Abstract MP30: Reporting of Sex-Specific Results in Randomized Clinical Trials of Acute Stroke (2010-2020)

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Julia Pudar ◽  
Brent Strong ◽  
Virginia J Howard ◽  
Mathew J Reeves
Keyword(s):  
Acute Stroke ◽  
Sample Size ◽  
Trial Type ◽  
Randomized Clinical Trials ◽  
Temporal Trends ◽  
Geographic Region ◽  
Outcome Data ◽  
Industry Funding ◽  
Stroke Type ◽  
Trial Phase

Introduction: When reporting primary results, it is recommended that RCTs report sex-specific outcomes. We reviewed the reporting of sex-specific outcomes in contemporary acute stroke RCTs. Methods: We searched MEDLINE for manuscripts published between 2010 and June 2020 in one of nine major clinical journals reporting the primary results of phase 2 or 3 stroke RCTs. Eligible trials tested a therapeutic intervention initiated within one month of stroke onset. Reporting of sex-specific primary results was the outcome of interest. We also investigated whether the trial formally tested for an interaction between sex and treatment and if that interaction test was statistically significant. We performed bivariate analyses using Fisher’s exact tests to identify study-level factors associated with sex-specific reporting including journal, geographic region, trial phase, sample size, stroke type, trial type (e.g. thrombolytic, EVT, secondary prevention), and industry funding. Temporal trends using two-year time periods were also explored. Results: Of the 115 studies identified, sex-specific primary outcome data were reported in 37% (n=42). Reporting varied significantly by journal, with NEJM (61%) and Lancet journals (40%) having the highest rates (p=0.03) (Table). Reporting also differed by geographic region (p=0.03), trial phase (p=0.05), and sample size (p<0.01). Reporting did not vary significantly by stroke type, trial type, or industry involvement. While not significant, there was a positive temporal trend in favor of greater reporting in later publications (p=0.09). Of the 29 trials that formally tested for an interaction between sex and treatment, only one significant interaction was found. Conclusions: Although reporting of sex-specific outcomes improved from 2010 to 2020, the prevalence of reporting in major journals is still low. Further efforts are required to ensure that journals and authors comply with reporting guidelines.

Reporting of Results by Sex in Randomized Controlled Trials of Acute Stroke Therapies (2010–2020)

Stroke ◽  
2021 ◽  
Author(s):  
Julia Pudar ◽  
Brent Strong ◽  
Virginia J. Howard ◽  
Mathew J. Reeves
Keyword(s):  
New England ◽  
Randomized Controlled Trials ◽  
Acute Stroke ◽  
Temporal Trends ◽  
Geographic Region ◽  
Controlled Trials ◽  
Phase 2 ◽  
Exact Test ◽  
Randomized Controlled ◽  
Trial Phase

Background and Purpose: When reporting primary results from randomized controlled trials, recommendations include reporting results by sex. We reviewed the reporting of results by sex in contemporary acute stroke randomized controlled trials. Methods: We searched MEDLINE for articles reporting the primary results of phase 2 or 3 stroke randomized controlled trials published between 2010 and June 2020 in one of nine major clinical journals. Eligible trials were restricted to those with a therapeutic intervention initiated within one month of stroke onset. Of primary interest was the reporting of results by sex for the primary outcome. We performed bivariate analyses using Fisher exact tests to identify study-level factors associated with reporting by sex and investigated temporal trends using an exact test for trend. Results: Of the 115 studies identified, primary results were reported by sex in 37% (n=42). Reporting varied significantly by journal, with the New England Journal of Medicine (61%) and Lancet journals (40%) having the highest rates ( P =0.03). Reporting also differed significantly by geographic region (21% Europe versus 48% Americas, P =0.03), trial phase (13% phase 2 versus 40% phase 3, P =0.05), and sample size (24% <250 participants versus 61% >750 participants, P <0.01). Although not statistically significant ( P =0.11), there was a temporal trend in favor of greater reporting among later publications (25% 2010–2012 versus 48% 2019–2020). Conclusions: Although reporting of primary trial results by sex improved from 2010 to 2020, the prevalence of reporting in major journals is still low. Further efforts are required to encourage journals and authors to comply with current reporting recommendations.

Abstract 28: The Representation of Women in Randomized Clinical Trials of Acute Stroke (2010-2020)

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Brent W Strong ◽  
Julia Pudar ◽  
Amanda G Thrift ◽  
Gustavo de los Campos ◽  
Virginia J Howard ◽  
...  
Keyword(s):  
Acute Stroke ◽  
Random Effects ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Geographic Location ◽  
Therapeutic Interventions ◽  
Eligibility Criteria ◽  
Novel Treatments ◽  
Subgroup Analyses ◽  
Stroke Type

Introduction: The inadequate enrollment of women in RCTs represents a threat to trial generalizability and potential inequities in access to novel treatments. We sought to determine whether women were under-enrolled in contemporary acute stroke trials. Methods: We searched MEDLINE for completed RCTs published in one of nine major journals between 2010 and 2020. Eligible studies were phase 2 or 3 trials undertaken to test therapeutic interventions within one month of stroke onset. For each trial we calculated the proportion of trial participants that were women (PPW). We used Global Burden of Disease (GBD) data to estimate the expected proportion of strokes occurring in women in the underlying stroke populations (PSW). We matched individual estimates from the GBD data to each trial based on geographic location, year, and stroke type. To quantify disparities, we calculated the enrollment disparity difference (EDD), defined as EDD = PSW - PPW. A positive EDD indicates that women were under-represented in the trial. We used random effects meta-analysis to pool individual EDDs and conducted subgroup analyses. Results: We identified 115 trials that met eligibility criteria. The random effects summary EDD was 0.053 (95% CI = 0.040, 0.053), indicating that women were under-enrolled in acute stroke trials by 5% relative to their representation in the underlying stroke population. However, there was substantial between-trial variability in the EDD (I 2 =84.4%). In subgroup analyses, the EDD was similar across subgroups except for stroke type (figure); trials that only included subarachnoid hemorrhages enrolled women in excess of their representation in the underlying population (summary EDD = -0.117 [95% CI = -0.150, -0.084]). Conclusions: Overall, women were modestly under-represented in contemporary acute stroke trials compared to their representation among all strokes. Further study is needed to elucidate factors driving sex differences in enrollment between RCTs.

Abstract 19735: Temporal Trends in Sample Size of RCTs in Published Cardiology Literature from 1970-2013

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sonia Jain ◽  
Sushil A Luis ◽  
Vivien Coelho ◽  
Limor Ilan Bushari ◽  
Hilma Holm ◽  
...  
Keyword(s):  
Sample Size ◽  
Randomized Clinical Trials ◽  
Search Algorithm ◽  
Temporal Trends ◽  
Cost Effective ◽  
Evidence Base ◽  
Sample Sizes ◽  
Study Designs ◽  
Journal Impact ◽  
Robust Evidence

Background: It is generally perceived that sample sizes of randomized clinical trials (RCTs) have increased over the years, particularly in specialties such as cardiology, with a robust evidence base. The aim of this study was to analyze temporal trends in sample sizes of RCTs in cardiology journals compared to other specialties. Methods: Abstracts of RCTs involving humans from PubMed for 1970-2013 were analyzed using a digital search algorithm. Sample sizes of studies were extracted from each abstract. Date of publication and journal name were collected. Journals from several medical subspecialties were selected for comparison, using the journal impact factor as a measure of clinical relevance. Sample sizes of studies in 1990 were compared to 2010 for each of the journals using the Mann-Whitney U test. Graphical comparisons of sample size trends are presented. Results: 272,054 abstracts of human RCTs were identified. Median sample sizes for the years 1990 and 2010 is shown in table 1. The median sample size for all RCTs published in Circulation was 99 subjects per study in 1990, increasing to 630 subjects per study in 2010 (p < 0.01). All cardiology journals had a significant increase in study sample size over the 20 year period, as did the multispecialty journals (JAMA, NEJM, Lancet). In contrast, only a few non-cardiology specialty journals published studies with increasing sample sizes (table 1). Figure 1 shows the sample size trend for 1970-2013. Conclusions: Our study demonstrates a dramatic temporal trend of increasing sample sizes in RCTs in cardiology compared to other specialties. Since sample size is estimated based on the effect size studied, one explanation for this observation is that the more obvious larger effects have been previously elucidated, leaving only smaller associations to be studied. This requires increasing resources, highlighting the importance of alternate study designs and collaborative registries to develop a cost effective evidence base.

Does progression-free-survival (PFS) correlate with overall- and cancer-specific survival (OS/CSS) in randomized clinical trials (RCTs) exploring the addition of hormonal therapy (HT) to radiotherapy (RT) for early prostate cancer (EPC)? Analysis of six RCTs

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5056-5056
Author(s):  
E. M. Ruggeri ◽  
E. Bria ◽  
P. Carlini ◽  
F. Cuppone ◽  
M. Milella ◽  
...  
Keyword(s):  
Sample Size ◽  
Randomized Clinical Trials ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Phase Iii ◽  
Cancer Specific Survival ◽  
End Point ◽  
Target Sample Size ◽  
Phase Iii Trials ◽  
Beta Coefficient

5056 Background: Although PFS is considered the standard primary end-point in EPC, the correlation with OS has never been explored in RCTs randomizing patients (pts) to HT plus radiotherapy (RT) versus RT. Given the relatively long prognosis in this disease setting, the correlation between PFS and CSS should be investigated as well. Methods: All phase III trials reporting all outcome’ data were considered eligible. The correlation has been explored according to a linear regression model considering both each single outcome pair (PFS, OS and CSS rates) for all arms, and each reported Hazard Ratio (HRs). The correlation was estimated according to both the Pearson- (r) and R2-coefficient (parametric) and the Spearman coefficient (Rho, non-parametric). A sensitivity analysis in 2 subgroups (long- and short-term HT) to test for effect robustness has been accomplished as well. A model to determine the target sample size to determine CSS benefit of 3%, 4%, 6% and 7% months, respectively, was calculated as well. Results: Six RCTs (4,212 pts) were collected (follow-up range: 4.5–7.6 years). In the overall population, when considering the crude rates, a linear stronger correlation was found between PFS and CSS (r=0.71, R2=0.51, p=0.003; Rho=0.75, p=0.005), rather than with OS (r=0.55, R2=0.30, p=0.06; Rho=0.78, p=0.11). Again, when considering HRs, a linear stronger correlation was found between PFS and CSS (r=0.87, R2=0.76, p=0.02; Rho=0.94, p=0.005), rather than with OS (r=0.75, R2=0.56, p=0.08; Rho=0.77, p=0.07). Similar correlations were found whatever subgroups was explored. The sample size model (on the basis of the beta-coefficient=0.71), calculate 4,575, 2,006, 1,115 and 700 pts to improve PFS of 4%, 6%, 8%, and 10% months, which means to improve CSS of 2.8%, 4.3%, 5.7% and 7.1%, respectively. Conclusions: The correlation between PFS and CSS in RCTs exploring the benefit of adding HT to RT for EPC is significant, and suggests its further investigation as surrogate end-point. The natural history of the disease clearly explains the stronger correlation of PFS with CSS rather than with OS. No significant financial relationships to disclose.

scholarly journals ‘Statistical Irreproducibility’ Does Not Improve with Larger Sample Size: How to Quantify and Address Disease Data Multimodality in Human and Animal Research

2021 ◽  
Vol 11 (3) ◽  
pp. 234
Author(s):  
Abigail R. Basson ◽  
Fabio Cominelli ◽  
Alexander Rodriguez-Palacios
Keyword(s):  
Sample Size ◽  
Data Visualization ◽  
Random Sampling ◽  
Intestinal Inflammation ◽  
Random Number Generation ◽  
Outcome Data ◽  
Multimodal Distributions ◽  
Disease Subtypes ◽  
Study Designs ◽  
Larger Sample

Poor study reproducibility is a concern in translational research. As a solution, it is recommended to increase sample size (N), i.e., add more subjects to experiments. The goal of this study was to examine/visualize data multimodality (data with >1 data peak/mode) as cause of study irreproducibility. To emulate the repetition of studies and random sampling of study subjects, we first used various simulation methods of random number generation based on preclinical published disease outcome data from human gut microbiota-transplantation rodent studies (e.g., intestinal inflammation and univariate/continuous). We first used unimodal distributions (one-mode, Gaussian, and binomial) to generate random numbers. We showed that increasing N does not reproducibly identify statistical differences when group comparisons are repeatedly simulated. We then used multimodal distributions (>1-modes and Markov chain Monte Carlo methods of random sampling) to simulate similar multimodal datasets A and B (t-test-p = 0.95; N = 100,000), and confirmed that increasing N does not improve the ‘reproducibility of statistical results or direction of the effects’. Data visualization with violin plots of categorical random data simulations with five-integer categories/five-groups illustrated how multimodality leads to irreproducibility. Re-analysis of data from a human clinical trial that used maltodextrin as dietary placebo illustrated multimodal responses between human groups, and after placebo consumption. In conclusion, increasing N does not necessarily ensure reproducible statistical findings across repeated simulations due to randomness and multimodality. Herein, we clarify how to quantify, visualize and address disease data multimodality in research. Data visualization could facilitate study designs focused on disease subtypes/modes to help understand person–person differences and personalized medicine.

Abstract P164: The Impact of the Expanded EVT Window on Acute Stroke Services: A Large Northwest Telestroke Network Experience

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Theodore Lowenkopf ◽  
Leslie Corless ◽  
Elizabeth Baraban
Keyword(s):  
Acute Stroke ◽  
Rural Areas ◽  
Treatment Time ◽  
Time Window ◽  
Tertiary Care ◽  
The United States ◽  
Geographic Region ◽  
Anterior Circulation ◽  
Stroke Subtypes ◽  
The Impact

Background: Telestroke has led the technological revolution in providing acute medical services to rural areas in the United States since the beginning of this century. In January 2018 the American Stroke Association made a level IA recommendation to expand the treatment time window for endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) from 6 to 24 hours for anterior circulation stroke based on perfusion imaging. Our study is the first to our knowledge to report the effect of the expanded time window on acute stroke consult and treatment volumes in a large rural supporting telestroke network. Methods: Stroke registry data from two tertiary care facilities from a 22 hospital telestroke network supporting a large (> 78,000 mi 2 ) primarily rural Northwest geographic region were used. Data included stroke patients arriving within 24 hours of last known well (LKW) between January 2017 and March 2019. Patients arriving January 2017 to December 2017 were grouped into the PRE-expanded time window and those arriving April 2018 to March 2019 into the POST-expanded time window. Stroke subtypes, transfers, telestroke consults (via phone or video), and EVT treatments were compared across time periods. Analyses were performed using Pearson’s chi square test, corrected for multiple comparisons. Results: A total of 1117 patients arrived with stroke symptoms within 24 hours of LKW, 567 (50.8%) in PRE and 550 (49.2%) in POST-window. The percentage of all stroke subtypes were not significantly different in the PRE and POST patient groups (p=.720). However, the percent of telestroke consults increased by 12.1% from 62.3% to 74.4% (p<.001) but the percent of video consults remained similar (25.9% vs 25.8%). The total number of transfers (142 vs 141) and percentage of transfers among AIS patients (25.0% vs 25.6%) from partner to hub did not change. The percentage of thrombectomies among transfers rose by 8.7% with the expanded time window, but was not statistically significant [p=0.118]. Conclusions: In a large Northwest telestroke rural network the expanded EVT treatment time window led to a marked increase in all telestroke consults but did not impact video consults, transfer, or percentage of patients treated.

scholarly journals Temporal Trends in Emergency Medical Services and General Practitioner Use for Acute Stroke After Australian Public Education Campaigns

Stroke ◽  
2018 ◽  
Vol 49 (12) ◽  
pp. 3078-3080 ◽  
Author(s):  
Janet E. Bray ◽  
Judith Finn ◽  
Peter Cameron ◽  
Karen Smith ◽  
Lahn Straney ◽  
...  
Keyword(s):  
General Practitioner ◽  
Public Education ◽  
Acute Stroke ◽  
Emergency Medical Services ◽  
Temporal Trends ◽  
Medical Services ◽  
Emergency Medical ◽  
Education Campaigns

scholarly journals Clinical trial research on COVID-19 in Germany – a systematic analysis

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 913
Author(s):  
Julian Hirt ◽  
Abeelan Rasadurai ◽  
Matthias Briel ◽  
Pascal Düblin ◽  
Perrine Janiaud ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Research Agenda ◽  
Randomized Clinical Trials ◽  
Median Number ◽  
First Year ◽  
Industry Funding ◽  
Systematic Analysis ◽  
Clinical Trial Research ◽  
German Contribution

Background: In 2020, the COVID-19 pandemic led to an unprecedented volume of almost 3,000 clinical trials registered worldwide. We aimed to describe the COVID-19 clinical trial research agenda in Germany during the first year of the pandemic. Methods: We identified randomized clinical trials assessing interventions to treat or prevent COVID-19 that were registered in 2020 and recruited or planned to recruit participants in Germany. We requested recruitment information from trial investigators as of April 2021. Results: In 2020, 65 trials were completely (n=27) or partially (n=38) conducted in Germany. Most trials investigated interventions to treat COVID-19 (86.2%; 56/65), in hospitalized patients (67.7%; 44/65), with industry funding (53.8%; 35/65). Few trials were completed (21.5%; 14/65). Overall, 187,179 participants were planned to be recruited (20,696 in Germany), with a median number of 106 German participants per trial (IQR 40 to 345).  From the planned German participants, 13.4%  were recruited (median 15 per trial (IQR 0 to 44). Conclusions: The overall German contribution to the worldwide COVID-19 clinical trial research agenda was modest. Few trials delivered urgently needed evidence. Most trials did not meet recruitment goals. Evaluation and international comparison of the challenges for conducting clinical trials in Germany is needed.

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