Top

BMC Medicine

Published in:

Open Access 01-12-2015 | Research article

Comparison of serious adverse events posted at ClinicalTrials.gov and published in corresponding journal articles

Authors: Eve Tang, Philippe Ravaud, Carolina Riveros, Elodie Perrodeau, Agnes Dechartres

Published in: BMC Medicine | Issue 1/2015

Abstract

Background

The reporting of serious adverse events (SAEs) in clinical trials is crucial to assess the balance between benefits and risks. For trials with serious adverse events posted at ClinicalTrials.gov, we assessed the consistency between SAEs posted at ClinicalTrials.gov and those published in corresponding journal articles.

Methods

All records from ClinicalTrials.gov up to February 2014 were automatically exported in XML format. Among these, we identified all phase III or IV randomized controlled trials with at least one SAE posted. For a random sample of 300 of these trials, we searched for corresponding publications using MEDLINE via PubMed and extracted safety results from the articles.

Results

Among the sample of 300 trials with SAEs posted at ClinicalTrials.gov, 78 (26 %) did not have a corresponding publication, and 20 (7 %) had a publication that did not match the ClinicalTrials.gov record. For the 202 remaining trials, 26 published articles (13 %) did not mention SAEs, 4 (2 %) reported no SAEs, and 33 (16 %) did not report the total number of SAEs per treatment group. Among the remaining 139 trials, for 44 (32 %), the number of SAEs per group published did not match those posted at ClinicalTrials.gov. For 31 trials, the number of SAEs was greater at ClinicalTrials.gov than in the published article, with a difference ≥30 % for at least one group for 21. Only 33 trials (11 %) had a publication reporting matching numbers of SAE and describing the type of SAE.

Conclusions

Many trials with SAEs posted at ClinicalTrials.gov are not yet published, omit the reporting of these SAEs in corresponding publications, or report a discrepant number of SAEs as compared with ClinicalTrials.gov. These results underline the need to consult ClinicalTrials.gov for more information on serious harms.

Antes G, Chalmers I. Under-reporting of clinical trials is unethical. Lancet. 2003;361:978–9.CrossRefPubMed

Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. Obstet Gynecol. 2009;114:1341–5.CrossRefPubMed

Chalmers I. Underreporting research is scientific misconduct. JAMA. 1990;263:1405–8.CrossRefPubMed

Ioannidis JA, Lau J. Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas. JAMA. 2001;285:437–43.CrossRefPubMed

Pitrou I, Boutron I, Ahmad N, Ravaud P. Reporting of safety results in published reports of randomized controlled trials. Arch Intern Med. 2009;169:1756–61.CrossRefPubMed

ClinicalTrials.gov “Basic Results” Data Element Definitions. 2013; http://prsinfo.clinicaltrials.gov/results_definitions.html#AdverseEventsDefinition. Accessed March 2015.

Ioannidis JP, Evans SJ, Gotzsche PC, O’Neill RT, Altman DG, Schulz K, et al. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. 2004;141:781–8.CrossRefPubMed

Ioannidis JPA, Contopoulos-Ioannidis DG. Reporting of safety data from randomised trials. Lancet. 1998;352:1752–3.CrossRefPubMed

Scharf O, Colevas AD. Adverse event reporting in publications compared with sponsor database for cancer clinical trials. J Clin Oncol. 2006;24:3933–8.CrossRefPubMed

10.

Curfman GD, Morrissey S, Drazen JM. Expression of concern: Bombardier et al., “Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis”, N Engl J Med 2000;343:1520–8. N Engl J Med. 2005;353:2813–4.CrossRefPubMed

11.

Curfman GD, Morrissey S, Drazen JM. Expression of concern reaffirmed. N Engl J Med. 2006;354:1193.CrossRefPubMed

12.

Krumholz HM, Ross JS, Presler AH, Egilman DS. What have we learnt from Vioxx? BMJ. 2007;334:120–3.CrossRefPubMedPubMedCentral

13.

Dickersin K, Rennie D. The evolution of trial registries and their use to assess the clinical trial enterprise. JAMA. 2012;307:1861–4.CrossRefPubMed

14.

Tse T, Williams RJ, Zarin DA. Reporting “basic results” in ClinicalTrials.gov. Chest. 2009;136:295–303.CrossRefPubMedPubMedCentral

15.

Tse T, Williams RJ, Zarin DA. Update on registration of clinical trials in ClinicalTrials.gov. Chest. 2009;136:304–5.CrossRefPubMedPubMedCentral

16.

Riveros C, Dechartres A, Perrodeau E, Haneef R, Boutron I, Ravaud P. Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals. PLoS Med. 2013;10:e1001566. Discussion e1001566.

17.

The R Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2014.

18.

Hartung DM, Zarin DA, Guise JM, McDonagh M, Paynter R, Helfand M. Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications. Ann Intern Med. 2014;160:477–83.CrossRefPubMedPubMedCentral

19.

Saini P, Loke YK, Gamble C, Altman DG, Williamson PR, Kirkham JJ. Selective reporting bias of harm outcomes within studies: findings from a cohort of systematic reviews. BMJ. 2014;349:g6501.CrossRefPubMedPubMedCentral

20.

Zorzela L, Golder S, Liu Y, Pilkington K, Hartling L, Joffe A, et al. Quality of reporting in systematic reviews of adverse events: systematic review. BMJ. 2014;348:f7668.CrossRefPubMedPubMedCentral

21.

Peron J, Maillet D, Gan HK, Chen EX, You B. Adherence to CONSORT adverse event reporting guidelines in randomized clinical trials evaluating systemic cancer therapy: a systematic review. J Clin Oncol. 2013;31:3957–63.CrossRefPubMed

22.

Sivendran S, Latif A, McBride RB, Stensland KD, Wisnivesky J, Haines L, et al. Adverse event reporting in cancer clinical trial publications. J Clin Oncol. 2014;32:83–9.CrossRefPubMed

23.

Hodkinson A, Kirkham JJ, Tudur-Smith C, Gamble C. Reporting of harms data in RCTs: a systematic review of empirical assessments against the CONSORT harms extension. BMJ Open. 2013;3, e003436.CrossRefPubMedPubMedCentral

24.

Smith SM, Chang RD, Pereira A, Shah N, Gilron I, Katz NP, et al. Adherence to CONSORT harms-reporting recommendations in publications of recent analgesic clinical trials: an ACTTION systematic review. Pain. 2012;153:2415–21.CrossRefPubMed

25.

Becker JE, Krumholz HM, Ben-Josef G, Ross JS. Reporting of results in ClinicalTrials.gov and high-impact journals. JAMA. 2014;311:1063–5.CrossRefPubMedPubMedCentral

26.

Becker JE, Ross JS. Reporting discrepancies between the clinicaltrials.gov results database and peer-reviewed publications. Ann Intern Med. 2014;161:760.CrossRefPubMed

27.

Europe votes for clinical trial transparency. http://www.alltrials.net/news/europe-votes-for-clinical-trial-transparency. Accessed March 2015.

28.

Posting of clinical trial summary results in European Clinical Trials Database (EudraCT) to become mandatory for sponsors as of 21 July 2014. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/06/news_detail_002127.jsp&mid=WC0b01ac058004d5c1. Accessed March 2015.

29.

Anderson ML, Chiswell K, Peterson ED, Tasneem A, Topping J, Califf RM. Compliance with results reporting at ClinicalTrials.gov. N Engl J Med. 2015;372:1031–9.CrossRefPubMedPubMedCentral

30.

Gill CJ. How often do US-based human subjects research studies register on time, and how often do they post their results? A statistical analysis of the Clinicaltrials.gov database. BMJ Open. 2012;2. doi:10.1136/bmjopen-2012-001186.

31.

Nguyen TA, Dechartres A, Belgherbi S, Ravaud P. Public availability of results of trials assessing cancer drugs in the United States. J Clin Oncol. 2013;31:2998–3003.CrossRefPubMed

32.

Prayle AP, Hurley MN, Smyth AR. Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study. BMJ. 2012;344:d7373.

33.

Saito H, Gill CJ. How frequently do the results from completed US clinical trials enter the public domain? A statistical analysis of the ClinicalTrials.gov database. PLoS One. 2014;9, e101826.CrossRefPubMedPubMedCentral

34.

Maruani A, Boutron I, Baron G, Ravaud P. Impact of sending email reminders of the legal requirement for posting results on ClinicalTrials.gov: cohort embedded pragmatic randomized controlled trial. BMJ. 2014;349:g5579.

Title: Comparison of serious adverse events posted at ClinicalTrials.gov and published in corresponding journal articles
Authors: Eve Tang
Philippe Ravaud
Carolina Riveros
Elodie Perrodeau
Agnes Dechartres
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2015
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-015-0430-4

At a glance: The STEP trials

Springer Medicine

Comparison of serious adverse events posted at ClinicalTrials.gov and published in corresponding journal articles

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

Implementing supported self-management for asthma: a systematic review and suggested hierarchy of evidence of implementation studies

Relevance of tumor-infiltrating lymphocytes in breast cancer

Integrating vector control across diseases

Holidays, celebrations, and commiserations: measuring drinking during feasting and fasting to improve national and individual estimates of alcohol consumption

Ethnicity and prostate cancer: the way to solve the screening problem?

Cardiovascular risk factor distribution and subjective risk estimation in urban women – The BEFRI Study: a randomized cross-sectional study