 2000 (79)
Country: Canada
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Mortality after myocardial infarction Risk Yes
Zeegers et al, 2000 (80)
Country: Netherlands
Journal: Cancer
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Urinary tract cancer Risk Yes
Danesh et al, 2001 (81)
Country: United Kingdom
Journal: Circulation
Sponsorship: Government, scholarship
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary heart disease Risk No
Eaden et al, 2001 (82)
Country: United Kingdom
Journal: Gut
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Colorectal cancer Risk Yes
Faraone et al, 2001 (83)
Country: United States
Journal: Am J Psychiatry
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Attention deficit hyperactivity disorder Risk Yes
Horta et al, 2001 (84)
Country: Brazil
Journal: Am J Public Health
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Early weaning Risk Yes
Rebora, 2001 (85)
Country: Italy
Journal: Arch Dermatol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary artery disease Risk Yes
Cannon et al, 2002 (86)
Country: United Kingdom
Journal: Am J Psychiatry
Sponsorship: Research fellowship, nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Schizophrenia Risk No
Hellermann et al, 2002 (87)
Country: United States
Journal: Am J Med
Sponsorship: Government, nonprofit organization, fellowship
COI: Not reported
Sponsor participation in data analyses: Not reported
Heart failure Risk No
Huang et al, 2002 (88)
Country: Canada
Journal: Lancet
Sponsorship: Not reported
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Peptic-ulcer disease Risk Yes
Huncharek et al, 2002 (89)
Country: United States
Journal: Am J Public Health
Sponsorship: Nonprofit organization, industry
COI: Not reported
Sponsor participation in data analyses: Not reported
Malignant melanoma Risk Yes
Juul et al, 2002 (90)
Country: Denmark
Journal: Blood
Sponsorship: Government, nonprofit organization
COI: Not reported
Sponsor participation in data analyses: "They had no role in gathering, analyzing, or interpreting the data and had no right to approve or disapprove the submitted paper."
Factor V Leiden Risk Yes
Kelly et al, 2002 (91)
Country: United States
Journal: Neurology
Sponsorship: Nonprofit organization, industry, fellowship
COI: Not reported
Sponsor participation in data analyses: Not reported
Risk of ischemic stroke Risk No
Klerk et al, 2002 (92)
Country: Netherlands
Journal: JAMA
Sponsorship: Government, "public/private partnership"
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary heart disease Risk Yes
Kozer et al, 2002 (93)
Country: Canada
Journal: Am J Obstet Gynecol
Sponsorship: Industry
COI: Not reported
Sponsor participation in data analyses: Not reported
Congenital anomalies Risk No
Law et al, 2002 (94)
Country: United Kingdom
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Death after myocardial infarction Risk No
Wald et al, 2002 (95)
Country: United Kingdom
Journal: BMJ
Sponsorship: None
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: None
Cardiovascular disease Risk No
Wald and Link, 2002 (96)
Country: United States
Journal: J Infect Dis
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Human immunodeficiency virus infection Risk No
Benjamin et al, 2003 (97)
Country: United States
Journal: Pediatrics
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
End-organ damage Prevalence No
Clarfield, 2003 (98)
Country: Israel
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Reversible dementias Prevalence No
Cole and Dendukuri, 2003 (99)
Country: Canada
Journal: Am J Psychiatry
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Depression among elderly community subjects Risk Yes
Gisbert et al, 2003 (100)
Country: Spain
Journal: Gastroenterology
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Hepatitis C virus infection Risk Yes
Glatt et al, 2003 (101)
Country: United States
Journal: Am J Psychiatry
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Schizophrenia Risk No
Halbert et al, 2003 (102)
Country: United States
Journal: Chest
Sponsorship: Industry
COI: Not reported
Sponsor participation in data analyses: Not reported
Prevalence estimates for chronic obstructive pulmonary disease Prevalence No
Huang et al, 2003 (103)
Country: Canada
Journal: Gastroenterology
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Gastric cancer Risk Yes
Rey et al, 2003 (104)
Country: Canada
Journal: Lancet
Sponsorship: Government
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Fetal loss Risk Yes
Riboli and Norat, 2003 (105)
Country: France
Journal: Am J Clin Nutr
Sponsorship: Government
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Cancer risk Risk No
Scholten-Peeters et al, 2003 (106)
Country: Netherlands
Journal: Pain
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Whiplash-associated disorders Risk Yes
Thurnham et al, 2003 (107)
Country: United Kingdom
Journal: Lancet
Sponsorship: Government, fellowship
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: "The funding source had no role in study design, data collection, data analysis, data interpretation, or in the writing of this report."
Vitamin A deficiency Continuous variable No
Zeegers et al, 2003 (108)
Country: Netherlands
Journal: Cancer
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Prostate carcinoma Risk No
Burzotta et al, 2004 (109)
Country: Italy
Journal: Heart
Sponsorship: Fellowship
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary ischemic syndromes Risk No
Casas et al, 2004 (110)
Country: United Kingdom
Journal: Circulation
Sponsorship: Government, 1 author holds a chair of nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Ischemic heart disease Risk No
Casas et al, 2004 (111)
Country: United Kingdom
Journal: Arch Neurol
Sponsorship: Fellowship
COI: Not reported
Sponsor participation in data analyses: Not reported
Ischemic stroke Risk No
He et al, 2004 (112)
Country: United States
Journal: Circulation
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary heart disease mortality Risk No
Huang et al, 2004 (113)
Country: United States
Journal: Neurology
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Sporadic Parkinson disease Risk No
Klement et al, 2004 (114)
Country: Israel
Journal: Am J Clin Nutr
Sponsorship: Medical center
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Inflammatory bowel disease Risk Yes
Kovalevsky et al, 2004 (115)
Country: United States
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Recurrent pregnancy loss Risk No
Levitan et al, 2004 (116)
Country: United States
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Cardiovascular disease Risk No
Lovett et al, 2004 (117)
Country: United Kingdom
Journal: Neurology
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Subtype of ischemic stroke Risk Yes
Mitsikostas et al, 2004 (118)
Country: Greece
Journal: Brain
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Headache Risk No
Montanez et al, 2004 (119)
Country: United States
Journal: Arch Intern Med
Sponsorship: Not reported
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Total and cardiovascular mortality and sudden death Risk No
Woodbury and Houghton, 2004 (120)
Country: Canada
Journal: Ostomy Wound Manage
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Pressure ulcers Prevalence Yes
Bolland et al, 2005 (121)
Country: New Zealand
Journal: J Clin Endocrinol Metab
Sponsorship: Scholarship
COI: Not reported
Sponsor participation in data analyses: Not reported
Increased body weight Risk Quality criteria abstracted
Contopoulos-Ioannidis et al, 2005 (122)
Country: Greece
Journal: J Allergy Clin Immunol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Asthma phenotypes Risk Quality criteria abstracted
Dauchet et al, 2005 (123)
Country: France
Journal: Neurology
Sponsorship: Nonprofit organization, educational institute
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Stroke Risk No
Etminan et al, 2005 (124)
Country: Canada
Journal: BMJ
Sponsorship: Government, fellowship
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Ischemic stroke Risk Yes
Fazel et al, 2005 (125)
Country: United Kingdom
Journal: Lancet
Sponsorship: Nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: "The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication."
Serious mental disorder Prevalence Quality criteria abstracted
García-Closas et al, 2005 (126)
Country: United States
Journal: Lancet
Sponsorship: Nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: "The study sponsors had no role in the design of the study; in the collection, analysis, or interpretation of the data; or in the writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit the paper for publication."
Bladder cancer Risk No
Lee et al, 2005 (127)
Country: United States
Journal: Arthritis Rheum
Sponsorship: Government, industry
COI: Not reported
Sponsor participation in data analyses: Unrestricted
Systemic lupus erythematosus Risk No
Lin and August, 2005 (128)
Country: United States
Journal: Obstet Gynecol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Preeclampsia Risk No
McDonald et al, 2005 (129)
Country: Canada
Journal: Am J Obstet Gynecol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Perinatal outcomes Risk Yes
Palmer, 2005 (130)
Country: United States
Journal: Arch Gen Psychiatry
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Lifetime risk of suicide in schizophrenia Prevalence Quality criteria abstracted
Sin et al, 2005 (131)
Country: Canada
Journal: Chest
Sponsorship: Nonprofit organization, educational institute
COI: Not reported
Sponsor participation in data analyses: Not reported
Cardiovascular mortality Risk Yes
Boudville et al, 2006 (132)
Country: Canada
Journal: Ann Intern Med
Sponsorship: Government, fellowship
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: "The study sponsors had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication."
Hypertension Risk No
Clark et al, 2006 (133)
Country: United Kingdom
Journal: Pediatrics
Sponsorship: Fellowship
COI: Not reported
Sponsor participation in data analyses: Not reported
Fractures Risk Yes
de Boer et al, 2006 (134)
Country: Netherlands
Journal: Cancer
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Unemployment Risk Yes
Di Castelnuovo et al, 2006 (135)
Country: Italy
Journal: Arch Intern Med
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: "The sponsor of the study had no involvement in study design; data collection, analysis, or interpretation; writing of the report; or in the decision to submit the paper for publication."
Total mortality in men and women Risk Yes
Flores-Mateo et al, 2006 (136)
Country: United States
Journal: Am J Clin Nutr
Sponsorship: Nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Coronary heart disease Risk Yes
Galassi et al, 2006 (137)
Country: United States
Journal: Am J Med
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Cardiovascular disease Risk Quality criteria abstracted
Huxley et al, 2006 (138)
Country: Australia
Journal: BMJ
Sponsorship: Government, fellowship, industry
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Unconditional
Fatal coronary heart disease Risk Quality criteria abstracted
Kahlenborn et al, 2006 (139)
Country: United States
Journal: Mayo Clin Proc
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Premenopausal breast cancer Risk Quality criteria abstracted
Larsson et al, 2006 (140)
Country: Sweden
Journal: Gastroenterology
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Esophageal, gastric, and pancreatic cancer Risk Quality criteria abstracted
Mahid et al, 2006 (141)
Country: United States
Journal: Mayo Clin Proc
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: Not reported
Inflammatory bowel disease Risk Yes
Owen et al, 2006 (142)
Country: United Kingdom
Journal: Am J Clin Nutr
Sponsorship: Nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Type 2 diabetes Risk Quality criteria abstracted
Ownby et al, 2006 (143)
Country: United States
Journal: Arch Gen Psychiatry
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Alzheimer disease Risk Yes
Pavia et al, 2006 (144)
Country: Italy
Journal: Am J Clin Nutr
Sponsorship: Not reported
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Oral cancer Risk Yes
Riddle et al, 2006 (145)
Country: United States
Journal: Am J Trop Med Hyg
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Diarrhea Prevalence Yes
Rutledge et al, 2006 (146)
Country: United States
Journal: J Am Coll Cardiol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Depression Prevalence/ risk Quality criteria abstracted
Smith et al, 2006 (147)
Country: United States
Journal: J Am Coll Cardiol
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Renal impairment Risk Yes
Weis et al, 2006 (148)
Country: United States
Journal: Arch Ophthalmol
Sponsorship: Government
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Uveal melanoma Risk Quality criteria abstracted
Williams et al, 2006 (149)
Country: United Kingdom
Journal: Arch Dis Child
Sponsorship: Nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Autism spectrum disorders Prevalence/ risk Quality criteria abstracted
Bahekar et al, 2007 (150)
Country: United States
Journal: Am Heart J
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Coronary heart disease Risk Yes
Baurecht et al, 2007 (151)
Country: Germany
Journal: J Allergy Clin Immunol
Sponsorship: Government, university
COI: Reported as a conflict of interest
Sponsor participation in data analyses: Not reported
Atopic eczema Risk No
Bellamy et al, 2007 (152)
Country: United Kingdom
Journal: BMJ
Sponsorship: Government, fellowship
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Cardiovascular disease Risk Quality criteria abstracted
Conde-Agudelo et al, 2007 (153)
Country: Colombia
Journal: Am J Obstet Gynecol
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: "The content of the paper has not been influenced by the sponsor."
Maternal health Risk Yes
Dehghan et al, 2007 (154)
Country: Netherlands
Journal: Diabetes
Sponsorship: University, government
COI: Not reported
Sponsor participation in data analyses: Not reported
Diabetes Risk No
Eichler et al, 2007 (155)
Country: Switzerland
Journal: Am Heart J
Sponsorship: Nonprofit organization
COI: Not reported
Sponsor participation in data analyses: "The funding source had no influence on study design; in the collection, analysis, and interpretation of the data; in the writing of the manuscript; and in the decision to submit the manuscript for publication."
First coronary events Risk Yes
Gami et al, 2007 (156)
Country: United States
Journal: J Am Coll Cardiol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Cardiovascular events and death Risk Yes
Grulich et al, 2007 (157)
Country: Australia
Journal: Lancet
Sponsorship: Government, fellowship, scholarship
COI: Reported as a conflict of interest
Sponsor participation in data analyses: "There was no funding source for this study. All authors had access to all the data. The corresponding author had final responsibility for the decision to submit for publication."
Cancers Risk Yes
Havemann et al, 2007 (158)
Country: United States
Journal: Gut
Sponsorship: Industry
COI: Reported as a conflict of interest
Sponsor participation in data analyses: Not reported
Asthma Risk Quality criteria abstracted
Hirtz et al, 2007 (159)
Country: United States
Journal: Neurology
Sponsorship: Not reported
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Common neurologic disorders Prevalence Yes
Huxley et al, 2007 (160)
Country: Australia
Journal: Am J Clin Nutr
Sponsorship: Government, nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: "None of the funding sources had any role in the study design, data analysis, data interpretation, writing of the paper, or the decision to submit the paper for publication."
Ischemic heart disease Risk Yes
Krishna and Kim, 2007 (161)
Country: United States
Journal: J Neurosurg
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: Not reported
Risk factors for subarachnoid hemorrhage Risk Quality criteria abstracted
Langan et al, 2007 (162)
Country: United Kingdom
Journal: Arch Dermatol
Sponsorship: Nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: "The sponsor had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript."
Eczema Risk Quality criteria abstracted
Larsson and Wolk, 2007 (163)
Country: Sweden
Journal: Am J Clin Nutr
Sponsorship: Nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Colon and rectal cancer risk Risk Quality criteria abstracted
Larsson and Wolk, 2007 (164)
Country: Sweden
Journal: Gastroenterology
Sponsorship: Nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: "The sponsor had no role in the study design or in the collection, analysis, and interpretation of the data."
Liver cancer Risk Quality criteria abstracted
Liu et al, 2007 (165)
Country: China
Journal: J Am Coll Cardiol
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Recurrence of atrial fibrillation after successful electrical cardioversion Risk Yes
Loza and Chang, 2007 (166)
Country: United States
Journal: J Allergy Clin Immunol
Sponsorship: Government, nonprofit organization
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Atopic asthma risk Risk Yes
Pittas et al, 2007 (167)
Country: United States
Journal: J Clin Endocrinol Metab
Sponsorship: Government
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Type 2 diabetes Risk No
Polanczyk et al, 2007 (168)
Country: Brazil
Journal: Am J Psychiatry
Sponsorship: Industry, foreign grants
COI: Not reported
Sponsor participation in data analyses: "There was no involvement of any funding source in the study design, data collection, analysis, interpretation of data, and writing of this article or in the decision to submit the article for publication."
Attention deficit hyperactivity disorder Prevalence No
Rona et al, 2007 (169)
Country: United Kingdom
Journal: J Allergy Clin Immunol
Sponsorship: Government
COI: Reported as a conflict of interest
Sponsor participation in data analyses: Not reported
Food allergy Prevalence Quality criteria abstracted
Sarwar et al, 2007 (170)
Country: United Kingdom
Journal: Circulation
Sponsorship: Government, scholarship, industry
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Unrestricted
Coronary heart disease Risk No
Snoep et al, 2007 (171)
Country: Netherlands
Journal: Am Heart J
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Clopidogrel nonresponsiveness Prevalence Yes
Zintzaras and Kaditis, 2007 (172)
Country: Greece
Journal: Arch Pediatr Adolesc Med
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Blood pressure Risk Yes
Ageno et al, 2008 (173)
Country: Italy
Journal: Circulation
Sponsorship: Not reported
COI: Not reported
Sponsor participation in data analyses: Not reported
Venous thromboembolism Risk Yes
Barclay et al, 2008 (174)
Country: Australia
Journal: Am J Clin Nutr
Sponsorship: Government
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Chronic disease risk Risk Quality criteria abstracted
Conde-Agudelo et al, 2008 (175)
Country: United States
Journal: Am J Obstet Gynecol
Sponsorship: Government
COI: Not reported
Sponsor participation in data analyses: "The views expressed in this document are solely the responsibility of the authors and do not necessarily represent the views of the World Health Organization."
Risk of preeclampsia Risk Yes
Schunkert et al, 2008 (176)
Country: Germany
Journal: Circulation
Sponsorship: Government
COI: Reported as not a conflict of interest
Sponsor participation in data analyses: Not reported
Coronary artery disease Risk No


Article Categories:
  • Systematic Review
Series: Peer Reviewed.


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