Non-publication is common among phase 1, single-center, not prospectively registered, or early terminated clinical drug trials

C. A. Van Den Bogert, Patrick C. Souverein, Cecile T.M. Brekelmans, Susan W.J. Janssen, Gerard H. Koeter, H. G.M. Leufkens, Lex M. Bouter

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The objective of this study was to investigate the occurrence and determinants of nonpublication of clinical drug trials in the Netherlands. All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followedup from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination. The main outcome was publication as peer reviewed article. The percentage of trials that were published, crude and adjusted odds ratio (OR), and 95% confidence interval (CI) were used to quantify the associations between determinants and publication. In 2007, 622 clinical drug trials were reviewed by IRBs in the Netherlands. By the end of followup, 19 of these were rejected by the IRB, another 19 never started inclusion, and 10 were still running. Of the 574 trials remaining in the analysis, 334 (58%) were published as peerreviewed article. The multivariable logistic regression model identified the following determinants with a robust, statistically significant association with publication: phase 2 (60% published; adjusted OR 2.6, 95% CI 1.15.9), phase 3 (73% published; adjusted OR 4.1, 95% CI 1.710.0), and trials not belonging to phase 14 (60% published; adjusted OR 3.2, 95% CI 1.5 to 6.5) compared to phase 1 trials (35% published); trials with a company or investigator as applicant (63% published) compared to trials with a Contract Research Organization (CRO) as applicant (50% published; adjusted OR 1.7; 95% CI 1.12.8) ; and multicenter trials also conducted in other EU countries (68% published; adjusted OR 2.2, 95% CI 1.14.4) or also outside the European Union (72% published; adjusted OR 2.0, 95% CI 1.04.0) compared to singlecenter trials (45% published). Trials that were not prospectively registered (48% published) had a lower likelihood of publication compared to prospectively registered trials (75% published; adjusted OR 0.5, 95% CI 0.30.8), as well as trials that were terminated early (33% published) compared to trials that were completed as planned (64% published; adjusted OR 0.2, 95% CI 0.10.3). The nonpublication rate of clinical trials seems to have improved compared to previous inception cohorts, but is still far from optimal, in particular among phase 1, singlecenter, not prospectively registered, and early terminated trials.

Translated title of the contributionNon-publication is common among phase 1, single-center, not prospectively registered, or early terminated clinical drug trials
Original languageDutch
Article numberd1498
JournalNederlands Tijdschrift voor Geneeskunde
Volume161
Issue number28
Publication statusPublished - 2017

Cite this

Van Den Bogert, C. A., Souverein, P. C., Brekelmans, C. T. M., Janssen, S. W. J., Koeter, G. H., Leufkens, H. G. M., & Bouter, L. M. (2017). Hoeveel klinische geneesmiddelenstudies worden uiteindelijk gepubliceerd?. Fase 1-studies blijven achter in aantal publicaties. Nederlands Tijdschrift voor Geneeskunde, 161(28), [d1498].
Van Den Bogert, C. A. ; Souverein, Patrick C. ; Brekelmans, Cecile T.M. ; Janssen, Susan W.J. ; Koeter, Gerard H. ; Leufkens, H. G.M. ; Bouter, Lex M. / Hoeveel klinische geneesmiddelenstudies worden uiteindelijk gepubliceerd?. Fase 1-studies blijven achter in aantal publicaties. In: Nederlands Tijdschrift voor Geneeskunde. 2017 ; Vol. 161, No. 28.
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title = "Hoeveel klinische geneesmiddelenstudies worden uiteindelijk gepubliceerd?. Fase 1-studies blijven achter in aantal publicaties",
abstract = "The objective of this study was to investigate the occurrence and determinants of nonpublication of clinical drug trials in the Netherlands. All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followedup from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination. The main outcome was publication as peer reviewed article. The percentage of trials that were published, crude and adjusted odds ratio (OR), and 95{\%} confidence interval (CI) were used to quantify the associations between determinants and publication. In 2007, 622 clinical drug trials were reviewed by IRBs in the Netherlands. By the end of followup, 19 of these were rejected by the IRB, another 19 never started inclusion, and 10 were still running. Of the 574 trials remaining in the analysis, 334 (58{\%}) were published as peerreviewed article. The multivariable logistic regression model identified the following determinants with a robust, statistically significant association with publication: phase 2 (60{\%} published; adjusted OR 2.6, 95{\%} CI 1.15.9), phase 3 (73{\%} published; adjusted OR 4.1, 95{\%} CI 1.710.0), and trials not belonging to phase 14 (60{\%} published; adjusted OR 3.2, 95{\%} CI 1.5 to 6.5) compared to phase 1 trials (35{\%} published); trials with a company or investigator as applicant (63{\%} published) compared to trials with a Contract Research Organization (CRO) as applicant (50{\%} published; adjusted OR 1.7; 95{\%} CI 1.12.8) ; and multicenter trials also conducted in other EU countries (68{\%} published; adjusted OR 2.2, 95{\%} CI 1.14.4) or also outside the European Union (72{\%} published; adjusted OR 2.0, 95{\%} CI 1.04.0) compared to singlecenter trials (45{\%} published). Trials that were not prospectively registered (48{\%} published) had a lower likelihood of publication compared to prospectively registered trials (75{\%} published; adjusted OR 0.5, 95{\%} CI 0.30.8), as well as trials that were terminated early (33{\%} published) compared to trials that were completed as planned (64{\%} published; adjusted OR 0.2, 95{\%} CI 0.10.3). The nonpublication rate of clinical trials seems to have improved compared to previous inception cohorts, but is still far from optimal, in particular among phase 1, singlecenter, not prospectively registered, and early terminated trials.",
author = "{Van Den Bogert}, {C. A.} and Souverein, {Patrick C.} and Brekelmans, {Cecile T.M.} and Janssen, {Susan W.J.} and Koeter, {Gerard H.} and Leufkens, {H. G.M.} and Bouter, {Lex M.}",
year = "2017",
language = "Dutch",
volume = "161",
journal = "Nederlands Tijdschrift voor Geneeskunde",
issn = "0028-2162",
publisher = "Bohn Stafleu van Loghum",
number = "28",

}

Van Den Bogert, CA, Souverein, PC, Brekelmans, CTM, Janssen, SWJ, Koeter, GH, Leufkens, HGM & Bouter, LM 2017, 'Hoeveel klinische geneesmiddelenstudies worden uiteindelijk gepubliceerd?. Fase 1-studies blijven achter in aantal publicaties' Nederlands Tijdschrift voor Geneeskunde, vol. 161, no. 28, d1498.

Hoeveel klinische geneesmiddelenstudies worden uiteindelijk gepubliceerd?. Fase 1-studies blijven achter in aantal publicaties. / Van Den Bogert, C. A.; Souverein, Patrick C.; Brekelmans, Cecile T.M.; Janssen, Susan W.J.; Koeter, Gerard H.; Leufkens, H. G.M.; Bouter, Lex M.

In: Nederlands Tijdschrift voor Geneeskunde, Vol. 161, No. 28, d1498, 2017.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Van Den Bogert, C. A.

AU - Souverein, Patrick C.

AU - Brekelmans, Cecile T.M.

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N2 - The objective of this study was to investigate the occurrence and determinants of nonpublication of clinical drug trials in the Netherlands. All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followedup from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination. The main outcome was publication as peer reviewed article. The percentage of trials that were published, crude and adjusted odds ratio (OR), and 95% confidence interval (CI) were used to quantify the associations between determinants and publication. In 2007, 622 clinical drug trials were reviewed by IRBs in the Netherlands. By the end of followup, 19 of these were rejected by the IRB, another 19 never started inclusion, and 10 were still running. Of the 574 trials remaining in the analysis, 334 (58%) were published as peerreviewed article. The multivariable logistic regression model identified the following determinants with a robust, statistically significant association with publication: phase 2 (60% published; adjusted OR 2.6, 95% CI 1.15.9), phase 3 (73% published; adjusted OR 4.1, 95% CI 1.710.0), and trials not belonging to phase 14 (60% published; adjusted OR 3.2, 95% CI 1.5 to 6.5) compared to phase 1 trials (35% published); trials with a company or investigator as applicant (63% published) compared to trials with a Contract Research Organization (CRO) as applicant (50% published; adjusted OR 1.7; 95% CI 1.12.8) ; and multicenter trials also conducted in other EU countries (68% published; adjusted OR 2.2, 95% CI 1.14.4) or also outside the European Union (72% published; adjusted OR 2.0, 95% CI 1.04.0) compared to singlecenter trials (45% published). Trials that were not prospectively registered (48% published) had a lower likelihood of publication compared to prospectively registered trials (75% published; adjusted OR 0.5, 95% CI 0.30.8), as well as trials that were terminated early (33% published) compared to trials that were completed as planned (64% published; adjusted OR 0.2, 95% CI 0.10.3). The nonpublication rate of clinical trials seems to have improved compared to previous inception cohorts, but is still far from optimal, in particular among phase 1, singlecenter, not prospectively registered, and early terminated trials.

AB - The objective of this study was to investigate the occurrence and determinants of nonpublication of clinical drug trials in the Netherlands. All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followedup from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination. The main outcome was publication as peer reviewed article. The percentage of trials that were published, crude and adjusted odds ratio (OR), and 95% confidence interval (CI) were used to quantify the associations between determinants and publication. In 2007, 622 clinical drug trials were reviewed by IRBs in the Netherlands. By the end of followup, 19 of these were rejected by the IRB, another 19 never started inclusion, and 10 were still running. Of the 574 trials remaining in the analysis, 334 (58%) were published as peerreviewed article. The multivariable logistic regression model identified the following determinants with a robust, statistically significant association with publication: phase 2 (60% published; adjusted OR 2.6, 95% CI 1.15.9), phase 3 (73% published; adjusted OR 4.1, 95% CI 1.710.0), and trials not belonging to phase 14 (60% published; adjusted OR 3.2, 95% CI 1.5 to 6.5) compared to phase 1 trials (35% published); trials with a company or investigator as applicant (63% published) compared to trials with a Contract Research Organization (CRO) as applicant (50% published; adjusted OR 1.7; 95% CI 1.12.8) ; and multicenter trials also conducted in other EU countries (68% published; adjusted OR 2.2, 95% CI 1.14.4) or also outside the European Union (72% published; adjusted OR 2.0, 95% CI 1.04.0) compared to singlecenter trials (45% published). Trials that were not prospectively registered (48% published) had a lower likelihood of publication compared to prospectively registered trials (75% published; adjusted OR 0.5, 95% CI 0.30.8), as well as trials that were terminated early (33% published) compared to trials that were completed as planned (64% published; adjusted OR 0.2, 95% CI 0.10.3). The nonpublication rate of clinical trials seems to have improved compared to previous inception cohorts, but is still far from optimal, in particular among phase 1, singlecenter, not prospectively registered, and early terminated trials.

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Van Den Bogert CA, Souverein PC, Brekelmans CTM, Janssen SWJ, Koeter GH, Leufkens HGM et al. Hoeveel klinische geneesmiddelenstudies worden uiteindelijk gepubliceerd?. Fase 1-studies blijven achter in aantal publicaties. Nederlands Tijdschrift voor Geneeskunde. 2017;161(28). d1498.