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

The 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. We 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. We 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. One 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

Permian high-temperature metamorphism in the Western Alps (NW Italy)

During the late Palaeozoic, lithospheric thinning in part of the Alpine realm caused high-temperature low-to-medium pressure metamorphism and partial melting in the lower crust. Permian metamorphism and magmatism has extensively been recorded and dated in the Central, Eastern, and Southern Alps. However, Permian metamorphic ages in the Western Alps so far are constrained by very few and sparsely distributed data. The present study fills this gap. We present U/Pb ages of metamorphic zircon from several Adria-derived continental units now situated in the Western Alps, defining a range between 286 and 266 Ma. Trace element thermometry yields temperatures of 580-890°C from Ti-in-zircon and 630-850°C from Zr-in-rutile for Permian metamorphic rims. These temperature estimates, together with preserved mineral assemblages (garnet-prismatic sillimanite-biotite-plagioclase-quartz-K-feldspar-rutile), define pervasive upper-amphibolite to granulite facies conditions for Permian metamorphism. U/Pb ages from this study are similar to Permian ages reported for the Ivrea Zone in the Southern Alps and Austroalpine units in the Central and Eastern Alps. Regional comparison across the former Adriatic and European margin reveals a complex pattern of ages reported from late Palaeozoic magmatic and metamorphic rocks (and relics thereof): two late Variscan age groups (~330 and ~300 Ma) are followed seamlessly by a broad range of Permian ages (300-250 Ma). The former are associated with late-orogenic collapse; in samples from this study these are weakly represented. Clearly, dominant is the Permian group, which is related to crustal thinning, hinting to a possible initiation of continental rifting along a passive margin

Stabilität von Silagen für Pferde bei der Fütterung

In der Pferdefütterung werden als Alternative zu Heu seit einigen Jahren vermehrt Silagen mit hohen TS-Gehalten, so genannte Haylage, eingesetzt.Bei der Verfütterung gibt es jedoch noch Fragen zur Haltbarkeit und den Lagerungsbedingungen. Im Rahmen von zwei Semesterarbeiten wurde untersucht, wie sich der TS-Gehalt respektive der Einsatz eines Siliermittels auf die Haltbarkeit der Silagen bei der Verfütterung auswirken. Dazu wurde ein Teil der Quaderballensilage nach dem Öffnen aufgeschüttelt und der restliche Teil der Balle jeweils kompakt gelagert. Die Ergebnisse haben gezeigt, dass der TS-Gehalt des Futters die Intensität der Gärung und die pH-Wert-Absenkung stark beeinflusst. Ein guter Indikator zur Bestimmung des Verderbs stellt die Messung der Temperaturen dar. Silagen mit TS-Gehalten über 60 %, die nach dem Öffnen der Ballen aufgeschüttelt werden, trocknen während der Lagerung unter Lufteinfluss stärker ab als kompakt gelagerte Ballen. Dadurch entwickeln sich die Schimmelpilze weniger stark. Durch den Siliermitteleinsatz konnte der Verderb teilweise länger verhindert werden. Es wird empfohlen, die geöffneten Ballen innerhalb einer Woche zu verfüttern. Bei Futter mit TS-Gehalten über 60 % bringt das Aufschütteln des Futters eine Verbesserung. Bei feuchterem Futter ist eine kompakte Lagerung der Ballen von Vorteil

Discontinuation and Publication of Randomized Clinical Trials supported by the Main Public Funding Body in Switzerland: a Retrospective Cohort Study

Roll 472a. Pre-Carnival Publicity & Quad. Image 13 of 36. (6 April, 1959) [PHO 1.472a.39]The Boleslaus Lukaszewski (Father Luke) Photographs contain more than 28,000 images of Saint Louis University people, activities, and events between 1951 and 1970. The photographs were taken by Boleslaus Lukaszewski (Father Luke), a Jesuit priest and member of the University's Philosophy Department faculty

Funding characteristics of randomised clinical trials supported by the Swiss National Science Foundation: a retrospective cohort study.

Failure to publish publicly funded research represents a waste of scarce research resources across medical disciplines and countries. In Switzerland, about 40% of randomised clinical trials (RCTs) supported by the Swiss National Science Foundation (SNSF) were not published. We aimed to describe funding characteristics of published and unpublished RCTs supported by the SNSF, to quantify the amount of money spent for unpublished studies, and to compare our results to a similar study performed in the UK. We established a retrospective cohort of RCTs funded by the SNSF up to 2015. For each RCT proposal, two investigators independently identified corresponding publications in electronic databases and trial registries. Teams of two investigators independently extracted details from the original SNSF proposal and, if available, from trial registries or publications. In addition, we surveyed principal investigators about trial costs and additional sources of funding. We included 101 RCTs supported by the SNSF between 1986 and 2015. Most were single-centre RCTs with a median of 138 participants (interquartile range [IQR] 76-400). Overall, 67 (67%) principal investigators responded to our main survey questions. Median total costs per RCT were CHF 428 000 (IQR 282 000-900 000) of which the SNSF provided a median CHF 222 000 (67% of total costs, IQR 40-80%). Most investigators (70%) mentioned additional funding, mainly from their own institution or private foundations. A total of CHF 6.7 million was granted to RCTs that remained unpublished. Funding characteristics were similar to publicly funded trials in the UK. A third of the total SNSF grant sum spent on healthcare RCTs between 1986 and 2015 did not result in peer-reviewed scientific publications. New SNSF grant schemes might improve publication outcomes but their effectiveness needs to be evaluated

Premature trial discontinuation often not accurately reflected in registries: comparison of registry records with publications.

One quarter of randomized clinical trials (RCTs) are prematurely discontinued and frequently remain unpublished. Trial registries can document whether a trial is ongoing, suspended, discontinued, or completed and therefore represent an important source for trial status information. The accuracy of this information is unclear. To examine the accuracy of completion status and reasons for discontinuation documented in trial registries as compared to corresponding publications of discontinued RCTs and to investigate potential predictors for accurate trial status information in registries. We conducted a cross-sectional study comparing information provided in publications (reference standard) to corresponding registry entries. First, we reviewed publications of RCTs providing information on both discontinuation and registration. We identified eligible publications through systematic searches of MEDLINE and EMBASE (2010-2014) and an international cohort of 1,017 RCTs initiated between 2000 and 2003. Second, pairs of investigators independently and in duplicate extracted data from publications and corresponding registry records. Third, for each discontinued RCT, we compared publication information to registry information. We used multivariable regression to examine whether accurate labeling of trials as discontinued (vs. other status) in the registry was associated with recent initiation of RCT, industry sponsorship, multicenter design, or larger sample size. We identified 173 publications of RCTs that were discontinued due to slow recruitment (55%), harm (16%), futility (11%), benefit (5%), other reasons (3%), or multiple reasons (9%). Trials were registered with clinicaltrials.gov (77%), isrctn.com (14%), or other registries (8%). Of the 173 corresponding registry records, 77 (45%) trials were labeled as discontinued and 57 (33%) provided a reason for discontinuation (of which 53, 93%, provided the same reason as in the publication). Labeling of discontinued trials as discontinued (vs. other label) in corresponding trial registry records improved over time (adjusted odds ratio 1.16 per year, confidence interval 1.04-1.30) and was possibly associated with industry sponsorship (2.01, 0.99-4.07) but unlikely with multicenter status (0.81, 0.32-2.04) or sample size (1.07, 0.89-1.29). Less than half of published discontinued RCTs were accurately labelled as discontinued in corresponding registry records. One-third of registry records provided a reason for discontinuation. Current trial status information in registries should be viewed with caution