Challenges and solutions to optimize stroke recovery trial enrollment and execution.
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ABSTRACT:
SUBMITTER: Feng W
PROVIDER: S-EPMC10928267 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Challenges and solutions to optimize stroke recovery trial enrollment and execution.
The Lancet regional health. Europe 20240118
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Project description:Stroke is the leading cause of disability in the USA and a major cause of mortality worldwide. One out of four strokes is recurrent. Secondary stroke prevention starts with deciphering the most likely stroke mechanism. In general, one of the main goals in stroke reduction is to control vascular risk factors such as hypertension, diabetes, dyslipidemia, and smoking cessation. Changes in lifestyle like a healthy diet and aerobic exercise are also recommended strategies. In the case of cardioembolism due to atrial fibrillation, mechanical valves, or cardiac thrombus, anticoagulation is the mainstay of therapy. The role of anticoagulation is less evident in the case of bioprosthetic valves, patent foramen ovale, and dilated cardiomyopathy with low ejection fraction. Strokes due to larger artery atherosclerosis account for approximately a third of all strokes. In the case of symptomatic extracranial carotid stenosis, surgical intervention as close as possible in time to the index event seems highly beneficial. In the case of intracranial large artery atherosclerosis, the best medical therapy consists of antiplatelets, high-dose statins, aggressive controls of vascular risk factors, and lifestyle modifications, with no role for intracranial arterial stenting or angioplasty. For patients with small artery occlusion (ie, lacunar stroke), the therapy is similar to that used in patients with intracranial large artery atherosclerosis. Despite the constant new evidence on how to best treat patients who have suffered a stroke, the risk of stroke recurrence remains unacceptably high, thus evidencing the need for novel therapies.
| S-EPMC4536764 | biostudies-other
Project description:BACKGROUND:More than half of the 40,000 incident rectal cancer patients in the United States each year are diagnosed at clinical stage II and III (locally advanced stage). For this group, high rates of cure can be achieved with the combination of pelvic radiation and sensitizing 5-fluorouracil (chemoradiation), surgery and chemotherapy, but treatment is long, arduous and toxicities are substantial. The PROSPECT trial (N1048, NCT01515787) was designed to determine whether neoadjuvant chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX) could be used as an alternative to neoadjuvant chemoradiation without compromising treatment outcomes and to spare these patients excess toxicity. The statistical design balanced the twin co-primary goals of achieving low local and distant recurrence rates. Study design features contended with the need for stringent safeguards given limited phase II data, the need for straightforward criteria to facilitate both accrual and protocol fidelity and the importance of patients' perspectives on symptom burden and treatment toxicity. METHODS:PROSPECT is an ongoing multi-site two-group seamless phase II/III randomized trial comparing standard neoadjuvant chemoradiation versus neoadjuvant chemotherapy with selective use of chemoradiation for patients with locally advanced rectal cancer. Challenges addressed in the design and conduct of PROSPECT have included the following: (1) setting safety thresholds given limited single-center phase II data, (2) establishing workable eligibility criteria, (3) balancing competing time to local and distant recurrence as co-primary endpoints and (4) obtaining reliable and complete data for patients' symptom burden. The design and implementation challenges, choices, modifications and their implications for the design of future national cooperative group clinical trials are presented. RESULTS:PROSPECT incorporated stringent thresholds for both complete surgical resection (R0) and the time to local recurrence as early stopping rules. When predetermined stopping criteria were not met after evaluation of the first 366 participants in the randomized phase II, the study transitioned seamlessly to phase III with cumulative accrual of over 1000 participants. Eligibility criteria stipulating rectal tumor location based on distance from the anal verge were unworkable, and the protocol was amended to a more pragmatic approach that assigned surgeons with primary responsibility for determining eligibility. Central radiology review was feasible and in some cases prompted discontinuation of protocol treatment. Participation in toxicity reporting using the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events was uniformly high and was well accepted by participants from over 200 sites in the United States, Canada and Switzerland. CONCLUSION:The strategies used to overcome these obstacles may inform the design of other studies that involve multi-modality treatment interventions, particularly trials where implementation of consistent criteria for eligibility and outcomes across hundreds of practice settings is necessary.
| S-EPMC6440868 | biostudies-literature
Project description:Background and purposeEnrollment into acute stroke clinical trials is limited to experienced tertiary centers with emergency research infrastructure. Feasibility of remote enrollment via telemedicine into an acute thrombolytic clinical trial has never been demonstrated.MethodsUsing telemedicine, our hub stroke research center partnered with two spoke community hospitals to jointly participate in a randomized, phase III adjunctive thrombolysis clinical trial in the first 3 h after symptom onset to expand recruitment of the trial. Eligible patients were successfully identified, consented, randomized, and received therapy/placebo at the spoke hospitals under real-time direction by hub trialists via telemedicine.ResultsTen patients were identified from May 2013 to July 2014, and six were enrolled via telemedicine. No study procedure delays, safety events, or major protocol violations occurred.ConclusionsIt is feasible to randomize and enroll stroke patients via remote telemedicine into an acute thrombolytic clinical trial. This novel approach could expand access and accelerate completion of clinical trials if widely implemented.
| S-EPMC4301673 | biostudies-literature
Project description:BackgroundEnrollment challenges for critical care research are common. Contributing factors include short enrollment windows, the crisis nature of critical illness, lack of research staff, unavailable legal proxy, family dynamics, and language barriers.ObjectiveTo describe enrollment statistics for an ongoing critical care nursing trial, barriers to recruitment, and strategies to enhance enrollment.MethodsTwo years' worth of recruitment and enrollment data from an oral care intervention trial in critically ill adults receiving mechanical ventilation at 1 hospital were analyzed. Recruitment logs include number of patients screened, eligible, enrolled, and declined and patients' sex, race, and ethnicity.ResultsTarget enrollment (15.5 patients per month) was based on experience and historical data. Strategies implemented to promote enrollment included providing study personnel at least 18 hours per day for 7 days per week, regular rounds, communication with direct care staff, and Spanish consent processes. In 2 years, 6963 patients were screened; 1551 (22%) were eligible. Consent was sought from 366 (24% of eligible patients). Enrollment averaged 13.3 patients per month (86% of projected target). The main factor impeding enrollment was unavailability of a legal proxy to provide consent (88%). The refusal rates of white (11%), black (13%), and Hispanic (16%) patients did not differ significantly. However, those classified as Asian or as more than 1 race declined significantly more often (35%) than did white or black patients (P = .02).ConclusionsUnavailability of a legal proxy within a short enrollment window was the major challenge to enrollment. Various factors influenced consent decisions. Clinical study design requires more conservative estimates.
| S-EPMC6015765 | biostudies-literature
Project description:Background and purposeThe enrollment yield and reasons for screen failure in prehospital stroke trials have not been well delineated.MethodsThe Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial identified patients for enrollment using a 2 stage screening process-paramedics in person followed by physician-investigators by cell phone. Outcomes of consecutive screening calls from paramedics to enrolling physician-investigators were prospectively recorded.ResultsFrom 2005 to 2012, 4458 phone calls were made by paramedics to physician-investigators, an average of 1 call per vehicle every 135.7 days. A total of 1700 (38.1%) calls resulted in enrollments. The rate of enrollment of stroke mimics was 3.9%. Among the 2758 patients not enrolled, 3140 reasons for screen failure were documented. The most common reasons for nonenrollment were >2 hours from last known well (17.2%), having a prestroke condition causing disability (16.1%), and absence of a consent provider (9.5%). Novel barriers for phone informed consent specific to the prehospital setting were infrequent, but included: cell phone connection difficulties (3.2%), patient being hard of hearing (1.4%), insufficient time to complete consent (1.3%), or severely dysarthric (1.3%).ConclusionsIn this large, multicenter prehospital trial, nearly 40% of every calls from the field to physician-investigators resulted in trial enrollments. The most common reasons for nonenrollment were out of window last known well time, prestroke confounding medical condition, and absence of a consent provider.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.
| S-EPMC4909489 | biostudies-literature
Project description:BackgroundSeeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) randomized controlled trial.MethodsConsent was provided by patients or by a relative or an independent doctor in incapacitated patients, using a 1-stage (full written consent) or 2-stage (initial brief consent followed by full written consent post-randomization) approach. The computed tomography-to-randomization time according to consent pathways was compared using the Kruskal-Wallis test. Multivariable logistic regression was performed to identify variables associated with onset-to-randomization time of ≤3 hours.ResultsOf 2325 patients, 817 (35%) gave self-consent using 1-stage (557; 68%) or 2-stage consent (260; 32%). For 1507 (65%), consent was provided by a relative (1 stage, 996 [66%]; 2 stage, 323 [21%]) or a doctor (all 2-stage, 188 [12%]). One patient did not record prerandomization consent, with written consent obtained subsequently. The median (interquartile range) computed tomography-to-randomization time was 55 (38-93) minutes for doctor consent, 55 (37-95) minutes for 2-stage patient, 69 (43-110) minutes for 2-stage relative, 75 (48-124) minutes for 1-stage patient, and 90 (56-155) minutes for 1-stage relative consents (P<0.001). Two-stage consent was associated with onset-to-randomization time of ≤3 hours compared with 1-stage consent (adjusted odds ratio, 1.9 [95% CI, 1.5-2.4]). Doctor consent increased the odds (adjusted odds ratio, 2.3 [1.5-3.5]) while relative consent reduced the odds of randomization ≤3 hours (adjusted odds ratio, 0.10 [0.03-0.34]) compared with patient consent. Only 2 of 771 patients (0.3%) in the 2-stage pathways withdrew consent when full consent was sought later. Two-stage consent process did not result in higher withdrawal rates or loss to follow-up.ConclusionsThe use of initial brief consent was associated with shorter times to enrollment, while maintaining good participant retention. Seeking written consent from relatives was associated with significant delays.RegistrationURL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.
| S-EPMC7612544 | biostudies-literature
Project description:BackgroundTreatment burden can be defined as the self-care practices that patients with chronic illness must perform to respond to the requirements of their healthcare providers, as well as the impact that these practices have on patient functioning and well being. Increasing levels of treatment burden may lead to suboptimal adherence and negative outcomes. Systematic review of the qualitative literature is a useful method for exploring the patient experience of care, in this case the experience of treatment burden. There is no consensus on methods for qualitative systematic review. This paper describes the methodology used for qualitative systematic reviews of the treatment burdens identified in three different common chronic conditions, using stroke as our exemplar.MethodsQualitative studies in peer reviewed journals seeking to understand the patient experience of stroke management were sought. Limitations of English language and year of publication 2000 onwards were set. An exhaustive search strategy was employed, consisting of a scoping search, database searches (Scopus, CINAHL, Embase, Medline & PsycINFO) and reference, footnote and citation searching. Papers were screened, data extracted, quality appraised and analysed by two individuals, with a third party for disagreements. Data analysis was carried out using a coding framework underpinned by Normalization Process Theory (NPT).ResultsA total of 4364 papers were identified, 54 were included in the review. Of these, 51 (94%) were retrieved from our database search. Methodological issues included: creating an appropriate search strategy; investigating a topic not previously conceptualised; sorting through irrelevant data within papers; the quality appraisal of qualitative research; and the use of NPT as a novel method of data analysis, shown to be a useful method for the purposes of this review.ConclusionThe creation of our search strategy may be of particular interest to other researchers carrying out synthesis of qualitative studies. Importantly, the successful use of NPT to inform a coding frame for data analysis involving qualitative data that describes processes relating to self management highlights the potential of a new method for analyses of qualitative data within systematic reviews.
| S-EPMC3568050 | biostudies-literature
Project description:The accelerated growth of proteomics data presents both opportunities and challenges. Large-scale proteomic profiling of biological samples such as cells, organelles or biological fluids has led to discovery of numerous key and novel proteins involved in many biological/disease processes including cancers, as well as to the identification of novel disease biomarkers and potential therapeutic targets. While proteomic data analysis has been greatly assisted by the many bioinformatics tools developed in recent years, a careful analysis of the major steps and flow of data in a typical highthroughput analysis reveals a few gaps that still need to be filled to fully realize the value of the data. To facilitate functional and pathway discovery for large-scale proteomic data, we have developed an integrated proteomic expression analysis system, iProXpress, which facilitates protein identification using a comprehensive sequence library and functional interpretation using integrated data. With its modular design, iProXpress complements and can be integrated with other software in a proteomic data analysis pipeline. This novel approach to complex biological questions involves the interrogation of multiple data sources, thereby facilitating hypothesis generation and knowledge discovery from the genomic-scale studies and fostering disease diagnosis and drug development.
| S-EPMC2474689 | biostudies-literature
Project description:Background and purposeMulticenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection.MethodsIn the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type.ResultsFor 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23-0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites.ConclusionsOverall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02089217.
| S-EPMC5575963 | biostudies-literature
Project description:As online content continues to grow, so does the spread of hate speech. We identify and examine challenges faced by online automatic approaches for hate speech detection in text. Among these difficulties are subtleties in language, differing definitions on what constitutes hate speech, and limitations of data availability for training and testing of these systems. Furthermore, many recent approaches suffer from an interpretability problem-that is, it can be difficult to understand why the systems make the decisions that they do. We propose a multi-view SVM approach that achieves near state-of-the-art performance, while being simpler and producing more easily interpretable decisions than neural methods. We also discuss both technical and practical challenges that remain for this task.
| S-EPMC6701757 | biostudies-literature