Uncovering key clinical trial features influencing recruitment.

Background: Randomized clinical trials (RCT) are the foundation for medical advances, but participant recruitment remains a persistent barrier to their success. This retrospective data analysis aims to (1) identify clinical trial features associated with successful participant recruitment measured by accrual percentage and (2) compare the characteristics of the RCTs by assessing the most and least successful recruitment, which are indicated by varying thresholds of accrual percentage such as ≥ 90% vs ≤ 10%, ≥ 80% vs ≤ 20%, and ≥ 70% vs ≤ 30%. Methods: Data from the internal research registry at Columbia University Irving Medical Center and Aggregated Analysis of ClinicalTrials.gov were collected for 393 randomized interventional treatment studies closed to further enrollment. We compared two regularized linear regression and six tree-based machine learning models for accrual percentage (i.e., reported accrual to date divided by the target accrual) prediction. The outperforming model and Tree SHapley Additive exPlanations were used for feature importance analysis for participant recruitment. The identified features were compared between the two subgroups. Results: CatBoost regressor outperformed the others. Key features positively associated with recruitment success, as measured by accrual percentage, include government funding and compensation. Meanwhile, cancer research and non-conventional recruitment methods (e.g., websites) are negatively associated with recruitment success. Statistically significant subgroup differences (corrected p-value < .05) were found in 15 of the top 30 most important features. Conclusion: This multi-source retrospective study highlighted key features influencing RCT participant recruitment, offering actionable steps for improvement, including flexible recruitment infrastructure and appropriate participant compensation.

Seven-Year Experience From the National Institute of Neurological Disorders and Stroke-Supported Network for Excellence in Neuroscience Clinical Trials.

Importance: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders. Observations: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings. Conclusions and Relevance: NeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.

Risk Factors for Tuberculosis and Effect of Preventive Therapy Among Close Contacts of Persons With Infectious Tuberculosis.

BACKGROUND: Close contacts of persons with pulmonary tuberculosis (TB) have high rates of TB disease. METHODS: We prospectively enrolled TB patients and their close contacts at 9 US/Canadian sites. TB patients and contacts were interviewed to identify index patient, contact, and exposure risk factors for TB. Contacts were evaluated for latent TB infection (LTBI) and TB, and the effectiveness of LTBI treatment for preventing contact TB was examined. RESULTS: Among 4490 close contacts, multivariable risk factors for TB were age ≤5 years, US/Canadian birth, human immunodeficiency virus infection, skin test induration ≥10 mm, shared bedroom with an index patient, exposure to more than 1 index patient, and index patient weight loss (P < .05 for each). Of 1406 skin test-positive contacts, TB developed in 49 (9.8%) of 446 who did not initiate treatment, 8 (1.8%) of 443 who received partial treatment, and 1 (0.2%) of 517 who completed treatment (1951, 290, and 31 cases/100 000 person-years, respectively; P < .001). TB was diagnosed in 4.2% of US/Canadian-born compared with 2.3% of foreign-born contacts (P = .002), and TB rates for US/Canadian-born and foreign-born contacts who did not initiate treatment were 3592 and 811 per 100 000 person-years, respectively (P < .001). CONCLUSIONS: Treatment for LTBI was highly effective in preventing TB among close contacts of infectious TB patients. Several index patient, contact, and exposure characteristics associated with increased risk of contact TB were identified. These findings help inform contact investigation, LTBI treatment, and other public health prevention efforts.

Risk and Timing of Tuberculosis Among Close Contacts of Persons with Infectious Tuberculosis.

Background: The risk and timing of tuberculosis among recently exposed close contacts of patients with infectious tuberculosis are not well established. Methods: We prospectively enrolled patients ≥15 years of age with culture-confirmed pulmonary tuberculosis and their close contacts at 9 health departments in the United States and Canada. Close contacts were screened and cross-matched with tuberculosis registries to identify those who developed tuberculosis. Results: Tuberculosis was diagnosed in 158 of 4490 contacts (4%) of 718 index patients with tuberculosis. Of tuberculosis cases among contacts, cumulative totals of 81 (51%), 119 (75%), 128 (81%), and 145 (92%) were diagnosed by 1, 3, 6, and 12 months, respectively, after the index patients' diagnosis. Tuberculosis rates among contacts were 2644, 115, 46, 69, and 25 cases per 100000 persons, respectively, in the 5 consecutive years after the index patients' diagnosis. Of the tuberculosis cases among contacts, 121 (77%) were identified by contact investigation and 37 (23%) by tuberculosis registry cross-match. Conclusions: Close contacts to infectious patients with tuberculosis had high rates of tuberculosis, with most disease diagnosed before or within 3 months after the index patient' diagnosis. Contact investigations need to be prompt to detect tuberculosis and maximize the opportunity to identify and treat latent infection, to prevent disease.

Prevalence and anatomical features of acute longitudinal stent deformation: An intravascular ultrasound study.

OBJECTIVES: We report the prevalence and anatomical features of longitudinal stent deformation as detected by intravascular ultrasound (IVUS) BACKGROUND: Angiographic studies have recently reported longitudinal stent deformation as a mechanical complication occurring during percutaneous coronary intervention; however, there are no IVUS studies on this phenomenon METHODS: We retrospectively analyzed 1,489 consecutive stent-treated lesions in 1,057 patients who underwent IVUS post-stent implantation RESULTS: Seventeen longitudinal stent deformations in 17 lesions (1.1% per lesion) in 17 patients (1.6% per patient) were identified by IVUS. Of the 17 IVUS-detected deformations, only three deformations (17.6%) were detectable by angiography. By IVUS, there were three patterns of longitudinal stent deformation: (1) Deformation with intra-stent wrinkling and overlapping of the proximal and distal stent fragments within a single stent (n = 14), (2) deformation with elongation (n = 2), and (3) deformation with shortening (n = 1). Most of the deformations were located near to the proximal stent edge (88%), consistent with the finding that they were observed in 11 ostial (65%) and eight left main lesions (47%), and 8.3% of 96 left main stented lesions had evidence of deformation CONCLUSIONS: By IVUS, longitudinal stent deformation during percutaneous coronary intervention was seen more frequently than in previous studies; however, it is still uncommon (1.1%) except in the left main location. The most frequent pattern was intrastent wrinkling and overlapping of the proximal and distal stent fragments.

Acceptability of interferon-gamma release assays among healthcare workers who receive routine employee tuberculosis testing.

BACKGROUND: Healthcare workers (HCWs) undergo annual testing for latent tuberculosis infection (LTBI). OBJECTIVE: Compare acceptability of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) among HCWs. METHODS: HCWs at four medical centers in the US were administered an acceptability questionnaire including a brief objective description of both tests and eliciting attitudes regarding TST and IGRAs, confidence in results, and likelihood of taking LTBI treatment. RESULTS: Of 406 participants, 75% had never heard of IGRAs. IGRAs were preferred to TST. Belief in accuracy of hypothetical positive results of TST or IGRA and willingness to accept LTBI treatment were similar across tests. When presented with hypothetical discordant results, HCWs expressed more confidence in IGRAs. Perceived accuracy of results was the most important factor in test preferences. CONCLUSIONS: Although HCWs preferred and indicated more confidence in IGRAs, the likelihood that HCWs would believe LTBI diagnosis and initiate treatment based on positive results was similar for TST and IGRAs.