PMID- 27649528
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20220408
IS  - 1549-1676 (Electronic)
IS  - 1549-1277 (Print)
IS  - 1549-1277 (Linking)
VI  - 13
IP  - 9
DP  - 2016 Sep
TI  - Reporting of Adverse Events in Published and Unpublished Studies of Health Care 
      Interventions: A Systematic Review.
PG  - e1002127
LID - 10.1371/journal.pmed.1002127 [doi]
LID - e1002127
AB  - BACKGROUND: We performed a systematic review to assess whether we can quantify 
      the underreporting of adverse events (AEs) in the published medical literature 
      documenting the results of clinical trials as compared with other nonpublished 
      sources, and whether we can measure the impact this underreporting has on 
      systematic reviews of adverse events. METHODS AND FINDINGS: Studies were 
      identified from 15 databases (including MEDLINE and Embase) and by handsearching, 
      reference checking, internet searches, and contacting experts. The last database 
      searches were conducted in July 2016. There were 28 methodological evaluations 
      that met the inclusion criteria. Of these, 9 studies compared the proportion of 
      trials reporting adverse events by publication status. The median percentage of 
      published documents with adverse events information was 46% compared to 95% in 
      the corresponding unpublished documents. There was a similar pattern with 
      unmatched studies, for which 43% of published studies contained adverse events 
      information compared to 83% of unpublished studies. A total of 11 studies 
      compared the numbers of adverse events in matched published and unpublished 
      documents. The percentage of adverse events that would have been missed had each 
      analysis relied only on the published versions varied between 43% and 100%, with 
      a median of 64%. Within these 11 studies, 24 comparisons of named adverse events 
      such as death, suicide, or respiratory adverse events were undertaken. In 18 of 
      the 24 comparisons, the number of named adverse events was higher in unpublished 
      than published documents. Additionally, 2 other studies demonstrated that there 
      are substantially more types of adverse events reported in matched unpublished 
      than published documents. There were 20 meta-analyses that reported the odds 
      ratios (ORs) and/or risk ratios (RRs) for adverse events with and without 
      unpublished data. Inclusion of unpublished data increased the precision of the 
      pooled estimates (narrower 95% confidence intervals) in 15 of the 20 pooled 
      analyses, but did not markedly change the direction or statistical significance 
      of the risk in most cases. The main limitations of this review are that the 
      included case examples represent only a small number amongst thousands of 
      meta-analyses of harms and that the included studies may suffer from publication 
      bias, whereby substantial differences between published and unpublished data are 
      more likely to be published. CONCLUSIONS: There is strong evidence that much of 
      the information on adverse events remains unpublished and that the number and 
      range of adverse events is higher in unpublished than in published versions of 
      the same study. The inclusion of unpublished data can also reduce the imprecision 
      of pooled effect estimates during meta-analysis of adverse events.
FAU - Golder, Su
AU  - Golder S
AD  - Department of Health Sciences, University of York, York, United Kingdom.
FAU - Loke, Yoon K
AU  - Loke YK
AUID- ORCID: 0000-0001-9109-2307
AD  - Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
FAU - Wright, Kath
AU  - Wright K
AD  - Centre for Reviews and Dissemination (CRD), University of York, York, United 
      Kingdom.
FAU - Norman, Gill
AU  - Norman G
AUID- ORCID: 0000-0002-3972-5733
AD  - School of Nursing, Midwifery & Social Work, University of Manchester, Manchester, 
      United Kingdom.
LA  - eng
GR  - PDF-2014-07-041/DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Review
PT  - Systematic Review
DEP - 20160920
PL  - United States
TA  - PLoS Med
JT  - PLoS medicine
JID - 101231360
SB  - IM
MH  - *Clinical Trials as Topic
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology
MH  - Humans
MH  - *Meta-Analysis as Topic
MH  - Publication Bias/*statistics & numerical data
MH  - *Review Literature as Topic
MH  - Risk Assessment
PMC - PMC5029817
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/09/21 06:00
MHDA- 2017/06/07 06:00
PMCR- 2016/09/20
CRDT- 2016/09/21 06:00
PHST- 2016/02/17 00:00 [received]
PHST- 2016/08/10 00:00 [accepted]
PHST- 2016/09/21 06:00 [entrez]
PHST- 2016/09/21 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2016/09/20 00:00 [pmc-release]
AID - PMEDICINE-D-16-00537 [pii]
AID - 10.1371/journal.pmed.1002127 [doi]
PST - epublish
SO  - PLoS Med. 2016 Sep 20;13(9):e1002127. doi: 10.1371/journal.pmed.1002127. 
      eCollection 2016 Sep.