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Enrollment bias: frequency and impact on patient selection in endovascular stroke trials.

ABSTRACT: Selection bias may have affected enrollment in first generation endovascular stroke trials. We investigate, evaluate, and quantify such bias for these trials at our institution.Demographic, clinical, imaging, and angiographic data were prospectively collected on a consecutive cohort of patients with acute ischemic stroke who were enrolled in formal trials of endovascular stroke therapy (EST) or received EST in clinical practice outside of a randomized trial for acute cerebral ischemia at a single tertiary referral center from September 2004 to December 2012.Among patients considered appropriate for EST in practice, 47% were eligible for trials, with rates for individual trials ranging from 17% to 70%. Compared with trial ineligible patients treated with EST, trial eligible patients were younger (67 vs. 74 years; p<0.05), more often treated with intravenous tissue plasminogen activator (53% vs. 34%; p<0.01), and had shorter last known well to puncture times (328 vs. 367?min; p<0.05). Focusing on the largest trial with a non-interventional control arm, compared with trial eligible patients treated with EST outside the trial, enrolled patients presented later (274 vs. 163?min; p<0.001), had higher National Institutes of Health Stroke Scale scores (20 vs. 17; p<0.05), and larger strokes (diffusion weighted imaging volumes 49 vs. 18; p<0.001).The majority of patients felt suitable for EST at our institution were excluded from recent trials. Formal entry criteria succeeded in selecting patients with better prognostic features, although many of these patients were treated outside of trials. Acknowledging and mitigating these biases will be crucial to ongoing investigations.

SUBMITTER: Sheth SA

PROVIDER: S-EPMC4544665 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Enrollment bias: frequency and impact on patient selection in endovascular stroke trials.

Sheth Sunil A SA Saver Jeffrey L JL Starkman Sidney S Grunberg Ileana D ID Guzy Judy J Ali Latisha K LK Kim Doojin D Gonzalez Nestor R NR Jahan Reza R Tateshima Satoshi S Duckwiler Gary G Liebeskind David S DS

Journal of neurointerventional surgery 20150219 4

<h4>Background</h4>Selection bias may have affected enrollment in first generation endovascular stroke trials. We investigate, evaluate, and quantify such bias for these trials at our institution.<h4>Methods</h4>Demographic, clinical, imaging, and angiographic data were prospectively collected on a consecutive cohort of patients with acute ischemic stroke who were enrolled in formal trials of endovascular stroke therapy (EST) or received EST in clinical practice outside of a randomized trial for ...[more]

PMID: 25700030

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Project description:Clinical trials are the hallmark of evidence-based medicine, but recruitment is often challenging, especially in stroke trials investigating patients not being able to give informed consent. In some nations, ethics committees will not approve of inclusion in a clinical study via consent of a legal representative. The ethical dilemma of including or excluding those patients has not been properly addressed, as there is little data on the effect of stroke characteristics on the ability to give informed consent.To examine differences between patients able and unable to consent at inclusion to an acute stroke trial, we conducted a post-hoc analysis of monitoring records from a multicentric interventional trial. These records listed patients who gave informed consent by themselves and those who needed a legal representative to do so. This exemplary STRAWINSKI trial aimed at improving stroke outcome by biomarker-guided antibiotic treatment of stroke associated pneumonia and included patients within 40 h after stroke onset, suffering from MCA infarctions with an NIHSS score?>?9 at admission. Standard descriptive and associative statistics were calculated to compare baseline characteristics and outcome measures between patients who were able to consent and those who were not.We identified the person giving consent in 228 out of 229 subjects. Patients with inability to consent were older (p?<?0.01), suffered from more left-hemispheric (p?<?0.01) and more severe strokes (NIHSS, p?<?0.01), were more likely to die during hospitalisation (p?<?0.01) or have unfavourable outcome at discharge (mRS, p?<?0.01), to develop fever (p?<?0.01) and tended to be more susceptible to infections (p?=?0.06) during the acute course of the disorder.Demographics, stroke characteristics and outcomes significantly affect stroke patients in their ability to consent. Where selection criteria and primary outcome measures of a trial are significantly affected by ability to consent, excluding patients unable to consent might be unethical.URL http://www.clinicaltrials.gov . Unique identifier: NCT01264549 .

Project description:Backgroundand Purpose Recent randomized controlled trials have demonstrated consistent effectiveness of endovascular treatment (EVT) for acute ischemic stroke, leading to update on stroke management guidelines. We conducted this meta-analysis to assess the efficacy and safety of EVT overall and in subgroups stratified by age, baseline stroke severity, brain imaging feature, and anesthetic type.MethodsPublished randomized controlled trials comparing EVT and standard medical care alone were evaluated. The measured outcomes were 90-day functional independence (modified Rankin Scale ?2), all-cause mortality, and symptomatic intracranial hemorrhage.ResultsNine trials enrolling 2476 patients were included (1338 EVT, 1138 standard medical care alone). For patients with large vessel occlusions confirmed by noninvasive vessel imaging, EVT yielded improved functional outcome (pooled odds ratio [OR], 2.02; 95% confidence interval [CI], 1.64-2.50), lower mortality (OR, 0.75; 95% CI, 0.58-0.97), and similar symptomatic intracranial hemorrhage rate (OR, 1.12; 95% CI, 0.72-1.76) compared with standard medical care. A higher proportion of functional independence was seen in patients with terminus intracranial artery occlusion (±M1) (OR, 3.16; 95% CI, 1.64-6.06), baseline Alberta Stroke Program Early CT score of 8-10 (OR, 2.11; 95% CI, 1.25-3.57) and age ?70 years (OR, 3.01; 95% CI, 1.73-5.24). EVT performed under conscious sedation had better functional outcomes (OR, 2.08; 95% CI, 1.47-2.96) without increased risk of symptomatic intracranial hemorrhage or short-term mortality compared with general anesthesia.ConclusionsVessel-imaging proven large vessel occlusion, a favorable scan, and younger age are useful predictors to identify anterior circulation stroke patients who may benefit from EVT. Conscious sedation is feasible and safe in EVT based on available data. However, firm conclusion on the choice of anesthetic types should be drawn from more appropriate randomized controlled trials.

Project description:Our purpose was to identify physicians' individual characteristics, attitudes, and organizational contextual factors associated with higher enrollment of patients in cancer clinical trials among physician participants in the National Cancer Institute's Community Clinical Oncology Program (CCOP). We hypothesized that physicians' individual characteristics, such as age, medical specialty, tenure, CCOP organizational factors (i.e. policies and procedures to encourage enrollment), and attitudes toward participating in CCOP would directly determine enrollment. We also hypothesized that physicians' characteristics and CCOP organizational factors would influence physicians' attitudes toward participating in CCOP, which in turn would predict enrollment.We evaluated enrollment in National Cancer Institute-sponsored cancer clinical trials in 2011 among 481 physician participants using Structural Equation Modeling. The data sources include CCOP Annual Progress Reports, two surveys of CCOP administrators and physician participants, and the American Medical Association Masterfile.Physicians with more positive attitudes toward participating in CCOP enrolled more patients than physicians with less positive attitudes. In addition, physicians who practiced in CCOPs that had more supportive policies and practices in place to encourage enrollment (i.e. offered trainings, provided support to screen and enroll patients, gave incentives to enroll patients, instituted minimum accrual expectations) also significantly enrolled more patients. Physician status as CCOP Principal Investigator had a positive direct effect on enrollment, while physician age and non-oncology medical specialty had negative direct effects on enrollment. Neither physicians' characteristics nor CCOP organizational factors indirectly influenced enrollment through an effect on physician attitudes.We examined whether individual physicians' characteristics and attitudes, as well as CCOP organizational factors, influenced patient enrollment in cancer clinical trials among CCOP physicians. Physician attitudes and CCOP organizational factors had positive direct effects, but not indirect effects, on physician enrollment of patients. Our results could be used to develop physician-directed strategies aimed at increasing involvement in clinical research. For example, administrators may want to ensure physicians have access to support staff to help screen and enroll patients or institute minimum accrual expectations. Our results also highlight the importance of recruiting physicians for volunteer clinical research programs whose attitudes and values align with programmatic goals. Given that physician involvement is a key determinant of patient enrollment in clinical trials, these interventions could expand the overall number of patients involved in cancer research. These strategies will be increasingly important as the CCOP network continues to evolve.

Project description:Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear.In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead).Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14).A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care. (Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE ClinicalTrials.gov number, NCT00389467.).

Project description:BACKGROUND AND PURPOSE:Despite strong evidence for endovascular therapy in adults with acute arterial ischemic stroke, limited data exist in children. We aimed to describe endovascular therapy utilization and explore outcomes in a national sample of pediatric arterial ischemic stroke. METHODS:We queried the 2012 Kids' Inpatient Database for children aged greater than 28 days to 20 years with the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for arterial ischemic stroke and evaluated groups based on the procedure code for endovascular therapy. Poor outcome was defined as need for tracheostomy or gastrostomy, discharge to rehabilitation facility, or death. Logistic regression evaluated the association between endovascular therapy and poor outcome, adjusted for age, disease severity (hemiplegia, critical care interventions, neurosurgical interventions), and comorbidities. RESULTS:We identified 3184 pediatric discharges with a diagnosis code for arterial ischemic stroke. Thirty-eight (1%) had an endovascular therapy procedure code. Endovascular therapy patients were older (10.2 versus 4.5 years, P < 0.001) and more likely to have hemiplegia/paresis (relative risk [RR] 3.8, 95% confidence interval [CI] 2.0-7.4), aphasia (RR 5.3, 95% CI 2.8-10.1), and facial droop (RR 4.0, 95% CI 1.9-8.7). Endovascular therapy was not associated with critical care and neurosurgical interventions or intracranial hemorrhage. Length of hospitalization, mortality, and discharge disposition were similar between groups. In a multivariable model, endovascular therapy was not associated with poor outcome (adjusted odds ratio 1.7, 95%, CI 0.7-4.1). CONCLUSIONS:In a national sample of children with a diagnosis of arterial ischemic stroke, endovascular therapy was infrequently utilized. Patients with a procedure code for endovascular therapy had significant stroke-related deficits, but outcomes were similar to those in children who did not receive endovascular therapy. Our data, in conjunction with evidence of benefit in adults, support consideration of endovascular therapy for select children with acute stroke.

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Enrollment bias: frequency and impact on patient selection in endovascular stroke trials.

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Enrollment bias: frequency and impact on patient selection in endovascular stroke trials.

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