Low dissemination rates, non-transparency of trial premature cessation and late registration in child mental health: observational study of registered interventional trials


The aim of this observational study was to explore trial premature cessation, non-publication and trial registration time in child mental health. Data were extracted for “closed” trials in Clinicaltrials.gov registry and European Union Clinical Trial Register (EUCTR) and corresponding publications of completed trials indexed in three data bases (PubMed, Scopus and Google Scholar). We restricted the extraction to the ‘Behaviours and Mental Disorders’ category and participants’ age of 0–17 years. Outcome measures were trial completion, results reporting within a year after the trial completion, publishing an article in a peer-reviewed journal within an average time to publish (729 days), and registration time. The number of EUCTR trials was relatively small (n = 35) and with many inconsistencies. Out of 827 “closed” trials extracted from ClinicalTrials.gov, 69% were completed, 24.2% of prematurely ceased trials did not report reasons for early termination, 12.2% of the completed trials had results reported within a year, and 29.3% had an article published within 24 months after completion. Middle-sized (100–499 participants) and behavioural trials had higher chances of being successfully completed. Middle-sized and industry-funded trials were associated with results reporting. Chances for publishing an article were lower for industry-funded trials. Industry funding and drug interventions were related to timely registration. Large sample and non-industry funding were related to retrospective registration, which was recorded more often in recent years than before (we observed trials registered from 2002 until 2017). This study found low dissemination rates in the field of child mental health, with worrying under-reporting of premature termination causes. These findings indicate that more children are being subjected to unnecessary risk that comes with trial participation.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Kipnis K (2003) Seven vulnerabilities in the pediatric research subject. Theor Med Bioeth 24(2):107–120

    Article  Google Scholar 

  2. 2.

    Denne SC (2012) Pediatric clinical trial registration and trial results: an urgent need for improvement. Pediatrics 129(5):e1320–e1321. https://doi.org/10.1542/peds.2012-0621

    Article  PubMed  Google Scholar 

  3. 3.

    Edwards SD, McNamee MJ (2005) Ethical concerns regarding guidelines for the conduct of clinical research on children. J Med Ethics 31(6):351–354. https://doi.org/10.1136/jme.2004.009555

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    National Institutes of Health. Policy and guidelines on the inclusion of children as participants in research involving human subjects. 1998. https://grants.nih.gov/grants/guide/notice-files/not98-024.html. Accessed 29 June 2017

  5. 5.

    Pica N, Bourgeois F (2016) Discontinuation and nonpublication of randomized clinical trials conducted in children. Pediatric. https://doi.org/10.1542/peds.2016-0223

  6. 6.

    Shamliyan T, Kane RL (2012) Clinical research involving children: registration, completeness, and publication. Pediatrics 129(5):e1291–e1300. https://doi.org/10.1542/peds.2010-2847

    Article  PubMed  Google Scholar 

  7. 7.

    World Medical Association. Declaration Of Helsinki – Ethical Principles For Medical Research Involving Human Subjects 2013. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. Accessed 29 June 2017

  8. 8.

    Hoop JG, Smyth AC, Roberts LW (2008) Ethical issues in psychiatric research on children and adolescents. Child Adoles Psych Cl. 17(1):127–148. https://doi.org/10.1016/j.chc.2007.07.003

    Article  Google Scholar 

  9. 9.

    Kolch M, Schnoor K, Fegert JM (2007) The EU-regulation on medicinal products for paediatric use: impacts on child and adolescent psychiatry and clinical research with minors. Eur Child Adoles Psy 16(4):229–235. https://doi.org/10.1007/s00787-006-0594-8

    Article  Google Scholar 

  10. 10.

    Tan JO, Koelch M (2008) The ethics of psychopharmacological research in legal minors. Child Adoles Psych Men 2(1):39. https://doi.org/10.1186/1753-2000-2-39

    Article  Google Scholar 

  11. 11.

    Fanelli D (2010) "Positive" results increase down the Hierarchy of the Sciences. PLoS ONE 5(4):e10068. https://doi.org/10.1371/journal.pone.0010068

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Dal-Re R, Bobes J, Cuijpers P (2017) Why prudence is needed when interpreting articles reporting clinical trial results in mental health. Trials 18(1):143. https://doi.org/10.1186/s13063-017-1899-2

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    ClinicalTrials.gov background. https://clinicaltrials.gov/ct2/about-site/background. Accessed 29 June 2017

  14. 14.

    Zarin DA, Williams RJ, Bergeris A, Dobbins HD, Ide NC, Loane RF, Robbins A, Tse T (2013) ClinicalTrials.gov and related projects: improving access to information about clinical trials. Technical report to the LHNCBC Board of Scientific Counselors. April

  15. 15.

    REGULATION (EC) No 1901/2006 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and regulation (EC) No 726/2004 (2006)

  16. 16.

    REGULATION (EC) No 1902/2006 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 20 December 2006 amending Regulation 1901/2006 on medicinal products for paediatric use (2006)

  17. 17.

    European Medicines Agency. Paediatric clinical trials. https://www.ema.europa.eu/human-regulatory/research-development/paediatric-medicines/paediatric-clinical-trials. Accessed 10 May 2018

  18. 18.

    European Medicines Agency. Posting of clinical trial summary results in European Clinical Trials Database (EudraCT) to become mandatory for sponsors as of 21 July 2014. https://www.ema.europa.eu/news/posting-clinical-trial-summary-results-european-clinical-trials-database-eudract-become-mandatory. Accessed 10 May 2018

  19. 19.

    Tse T, Williams RJ, Zarin DA (2009) Reporting "basic results" in ClinicalTrialsgov. Chest 136(1):295–303. https://doi.org/10.1378/chest.08-3022

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Chen R, Desai NR, Ross JS, Zhang W, Chau KH, Wayda B et al (2016) Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers. BMJ 352:i637. https://doi.org/10.1136/bmj.i637

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Jones CW, Handler L, Crowell KE, Keil LG, Weaver MA, Platts-Mills TF (2013) Non-publication of large randomized clinical trials: cross sectional analysis. BMJ 347:f6104. https://doi.org/10.1136/bmj.f6104

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R et al (2004) Clinical trial registration: a statement from the International Committee of Medical Journal Editors. Lancet 364(9438):911–912. https://doi.org/10.1016/S0140-6736(04)17034-7

    Article  PubMed  Google Scholar 

  23. 23.

    Anderson ML, Chiswell K, Peterson ED, Tasneem A, Topping J, Califf RM (2015) Compliance with results reporting at ClinicalTrials.gov. New Engl J Med 372(11):1031–1039. https://doi.org/10.1056/NEJMsa1409364

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Zarin DA, Keselman A (2007) Registering a clinical trial in ClinicalTrials.gov. Chest 131(3):909–912. https://doi.org/10.1378/chest.06-2450

    Article  PubMed  Google Scholar 

  25. 25.

    Gill CJ (2012) 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. https://doi.org/10.1136/bmjopen-2012-001186

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Goldacre B, DeVito NJ, Heneghan C, Irving F, Bacon S, Fleminger J et al (2018) Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource. BMJ 362:k3218. https://doi.org/10.1136/bmj.k3218

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Vaughan B, Goldstein MH, Alikakos M, Cohen LJ, Serby MJ (2014) Frequency of reporting of adverse events in randomized controlled trials of psychotherapy vs. psychopharmacotherapy. Compr Psychiatry 55(4):849–855. https://doi.org/10.1016/j.comppsych.2014.01.001

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Carlisle B, Kimmelman J, Ramsay T, MacKinnon N (2015) Unsuccessful trial accrual and human subjects protections: an empirical analysis of recently closed trials. Clin Trials 12(1):77–83. https://doi.org/10.1177/1740774514558307

    Article  PubMed  Google Scholar 

  29. 29.

    Williams RJ, Tse T, DiPiazza K, Zarin DA (2015) Terminated trials in the clinicaltrials.gov results database: evaluation of availability of primary outcome data and reasons for termination. PloS One 10(5):0127242. https://doi.org/10.1371/journal.pone.0127242

  30. 30.

    Kasenda B, von Elm E, You J, Blumle A, Tomonaga Y, Saccilotto R et al (2014) Prevalence, characteristics, and publication of discontinued randomized trials. JAMA 311(10):1045–1051. https://doi.org/10.1001/jama.2014.1361

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Woodall A, Morgan C, Sloan C, Howard L (2010) Barriers to participation in mental health research: are there specific gender, ethnicity and age related barriers? BMC Psychiatry 10:103. https://doi.org/10.1186/1471-244X-10-103

    Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Bhurke S, Cook A, Tallant A, Young A, Williams E, Raftery J (2015) Using systematic reviews to inform NIHR HTA trial planning and design: a retrospective cohort. BMC Med Res Methodol 15:108. https://doi.org/10.1186/s12874-015-0102-2

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Prayle AP, Hurley MN, Smyth AR (2012) Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study. BMJ 344:d7373. https://doi.org/10.1136/bmj.d7373

    Article  PubMed  Google Scholar 

  34. 34.

    Malicki M, Marusic A, Consortium O (2014) Is there a solution to publication bias? Researchers call for changes in dissemination of clinical research results. J Clin Epidemiol 67(10):1103–1110. https://doi.org/10.1016/j.jclinepi.2014.06.002

    Article  Google Scholar 

  35. 35.

    Ross JS, Mocanu M, Lampropulos JF, Tse T, Krumholz HM (2013) Time to publication among completed clinical trials. JAMA Intern Med 173(9):825–828. https://doi.org/10.1001/jamainternmed.2013.136

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    World Health Organisation. Statement on public disclosure of clinical trial results 2015. https://www.who.int/ictrp/results/reporting/en/. Accessed 29 June 2017

  37. 37.

    Ioannidis JP (2005) Why most published research findings are false. PLoS Med 2(8):e124. https://doi.org/10.1371/journal.pmed.0020124

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Scott A, Rucklidge JJ, Mulder RT (2015) Is mandatory prospective trial registration working to prevent publication of unregistered trials and selective outcome reporting? An observational study of five psychiatry journals that mandate prospective clinical trial registration. PLoS ONE 10(8):e0133718. https://doi.org/10.1371/journal.pone.0133718

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Califf RM, Zarin DA, Kramer JM, Sherman RE, Aberle LH, Tasneem A (2012) Characteristics of clinical trials registered in ClinicalTrials.gov, 2007–2010. JAMA 307(17):1838–1847. https://doi.org/10.1001/jama.2012.3424

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    van Lent M, IntHout J, Out HJ (2014) Differences between information in registries and articles did not influence publication acceptance. J Clin Epidemiol 68(9):1059–1067. https://doi.org/10.1016/j.jclinepi.2014.11.019

    Article  PubMed  Google Scholar 

  41. 41.

    Knuppel H, Metz C, Meerpohl JJ, Strech D (2013) How psychiatry journals support the unbiased translation of clinical research. A cross-sectional study of editorial policies. PLoS ONE 8(10):e75995. https://doi.org/10.1371/journal.pone.0075995

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Mathieu S, Chan AW, Ravaud P (2013) Use of trial register information during the peer review process. PLoS ONE 8(4):e59910. https://doi.org/10.1371/journal.pone.0059910

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Dal-Re R, Caplan AL (2015) Journal editors impasse with outcome reporting bias. Eur J Clin Invest 45(9):895–898. https://doi.org/10.1111/eci.12484

    Article  PubMed  Google Scholar 

  44. 44.

    Trinquart L, Dunn AG, Bourgeois FT (2018) Registration of published randomized trials: a systematic review and meta-analysis. BMC Med 16(1):173. https://doi.org/10.1186/s12916-018-1168-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Huser V, Cimino JJ (2013) Evaluating adherence to the International Committee of Medical Journal Editors' policy of mandatory, timely clinical trial registration. JAMIA 20(e1):e169–e174. https://doi.org/10.1136/amiajnl-2012-001501

    Article  PubMed  Google Scholar 

  46. 46.

    National Institutes of Health. Policy on the Dissemination of NIH-Funded Clinical Trial Information 2016. https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-149.html. Accessed 29 June 2017

  47. 47.

    Zarin DA, Tse T, Sheehan J (2015) The proposed rule for U.S. clinical trial registration and results submission. New Engl J Med. 372(2):174–180. https://doi.org/10.1056/NEJMsr1414226

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Doshi P, Dickersin K, Healy D, Vedula SS, Jefferson T (2013) Restoring invisible and abandoned trials: a call for people to publish the findings. BMJ 346:f2865. https://doi.org/10.1136/bmj.f2865

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    RIAT. Restoring invisible & abandoned trials. https://restoringtrials.org/riat-studies/. Accessed 31 Oct 2018

  50. 50.

    Dal-Re R, Ross JS, Marusic A (2016) Compliance with prospective trial registration guidance remained low in high-impact journals and has implications for primary end point reporting. J Clin Epidemiol 75:100–107. https://doi.org/10.1016/j.jclinepi.2016.01.017

    Article  PubMed  Google Scholar 

  51. 51.

    Gopal AD, Wallach JD, Aminawung JA, Gonsalves G, Dal-Re R, Miller JE et al (2018) Adherence to the International Committee of Medical Journal Editors' (ICMJE) prospective registration policy and implications for outcome integrity: a cross-sectional analysis of trials published in high-impact specialty society journals. Trials 19(1):448. https://doi.org/10.1186/s13063-018-2825-y

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Tse T, Fain KM, Zarin DA (2018) How to avoid common problems when using ClinicalTrials.gov in research: 10 issues to consider. BMJ 361:1452. https://doi.org/10.1136/bmj.k1452

    Article  Google Scholar 

  53. 53.

    Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R (2008) Selective publication of antidepressant trials and its influence on apparent efficacy. New Engl J Med 358(3):252–260. https://doi.org/10.1056/NEJMsa065779

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Driessen E, Hollon SD, Bockting CL, Cuijpers P, Turner EH (2015) Does Publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of us National Institutes of Health-Funded Trials. PLoS ONE 10(9):e0137864. https://doi.org/10.1371/journal.pone.0137864

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Roest AM, de Jonge P, Williams CD, de Vries YA, Schoevers RA, Turner EH (2015) Reporting bias in clinical trials investigating the efficacy of second-generation antidepressants in the treatment of anxiety disorders: a report of 2 meta-analyses. JAMA Psychiatry 72(5):500–510. https://doi.org/10.1001/jamapsychiatry.2015.15

    Article  PubMed  Google Scholar 

  56. 56.

    Hart B, Lundh A, Bero L (2012) Effect of reporting bias on meta-analyses of drug trials: reanalysis of meta-analyses. BMJ 344:d7202. https://doi.org/10.1136/bmj.d720

    Article  PubMed  Google Scholar 

Download references


The authors received no funding for this research. S.P. Singh is partly funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care WM (NIHR CLAHRC WM). We thank Elena Račevska for her contribution to the first draft of the manuscript and help with its organization and structure. We are also thankful to Shelly Pranić for her help with the language editing of the revised manuscript.

Author information



Corresponding author

Correspondence to Nikolina Vrljičak Davidović.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The manuscript does not contain clinical studies or patient data.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 12 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vrljičak Davidović, N., Tokalić, R., Burilović, E. et al. Low dissemination rates, non-transparency of trial premature cessation and late registration in child mental health: observational study of registered interventional trials. Eur Child Adolesc Psychiatry 29, 813–825 (2020). https://doi.org/10.1007/s00787-019-01392-8

Download citation


  • Child mental health
  • Trial premature cessation
  • Result reporting
  • Non-publication
  • Trial registration