Unit-Level Variations in Healthcare Professionals' Availability for Preterm Neonates <29 Weeks' Gestation: An International Survey.

INTRODUCTION: The availability of and variability in healthcare professionals in neonatal units in different countries has not been well characterized. Our objective was to identify variations in the healthcare professionals for preterm neonates in 10 national or regional neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of neonates. METHOD: Online, pre-piloted questionnaires about the availability of healthcare professionals were sent to the directors of 390 tertiary neonatal units in 10 international networks: Australia/New Zealand, Canada, Finland, Illinois, Israel, Japan, Spain, Sweden, Switzerland, and Tuscany. RESULTS: Overall, 325 of 390 units (83%) responded. About half of the units (48%; 156/325) cared for 11-30 neonates/day and had team-based (43%; 138/325) care models. Neonatologists were present 24 h a day in 59% of the units (191/325), junior doctors in 60% (194/325), and nurse practitioners in 36% (116/325). A nurse-to-patient ratio of 1:1 for infants who are unstable and require complex care was used in 52% of the units (170/325), whereas a ratio of 1:1 or 1:2 for neonates requiring multisystem support was available in 59% (192/325) of the units. Availability of a respiratory therapist (15%, 49/325), pharmacist (40%, 130/325), dietitian (34%, 112/325), social worker (81%, 263/325), lactation consultant (45%, 146/325), parent buddy (6%, 19/325), or parents' resource personnel (11%, 34/325) were widely variable between units. CONCLUSIONS: We identified variability in the availability and organization of the healthcare professionals between and within countries for the care of extremely preterm neonates. Further research is needed to associate healthcare workers' availability and outcomes.

In vivo precision assessment of a near-infrared spectroscopy-based tissue oximeter (OxyPrem v1.3) in neonates considering systemic hemodynamic fluctuations.

The aim was to determine the precision of a noninvasive near-infrared spectroscopy (NIRS)-based tissue oximeter (OxyPrem v1.3). Using a linear mixed-effects model, we quantified the variability for cerebral tissue oxygenation (StO2) measurements in 35 preterm neonates to be 2.64%, a value that meets the often-articulated clinicians' demand for a precise tissue oxygenation measurement. We showed that the variability of StO2 values measured was dominated by spontaneous systemic hemodynamic fluctuations during the measurement, meaning that precision of the instrument was actually even better. Based on simultaneous and continuous measurements of peripheral arterial oxygenation and cerebral StO2 with a second sensor, we were able to determine and quantify the physiological instability precisely. We presented different methods and analyses aiming at reducing this systematic physiological error of in vivo precision assessments. Using these methods, we estimated the precision of the OxyPrem tissue oximeter to be ≤ 1.85 % . With our study, we deliver relevant information to establish highly precise cerebral oxygenation measurements with NIRS-based oximetry, facilitating the further development toward a substantially improved diagnosis and treatment of patients with respect to brain oxygenation.

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.

BACKGROUND: Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. METHODS AND FINDINGS: We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. CONCLUSIONS: Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol.

Evidence-informed recommendations to reduce dissemination bias in clinical research: conclusions from the OPEN (Overcome failure to Publish nEgative fiNdings) project based on an international consensus meeting.

BACKGROUND: Dissemination bias in clinical research severely impedes informed decision-making not only for healthcare professionals and patients, but also for funders, research ethics committees, regulatory bodies and other stakeholder groups that make health-related decisions. Decisions based on incomplete and biased evidence cannot only harm people, but may also have huge financial implications by wasting resources on ineffective or harmful diagnostic and therapeutic measures, and unnecessary research. Owing to involvement of multiple stakeholders, it remains easy for any single group to assign responsibility for resolving the problem to others. OBJECTIVE: To develop evidence-informed general and targeted recommendations addressing the various stakeholders involved in knowledge generation and dissemination to help overcome the problem of dissemination bias on the basis of previously collated evidence. METHODS: Based on findings from systematic reviews, document analyses and surveys, we developed general and targeted draft recommendations. During a 2-day workshop in summer 2013, these draft recommendations were discussed with external experts and key stakeholders, and refined following a rigorous and transparent methodological approach. RESULTS: Four general, overarching recommendations applicable to all or most stakeholder groups were formulated, addressing (1) awareness raising, (2) implementation of targeted recommendations, (3) trial registration and results posting, and (4) systematic approaches to evidence synthesis. These general recommendations are complemented and specified by 47 targeted recommendations tailored towards funding agencies, pharmaceutical and device companies, research institutions, researchers (systematic reviewers and trialists), research ethics committees, trial registries, journal editors and publishers, regulatory agencies, benefit (health technology) assessment institutions and legislators. CONCLUSIONS: Despite various recent examples of dissemination bias and several initiatives to reduce it, the problem of dissemination bias has not been resolved. Tailored recommendations based on a comprehensive approach will hopefully help increase transparency in biomedical research by overcoming the failure to disseminate negative findings.

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.

Choice of data extraction tools for systematic reviews depends on resources and review complexity.

OBJECTIVE: To assist investigators planning, coordinating, and conducting systematic reviews in the selection of data-extraction tools for conducting systematic reviews. STUDY DESIGN AND SETTING: We constructed an initial table listing available data-collection tools and reflecting our experience with these tools and their performance. An international group of experts iteratively reviewed the table and reflected on the performance of the tools until no new insights and consensus resulted. RESULTS: Several tools are available to manage data in systematic reviews, including paper and pencil, spreadsheets, web-based surveys, electronic databases, and web-based specialized software. Each tool offers benefits and drawbacks: specialized web-based software is well suited in most ways, but is associated with higher setup costs. Other approaches vary in their setup costs and difficulty, training requirements, portability and accessibility, versatility, progress tracking, and the ability to manage, present, store, and retrieve data. CONCLUSION: Available funding, number and location of reviewers, data needs, and the complexity of the project should govern the selection of a data-extraction tool when conducting systematic reviews.