Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE)

OBJECTIVES Comprehensive protocols are key for the planning and conduct of randomised clinical trials (RCTs). Evidence of low reporting quality of RCT protocols led to the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist in 2013. We aimed to examine the quality of reporting of RCT protocols from three countries before and after the publication of the SPIRIT checklist. DESIGN Repeated cross sectional study. SETTING Swiss, German and Canadian research ethics committees (RECs). PARTICIPANTS RCT protocols approved by RECs in 2012 (n=257) and 2016 (n=292). PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcomes were the proportion of reported SPIRIT items per protocol and the proportion of trial protocols reporting individual SPIRIT items. We compared these outcomes in protocols approved in 2012 and 2016, and built regression models to explore factors associated with adherence to SPIRIT. For each protocol, we also extracted information on general trial characteristics and assessed whether individual SPIRIT items were reported RESULTS: The median proportion of reported SPIRIT items among RCT protocols showed a non-significant increase from 72% (IQR, 63%-79%) in 2012 to 77% (IQR, 68%-82%) in 2016. However, in a preplanned subgroup analysis, we detected a significant improvement in investigator-sponsored protocols: the median proportion increased from 64% (IQR, 55%-72%) in 2012 to 76% (IQR, 64%-83%) in 2016, while for industry-sponsored protocols median adherence was 77% (IQR 72%-80%) for both years. The following trial characteristics were independently associated with lower adherence to SPIRIT: single-centre trial, no support from a clinical trials unit or contract research organisation, and investigator-sponsorship. CONCLUSIONS In 2012, industry-sponsored RCT protocols were reported more comprehensively than investigator-sponsored protocols. After publication of the SPIRIT checklist, investigator-sponsored protocols improved to the level of industry-sponsored protocols, which did not improve

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis

BACKGROUND We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research

Die Hospiz- und Palliativversorgung in Mecklenburg-Vorpommern - eine versorgungsepidemiologische Analyse auf der Basis verschiedener Datenquellen

Die Hospiz- und Palliativversorgung hat zum Ziel die Lebensqualität von Patient*innen mit einer unheilbaren Erkrankung zu erhalten und zu fördern. Jeder schwerkranke Mensch, der durch eine unheilbare Erkrankung eine Lebenserwartung von wenigen Tagen, Wochen oder Monaten hat, soll Zugang zur Hospiz- und Palliativversorgung erhalten. Im Rahmen der Hospiz- und Palliativversorgung werden neben der pflegerischen und medizinischen Ebene, Betroffene und deren Angehörige auf psychischer und spiritueller Ebene begleitet. Dies setzt eine gute interdisziplinäre und sektorübergreifende Zusammenarbeit voraus. Ziel der vorliegenden kumulativen Dissertation ist die Erstellung einer versorgungsepidemiologischen Analyse der Hospiz- und Palliativversorgung in Mecklenburg-Vorpommern auf Basis von Interviews, einer standardisierten schriftlichen Befragung und einer Analyse von Krankenkassendaten. Spezielles Augenmerk hat die Identifizierung von Problemen sowie Brüchen in der Kontinuität der Hospiz- und Palliativversorgung. Die Dissertation besteht aus zwei Publikationen zur Hospiz- und Palliativversorgung in Mecklenburg-Vorpommern. In der ersten Publikation wurden mögliche Problembereiche und Barrieren in der Palliativ- und Hospizversorgung in Mecklenburg-Vorpommern anhand von qualitativen Interviews und einer darauf aufbauenden schriftlichen Befragung mit Leistungserbringer*innen der allgemeinen und spezialisierten Palliativversorgung und der Hospizversorgung ermittelt (im weiteren Verlauf der Dissertation „Befragungsstudie“ genannt). In der zweiten Publikation wurde die Kontinuität der Palliativ- und Hospizversorgung auf der Basis von Abrechnungsdaten der Krankenkasse AOK-Nordost untersucht (im weiteren Verlauf der Dissertation „Kontinuitätsstudie“ genannt). Wichtigste Ergebnisse der qualitativen Interviews und der Befragungsstudie sind eine teilweise unzureichende Zusammenarbeit zwischen dem ambulanten und stationären Sektor sowie zwischen der allgemeinen und der spezialisierten Palliativ- und Hospizversorgung. Insbesondere die Zusammenarbeit der Hausärzt*innen mit spezialisierten palliativmedizinischen Leistungserbringer*innen wurde weniger gut bewertet. Die Bewertungen der Zusammenarbeit der einzelnen Leistungserbringer*innen deutet drauf hin, dass die Kooperation der Versorgung einer besseren Koordination bedarf. Dieses Ergebnis wurde anhand von Routinedaten im Rahmen der Kontinuitätsstudie untersucht. Die Kontinuitätsstudie zeigt, dass ein Großteil der Palliativpatient*innen nach einer palliativmedizinischen stationären Versorgung eine palliativmedizinische Anschlussversorgung erhielt, jedoch nicht immer binnen 14 Tage. Die durch die Befragungen erwarteten Versorgungslücken in Form von großen zeitlichen Abständen konnten anhand der Kontinuitätsstudie teilweise gefunden werden

Middle-income families in the economic downturn: challenges and management strategies over time

The “Great Recession” has hurt many families across the United States, yet most research has examined its impact on those already considered poor or working poor. However, this recession has affected middle-income families, whose experiences with economic challenge have seldom been looked at in any detail. Such families have been recently called “the new poor,” “the missing middle,” and “families in the middle.” One in seven American children under age 18 (10.5 million) has an unemployed parent as a result of this recession, and because economic mobility for children in the U.S. is affected by their parents’ earning capacities, their mobility potential may be mediated by parents’ strategies for children’s educational futures. The research presented here, which is informed by Weberian stratification theory and capital theories, is based on a longitudinal subset of a larger two-country, multicity, mixed-methods study that used surveys and qualitative semi-structured interviews to explore how middle-income families contend with economic downturn and how their adolescent children’s educational futures might be influenced. Our findings suggest that most families maintain their children’s developmental and educational status quo, but their strategies to do so constrict the potential for educational attainment. As such, the American approach to off-loading much of the cost of higher education to middle-income families who are economically stressed is not viable if we hope to maximize the number of children who will receive mobility-enhancing postsecondary education

Comparison of survival between patients receiving general outpatient palliative care and patients receiving other palliative care - analysis of data of a statutory health insurance data

Background The care of palliative patients takes place as non-specialized and specialized care, in outpatient and inpatient settings. However, palliative care is largely provided as General Outpatient Palliative Care (GOPC). This study aimed to investigate whether the survival curves of GOPC patients differed from those of the more intensive palliative care modalities and whether GOPC palliative care was appropriate in terms of timing. Methods The study is based on claims data from a large statutory health insurance. The analysis included 4177 patients who received palliative care starting in 2015 and who were fully insured 1 year before and 1 year after palliative care or until death. The probability of survival was observed for 12 months. Patients were classified into group A, which consisted of patients who received palliative care only with GOPC, and group B including patients who received inpatient or specialized outpatient palliative care. Group A was further divided into two subgroups. Patients who received GOPC on only 1 day were assigned to subgroup A1, and patients who received GOPC on two or more days were assigned to subgroup A2. The survival analysis was carried out using Kaplan-Meier curves. The median survival times were compared with the log-rank test. Results The survival curves differed between groups A and B, except in the first quartile of the survival distribution. The median survival was significantly longer in group A (137 days, n = 2763) than in group B (47 days, n = 1424, p < 0.0001) and shorter in group A1 (35 days, n = 986) than in group A2 (217 days, n = 1767, p < 0.0001). The survival rate during the 12-month follow-up was higher in group A (42%) than in group B (11%) and lower in group A1 (38%) than in group A2 (44%). Conclusions The results of the analysis revealed that patients who received the first palliative care shortly before death suspected insufficient care, especially patients who received GOPC for only 1 day and no further palliative care until death or 12-month follow-up. Palliative care should start as early as necessary and be continuous until the end of life

Continuity in palliative care – analysis of intersectoral palliative care based on routine data of a statutory health insurance

Background!#!The goal of palliative care is to prevent and alleviate a suffering of incurable ill patients. A continuous intersectoral palliative care is important. The aim of this study is to analyse the continuity of palliative care, particularly the time gaps between hospital discharge and subsequent palliative care as well as the timing of the last palliative care before the patient's death.!##!Methods!#!The analysis was based on claims data from a large statutory health insurance. Patients who received their first palliative care in 2015 were included. The course of palliative care was followed for 12 months. Time intervals between discharge from hospital and first subsequent palliative care as well as between last palliative care and death were analysed. The continuity in palliative care was defined as an interval of less than 14 days between palliative care. Data were analysed using descriptive statistics and Chi-Square.!##!Results!#!In 2015, 4177 patients with first palliative care were identified in the catchment area of the statutory health insurance. After general inpatient palliative care, 415 patients were transferred to subsequent palliative care, of these 67.7% (n = 281) received subsequent care within 14 days. After a stay in a palliative care ward, 124 patients received subsequent palliative care, of these 75.0% (n = 93) within 14 days. Altogether, 147 discharges did not receive subsequent palliative care. During the 12-months follow-up period, 2866 (68.7%) patients died, of these 78.7% (n = 2256) received palliative care within the last 2 weeks of life. Of these, 1223 patients received general ambulatory palliative care, 631 patients received specialised ambulatory palliative care, 313 patients received their last palliative care at a hospital and 89 patients received it in a hospice.!##!Conclusions!#!The majority of the palliative care patients received continuous palliative care. However, there are some patients who did not receive continuous palliative care. After inpatient palliative care, each patient should receive a discharge management for a continuation of palliative care. Readmissions of patients after discharge from inpatients palliative care can be an indication for a lack of support in the ambulatory health care setting and for an insufficient discharge management. Palliative care training and possibilities for palliative care consultations by specialists should strengthen the GPs in palliative care

Population-Based, Spatial Analysis of Specialised Ambulatory Palliative Care in Mecklenburg-Western Pomerania, Germany, on the Basis of Reimbursement Data

In rural areas, healthcare providers, patients and relatives have to cover long distances. For specialised ambulatory palliative care (SAPV), a supply radius of max. 30 km is recommended. The aim of this study was to analyse whether there are regional disparities in the supply of SAPV and whether it is associated with the distance between the SAPV team&rsquo;s site and the patient&rsquo;s location. Therefore, anonymised data of the Association of Statutory Health Insurance Physicians of the Federal State of Mecklenburg-Western Pomerania (M-V) were retrospectively analysed for the period of 2014&ndash;2017. Identification as a palliative patient was based on palliative-specific items from the ambulatory reimbursement catalogue. In total, 6940 SAPV patients were identified; thereof, 48.9% female. The mean age was 73.3 years. For 28.3% of the identified SAPV patients (n = 1961), the SAPV teams had a travel distance of &gt;30 km. With increasing distance, the average number of treatment days per patient increased. It was found that there are regional disparities in the provision of SAPV services in M-V and that local structures have an important impact on regional supply patterns. The distance between the SAPV team&rsquo;s site and the patient&rsquo;s location is not the only determining factor; other causes must be considered

Rationale and design of repeated cross-sectional studies to evaluate the reporting quality of trial protocols: the Adherence to SPIrit REcommendations (ASPIRE) study and associated projects

BACKGROUND Clearly structured and comprehensive protocols are an essential component to ensure safety of participants, data validity, successful conduct, and credibility of results of randomized clinical trials (RCTs). Funding agencies, research ethics committees (RECs), regulatory agencies, medical journals, systematic reviewers, and other stakeholders rely on protocols to appraise the conduct and reporting of RCTs. In response to evidence of poor protocol quality, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline was published in 2013 to improve the accuracy and completeness of clinical trial protocols. The impact of these recommendations on protocol completeness and associations between protocol completeness and successful RCT conduct and publication remain uncertain. OBJECTIVES AND METHODS Aims of the Adherence to SPIrit REcommendations (ASPIRE) study are to investigate adherence to SPIRIT checklist items of RCT protocols approved by RECs in the UK, Switzerland, Germany, and Canada before (2012) and after (2016) the publication of the SPIRIT guidelines; determine protocol features associated with non-adherence to SPIRIT checklist items; and assess potential differences in adherence across countries. We assembled an international cohort of RCTs based on 450 protocols approved in 2012 and 402 protocols approved in 2016 by RECs in Switzerland, the UK, Germany, and Canada. We will extract data on RCT characteristics and adherence to SPIRIT for all included protocols. We will use multivariable regression models to investigate temporal changes in SPIRIT adherence, differences across countries, and associations between SPIRIT adherence of protocols with RCT registration, completion, and publication of results. We plan substudies to examine the registration, premature discontinuation, and non-publication of RCTs; the use of patient-reported outcomes in RCT protocols; SPIRIT adherence of RCT protocols with non-regulated interventions; the planning of RCT subgroup analyses; and the use of routinely collected data for RCTs. DISCUSSION The ASPIRE study and associated substudies will provide important information on the impact of measures to improve the reporting of RCT protocols and on multiple aspects of RCT design, trial registration, premature discontinuation, and non-publication of RCTs observing potential changes over time

Systematic Cross-biospecimen Evaluation of DNA Extraction Kits for Long- and Short-read Multi-metagenomic Sequencing Studies

High-quality DNA extraction is a crucial step in metagenomic studies. Bias by different isolation kits impairs the comparison across datasets. A trending topic is, however, the analysis of multiple metagenomes from the same patients to draw a holistic picture of microbiota associated with diseases. We thus collected bile, stool, saliva, plaque, sputum, and conjunctival swab samples and performed DNA extraction with three commercial kits. For each combination of the specimen type and DNA extraction kit, 20-gigabase (Gb) metagenomic data were generated using short-read sequencing. While profiles of the specimen types showed close proximity to each other, we observed notable differences in the alpha diversity and composition of the microbiota depending on the DNA extraction kits. No kit outperformed all selected kits on every specimen. We reached consistently good results using the Qiagen QiAamp DNA Microbiome Kit. Depending on the specimen, our data indicate that over 10 Gb of sequencing data are required to achieve sufficient resolution, but DNA-based identification is superior to identification by mass spectrometry. Finally, long-read nanopore sequencing confirmed the results (correlation coefficient > 0.98). Our results thus suggest using a strategy with only one kit for studies aiming for a direct comparison of multiple microbiotas from the same patients