Prevalence, characteristics, and publication of discontinued randomized trials.

IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES: To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

Learning from failure - rationale and design for a study about discontinuation of randomized trials (DISCO study).

BACKGROUND: Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. METHODS/DESIGN: Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs.We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. DISCUSSION: Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements.

Completion and Publication Rates of Randomized Controlled Trials in Surgery: An Empirical Study.

OBJECTIVE: To investigate the prevalence of discontinuation and nonpublication of surgical versus medical randomized controlled trials (RCTs) and to explore risk factors for discontinuation and nonpublication of surgical RCTs. BACKGROUND: Trial discontinuation has significant scientific, ethical, and economic implications. To date, the prevalence of discontinuation of surgical RCTs is unknown. METHODS: All RCT protocols approved between 2000 and 2003 by 6 ethics committees in Canada, Germany, and Switzerland were screened. Baseline characteristics were collected and, if published, full reports retrieved. Risk factors for early discontinuation for slow recruitment and nonpublication were explored using multivariable logistic regression analyses. RESULTS: In total, 863 RCT protocols involving adult patients were identified, 127 in surgery (15%) and 736 in medicine (85%). Surgical trials were discontinued for any reason more often than medical trials [43% vs 27%, risk difference 16% (95% confidence interval [CI]: 5%-26%); P = 0.001] and more often discontinued for slow recruitment [18% vs 11%, risk difference 8% (95% CI: 0.1%-16%); P = 0.020]. The percentage of trials not published as full journal article was similar in surgical and medical trials (44% vs 40%, risk difference 4% (95% CI: -5% to 14%); P = 0.373). Discontinuation of surgical trials was a strong risk factor for nonpublication (odds ratio = 4.18, 95% CI: 1.45-12.06; P = 0.008). CONCLUSIONS: Discontinuation and nonpublication rates were substantial in surgical RCTs and trial discontinuation was strongly associated with nonpublication. These findings need to be taken into account when interpreting surgical literature. Surgical trialists should consider feasibility studies before embarking on full-scale trials.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND: Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN: Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS: Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS: About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.

An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES: To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING: We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS: Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION: Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

Premature Discontinuation of Randomized Trials in Critical and Emergency Care: A Retrospective Cohort Study.

OBJECTIVES: Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. DESIGN: Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. SETTING: Randomized clinical trials involving patients in an acute or nonacute care setting. SUBJECTS AND INTERVENTIONS: We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. MEASUREMENTS AND MAIN RESULTS: Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. CONCLUSIONS: Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.

J.W. Spencer fonds, 1866, 1881-1921

Joseph William Winthrop Spencer (commonly known as J.W. Spencer) was a geologist and geomorphologist best known for his work on the geology of southern Ontario and the Great Lakes. He was born in Dundas, Upper Canada in 1851, but moved to Hamilton, Ontario in 1867. In 1871, he began studies in geology at McGill College in Montreal. In 1875 he worked in the Michigan copper mines and shortly afterwards prepared a thesis on the copper deposits. He submitted this thesis to the University of Gottingen in Germany in 1877 and was awarded a doctorate in geology, the second Canadian to earn a doctorate in this field. In 1880, he became a professor of geology and chemistry at King’s College in Windsor, N.S. Subsequently, he taught at the University of Missouri, and then the University of Georgia, but moved to Washington, D.C. in 1894, where he worked as a consultant geologist. Spencer spent much of his life studying preglacial river valleys in Ontario and the origins of the Great Lakes, as well as the Niagara River and Falls. In 1907, he published a book titled The Falls of Niagara: their evolution and varying relations to the Great Lakes. His opinions in these areas differed from some of his contemporaries, namely the American geologist Grove Karl Gilbert. Gilbert published a review of the The Falls of Niagara that exposed some flaws and inaccuracies in Spencer’s estimate of the age of the falls. Spencer’s studies also took him to the Caribbean and Central America. In 1920 he moved back to Canada, but died the following year.

Tin box "Waldmeister zur Bowle, Woodruff"

Tin box with the title “Waldmeister zur Bowle, Woodruff” on it, 10 cm x 16 cm. The box is from Julius Schade and Co., German Army and Navy Contractors, Leipzig-Lindenau, Germany. This box contains dried woodruff leaves. Accompanying this box of woodruff is a handwritten recipe for woodruff brew, n.d.

Corrupción y delitos contra la administración pública especial referencia a los delitos cometidos en la contratación

La corrupción sigue siendo uno de los principales problemas del Estado de Derecho en el siglo XXI. Su incidencia reduce la eficacia de la inversión, aumenta el valor de los bienes y servicios, reduce la competitividad de las empresas, vulnera la confianza de los ciudadanos en el ordenamiento jurídico y sobre todo condena a la miseria a quienes deben ser destinatarios de las políticas públicas.Sin embrago, la lucha que han realizado muchos gobiernos y funcionarios judiciales contra este fenómeno ha modificado sus formas de aparición, pues es cada vez menos frecuente la apropiación directa de los caudales públicos o la entrega de sobornos a los funcionarios, prefiriéndose métodos mucho más sutiles como los sobrecostos, la subcontratación masiva o la constitución de complicadas sociedades, en las cuales tienen participación los funcionarios públicos o sus familias.Este libro constituye un esfuerzo por el estudio jurídico y criminológico de la corrupción y los delitos contra la administración pública en Europa y Latinoamérica y reúne la selección de los temas penales más relevantes de la tesis doctoral del profesor Carlos Guillermo Castro Cuenca, denominada Aproximación a la Corrupción en la contratación pública y defendida en la universidad de Salamanca en febrero de 2008, con lo cual obtuvo la calificación de sobresaliente por unanimidad.

Evaluating the structure and magnitude of the ash plume during the initial phase of the 2010 Eyjafjallajökull eruption using lidar observations and NAME simulations

The Eyjafjallajökull volcano in Iceland erupted explosively on 14 April 2010, emitting a plume of ash into the atmosphere. The ash was transported from Iceland toward Europe where mostly cloud-free skies allowed ground-based lidars at Chilbolton in England and Leipzig in Germany to estimate the mass concentration in the ash cloud as it passed overhead. The UK Met Office's Numerical Atmospheric-dispersion Modeling Environment (NAME) has been used to simulate the evolution of the ash cloud from the Eyjafjallajökull volcano during the initial phase of the ash emissions, 14–16 April 2010. NAME captures the timing and sloped structure of the ash layer observed over Leipzig, close to the central axis of the ash cloud. Relatively small errors in the ash cloud position, probably caused by the cumulative effect of errors in the driving meteorology en route, result in a timing error at distances far from the central axis of the ash cloud. Taking the timing error into account, NAME is able to capture the sloped ash layer over the UK. Comparison of the lidar observations and NAME simulations has allowed an estimation of the plume height time series to be made. It is necessary to include in the model input the large variations in plume height in order to accurately predict the ash cloud structure at long range. Quantitative comparison with the mass concentrations at Leipzig and Chilbolton suggest that around 3% of the total emitted mass is transported as far as these sites by small (<100 μm diameter) ash particles.

Brodifacoum is effective against Norway Rats (Rattus norvegicus) in a tyrosine139cysteine focus of anticoagulant resistance, Westphalia, Germany

BACKGROUND: The single nucleotide polymorphism (SNP), and consequent amino acid exchange from tyrosine to cysteine at location 139 of the vkorc1 gene (i.e. tyrosine139cysteine or Y139C), is the most widespread anticoagulant resistance mutation in Norway rats (Rattus norvegicus Berk.) in Europe. Field trials were conducted to determine incidence of the Y139C SNP at two rat infested farms in Westphalia, Germany, and to estimate the practical efficacy against them of applications, using a pulsed baiting treatment regime, of a proprietary bait (KleratTM) containing 50 ppm brodifacoum. RESULTS: DNA analysis for the Y139C mutation showed that resistant rats were prevalent at the two farms, with an incidence of 80.0% and 78.6% respectively. Applications of brodifacoum bait achieved results of 99.2% and 100.0% control at the two farms, when measured by census baiting, although the treatment was somewhat prolonged at one site due to the abundance of attractive alternative food. CONCLUSION: The study showed that 50 ppm brodifacoum bait is fully effective against the Y139C SNP at the Münsterland focus and is likely to be so elsewhere in Europe where this mutation is found. The pulsed baiting regime reduced to relatively low levels the quantity of bait required to control these two substantial resistant Norway rat infestations. Previous studies had shown much larger quantities of bromadiolone and difenacoum baits used in ineffective treatments against Y139C resistant rats in the Münsterland. These results should be considered when making decisions about the use of anticoagulant against resistant Norway rats and their potential environmental impacts.

Das moderne Buch: Harry Graf Kesslers Ästhetik der Lebenskunst im Spiegel der Großherzog Wilhelm Ernst Ausgabe deutscher Klassiker

Die Großherzog Wilhelm Ernst Ausgabe deutscher Klassiker wurde seit 1904 bis in die Zwanziger Jahre hinein im Insel Verlag in Leipzig publiziert. Die Buchreihe hat nicht nur für den Verlag und die Druckerei Poeschel in der sie gedruckt wurde eine ganze Reihe von Neuerungen nach sich gezogen, auch für den deutschen Buchmarkt hat die Klassikerausgabe einen Meilenstein bedeutet. Sie hat einige Eigenschaften des Taschenbuches vorweggenommen. Sie orientierte sich an der Qualität bibliophiler Buchpublikationen, aber war dennoch preislich erschwinglich. Zeitgenössische Klassikerausgaben erschienen zumeist mit einem Kommentar. Nicht so die Großherzog Wilhelm Ernst Ausgabe. Der Text wurde zwar von führenden Wissenschaftlern editiert, aber sie war dennoch unkommentiert. Der Text war in einer Jenson-Antiqua gesetzt obwohl die Debatte um individuell gestaltete Künstlerschriften und die Diskussion um die als deutsche Schrift begriffene Fraktur unter den wichtigsten Protagonisten des deutschen Buchgewerbes ihren Höhepunkt noch nicht erreicht hatte. Ziel für die Klassikerausgabe war darüber hinaus, das zur Jahrhundertwende leicht angestaubte Image der Stadt Weimar aufzupolieren. Über das Patronat des Großherzogs hinaus hätte man die Gewinne aus dem Verkauf der Bücher der Permanenten Ausstellung für die Anschaffung von modernen Kunstobjekten zur Verfügung stellen wollen, die unter der Leitung von Harry Graf Kessler stand. Sieht man den Inhalt der Werke der in der Klassikerreihe erschienen Dichter Goethe, Schiller und Körner in einem ästhetischen Kontext mit dem der Philosophen Schopenhauer und Kant, wird im Spiegel der Formalästhetik der Klassikerausgabe Graf Kesslers Bildungs- und Kulturbegriff erkennbar, der sich in den Jahren nach der Jahrhundertwende zu seinem Lebenskunstideal verdichtete. Der zerrütteten Existenz der Zeitgenossen, wie Friedrich Nietzsche sie beschrieben hatte, sollte der Inhalt der Ausgabe in seiner modernen Form eine moderne Wertehaltung entgegensetzen. Die Lektüre der Klassiker sollte den deutschen Philister „entkrampfen“ und ihm ein Stück der verloren geglaubten Lebensfreude wieder zurück bringen, in dem dieser auch die Facetten des Lebensleids als normal hinnehmen und akzeptieren lernte. Die Klassikerausgabe repräsentierte aus diesem Grund auch den kulturellen und politischen Reformwillen und die gesellschaftlichen Vorstellungen die der Graf für ein modernes Deutschland als überfällig erachtete. Die Buchreihe war aus diesem Grund auch ein politisches Statement gegen die Beharrungskräfte im deutschen Kaiserreich. Die Klassikerreihe wurde in der buchhistorischen Forschung zwar als bedeutender Meilenstein charakterisiert und als „wichtiges“ oder gar „revolutionäres“ Werk der Zeit hervorgehoben, die Ergebnisse der Forschung kann man überspitzt aber in der Aussage zusammenfassen, dass es sich bei der Großherzog Wilhelm Ernst Ausgabe um einen „zufälligen Glückstreffer“ deutscher Buchgestaltung zu handeln scheint. Zumindest lassen die Aussagen, die bisher in dieser Hinsicht gemacht wurden, keine eindeutige Einordnung zu, außer vielleicht der, dass die Klassiker von der englischen Lebensreform inspiriert wurden und Henry van de Velde und William Morris einen Einfluss auf ihre äußere Form hatten. Gerade die Gedankenansätze dieser Beiden nutzte Graf Kessler aber für eigene Überlegungen, die ihn schließlich auch zu eigenen Vorstellungen von idealer Buchgestaltung brachten. Da für Kessler auch Gebrauchsgegenstände Kunst sein konnten, wird das Konzept der Klassikerausgabe bis zur Umsetzung in ihrer `bahnbrechenden´ Form in das ideengeschichtliche und ästhetische Denken des Grafen eingeordnet. Die Klassiker werden zwar in buchhistorischen Einzeluntersuchungen bezüglich ihrer Komponenten, dem Dünndruckpapier, ihrem Einband oder der Schrifttype exponiert. In buchwissenschaftlichen Überblicksdarstellungen wird ihr Einfluss hingegen weniger beachtet, denn verschiedene Kritiker bezogen sie seit ihrem ersten Erscheinen nicht als deutsches Kulturgut mit ein, denn sie lehnten sowohl die englischen Mitarbeiter Emery Walker, Edward Johnston, Eric Gill und Douglas Cockerell wie auch ihre Gestaltung als „welsche“ Buchausgabe ab. Richtig ist, die Großherzog Wilhelm Ernst Ausgabe hatte dieselbe Funktion wie die von Graf Kessler in Weimar konzipierten Kunstausstellungen und die dortige Kunstschule unter der Leitung seines Freundes Henry van de Velde. Auch das für Weimar geplante Theater, das unter der Leitung von Hugo von Hofmannsthal hätte stehen sollen und die Großherzog Wilhelm Ernst Schule, hätten dieselben Ideen der Moderne mit anderen Mitteln transportieren sollen, wie die Großherzog Wilhelm Ernst Ausgabe deutscher Klassiker.

Learning from failure--rationale and design for a study about discontinuation of randomized trials (DISCO study)

Background Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. Methods/Design Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs. We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. Discussion Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements.

Prevalence, characteristics, and publication of discontinued randomized trials.

IMPORTANCE The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). CONCLUSIONS AND RELEVANCE In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.