Non-Publication Is Common among Phase 1, Single-Center, Not Prospectively Registered, or Early Terminated Clinical Drug Trials

Abstract

The objective of this study was to investigate the occurrence and determinants of non-publication 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 followed-up 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 follow-up, 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 peer-reviewed 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 1.1–5.9), phase 3 (73% published; adjusted OR 4.1, 95% CI 1.7–10.0), and trials not belonging to phase 1–4 (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 1.1–2.8); and multicenter trials also conducted in other EU countries (68% published; adjusted OR 2.2, 95% CI 1.1–4.4) or also outside the European Union (72% published; adjusted OR 2.0, 95% CI 1.0–4.0) compared to single-center 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 0.3–0.8), 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 0.1–0.3). The non-publication rate of clinical trials seems to have improved compared to previous inception cohorts, but is still far from optimal, in particular among phase 1, single-center, not prospectively registered, and early terminated trials.

Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency

“…We found a publication rate of 61% of approved trials (71% of completed trials), which seems high compared to previous studies (range: 33–74% of completed trials [10–14, 16]) and comparable to a recent study by van den Bogert (clinical drug RCTs approved by Dutch Independent Review Boards in 2007)[15]. The difference to previous studies may be attributed to several factors: Firstly, the publication rate may have increased over time.…”

Relationship Between Response and Dose in Published, Contemporary Phase I Oncology Trials

“…Earlier research has established that not all phase I trials conducted are represented in the literature, nor do all phase I trials report specific dose levels, RP2D, and efficacy data by dose levels. [16][17][18][19] Whether our results would materially change with the addition of unpublished trials remains unknown but warrants exploration.…”

Primary endpoint discrepancies were found in one in ten clinical drug trials. Results of an inception cohort study

“…In short, we selected all the clinical drug trials that were reviewed by the Dutch-accredited institutional review boards (IRBs) in 2007, and we followed these trials until publication as peer-reviewed article in the scientific literature. The results of the study on nonpublication have been published and showed that of the 574 trials in the cohort, 240 (42%) remained unpublished [21]. For this follow-up study, we included the 334 trials in the cohort of which we found at least one publication by January 2016 in the scientific literature presenting results (Fig.…”

“…We analyzed the association between the trial characteristics that were considered as being potential determinants of protocol-publication discrepancies. In addition to the sponsor type, we analyzed the trial characteristics that were significantly associated with nonpublication in the same cohort [21]: phase, centers involved, prospective registration, and completion. Furthermore, in line with previous studies [9,10], we also analyzed the association of the trial design and the treatment arms with discrepancies in the primary endpoints.…”