Publication Of Trials Research Articles

Trial characteristics, geographic distribution and selected methodological issues of 1425 infertility trials published from 2012 to 2023: a systematic review

Abstract STUDY QUESTION What are the trial characteristics, geographic distribution and selected methodological issues of randomised clinical trials (RCTs) in infertility published from 2012 to 2023? SUMMARY ANSWER Of the 1,425 infertility RCTs, over two-thirds focused on IVF, nearly two-fifths did not use pregnancy or live birth as the primary outcome, a third lacked a primary outcome, a half were unregistered, and just over half were conducted in China (22%), Iran (20%), or Egypt (10%). WHAT IS KNOWN ALREADY RCTs are the main source of evidence on the effectiveness of interventions. Knowledge about RCTs in infertility from the recent past will help to pinpoint research gaps and prioritize the future research agenda. Here, we aim to present a descriptive analysis of trial characteristics, geographic distribution and selected methodological issues in infertility trials published in the last decade. STUDY DESIGN, SIZE, DURATION This is a systematic review. We systematically searched Embase, Medline and Cochrane Central for RCTs in infertility from January 2012 to August 2023. RCTs involving subfertile women and that reported pregnancy endpoints were eligible, while conference abstracts or secondary analyses were not. We did not limit our search based on the language of the articles. PARTICIPANTS/MATERIALS, SETTING, METHODS The full articles were text-mined and manually extracted for the description of trials’ characteristics (e.g., sample size, blinding method, types of intervention), the country where the patients were recruited, and methodological issues (trial registrations and specification of primary outcomes). We extracted funding statements from Dimensions, a literature database chosen for its comprehensive and robust metadata. Gross domestic product (GDP) data were obtained from the United Nations’ official website. The accuracy of extracted data was validated in a random sample of 50 articles, and false positivity and false negativity were all at or below 8%. We used descriptive statistics, including frequencies and percentages to illustrate the overall and temporal trends. MAIN RESULTS AND THE ROLE OF CHANCE Among 8,757 records, we found 1,425 eligible RCTs, with a median sample size of 140, and 33.3% had a sample size <100. Most (69.6%) of the trials focused on IVF, with the rest focusing on ovulation induction (12.4%), intrauterine insemination (10.6%), surgeries (4.8%) or other interventions (2.6%). Regarding the geographic distribution, China (n = 310), Iran (n = 284) and Egypt (n = 138) contributed to 51% of the RCTs, followed by Turkey (n = 82), India (n = 71) and the United States (n = 69); mainland Europe produced 343 trials. Ranked by publications of trials per trillion GDP, Greece had the most papers with 4.6, followed by Iraq at 3.9, and Iran at 2.5. Regarding trial registration, 47.8% of trials were unregistered, the proportion of studies that were unregistered halved from 70.0% in 2012 to 34.6% in 2022. Of all RCTs, 37.6% had primary outcomes unspecified; the proportion of trials specifying primary outcomes increased from 49.5% in 2012 to 61.4% in 2022. The proportion of trials which declared receiving no funding was 76.9%. LIMITATIONS, REASONS FOR CAUTION We primarily used text mining for data extraction. Despite optimizing the algorithm to identify all outcome definitions and manually curating the extracted data, there were inaccuracies in data extraction; however, the false positivity and false negativity of data extraction were all at or below 8%. Also, we focused on trials reporting pregnancy outcomes, as these are of primary interest to patients and carry significant implications on clinical practice. However, we acknowledge that early-stage trials with only upstream endpoints also play an important role and should be considered when evaluating the full spectrum of infertility trials. Finally, we only included published RCTs and hence, our results cannot be extrapolated to unpublished RCTs. WIDER IMPLICATIONS OF THE FINDINGS The domination of RCTs on IVF calls for a reconsideration of other topics to be studied and a realignment of research priorities. The imbalanced geographic distribution of infertility trials raises questions about the generalizability of study results and equity in the distribution of health care resources. The prevalence of trials without registration or primary outcomes specified highlights the imperative to improve trial design and reporting quality. Encouragingly, the improving trial registrations suggest the enforcement of trial registrations from the journals is effective. STUDY FUNDING/COMPETING INTEREST(S) B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). W.T.L. is supported by a NHMRC Investigator grant (GTN2016729). W.L.L. reports receiving a PhD scholarship from the China Scholarship Council. Q.F. reports receiving a PhD scholarship from Merck. B.W.M. reports receiving consultancy fees, travel support and research funding from Merck; consultancy fees from Organon and Norgine; and stock ownership in ObsEva. T.D.H and S.L. are employees of Merck. W.T.L., W.L.L. and J.C. report no conflicts of interest. REGISTRATION NUMBER PROSPERO CRD42024498624

Perinatal mortality trend associated with maternal obesity in United States between 2015 - 2020.

Obesity is associated with an increased risk of stillbirth and neonatal death. Since the publication of A Randomized Trial of Induction Versus Expectant Management (ARRIVE) in 2018, there was an increase in 39 weeks deliveries. The objective of this study was to evaluate the trends in perinatal mortality by BMI category from 2015 to 2020. This was a retrospective cohort study of US births between 2015 and 2020. The rates of stillbirths, infant deaths, and perinatal mortality were calculated for each BMI category. Logistic regression models were constructed based on specific outcome rates from 2015 - 2018 to predict the rates in 2019 and 2020. The predicted rates were compared with the actual rates to determine possible deviations due to policy and practice changes that occurred. Between 2015 - 2018, the stillbirth rate increased for ascending BMI categories. Whereas the neonatal death rate decreased for all except the underweight group, the perinatal death rate increased in all except for those with category III obesity. In 2019 the perinatal mortality rate decreased for every BMI category except underweight group. In 2020, the rate of infant deaths increased for all BMI categories compared with the predicted rates. The results were similar after excluding common comorbidities. Perinatal mortality rates improved in 2019, reversing the increasing trend from 2015-2018. However this trend did not persist for some BMI categories in 2020. These findings may suggest a beneficial effect of policy changes since the ARRIVE trial publication and the negative effects from the COVID-19 pandemic.

Health-Related Quality of Life in Juvenile Idiopathic Arthritis: A Systematic Review of Phase III Clinical Trials.

Background/objectives: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, leading to severe disability and negatively affecting patients' health-related quality of life (HRQoL). The aim of this systematic review was to evaluate the adoption, reporting and assessment methodology of HRQoL in phase III clinical trials involving children with JIA. Methods: An electronic and manual search was conducted to identify primary and secondary publications of pharmacological trials conducted between 2012 and 2023. Data were extracted and recorded in duplicate. Results: A total of 222 studies were screened and 24 articles (22 primary and 2 secondary publications) were included in the review. HRQoL was not listed among the endpoints in 10 trials (45.5%), while it was a secondary endpoint in 12 trials (54.5%). The proportion of trials that did not consider HRQoL was equally relevant in both for-profit and no-profit settings (44.4% versus 50.0%), but it was higher in studies on systemic JIA compared to other JIA subtypes (62.5%), and on IL inhibitor treatment (72.7%) with respect to other disease-modifying antirheumatic drugs. Information on HRQoL was usually collected from parents/caregivers, and only three studies were categorized as "probably robust" with regard to HRQoL assessment. Conclusions: Systematic incorporation of HRQoL measures represents an urgent need in pediatric rheumatology, aiding clinicians in their decision-making in relation to treatment effectiveness and considering the children's perspective.

Discordant Information on Blinding in Trial Registries and Published Research

Blinding of individuals involved in randomized clinical trials (RCTs) can be used to protect against performance and biases, but discrepancies in the reporting of methodological features between registered protocols and subsequent trial publications may lead to inconsistencies, thereby reintroducing bias. To investigate inconsistency in blinding as reported in trial registries and publications. An exploratory dataset and a validation dataset were created. The exploratory dataset consisted of RCTs included in systematic reviews of adverse events from the SMART Safety database published between January 1, 2015, to January 1, 2020. The validation dataset was based on a literature search on PubMed for all registered RCTs published within the same time frame. Eligible RCTs for the exploratory dataset included were those that specified drug safety as the exclusive outcome and included at least 1 pairwise meta-analysis involving 5 or more RCTs of health care interventions. The validation dataset included a random selection of RCTs without restriction on outcome. Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed during data extraction. RCTs were matched to their registries and information on blinding was extracted from both the journal publication and trial registry. Extraction was performed by 1 author and cross-checked by 2 additional authors, with discrepancies resolved via consensus. The data analysis was conducted between July 2023 and January 2024. The primary outcome was inconsistency in blinding reports in the publication and the associated trial registry. Factors associated with the inconsistency were further investigated using multivariable logistic regression. The results were then compared with the validation dataset. A total of 1340 RCTs were included, with a median (IQR) sample size of 338 (152-772) participants. Of these, 749 (55.90%) were multiregional, 1220 (91.04%) were multicenter, and 835 (62.31%) were prospectively registered. The most frequently studied condition was cancer, representing 472 trials (35.22%). In the exploratory dataset, 1080 trials (80.60%) had inconsistent reporting of blinding in their published trial registry. Higher odds of inconsistency were associated with trials conducted as single-center (OR, 2.84; 95% CI, 1.24-7.74; P = .02) or those focused on cancer (OR, 3.26; 95% CI, 2.04-5.38; P < .001). Evaluation of the 98 RCTs in the validation dataset revealed that 70 (71.43%) had inconsistencies between the published trial and its registries. The occurrence of inconsistencies was significantly higher in the exploratory dataset than the validation dataset (P = .03). In this systematic review of RCTs, there were significant inconsistencies in the reporting of blinding between trial publications and their corresponding registries. These findings underscore the importance of maintaining consistency between registered protocols and published trial reports to ensure methodological transparency and minimize bias.

Has the UK lost its position as a destination for world-leading clinical research? A comparative analysis of haematological cancer clinical trials performance before Brexit

ObjectivesTo understand the competitive position of the UK in comparison to Europe and the USA for haematological cancer clinical research.DesignUsing commercially available databases, clinical trial numbers, their effectiveness and publication...

The Impact of Temperature on Extracting Information From Clinical Trial Publications Using Large Language Models.

Introduction The application of natural language processing (NLP) for extracting data from biomedical research has gained momentum with the advent of large language models (LLMs). However, the effect of different LLM parameters, such as temperature settings, on biomedical text mining remains underexplored and a consensus on what settings can be considered "safe" is missing. This study evaluates the impact of temperature settings on LLM performance for a named entity recognition and a classification task in clinical trial publications. Methods Two datasets were analyzed using GPT-4o and GPT-4o-mini models at nine different temperature settings (0.00-2.00). The models were used to extract the number of randomized participants and classify abstracts as randomized controlled trials (RCTs) and/or as oncology-related. Different performance metrics were calculated for each temperature setting and task. Results Both models provided correctly formatted predictions for more than 98.7% of abstracts across temperatures from 0.00 to 1.50. While the number of correctly formatted predictions started to decrease afterwardwith the most notable drop between temperatures 1.75 and 2.00, the other performance metrics remained largely stable. Conclusion Temperature settings at or below 1.50 yielded consistent performance across text-mining tasks, with performance declines at higher settings. These findings are aligned with research on different temperature settings for other tasks, suggesting stable performance within a controlled temperature range across various NLP applications.

Analysis of Ophthalmology Drug Clinical Trial Institutions in China: Challenges and Opportunities Under the Registration System

Objective: To analyze the status of ophthalmology drug clinical trial institutions in China following the implementation of the registration system and provide a reference for their development. Methods: An analysis was conducted using data from the Drug Clinical Trial Institution Registration Management Information Platform and the Drug Clinical Trial Registration and Information Publicity Platform of the National Medical Products Administration. The search period was up to April 19, 2024. Results: As of April 19, 2024, 314 ophthalmology-specific institutions were registered nationwide, comprising 274 comprehensive medical institutions and 40 specialized ophthalmology institutions, representing a 245% increase compared to the qualification certification phase. There were 965 major researchers in ophthalmology, accounting for 6.3% of the total number of researchers across all registered ophthalmology institutions. These institutions were predominantly located in economically developed areas such as Guangdong, Zhejiang, and Jiangsu Provinces, with the top five provinces and cities comprising 39.8% of the total registered institutions. Beijing had the highest number of major researchers (126), with their distribution positively correlated with the geographic spread of registered institutions. Furthermore, as of April 19, 2024, there were 216 clinical drugs related to eye diseases, with the top three provinces conducting 77.8% of national clinical trial projects. The number of institutions was directly proportional to the volume of clinical trials conducted. Conclusion: The implementation of the registration system has facilitated the release of ophthalmic medical resources. However, regional disparities remain in the number of ophthalmology-specific institutions, the availability of major investigators, and the distribution of clinical trial projects.

Traditional Chinese medicine for cardiovascular disease: efficacy and safety.

In China and other Asian nations, traditional medicine has long been utilized in the treatment of cardiovascular diseases (CVD). While Chinese authorities have incorporated traditional Chinese medicine (TCM) treatment experiences as a supplementary guide for CVD, its international recognition remains limited due to a scarcity of high-quality and reliable randomized controlled trials (RCTs) evidence. The purpose of this study was to examine the clinical outcomes with TCM for CVD after the recent publication of large trials adding >20,000 individuals to the published data. Here, we systematically reviewed 55 published RCTs (modified Jadad scores > 4) in the past 20 years, involving a total of 36,261 patients. In most studies, TCM has been associated with significant improvements in alternative endpoints such as hypertension, coronary heart disease, stroke and heart failure. A total of 19 trials reported on primary outcomes such as cardiovascular events and death events. During the follow-up period, some Chinese patent medicines can effectively reduce the "hard" endpoints of coronary heart disease, stroke, and heart failure, the overall trend of cardiovascular outcomes is lower. The risk of adverse effects was not significantly increased compared to the control group, suggesting its potential as an alternative approach for primary and secondary prevention of CVD based on the available evidence.

First real-world evidence of sparsentan efficacy in patients with IgA nephropathy treated with SGLT2 inhibitors.

Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach. A total of 23 patients with IgAN were treated with sparsentan via the Managed Access Programme between December 2023 and August 2024. The patients were stable on maximum tolerated doses of renin-angiotensin system (RAS) and SGLT2 inhibitors, with an estimated glomerular filtration rate (eGFR) >30mL/min/1.73m² and a urine protein/creatinine ratio (UPCR) >0.75g/g. In the 23 patients, median (IQR) baseline eGFR (CKD-EPI) was 42mL/min/1.73m2 (32-63) and median baseline UPCR was 1.5g/g (0.9-1.8). After initiation of sparsentan, UPCR significantly decreased (P<0.0001) to a median of 0.85g/g (0.42-1.15) in the 2-week follow-up and further declined (P=0.001) to a median of 0.60g/g (0.32-0.82) after 14 weeks, equivalent to a relative reduction in proteinuria up to 62% (45-74). A similar significant reduction was observed for the urine albumin/creatinine ratio. No drug-related serious adverse events were reported. In this real-world setting, sparsentan shows a significant impact on proteinuria, leading to a relative reduction of 62% in UPCR after 14 weeks and beyond, even in patients already receiving SGLT2 inhibitors.

Global trends in the rate of axillary clearance following publication of the ACOSOG Z0011 trial: a systematic review

Global trends in the rate of axillary clearance following publication of the ACOSOG Z0011 trial: a systematic review

Identification of latent classes of randomized controlled trials based on integrity and reporting characteristics.

Reliable, well conducted and adequately reported research is essential for decision-making. This study uses an exploratory clustering approach to identify patterns (subgroups) of trials based on research conduct and reporting characteristics to better understand heterogeneity. Describing features of these subgroups may help elucidate mechanisms of poor planning and reporting that can be acted upon by the research community to improve the research practices. Estimating the impact of trials from specific subgroup classes on pooled treatment effects and overall certainty of evidence may inform conduct and interpretation of systematic reviews in the future. Our study used data from 456 randomized controlled trials included in our recent update of a Cochrane review, Exercise treatment for chronic low back pain, to explore groups of trials that have various characteristic patterns of research planning, conduct, reporting and publication. Using latent class analysis, we explored the patterns that exist in 43 characteristics of trial planning, conduct, reporting and publication characteristics. We identified a four-class model as the best fit for the data; classes were labelled based on the patterns of characteristics that emerged: 1. Well Resourced & Thorough, 155 trials (34%), 2. Dated, 92 trials (20%), 3. Fundamental Deficiencies, 102 trials (22%), and 4. Research Waste, 107 trials (24%). The characteristics that best differentiated the classes were: trial registration status, institution/ethics board approval, conflict of interest reported, and reporting of adverse events. There were no significant differences for estimates of treatment effect in the four classes for all comparisons of treatments with pain intensity outcomes; two classes overestimated functional limitations outcomes for exercise compared to no trial treatment and compared to other conservative treatments. Using a single characteristic to define quality or trustworthiness is no longer sufficient; individual 'problematic' characteristics could be found in all four classes. This novel research could be used as a framework for further exploration of research integrity issues in the health sciences, and the development of interventions to improve our evidence-base, taking into consideration the research motivations and means of trialists.

Exploring the characteristics, methods and reporting of systematic reviews with meta-analyses of time-to-event outcomes: a meta-epidemiological study

BackgroundTime-to-event analysis is associated with methodological complexities. Previous research identified flaws in the reporting of time-to-event analyses in randomized trial publications. These hardships impose challenges for meta-analyses of time-to-event outcomes based on aggregate data. We examined the characteristics, reporting and methods of systematic reviews including such analyses.MethodsThrough a systematic search (02/2017-08/2020), we identified 50 Cochrane Reviews with ≥ 1 meta-analysis based on the hazard ratio (HR) and a corresponding random sample (n = 50) from core clinical journals (Medline; 08/02/2021). Data was extracted in duplicate and included outcome definitions, general and time-to-event specific methods and handling of time-to-event relevant trial characteristics.ResultsThe included reviews analyzed 217 time-to-event outcomes (Median: 2; IQR 1–2), most frequently overall survival (41%). Outcome definitions were provided for less than half of time-to-event outcomes (48%). Few reviews specified general methods, e.g., included analysis types (intention-to-treat, per protocol) (35%) and adjustment of effect estimates (12%). Sources that review authors used for retrieval of time-to-event summary data from publications varied substantially. Most frequently reported were direct inclusion of HRs (64%) and reference to established guidance without further specification (46%). Study characteristics important to time-to-event analysis, such as variable follow-up, informative censoring or proportional hazards, were rarely reported. If presented, complementary absolute effect estimates calculated based on the pooled HR were incorrectly calculated (14%) or correct but falsely labeled (11%) in several reviews.ConclusionsOur findings indicate that limitations in reporting of trial time-to-event analyses translate to the review level as well. Inconsistent reporting of meta-analyses of time-to-event outcomes necessitates additional reporting standards.

Abstract 4136724: Early Adoption of Sodium-Glucose Cotransporter-2 Inhibitor Among Patients Hospitalized with Heart Failure and Preserved Ejection Fraction in the United States

Introduction: In August 2021, the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) found that empagliflozin reduced rates of cardiovascular death and hospitalization by 21% in patients with heart failure with mildly reduced ejection fraction of 41-49% (HFmrEF) and with preserved ejection fraction of &gt; 50% (HFpEF). National trends in Sodium-Glucose Cotransporter-2 Inhibitors ( SGLT2i) use among patients with HFmrEF and HFpEF following this trial are unknown. Methods: We identified patients hospitalized for HFmrEF and HFpEF in the AHA Get With The Guidelines-Heart Failure registry between July 2021 and September 2023. We examined temporal trends in SGLT2i prescriptions at discharge after the publication of the EMPEROR-Preserved trial using the Cochran-Armitage trend test. Results: Among 158,849 hospitalizations with an EF &gt; 40% across 557 hospitals, 27,712 (17.4%) had HFmrEF, and 131,137 (82.6%) had HFpEF. Overall, 22,126 (13.9%) patients were discharged with a prescription for SGLT2i, with higher rates among those with HFmrEF (18.5% vs. 13.0% in those with HFpEF). Patients prescribed SGLT2i were more likely to be younger, male, of Black race, have type II diabetes, have Medicaid insurance, and be discharged from large hospitals. After publication of the EMPEROR-Preserved trial during Q3 2021, rates of SGLT2i prescription at hospital discharge increased from 4.2% in Q3 2021 to 23.5% in Q3 2023, with a 29% relative increase in the rate of SGLT2i prescription for each quarter (adjusted OR, 1.29 [95% CI: 1.28, 1.29]; P&lt;.001). Prescription rates increased from 6.1% in Q3 2021 to 31.6% in Q3 2023 among patients with HFmrEF and from 3.8% to 21.9% for patients with HFpEF (Figure). Conclusion: In the U.S., the use of SGLT2i at discharge has increased for patients hospitalized with HFmrEF and HFpEF following the publication of the EMPEROR-Preserved trial. However, the majority of eligible patients hospitalized for decompensated HF remain untreated with SGLT2i, indicating the need for further efforts to apply the scientific findings into clinical practice.

Abstract Su1203: Temporal Trends in Post-Resuscitation Fever After In-Hospital Cardiac Arrest

Background: A goal of post-resuscitation care among patients successfully resuscitated from in-hospital cardiac arrest (IHCA) is avoidance of fever. However, the incidence of post-resuscitation fever after the initial therapeutic hypothermia trials in 2002 and after the recent Targeted Temperature Management (TTM) trial in 2013 is unknown. Objective: Examine temporal trends in fever during the first 24 hours after return of spontaneous circulation (ROSC) from IHCA during 2005-2013 (after the initial hypothermia trials) and then during 2014-2022 (after the TTM trial). Methods: Within the Get With The Guidelines-Resuscitation registry for IHCA in the U.S., we identified adult patients with ROSC after an index IHCA from 127 hospitals that submitted data on IHCA during both time periods between 2005 and 2022. Patients with sepsis and COVID-19 infection were excluded. We evaluated temporal trends in post-resuscitation fever (defined as &gt; 100 ° F ) during 2005-2013 after the initial hypothermia trials, and then between 2014-2022 after the TTM trial. Results: Among 41,155 patients with ROSC after IHCA, the mean age was 64.8 years (±15.0); 60.0% were male, and 68.6% were of White race. Overall, 11,745 (28.5%) developed post-resuscitation fever (Figure 1). Following the therapeutic hypothermia trials in late 2002, the incidence of fever decreased from 39.1% in 2005 to 29.0% in 2013 ( P for trend &lt; 0.001) (Figure 2). After the publication of the TTM trial in late 2013, post-resuscitation fever in the years 2014-2022 did not go up but declined more modestly ( P for trend = 0.003). Conclusions: Between 2005 and 2013, the incidence of post-resuscitation fever after IHCA decreased substantially. Since the publication of the TTM trial in late 2013, fever incidence has not increased; rather, it has remained relatively stable, even as reported use of therapeutic hypothermia has declined.

Transcatheter aortic valve replacement use in young patients before and after the first low-risk trial publication

Transcatheter aortic valve replacement use in young patients before and after the first low-risk trial publication

Delayed publication of gynecologic oncology clinical trials

Delayed publication of gynecologic oncology clinical trials

Development of the World Federation of Hemophilia Shared Decision-Making Tool.

The use of shared decision-making (SDM) in clinical settings is becoming more prevalent. The evolving and increasingly complex treatment landscape of haemophilia management has augmented the need and desire for SDM between patients and their healthcare team. SDM tools have been used in other chronic conditions and can be an effective form of education for patients and clinicians. The World Federation of Hemophilia (WFH) partnered with people with haemophilia (PWH), patient advocacy groups, and healthcare practitioners to form an expert working group to develop an educational tool for PWH and their caregivers. The primary objectives included educating PWH on the available prophylactic treatments and facilitating discussion between PWH and their healthcare team. The tool was proposed and developed by the expert working group, workshopped at conference round tables, and evaluated in two focus groups. The interactive WFH SDM Tool guides users through the SDM treatment journey and provides an opportunity for reflection on current disease impact and treatment preferences, educational fact sheets and videos, and a comparison between treatment classes. Two forms of the SDM Tool are available: an online platform with a summary page that may be printed and shared and a printable workbook. All evidence in the tool is based on the prescribing information or phase III clinical trial publications. The Tool will be updated twice each year. The WFH SDM Tool is the first available resource that translates published guidance on SDM in haemophilia into a practical, user-friendly tool aimed at facilitating patient-centred treatment decisions.

Changes in length of hospital stay for infective endocarditis - data from before and after the POET trial

Abstract Background The results from the Partial Oral Treatment of left-sided Endocarditis (POET) trial was published in August 2018 and established non-inferiority of a switch to oral step-down antibiotic treatment in stabilized patients with infective endocarditis (IE). However, data on length of hospital stay and safety following the POET trial are warranted. Purpose To examine the changes in length of hospital stay before and after POET publication. Further, to assess safety (relapse of bacteremia and 180 days of mortality) before and after POET publication. Methods By cross-linkage of Danish nationwide registries, patients with first-time IE caused by Streptococcus spp., Enterococcus faecalis, Staphylococcus aureus, or coagulase negative staphylococci from 2012-2021 were identified. Immediately following the publication of the POET trial, the POET criteria was implemented and used in Denmark. The study period was categorized according to publication date (before and after September 2018). Median length of hospital stay was examined according to calendar period. Mortality (from admission date) and relapse of bacteremia (after discharge) at 180 days of follow-up were examined with the Kaplan-Meier estimator and the Cumulative Incidence Function, respectively. Results We identified 3,008 patients before publication of the POET trial (median age 72.8 years) and 1,740 after the publication (median age 75.2 years) (p&amp;lt;0.0001). The burden of comorbidities was comparable between groups. The median length of hospital stay decreased by 8 days: 41 days (IQR: 29-49) before POET publication and 33 days (IQR: 21-44) after POET publication (p&amp;lt;0.0001 for difference), Figure 1. Similar reductions in length of hospital stay were seen across different microbiological etiologies and age groups. The reduction in length of hospital stay was most pronounced in non-surgically treated patients. The mortality from IE admission with a maximum of 180 days follow-up was 27.5% before POET publication and 28.3% after POET publication (p-value=0.41 for difference). The bacteremia relapse rate within 180 days was 3.5% before POET publication and 1.6% after POET publication (p-value=0.0002 for difference), Figure 2. Conclusion Following the POET trial, we found an 8 days reduction in median length of hospital stay with no change in mortality and an associated lower rate of relapse of bacteremia.

Factors associated with non-publication of clinical trials in cardiovascular medicine: a cross-sectional analysis

Abstract Background/introduction Cardiovascular medicine is the fourth most-funded area of clinical research as it received an estimate for 7% of the total research funding. Nearly 8% of all clinical trials are cardiovascular-related (1,2). Non-publication of the registered clinical trials wastes money and time, encourages dissemination bias, and creates a body of possibly inaccurate literature, all of which obstruct scientific advancement. (3) Purpose To study the factors associated with the non-publication of cardiovascular clinical trials between January 2000 and June 2022. Methods We performed a cross-sectional analysis using ClinicalTrials.gov to determine all completed, discontinued, published, and unpublished cardiovascular medicine clinical trials between January 2000 and June 2022. For each trial, data on the trial phase, funding source, intervention type, enrolment size, trial completion, and publication status were extracted and subjected to logistic regression to determine clinical trial publication predictor factors. Results Among 3946 trials in cardiovascular medicine registered in ClinicalTrials.gov, there were 3215 completed trials included in the analysis. Of these, 34.2% (n=1100) were unpublished. On multivariate logistic regression, triple-blinded and quadruple-blinded trials were less likely to be unpublished compared to open-label trials (odds ratio [OR] 0.622; 95% confidence interval [CI] 0.45-0.85; p=0.003) and (OR 0.54; CI 0.42-0.69; p&amp;lt;0.001), respectively. Enrolment of 100 participants or more was associated with a decreased likelihood of non-publication (OR 0.46; CI 0.39-0.55; p&amp;lt;0.001). In addition, randomised trials were less likely to be unpublished than non-randomised trials (OR 0.67; CI 0.50-0.88; p=0.004). There was no significant effect of the intervention type, phase of the trial, trial participants' age and gender, or the trial funding resource on the publication status of cardiovascular medicine clinical trials. Conclusions It is observed that a considerable number of clinical trials in cardiovascular medicine remain unpublished. This issue raises some concerns regarding the risks and discomfort participants may encounter during the trial, while no results are added to the literature. Blinding of the trials, enrolment size, and allocation methods are the main predictors of trial publication.Forest plot of logistic regression

Impact of chemotherapy on patients with mismatch repair deficient advanced endometrial carcinomas-a meta-analysis.

Chemo-immunotherapy is standard of care for women with recurrent or advanced mismatch repair deficient endometrial carcinoma. However, it is uncertain whether patients with mismatch repair deficient advanced or recurrent endometrial carcinoma derive less benefit from chemotherapy than those with mismatch repair proficient endometrial carcinoma. We performed a meta-analysis of randomized controlled trials (RCTs) in advanced or recurrent endometrial carcinoma to determine the difference in the benefit of chemotherapy in mismatch repair deficient vs mismatch repair proficient endometrial carcinoma. Data on chemotherapy outcomes including objective response rate, progression-free survival (PFS), and overall survival were retrieved. We pooled these data using the inverse variance method and examined subgroup difference by mismatch repair status. We also compared differences in PFS and overall survival outcomes by creating individual patient data from the Kaplan-Meier curves of trial publications for sensitivity analyses. A total of 5 RCTs with 1137 participants (mismatch repair deficient, 26%; mismatch repair proficient, 74%) were included. All participants were treated with carboplatin-based chemotherapy. There was no difference between the mismatch repair deficient and mismatch repair proficient subgroups for objective response rate (66.5% vs 64.0%; P = .20 for subgroup difference), PFS (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.77 to 1.12; P = .44; median PFS = 7.6 vs 9.5 months) or overall survival (HR = 1.03, 95% CI = 0.73 to 1.44; P = .88; median overall survival = not reached vs 28.6 months). Objective response rate, PFS, and overall survival were similar among those with mismatch repair deficient vs mismatch repair proficient endometrial cancer treated with front-line, platinum-doublet chemotherapy in RCTs. These findings reinforce the importance of combining chemotherapy together with immune checkpoint inhibitors until the results of trials comparing immune checkpoint therapy alone with combination therapy are available.