Analysis of eligibility criteria in Alzheimer’s and related dementias clinical trials

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer’s Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.</p

Challenges recruiting to a proof-of-concept pharmaceutical trial for a rare disease: The trigeminal neuralgia experience

Background: This study aimed to describe recruitment challenges encountered during a phase IIa study of vixotrigine, a state and use-dependent Nav1.7 channel blocker, in individuals with trigeminal neuralgia. Methods: This was an international, multicenter, placebo-controlled, randomized withdrawal study that included a 7-day run-in period, a 21-day open-label phase, and a 28-day double-blind phase in which patients (planned n = 30) were randomized to vixotrigine or placebo. Before recruitment, all antiepileptic drugs had to be stopped, except for gabapentin or pregabalin. After the trial, patients returned to their original medications. Patient recruitment was expanded beyond the original five planned (core) centers in order to meet target enrollment (total recruiting sites N = 25). Core sites contributed data related to patient identification for study participation (prescreening data). Data related to screening failures and study withdrawal were also analyzed using descriptive statistics. Results: Approximately half (322/636; 50.6%) of the patients who were prescreened at core sites were considered eligible for the study and 56/322 (17.4%) were screened. Of those considered eligible, 26/322 (8.1%) enrolled in the study and 6/322 (1.9%) completed the study. In total, 125 patients were screened across all study sites and 67/125 (53.6%) were enrolled. At prescreening, reasons for noneligibility varied by site and were most commonly diagnosis change (78/314; 24.8%), age &gt; 80 years (75/314; 23.9%), language/distance/mobility (61/314; 19.4%), and noncardiac medical problems (53/314; 16.9%). At screening, frequently cited reasons for noneligibility included failure based on electrocardiogram, insufficient pain, and diagnosis change. Conclusions: Factors contributing to recruitment challenges encountered in this study included diagnosis changes, anxiety over treatment changes, and issues relating to distance, language, and mobility. Wherever possible, future studies should be designed to address these challenges. Trial registration: ClinicalTrials.gov, NCT01540630. EudraCT, 2010-023963-16. 07 Aug 2015

Characterizing the Population in Clinical Trials: Barriers, Comparability, and Implications for Review

The definition of the study population for a clinical trial via the criteria for trial eligibility has implications for the validity of the study and its applicability to clinical practice. Though issues of equity regarding the selection of subjects for research have long been a concern of ethicists, issues regarding the impact of subject selection on a trial\u27s generalizability have only recently attracted ethical scrutiny. After a review of the history of the ethics of subject selection, I focus on three empirical questions regarding the generalizability of clinical trials. (1) What proportion of diseased populations are studied in clinical trials? (2) How are subjects selected for clinical trial participation (and what are the main barriers to participation)? (3) Are clinical trial participants comparable to non-participants? Finally, the role of the Institutional Review Board--Research Ethics Board in Canada--in assessing the generalizability of clinical research is discussed

Evaluating the design and reporting of pragmatic trials in osteoarthritis research

Objectives. Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. Methods. We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic–explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. Results. None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Conclusion. Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care

Research in Home-Care Telemedicine: Challenges in Patient Recruitment

This study reports challenges in recruiting patients for a randomized controHed trial of home-care telemedicinae. Descriptive statistics on patient eligibility for home-care telemedidne services and patient refusals for participation are provided. Frequency counts of reasons for study exclusion and participant refusal and Chi-square tests to compare race and age-related differences are given. Of 302 home-care patients reviewed, 197 (65.2%) did not meet inclusion criteria. The most common reasons for study exclusion were patients either needing \u3c2 visits per month (n = 59, 30%) or \u3e3 skilled nurse visits per week (n = 46, 23.4%). Of the eligible patients (n = 105), 79 persons (75.2%) refused participation. The most common reasons for refusals were lack of perceived addition benefit of telemedicine (n = 27, 34.2%), and that routine health care was sufficient (n = 23, 29.1%). Higher than expected proportions of patients did not meet chosen eligibility criteria or refused to participate. These results should be helpful in designing home-care telemedidne programs and clinical trials

DIFFERENTIATING EFFICACY AND EFFECTIVENESS IN STROKE REHABILITATION STUDIES: EVALUATION OF A SCALE

Differentiating between efficacy and effectiveness research approaches has become increasingly recognized as a critical step in the evidence-based decision-making process. A critical review of these archetypal approaches, as well as an evaluation of a new tool that purports to distinguish between them, was undertaken. Three raters independently applied the tool to 151 randomized controlled trials that evaluated either a pharmacological or non-pharmacological intervention in stroke rehabilitation. Inter-rater reliability was assessed both for individual items and total scores. Validity was assessed by examining associations between the total scale score and key study characteristics consistent with the effectiveness design. Inter-rater reliability values were sub-optimal for most items; however, there was support for basic scale validity. Further item standardization is required before the scale can be incorporated into the critical appraisal process; however, the tool provides a solid foundation upon which to base further discussion of the differential criteria of efficacy-effectiveness trial design

Representativeness of Patients Enrolled in a Primary Care Clinical Trial for Substance Use Disorders

Understanding the characteristics of research participants is crucial to ensuring sample representativeness and generalizability of findings to broader patient groups with substance use disorders. Using anonymous computer-administered health survey data, the present study had a unique opportunity to compare patients who chose to participate in an RCT for heavy/problem drinking or drug use (N=713; consenters) with those that chose not to participate (N=625; non-consenters). The sample was 40% male, 76% African American, and had a mean age of 45.2 years. Using multivariate regression, the most parsimonious model found older age, unemployment, prescription misuse, positive screen for drug problems (CAGE), having a grandmother with an alcohol problem, trouble falling asleep (past 30 days), health professional recommendation to go on a diet, and feeling unsafe due to a previous partner were all associated with consenting to participate. The present study provides benchmark data on sample representativeness in a clinical trial of SBIRT

Enhancing assertive community treatment with cognitive behavioral social skills training for schizophrenia: study protocol for a randomized controlled trial.

BackgroundSchizophrenia leads to profound disability in everyday functioning (e.g., difficulty finding and maintaining employment, housing, and personal relationships). Medications can effectively reduce positive symptoms (e.g., hallucinations and delusions), but they do not meaningfully improve daily life functioning. Psychosocial evidence-based practices (EBPs) improve functioning, but these EBPs are not available to most people with schizophrenia. The field must close the research and service delivery gap by adapting EBPs for schizophrenia to facilitate widespread implementation in community settings. Our hybrid effectiveness and implementation study represents an initiative to bridge this divide. In this study we will test whether an existing EBP (i.e., Cognitive Behavioral Social Skills Training (CBSST)) modified to work in practice settings (i.e., Assertive Community Treatment (ACT) teams) commonly available to persons with schizophrenia results in better consumer outcomes. We will also identify key factors relevant to developing future CBSST implementation strategies.Methods/designFor the effectiveness study component, persons with schizophrenia will be recruited from existing publicly funded ACT teams operating in community settings. Participants will be randomized to one of the 2 treatments (ACT alone or ACT + Adapted CBSST) and followed longitudinally for 18 months with assessments every 18 weeks after baseline (5 in total). The primary outcome domain is psychosocial functioning (e.g., everyday living skills and activities related to employment, education, and housing) as measured by self-report, testing, and observation. Additional outcome domains of interest include mediators of change in functioning, symptoms, and quality of services. Primary analyses will be conducted using linear mixed-effects models for continuous data. The implementation study component consists of a structured, mixed qualitative-quantitative methodology (i.e., Concept Mapping) to characterize and assess the implementation experience from multiple stakeholder perspectives in order to inform future implementation initiatives.DiscussionAdapting CBSST to fit into the ACT service delivery context found throughout the United States creates an opportunity to substantially increase the number of persons with schizophrenia who could have access to and benefit from EBPs. As part of the implementation learning process training materials and treatment workbooks have been revised to promote easier use of CBSST in the context of brief community-based ACT visits.Trial registrationClinicalTrials.gov NCT02254733 . Date of registration: 25 April 2014

Scaling Clinical Trial Matching Using Large Language Models: A Case Study in Oncology

Clinical trial matching is a key process in health delivery and discovery. In practice, it is plagued by overwhelming unstructured data and unscalable manual processing. In this paper, we conduct a systematic study on scaling clinical trial matching using large language models (LLMs), with oncology as the focus area. Our study is grounded in a clinical trial matching system currently in test deployment at a large U.S. health network. Initial findings are promising: out of box, cutting-edge LLMs, such as GPT-4, can already structure elaborate eligibility criteria of clinical trials and extract complex matching logic (e.g., nested AND/OR/NOT). While still far from perfect, LLMs substantially outperform prior strong baselines and may serve as a preliminary solution to help triage patient-trial candidates with humans in the loop. Our study also reveals a few significant growth areas for applying LLMs to end-to-end clinical trial matching, such as context limitation and accuracy, especially in structuring patient information from longitudinal medical records.Comment: 24 pages, 5 figures, accepted at Machine Learning for Healthcare (MLHC) 202

Exploring the Prevalence of Suboptimal Effort Among Children and Adolescents on Psychoeducational Evaluations

This study represents one of the first known studies to explore suboptimal effort in children and adolescents as part of psychoeducational evaluations conducted within a school setting. Only recently has attention been given to pediatric performance validity testing. With the assistance of five credentialed school psychologists across two midwestern states, 52 students were administered the Test of Memory Malingering (TOMM) as part of their psychoeducational evaluation. The findings of the current study suggested that 19.2% of these students failed Trial 2 on the TOMM, a suggested indicator of suboptimal performance. Furthermore, school psychologists’ ratings of observed effort did not correlate with failure on Trial 2 of the TOMM and there were no discernible patterns across disability area. Full scale ability scores provided a good predictor of performance on the TOMM. Overall, the findings from this study suggest the importance of including an objective performance validity measure for school psychologists in order to improve their ability to identify students who might be demonstrating suboptimal performance. Additional implications for practice and research are provided