Publication Of Trials Research Articles

Delayed publication of gynecologic oncology clinical trials

Delayed publication of gynecologic oncology clinical trials

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

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<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<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<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<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 (dMMR) endometrial carcinomas (EC). However, it is uncertain whether patients with dMMR advanced or recurrent EC derive less benefit from chemotherapy than those with mismatch repair proficient (pMMR) EC. We performed a meta-analysis of randomized controlled trials (RCTs) in advanced/recurrent EC to determine the difference in the benefit of chemotherapy in dMMR vs pMMR EC. Data on chemotherapy outcomes including objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were retrieved. We pooled these data using the inverse variance method and examined subgroup difference by MMR status. We also compared differences in PFS and OS outcomes by creating individual patient data from the Kaplan-Meier curves of trial publications for sensitivity analyses. A total of five RCTs with 1137 participants (dMMR, 26%; pMMR, 74%) were included. All participants were treated with carboplatin-based chemotherapy. There was no difference between the dMMR and pMMR subgroups for ORR (66.5% vs 64.0%, P = .20 for subgroup difference), PFS (HR 0.93, 95% CI 0.77-1.12, P = .44; median PFS 7.6 vs 9.5 months) or OS (HR 1.03, 95% CI 0.73-1.44, P = .88; median OS not reached vs 28.6 months). ORR, PFS and OS were similar among those with dMMR vs pMMR endometrial cancer treated with front-line, platinum-doublet chemotherapy in randomized clinical trials. 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.

Reasons for retraction of clinical research articles in PubMed indexed medical journals from 2012 to 2022

Background: Misconduct in the publication of research articles is a serious concern for the scientific community. This study was conducted with the objective to assess various reasons for retraction of clinical research articles published in PubMed indexed journals from all over the world since 2012 to 2022. Methods: A search was performed on the PubMed database for retracted research articles using filters for “retracted publication”. A total of 314 eligible research articles were assessed for studying basic details. The study outcome measures were to evaluate the reasons for the retraction and authors’ and journal editors’ responses to retractions. Results: Of the original research articles retracted, 150/242 (61.98%) were clinical trial publications. Of the total 314 retracted research articles, the most retractions were in 2014 (47, 14.96%) and 2013 (40, 12.73%) while the fewest retractions were in 2012 (3, 0.95%) and 2022 (9, 2.86%). The most common reasons for retraction were data errors or data analysis errors (120/314, 38.21%) followed by plagiarism (37/314, 11.8%), duplicate publication (35/314, 11.1%), ethical concerns (23/314, 7.3%) and methodological flaws (22/314, 7%). These concerns were raised mainly by the editor or editor-in-chief (228/314, 72.61%), followed by authors (29/314, 9.23%). Out of 228 editorial concerns on publications, authors of only 91/228 (39.91%) agreed and 17/228 (7.45%) completely disagreed with the editorial decision. Conclusion: Authors need to be more careful about data analysis errors, fabricated or falsified data, and plagiarism while submitting their research papers. On the part of editors, detecting misconduct at the submission and peer review stages will help lower the retraction rate and avoid citation of such articles by other authors.

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.

Adaptive designs in clinical trials: a systematic review-part I

BackgroundAdaptive designs (ADs) are intended to make clinical trials more flexible, offering efficiency and potentially cost-saving benefits. Despite a large number of statistical methods in the literature on different adaptations to trials, the characteristics, advantages and limitations of such designs remain unfamiliar to large parts of the clinical and research community. This systematic review provides an overview of the use of ADs in published clinical trials (Part I). A follow-up (Part II) will compare the application of AD in trials in adult and pediatric studies, to provide real-world examples and recommendations for the child health community.MethodsPublished studies from 2010 to April 2020 were searched in the following databases: MEDLINE (Ovid), Embase (Ovid), and International Pharmaceutical s (Ovid). Clinical trial protocols, reports, and a secondary analyses using AD were included. We excluded trial registrations and interventions other than drugs or vaccines to align with regulatory guidance. Data from the published literature on study characteristics, types of adaptations, statistical analysis, stopping boundaries, logistical challenges, operational considerations and ethical considerations were extracted and summarized herein.ResultsOut of 23,886 retrieved studies, 317 publications of adaptive trials, 267 (84.2%) trial reports, and 50 (15.8%) study protocols), were included. The most frequent disease was oncology (168/317, 53%). Most trials included only adult participants (265, 83.9%),16 trials (5.4%) were limited to only children and 28 (8.9%) were for both children and adults, 8 trials did not report the ages of the included populations. Some studies reported using more than one adaptation (there were 390 reported adaptations in 317 clinical trial reports). Most trials were early in drug development (phase I, II (276/317, 87%). Dose-finding designs were used in the highest proportion of the included trials (121/317, 38.2 %). Adaptive randomization (53/317, 16.7%), with drop-the-losers (or pick-the-winner) designs specifically reported in 29 trials (9.1%) and seamless phase 2-3 design was reported in 27 trials (8.5%). Continual reassessment methods (60/317, 18.9%) and group sequential design (47/317, 14.8%) were also reported. Approximately two-thirds of trials used frequentist statistical methods (203/309, 64%), while Bayesian methods were reported in 24% (75/309) of included trials.ConclusionThis review provides a comprehensive report of methodological features in adaptive clinical trials reported between 2010 and 2020. Adaptation details were not uniformly reported, creating limitations in interpretation and generalizability. Nevertheless, implementation of existing reporting guidelines on ADs and the development of novel educational strategies that address the scientific, operational challenges and ethical considerations can help in the clinical trial community to decide on when and how to implement ADs in clinical trials.Study protocol registrationhttps://doi.org/10.1186/s13063-018-2934-7.

Rapid uptake of adjunctive corticosteroids for critically ill adults with septic shock following publication of ADRENAL trial. A multicenter, retrospective analysis of prescribing practices in Queensland Intensive Care Units

BackgroundSeptic shock is common and associated with significant morbidity and mortality. The ADRENAL trial examined the use of hydrocortisone in patients with septic shock, demonstrating no difference in patient-centred outcomes but a decrease in the time to shock resolution. The change in clinical practice related to the publication of the ADRENAL trial is currently unknown. MethodsA retrospective cohort study examining the use of hydrocortisone in patients with septic shock was conducted in 12 intensive care units (ICUs). A segmented linear regression was performed to identify a stepwise change in hydrocortisone administration and 90-day mortality associated with the publication of the ADRENAL trial. ResultsWe included 4,198 patients with a mean age of 58 years (standard deviation, SD17), and the median noradrenaline equivalent score (NEE) was 0.07 µg/kg/min (IQR 0.02 – 0.17). Segmented regression analysis for hydrocortisone administration identified two breakpoints, 3 months before and 6 months after publication, leading to three periods: Pre-publication, Transition and Post-publication. Compared to the pre-publication period, the Transition and Post-publication cohorts had a higher proportion of hydrocortisone administration (28% vs. 34% vs. 43%; p < 0.0001). Furthermore, after adjustment for temporal change, the transition period had a significant change in the slope of the proportion of patients receiving hydrocortisone (-0.1% per month vs. +1.4% per month; p = 0.026), whereas this was not statistically significant during the post-publication period (+0.1% per month, p = 0.66). After adjusting for confounders, the Transition and Post-publication periods were independently associated with an increase in hydrocortisone (OR 1.4, 95% CI 1.14 – 1.77; p = 0.0015 and OR 2.03; 95% CI 1.74 – 2.36; p < 0.001, respectively). Furthermore, after adjusting for confounders, when compared to the Pre-transition period, the use of hydrocortisone was associated with a statistically significant decrease in 90-day mortality (14% vs. 24% absolute difference, aHR for hydrocortisone effect -0.81; 95% CI 0.65 – 0.99; p = 0.044). ConclusionPublication of the ADRENAL trial changed clinical practice in Queensland ICUs with increased prescription of hydrocortisone for patients with septic shock with an associated reduction in mortality.

Toxicity surveillance in FDA pivotal registration trials for immune checkpoint inhibitors: Are we missing the mark?

215 Background: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for a multitude of malignancies, leading to prolonged survival and durable responses. Despite this, a significant number of patients will develop immune-related adverse events (irAEs) with significant associated morbidity and mortality. A retrospective study has previously demonstrated that 28% of patients can develop IrAEs from 6 months up to 2 years after starting therapy (1). Surveillance for toxicity is essential for understanding the long-term risk associated with ICIs. We aimed to analyze the reporting timeframes used in clinical trials of immuno-oncology agents leading to FDA approval. Methods: In this retrospective study, we interrogated the HemeOnc knowledgebase to curate a list of all clinical trial publications leading to FDA approval from 2011 to 2024. We manually selected from this list any trial including an immune checkpoint inhibitor either as monotherapy or in combination with another systemic therapy. The adverse event follow-up time was then extrapolated by manually reviewing the trial publication, supplemental materials or the trial protocol depending on where this information was listed. All trials were categorized based on trial initiation dates. Results: We identified 175 clinical trials leading to FDA approvals, with trial initiation dates ranging from 2004 to 2019. 165 trials were included in the analysis with 10 being excluded due to lack of language regarding follow-up. 62% of the trials included were Phase III trials with the remaining 38% Phase I/II trials. The median follow-up days for all trials across this timeframe was 90, with a range of 28 to 135. The median follow-up time for AE monitoring increased by nearly 30%, rising from 70 days in 2004 to 90 days in 2013. Subsequently, we observed a consistent median follow-up time of 90 days (28 to 130 days) from that point onward, with no further increase. Conclusions: To our knowledge this is the first systematic review of IrAE monitoring in clinical trials leading to FDA approval. In our study we revealed that, despite advancements in the understanding of IrAEs and their potential for late presentation, registration trials leading to regulatory approval remain inadequately designed to capture chronic and delayed immunotherapy toxicities. As these therapies advance into earlier stages of disease with longer life expectancy, it will be critical for regulatory bodies, study sponsors, and trial investigators to either redesign clinical trials or for there to be an alternative method that comprehensively captures the incidence and pattern of late-presenting toxicities. 1. Durbin, ASCO 2023.

Complicated Pleural Infection is Associated With Prolonged Recovery and Reduced Functional Ability.

Management of complicated pleural infections (CPIs) had historically been surgical; however, following the publication of the second multicenter intrapleural sepsis trial (MIST-2), combination tissue plasminogen (tPA) and dornase (DNase) offers a less invasive and effective treatment. Our aim was to assess the quality of life (QOL) and functional ability of patients' recovery from a CPI managed with either intrapleural fibrinolytic therapy (IPFT) or surgery. We identified 565 patients managed for a CPI between January 1, 2013 and March 31, 2018. There were 460 patients eligible for contact, attempted through 2 phone calls and one mailer. Two questionnaires were administered: the Short Form 36-Item Health Survey (SF-36) and a functional ability questionnaire. Contact was made in 35% (159/460) of patients, and 57% (90/159) completed the survey. Patients had lower QOL scores compared to average US citizens; those managed with surgery had higher scores in physical functioning (surgery: 80, IPFT: 70, P=0.040) but lower pain scores (surgery: 58, IPFT: 68, P=0.045). Of 52 patients who returned to work, 48% (25) reported an impact on their work effectiveness during recovery, similarly between management strategies (IPFT: 50%, 13/26 vs. surgery: 46%, 12/26; P=0.781). Patients with a CPI had a lower QOL compared with average US citizens. Surgically managed patients reported improved physical functioning but worse pain compared with patients managed with IPFT. Patients returned to work within 4 weeks of discharge, and nearly half reported their ability to work effectively was impacted by their recovery. With further research into recovery timelines, patients may be appropriately counselled for expectations.

Poor registration and publication practices in clinical trials of targeted therapeutics for endocrine and metabolic diseases: an observational study

ObjectiveTo assess the completeness and concordance of reporting in registries and corresponding publications of interventional trials on targeted therapeutics for endocrine and metabolic disorders. Study Design and SettingWe searched clinical trial registries in September 2022 for completed interventional trials of target therapeutics for endocrine and metabolic disorders registered from 2005 onwards. We used ClinicalTrials.gov and the World Health Organization International Clinical Trial Registration Platform (WHO ICTRP) registration requirements to extract data and assess the completeness of initial entry and final updates to trial registration and concordance with their published journal articles. ResultsAmong 149 clinical trials included, 121 (81%) had corresponding publications. Missing mandatory registration data items were identified in 88 (67%) trials at the initial registration, 17 (13%) at the last registration, and in 85 (77%) corresponding publications. All trials showed changes between initial registration and final registration update, and 98% showed changes from the initial registration to publication. Changes between initial registration and final update were most common in the categories ‘Completion date’ (92%), ‘Key secondary outcomes’ (82%), and ‘Date of first enrolment’ (70%). Changes between initial registration and publication were most common in categories ‘Sample size’ (91%), ‘Key inclusion and exclusion criteria’ (81%), ‘Key secondary outcomes’ (84%), and ‘Completion date’ (83%). ConclusionDespite the legal and journal registration requirements, the completeness and consistency of reporting mandatory data items in registries and corresponding publications regarding targeted therapeutics for endocrine and metabolic disorders are inadequate. Our findings raise questions about the integrity and reliability of clinical trials focusing on targeted therapeutics.

Race and ethnicity representation in phase 2/3 oncology clinical trial publications in the United States: A systematic review.

20 Background: The five 1997 Office of Management and Budget (OMB) races in the US include American Indian or Alaskan Native (AI/AN), Asian, Black or African American, Native Hawaiian or Other Pacific Islander (NHPI), and White, with Hispanic ethnicity. Despite the Affordable Care Act (ACA) mandating OMB-based collecting/reporting standards, race and ethnicity publishing in medical journals is inconsistent, despite being necessary to achieve health equity. We aimed to quantify race and ethnicity reporting rates and calculate representation quotients (RQs) in published oncology clinical trials. Methods: In this systematic review, PubMed/Embase were queried for phase 2/3 clinical trials of the 6 most common noncutaneous solid malignancies, published between 2012-2022, in 4 high-impact journals. Trial characteristics were recorded. The RQs for each race and ethnicity were calculated by dividing the percent of representation in clinical trial publications by the percent of year-matched, site-specific incident cancers in the US, compared with Kruskal-Wallis tests with Bonferroni Correction (BC). Reporting was compared between journal publications and ClinicalTrials.gov. Results: Among 1,202 publications evaluated, 364 met inclusion criteria: 16 JAMA , 241 JCO , 19 Lancet , and 88 NEJM . Publications included 268,209 patients (171,132 women [64%]), with a median of 356 (IQR, 131-800) patients per publication. Reported race and ethnicity included AI/AN in 52 (14%) publications, Asian in 196 (54%), Black or African American in 215 (59%), Hispanic in 67 (18%), NHPI in 28 (8%), and White in 254 (70%). Median RQ varied across race (P &lt; .001 BC) with 1.04 (IQR, 0.09-4.77) for Asian, 0.98 (IQR, 0.86-1.06) for White, 0.42 (IQR, 0.12-0.75) for Black or African American, and 0.00 (IQR, 0.00-0.00) for both AI/AN and NHPI patients. Sensitivity analyses showed similar findings upon subset analysis for US-only clinical trials. There was significantly less race and ethnicity reporting in the clinical trial publications compared with ClinicalTrials.gov documentation for AI/AN (14% vs 45%, P &lt; .001 per McNemar χ 2 with continuity correction [MC]) and NHPI (7.7% vs 43%; P &lt; .001 MC). Conclusions: While most phase 2/3 oncology clinical trials published in high-impact journals report race and ethnicity, most did not report AI/AN and NHPI racial categories. Our findings support a call to action for consistent journal policies and transparent race and ethnicity reporting, in alignment with ACA-concordant race and ethnicity federal reporting requirements.

Epidemiology, survival and new treatment modalities for intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a rare biliary tract cancer with increasing incidence and poor survival rates. This study aims to evaluate the incidence and survival trends of iCCA patients over 20 years using a national cancer database, and assess the temporal association between survival and landmark clinical trials. Data was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Age-adjusted incidence rates (AAIRs) were calculated from 2000 to 2020. Overall survival was analyzed based on diagnosis time and disease stage. Subgroup analysis was performed for patients diagnosed between 2015 and 2020. Landmark clinical trials were reviewed to determine temporal changes in survival. In this analysis of 28,918 iCCA patients, the AAIR increased from 0.49 per 100,000 in 2000 to 1.38 in 2020 [annual percent change (APC) 6.94, 95% confidence interval (CI): 6.32 to 7.56], with a notable decline from 2019 to 2020. Incidence rates overall displayed an uptrend course across subgroups divided by sex, race, age, and disease stage. The age-adjusted median overall survival (mOS) improved from 5.28 months in 2000 to 9.3 months in 2013, then stabilized between 8.0-9.0 months after 2013. Using 2010 as a cutoff, when the ABC-02 trial was published, the decade-based mOS increased from 6.55 months in 2000-2010 to 9.06 months in 2010-2020. During 2015-2020, the overall mOS was 8.8 months, with mOS of 24.3, 12.1, and 5.4 months for local, regional, and distant stages, respectively. The study indicates a steady rise in iCCA incidence since 2000 across all subgroups. Survival rates improved since 2000 but stabilized after 2013, following the ABC-02 trial publication in 2010. The impact of more recent clinical trials on survival rates requires further analysis in the coming years.

Zero- and few-shot prompting of generative large language models provides weak assessment of risk of bias in clinical trials.

Existing systems for automating the assessment of risk-of-bias (RoB) in medical studies are supervised approaches that require substantial training data to work well. However, recent revisions to RoB guidelines have resulted in a scarcity of available training data. In this study, we investigate the effectiveness of generative large language models (LLMs) for assessing RoB. Their application requires little or no training data and, if successful, could serve as a valuable tool to assist human experts during the construction of systematic reviews. Following Cochrane's latest guidelines (RoB2) designed for human reviewers, we prepare instructions that are fed as input to LLMs, which then infer the risk associated with a trial publication. We distinguish between two modelling tasks: directly predicting RoB2 from text; and employing decomposition, in which a RoB2 decision is made after the LLM responds to a series of signalling questions. We curate new testing data sets and evaluate the performance of four general- and medical-domain LLMs. The results fall short of expectations, with LLMs seldom surpassing trivial baselines. On the direct RoB2 prediction test set (n = 5993), LLMs perform akin to the baselines (F1: 0.1-0.2). In the decomposition task setup (n = 28,150), similar F1 scores are observed. Our additional comparative evaluation on RoB1 data also reveals results substantially below those of a supervised system. This testifies to the difficulty of solving this task based on (complex) instructions alone. Using LLMs as an assisting technology for assessing RoB2 thus currently seems beyond their reach.

Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta-analysis of randomized controlled trials.

Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS. Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity. Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62-.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005). PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years.

Towards a minimum data set for the female stress urinary incontinence surgical literature: a collaborative work from Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction, American Urogynecologic Society, and International Continence Society.

There has been a need for an acceptable common minimum data set in the scientific literature as regards the surgical treatment of female stress urinary incontinence (SUI). Such a data set, if widely adopted, would improve the quality of the literature and allow objective comparisons between and across interventions. The surgical treatment of female stress urinary incontinence has evolved considerably over the past few decades. The corresponding body of literature has grown exponentially describing the outcomes of hundreds of studies of these novel interventions. However, historically, the literature in this space has been of uneven quality. In order to improve the reporting of clinical studies, and ultimately patient outcomes, a standard minimum data set for trial design and publications was created by a collaborative group formed from leading scientific societies. The consensus document created from this novel collaboration between members of SUFU (Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction), AUGS (American Urogynecologic Society), and ICS (International Continence Society) provides clear guidance for the structure of clinical studies and reporting of results in the peer-reviewed literature. This has substantial potential ramifications for scientific journals, journal editors, peer reviewers, investigators, regulatory agencies, industry, clinicians, and patients.

Approach to radical hysterectomy for cervical cancer after the LACC trial and associated complications: a NSQIP study

BackgroundThe Laparoscopic Approach to Cervical Cancer (LACC) study results revolutionized our understanding of the best surgical management for this disease. Following its publication, guidelines state that the standard and recommended approach for radical hysterectomy is with an open abdominal approach. Nevertheless, the impact of the LACC trial on real-world changes in the surgical approach to radical hysterectomy remains elusive. ObjectiveWe aimed to study the trends and routes of radical hysterectomies and to evaluate post-operative complication rates before and after the LACC trial (2018). Study DesignThe National Surgical Quality Improvement Program registry was used to examine radical hysterectomies performed for cervical cancer between 2012-2022. We excluded vaginal radical hysterectomies and simple hysterectomies. The primary outcome measures were the trends in route of surgery [minimally invasive surgery (MIS) vs. laparotomy] and surgical complications rate, stratified by periods before and after the publication of the LACC trial in 2018 (2012-2017 vs. 2019-2022). The secondary outcome measure was major complications associated specifically with the different routes of surgery. ResultsOf the 3,611 patients included, 2,080 (57.6%) underwent laparotomy and 1,531 (42.4%) underwent MIS radical hysterectomy. There was a significant increase in the MIS approach from 2012 to 2017 (45.6% MIS in 2012 to 75.3% MIS in 2017, p<.001), and a significant decrease in MIS from 2018 to 2022 (50.4% MIS in 2018 to 11.4% MIS in 2022, p<.001).The rate of minor complications was lower in the period before the LACC trial [317 (16.9%) vs. 288 (21.3%), p=.002]. Major complications rate was similar before and after the LACC trial [139 (7.4%) vs. 78 (5.8%), p=.26]. The rates of blood transfusions and superficial surgical site infections were lower in the period before the LACC trial [137 (7.3%) vs. 133 (9.8%), p=.012 and 20 (1.1%) vs. 53 (3.9%), p<.001, respectively]. In a comparison of MIS vs. laparotomy radical hysterectomy during the entire study period, patients in the MIS group had lower rates of minor complications [190 (12.4%) vs. 472 (22.7%), p<.001] and the rate of major complications was similar in both groups [100 (6.5%) in the MIS group vs. 139 (6.7%) in the laparotomy group, p=.89]. In a specific complications analysis, the rates of blood transfusion and superficial surgical site infections were lower in the MIS groups (2.4% vs. 12.7%, and 0.6% vs. 3.4%, p<.001 for both comparisons) and the rate of deep incisional surgical site infections was lower in the MIS group (0.2% vs. 0.7%, p=.048). In a multiple logistic regression analysis, the route of radical hysterectomy was not independently associated with occurrence of major complications [aOR 95% CI 1.02 (0.63-1.65)]. ConclusionWhile the proportion of MIS radical hysterectomy decreased abruptly following the LACC trial, there was no change in the rate of major post-operative complications. In addition, hysterectomy route was not associated with major post-operative complications.

Clinical Trials Gone Missing—A Potential Source for Publication Bias in Dentistry

Background: The aim of this study was to examine publication bias associated with a failure to report research results of studies that were initially posted on the ClinicalTrials.gov registry and to examine factors associated with this phenomenon. Methods: A search was conducted in the ClinicalTrials.gov registry using six dental-related topics. Corresponding publications for trials completed between 2016 and 2019 were then searched using PUBMED, EMBASE and Google Scholar. For studies lacking matching publications, we emailed the primary investigator and received some additional data. For included studies, we recorded additional variables: industry funding, site setting (academic, private research facilities or private practice), design (single or multi-center), geographical location and commencement date vis a vis registration and publication dates. Results: A total of 744 entries were found, of which 7 duplicates were removed; an additional 67 entries just recently completed were removed. An additional 7 studies were in different fields and thus removed. Thus, 663 trials were included; of these, only 337 studies (50.8%) were published. The mean registration to publication interval was 29.01 ± 25.7 months, ranging from +142 to −34 months (post factum registration). Less than 1/3 of the studies were posted prior to commencement, of which much smaller proportions were published (37.3%). Studies that were posted after commencement (n = 462) had a much higher publication rate (56.7%), p &lt; 0.001. Multi-center studies and those conducted in commercial facilities had much higher, though non-significant, publication rates (56.5% and 58.3%, respectively). Conclusions: With only half of the studies registered being published, a major source for publication bias is imminent.

Discontinuation and non-publication of randomized controlled trials on cervical cancer or precancer.

Research waste is a considerable problem in clinical trials, with nonpublication being a significant contributor. We aimed to determine the prevalence of discontinuation and nonpublication of randomized controlled trials (RCTs) on cervical cancer or precancer. We searched ClinicalTrials.gov for registered RCTs investigating cervical cancer or precancer that started between January 2000 and December 2020. The primary and secondary outcomes were trial nonpublication and premature discontinuation, respectively. Publication status was determined by systematic searches of peer-reviewed journals using the PubMed and Scopus databases. A total of 113 RCTs met the inclusion criteria. Among the 85 trials completed before December 2020, 44 (51.8%) were prematurely discontinued and 40 (47.1%) were unpublished. A single-center design (61.4% vs. 34.1%, P=.012) and lack of external funding (59.1% vs. 36.6%, P=.038) were significantly associated with trial discontinuation. Large-scale (target sample size >400; 46.7% vs. 17.5%, P=.004) and externally funded trials (66.7% vs. 35.0%, P=.004) were more likely to be published. Multivariate logistic analysis revealed that a large sample size [odd ratio (OR): 4.125, 95% confidence interval (CI): 1.511-11.259, P=.006] and presence of external funding (OR: 3.714, 95% CI: 1.513-9.117, P=.004) were independent positive factors for trial publication. A significant proportion of RCTs related to cervical cancer or precancer were discontinued early or remain unpublished, resulting in a waste of research resources.