This is in line with campaigns such as AllTrials, which are calling for all those trials to be registered and the full methods and results to be reported. sources. In Jefferson 2011 [26], the number of adverse events is usually small (10 events) and therefore does not show up in Fig 4 given the scale of the em y /em -axis.(TIFF) pmed.1002127.s003.tiff (364K) GUID:?5A7F1580-284B-4B8B-87E5-27116D7FB19F S4 Fig: Percentage of severe adverse Coluracetam events missed without matched unpublished data. (TIFF) pmed.1002127.s004.tiff (360K) GUID:?FF21C063-AC27-4108-9909-116B1F18DA9A S1 Table: Search results for each database and/or source. (DOCX) pmed.1002127.s005.docx (16K) GUID:?5D4FFBBD-87BB-4B78-A1D1-501151BFAB0A S2 Table: Excluded studies. (DOCX) pmed.1002127.s006.docx (46K) GUID:?DC18E588-36F3-4015-AE43-5A02286393B7 S3 Table: Design and risk of bias. (DOCX) pmed.1002127.s007.docx (35K) GUID:?B6F6B9A0-0B56-40B2-B65D-F329525406AC S4 Table: Main outcome steps and results of included studies. (DOCX) pmed.1002127.s008.docx (33K) GUID:?F14D7803-2F00-4495-8D48-F75C238F4F25 S1 Text: PRISMA checklist. (DOC) pmed.1002127.s009.doc (64K) GUID:?94D6D1A5-A0F9-45C7-9B19-E352292B9EBE S2 Text: Review protocol. (DOCX) pmed.1002127.s010.docx (25K) GUID:?76A29177-ED55-4C27-9A8F-72B762E5931A S3 Text: Data sources searched. (DOCX) pmed.1002127.s011.docx (14K) GUID:?2D4B0CA6-4655-4076-81E2-085790E7FF40 S4 Text: MEDLINE search strategy. (DOCX) pmed.1002127.s012.docx (16K) GUID:?2C6C2551-10A4-4B61-8DBD-2C80BFBE62B5 Data Availability StatementAll data are within the paper and its Supporting Information files. Abstract 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median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents.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 Coluracetam 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 Coluracetam 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 MGC33570 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. Author Summary Why Was This Study Done? Research on medical treatments provides information on the efficacy of such treatments, and on side effects. The balance between efficacy and side effects is important in assessing the overall benefit of a new treatment. How much information on the side effects of medical treatments that is currently not published in journal articles is not known. What Did the Researchers Do and Find? We searched several databases and other sources, and found 28 studies that provided information on the amount of data on side effects in published journal articles as compared to other sources (such as websites, conferences, and industry-held data). The 28 studies found that a lower percentage of published studies than unpublished studies contain information on side effects of treatments. A lower number of.Wieseler Coluracetam 2012 [44] and 2013a [43] and Wieseler 2012 [44] and 2013b [43] compare published sources with clinical study reports (CSRs) and registry reports, respectively. (TIFF) Click here for additional data file.(392K, tiff) S3 FigSerious adverse events in matched published and unpublished sources. versus incompletely reported. Incompletely reported adverse events could lack numerical data or include only selected adverse events for example. Hemminki 1980a [23], 1980b [23], and 1980c [23] compare different drugs in different countries. Wieseler 2012 [44] and 2013a [43] and Wieseler 2012 [44] and 2013b [43] compare published sources with clinical study reports (CSRs) and registry reports, respectively.(TIFF) pmed.1002127.s002.tiff (392K) GUID:?764BBACF-3EF1-4A85-8E32-C0CA814C0013 S3 Fig: Serious adverse events in matched published and unpublished sources. In Jefferson 2011 [26], the number of adverse events is small (10 events) and therefore does not show up in Fig 4 given the scale of the em y /em -axis.(TIFF) pmed.1002127.s003.tiff (364K) GUID:?5A7F1580-284B-4B8B-87E5-27116D7FB19F S4 Fig: Percentage of serious adverse events missed without matched unpublished data. (TIFF) pmed.1002127.s004.tiff (360K) GUID:?FF21C063-AC27-4108-9909-116B1F18DA9A S1 Table: Search results for each database and/or source. (DOCX) pmed.1002127.s005.docx (16K) GUID:?5D4FFBBD-87BB-4B78-A1D1-501151BFAB0A S2 Table: Excluded studies. (DOCX) pmed.1002127.s006.docx (46K) GUID:?DC18E588-36F3-4015-AE43-5A02286393B7 S3 Table: Design and risk of bias. (DOCX) pmed.1002127.s007.docx (35K) GUID:?B6F6B9A0-0B56-40B2-B65D-F329525406AC S4 Table: Main outcome measures and results of included studies. (DOCX) pmed.1002127.s008.docx (33K) GUID:?F14D7803-2F00-4495-8D48-F75C238F4F25 S1 Text: PRISMA checklist. (DOC) pmed.1002127.s009.doc (64K) GUID:?94D6D1A5-A0F9-45C7-9B19-E352292B9EBE S2 Text: Review protocol. (DOCX) pmed.1002127.s010.docx (25K) GUID:?76A29177-ED55-4C27-9A8F-72B762E5931A S3 Text: Data sources searched. (DOCX) pmed.1002127.s011.docx (14K) GUID:?2D4B0CA6-4655-4076-81E2-085790E7FF40 S4 Text: MEDLINE search strategy. (DOCX) pmed.1002127.s012.docx (16K) GUID:?2C6C2551-10A4-4B61-8DBD-2C80BFBE62B5 Data Availability StatementAll data are within the paper and its Supporting Information files. Abstract Background We performed a systematic review to assess whether we Coluracetam 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 recognized from 15 databases (including MEDLINE and Embase) and by handsearching, research checking, internet searches, and contacting specialists. The last database searches were carried out 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 info was 46% compared to 95% in the related 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 paperwork. The percentage of adverse events that would have been missed had each analysis relied only within the published versions diverse between 43% and 100%, having a median of 64%. Within these 11 studies, 24 comparisons of named adverse events such as death, suicide, or respiratory adverse events were carried out. In 18 of the 24 comparisons, the number of named adverse events was higher in unpublished than published paperwork. Additionally, 2 additional 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 improved the precision of the pooled estimations (narrower 95% confidence intervals) in 15 of the 20 pooled analyses, but did not markedly switch the direction or statistical significance of the risk in most cases. The main limitations of this review are the included case good examples represent only a small number amongst thousands of meta-analyses of harms and that the included studies may suffer from publication bias, whereby considerable 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 definitely higher in unpublished.