Discontinuation and non-publication of randomised clinical trials supported by the main public funding body in Switzerland: a retrospective cohort study

Abstract

ObjectiveThe Swiss National Science Foundation (SNSF) promotes academic excellence through competitive selection of study proposals and rigorous evaluation of feasibility, but completion status and publication history of SNSF-supported randomised clinical trials (RCTs) remain unclear. The main objectives were to review all healthcare RCTs supported by the SNSF for trial discontinuation and non-publication, to investigate potential risk factors for trial discontinuation due to poor recruitment and non-publication, and to compare findings to other Swiss RCTs not supported by the SNSF.DesignWe established a retrospective cohort of all SNSF-supported RCTs for which recruitment and funding had ended in 2015 or earlier. For each RCT, two investigators independently searched corresponding publications in electronic databases. In addition, we approached all principal investigators to ask for additional publications and information about trial discontinuation. Teams of two investigators independently extracted details about study design, recruitment of participants, outcomes, analysis and sample size from the original proposal and, if available, from trial registries and publications. We used multivariable regression analysis to explore potential risk factors associated with discontinuation due to poor recruitment and with non-publication, and to compare our results with data from a previous cohort of Swiss RCTs not supported by the SNSF.ResultsWe included 101 RCTs supported by the SNSF between 1986 and 2015. Eighty-seven (86%) principal investigators responded to our survey. Overall, 69 (68%) RCTs were completed, 26 (26%) RCTs were prematurely discontinued (all due to slow recruitment) and the completion status remained unclear for 6 (6%) RCTs. For analysing publication status, we excluded 4 RCTs for which follow-up was still ongoing and 9 for which manuscripts were still in preparation. Of the remaining 88 RCTs, 53 (60%) were published as full articles in peer-reviewed journals. Multivariable regression models suggested that discontinued trials were at higher risk for non-publication than completed trials (adjusted OR 7.61; 95% CI 2.44 to 27.09). Compared with other Swiss RCTs, the risk of discontinuation for SNSF-supported RCTs was higher than in industry-initiated RCTs (adjusted OR 3.84; 95% CI 1.68 to 8.74), but not significantly different from investigator-initiated RCTs not supported by the SNSF (adjusted OR 1.05; 95% CI 0.51 to 2.11). We found no evidence that the proportion of discontinued or unpublished RCTs decreased over the last 20 years.ConclusionsOne out of four SNSF-supported RCTs were prematurely discontinued due to slow recruitment, 40% of all included RCTs and 70% of all discontinued RCTs were not published in peer-reviewed journals. There is a case to reconsider how public funding bodies such as the SNSF could improve their feasibility assessment and promote publication of RCTs irrespective of completion status.

Burden or Opportunity? Parent Experiences When Approached for Research in a Pediatric Intensive Care Unit

“…1 Among parents who enroll their children and children who assent to enrollment, motivations for participation include research that provides benefit to the child, altruism, and familiarity with the care team and the research personnel. 1 Among parents who enroll their children and children who assent to enrollment, motivations for participation include research that provides benefit to the child, altruism, and familiarity with the care team and the research personnel.…”

“…4 Enrollment may be particularly difficult in the critical care setting, where parents are likely to be experiencing stress because of their child's condition. 6 The study found that factors related to willingness to enroll their child in research included (1) characteristics of the recruitment-consent encounter, such as timing, location, and information presented; In a prospective cohort study observing 271 consent encounters in pediatric critical care research, Menon et al reported that consent rates were lower for cardiac surgery than other pediatric intensive care encounters and that consent rates were better when the research team was introduced by a member of the patient's care team.…”

“…7 The insights from this qualitative study demonstrated a need to explore the multiple factors relevant to participation in pediatric critical care research in a larger sample. The objectives of our study were to (1) learn about the experiences of parents who are approached in the PICU to enroll their child in a research study, including what parents perceive to be research in the context of clinical care; (2) assess motivations and barriers for research participation; (3) evaluate associations between parental stress, child demographic and health characteristics, research characteristics, and concurrent eligibility for research and our primary outcome of research participation; and (4) evaluate associations between stress and barriers or motivations for research participation. 8 Varying enrollment rates across multiple studies may result in strategies to increase enrollment such as approaching parents about multiple studies for which their child is eligible.…”

“…D espite an ongoing need for pediatric research, low enrollment across studies may impede completion of research objectives. 1 Among parents who enroll their children and children who assent to enrollment, motivations for participation include research that provides benefit to the child, altruism, and familiarity with the care team and the research personnel. 2 Barriers include risks to the child, the added burden of the research in addition to clinical care or disruption to daily routine, and the timing and the way in which information about a study is presented to parents.…”

Publish or Perish v2

“…A Danish group found that 73% of completed trials were published . Among randomized clinical trials supported by the Swiss National Science Foundation, 40% were not published in peer‐reviewed journals, with the number rising to 70% for discontinued randomized clinical trials . And among clinical trials in The Netherlands, trials that were terminated early had a much lower rate of publication, at 33% published, compared with trials that were completed as planned (64% published; adjusted OR 0.2, 95% CI 0.1–0.3) .…”