Patient Enrollment Research Articles

Nested Randomized Controlled Trials in Large Databases: An Opportunity for Inflammatory Bowel Disease?

Although randomized controlled trials (RCTs) are the gold standard for investigating the efficacy and safety of interventions, they present major operational challenges due to their complexity, time-consuming nature, and high costs. To address some of these difficulties, RCTs nested in cohorts (RCTsNC) have been developed to enable patient enrolment and randomization from existing databases. RCTsNC is an emerging trial design, which has been successfully utilized across several medical disciplines but not inflammatory bowel disease (IBD). This narrative review outlines the principles of RCTsNC and discusses the numerous advantages it affords for IBD, including harnessing longer-term longitudinal data for safety and efficacy assessment, and enhanced recruitment and follow up processes. Leveraging pre-existing cohorts and their organizational structures improves patient acceptance and is more economical compared to traditional randomized trials. Observational data for IBD, derived from research (cohort and case-control studies) and non-research sources (electronic health records and registries), provides access to comprehensive records for a large number of IBD patients. It permits researchers to address knowledge gaps in IBD where traditional RCTs have had a limited role, such as specific sub-populations typically excluded from pivotal trials, or assessing the effect of environmental exposures on disease course. This review also details caveats of this study design that include the risk of selection bias and constraints related to comparisons with placebo. In conclusion, RCTsNC offers a promising opportunity IBD research given the challenges of the current IBD RCT landscape.

Impact of a ketogenic diet on sleep quality in people with relapsing multiple sclerosis

BackgroundSleep disturbance in MS is common and can significantly impair overall quality of life. The ketogenic diet (KD) associates with improved sleep quality in people living with epilepsy and may have similar benefits when used within MS; however, the impact of a KD on sleep in this population remains poorly defined. MethodsForty-five patients with relapsing MS enrolled into a 6-month KD intervention trial and completed self-reported assessments of sleep quality and sleep disorder symptoms prior to diet initiation and while on diet, using the Epworth Sleepiness Scale (ESS) and Sleep Disorders Symptom Checklist-25 (SDS). Participants who did not complete sleep assessments at baseline and 6-months were excluded from analysis. In addition to sleep metrics, data collection included anthropometrics and MS-related fatigue scores. ResultsThirty-nine of 45 (87 %) participants completed the required sleep assessments. There was a mean reduction in ESS score of 1.90 (95 % CI [-2.85, −0.94], p < 0.001). Total SDS score decreased at 6-months on KD (−4.4, 95 % CI [-7.1, −1.7], p = 0.002), with improvements noted in insomnia (−1.55, 95 % CI [-2.66, −0.43], p = 0.008), obstructive sleep apnea (−0.91, 95 % CI [-1.57, −0.25], p = 0.008), and restless leg syndrome screening scores (−1.00, 95 % CI [-1.95, −0.051], p = 0.04). Sleep duration was unchanged on KD. ConclusionKD associates with improvements in daytime sleepiness, independent of sleep duration, and common comorbid sleep disorders in people living with relapsing MS. The findings herein support the benefits of KD on sleep quality and highlight the potential role of dietary therapeutics for sleep disorders in neurological disease. Trial registration informationRegistered on Clinicaltrials.gov under registration number NCT03718247, posted on Oct 24, 2018. First patient enrollment date: Nov 1, 2018. Link: https://clinicaltrials.gov/ct2/show/NCT03718247?term=NCT03718247&draw=2&rank=1.

Personalized dose selection for the first Waldenström macroglobulinemia patient on the PRECISE CURATE.AI trial

The digital revolution in healthcare, amplified by the COVID-19 pandemic and artificial intelligence (AI) advances, has led to a surge in the development of digital technologies. However, integrating digital health solutions, especially AI-based ones, in rare diseases like Waldenström macroglobulinemia (WM) remains challenging due to limited data, among other factors. CURATE.AI, a clinical decision support system, offers an alternative to big data approaches by calibrating individual treatment profiles based on that individual’s data alone. We present a case study from the PRECISE CURATE.AI trial with a WM patient, where, over two years, CURATE.AI provided dynamic Ibrutinib dose recommendations to clinicians (users) aimed at achieving optimal IgM levels. An 80-year-old male with newly diagnosed WM requiring treatment due to anemia was recruited to the trial for CURATE.AI-based dosing of the Bruton tyrosine kinase inhibitor Ibrutinib. The primary and secondary outcome measures were focused on scientific and logistical feasibility. Preliminary results underscore the platform’s potential in enhancing user and patient engagement, in addition to clinical efficacy. Based on a two-year-long patient enrollment into the CURATE.AI-augmented treatment, this study showcases how AI-enabled tools can support the management of rare diseases, emphasizing the integration of AI to enhance personalized therapy.

Locoregional recurrence in studies of primary systemic therapy in early invasive breast cancer

IntroductionThe use of primary systemic therapy (PST) in early invasive breast cancer is routine but there are concerns about risk of locoregional recurrence. MethodsWe conducted a systematic literature review to identify studies of locoregional treatment and recurrence in patients with early invasive breast cancer who received non-endocrine PST. ResultsWe identified 112 studies (18 prospective trials and 94 non-interventional studies). The use of surgery and radiotherapy after PST was recorded in 65 (58 %) and 50 (45 %) of studies respectively. 66 (59 %) studies reported locoregional recurrence. Cumulative 5-year locoregional recurrence risks varied from 1 % to 23 %. Locoregional recurrence was higher in patients under the age of 40, those who did not achieve a pathological complete remission after PST, had ER-negative or HER2 negative tumours, were recorded to have inoperable disease before PST, and did not have radiotherapy. LRR rates in these studies have not fallen over the overall calendar period of patient enrollment (1999–2016). ConclusionThe recording of locoregional treatments and outcomes is suboptimal in studies of PST and efforts to improve this are required. In the absence of randomised evidence, our findings may help to inform care and guideline development. We were unable to exclude concern that the use of PST is associated with a higher than desired risk of locoregional recurrence.

Factors Influencing Discharges to Hospice for Patients With Late-Stage Huntington's Disease.

Background: Hospice services for patients with Huntington's disease (HD) are likely beneficial in relieving significant burdens and minimizing costly hospitalizations at the end of life, though there has been little study or clinical guidance on hospice enrollment for patients with HD. Objectives: The primary objective of this study was to identify clinical, sociodemographic, and system-level factors associated with discharges to hospice compared to other dispositions for hospitalized patients with late-stage HD. Methods: These analyses used data from the Nationwide Inpatient Sample between the years 2007 and 2011. Weighted logistic regression with a forward selection approach was performed to identify factors associated with discharge to hospice compared to discharge to home, facility, other locations, and death in hospital. Results: These analyses included 6544 hospitalizations of patients with late-stage HD. There was a significant increasing trend in discharges to hospice over the study period (P < 0.001). After adjustment, multiple clinical, sociodemographic, and system-level variables were identified as being associated with discharges to hospice. Patients with aspiration pneumonia and non-aspiration pneumonias had lower odds of being discharged to hospice compared to dying in the hospital. When comparing to discharges to facilities and home, weight loss and palliative care consultation were associated with greater odds of discharge to hospice. Conclusions: Our findings serve as a foundation for future studies on these factors, and thus help clinician decision-making on when to start advance care planning or end-of-life care for patients with HD. These results also support studies developing hospice referral criteria specific to patients with HD.

A PROMPT Update on Partial REBOA: Initial Clinical Data and Overview of the DoD-Funded Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) Study.

Retrograde Endovascular Balloon Occlusion of the Aorta (REBOA) is an effective management for the transient responder, but the ischemic consequences of complete aortic occlusion currently limit its use. Multiple DoD-funded preclinical studies have clearly demonstrated that partial REBOA reduces distal ischemia to potentially extend safe occlusion times, while still providing effective temporization of noncompressible torso hemorrhage. Early versions of REBOA devices were designed to completely occlude the aorta and had little ability to provide partial occlusion. Recently, a new REBOA device (pREBOA-PRO) was designed specifically to allow for partial occlusion, with the hypothesis that this may reduce the complications of aortic occlusion and extend safe occlusion times while maintaining the benefits on cardiac and cerebrovascular circulation as well as reductions in resuscitation requirements. To ascertain the impact of a new purpose-built partial REBOA device on the extension of safe occlusion time, the Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) trial compared available data from the pREBOA-PRO with existing data from 200 clinical uses of pREBOA-PRO and available data in the AAST AORTA Registry were reviewed to design primary endpoints and clinical evidence for a prospective multi-center trial, the PROMPT Study. Together with the endpoints identified in preclinical studies of partial REBOA, primary endpoints for the PROMPT study were identified and power analyses were conducted to determine the target patient enrollment goals. Results from the clinical implementation of partial REBOA at a single trauma center were used to conduct the initial power analysis for the primary endpoint of Acute Kidney Injury (AKI) after prolonged occlusion. The rate of AKI after complete REBOA was 55% (12/20) compared to 33% (4/12) after partial REBOA (Madurska etal., 2021). With an alpha of 0.05 and power (β) of 0.8, the projected sample size for comparison on a dichotomous outcome is 85 patients for the assessment of AKI. Initial power and endpoint analyses have been confirmed and extended with the ongoing analysis of partial and complete REBOA reported in the AORTA database. These analyses confirm preclinical findings which show that compared to complete REBOA, partial REBOA is associated with extended occlusion time in zone 1 (complete: 31 min vs. partial: 45 min, P = 0.003), lower rates of AKI after zone 1 occlusion (complete: 33% vs. partial: 19%, P = 0.05) and reduced resuscitation requirements (e.g., 25% reduction in pRBC administration: complete: 18 units vs. partial: 13 units, P = 0.02). The DoD-funded PROMPT study of partial REBOA will provide prospective observational clinical data on patients being treated with pREBOA-PRO. Outcomes will be stratified based on partial or complete occlusion to address whether partial REBOA has additional clinical benefits over complete REBOA, such as decreased distal ischemia, extension of safe occlusion time, improved hemodynamics during transition to and from occlusion, and reduced interoperative bleeding and blood product use. The results from this study are expected to confirm previous data demonstrating reduction of ischemic sequalae, improved transition to reperfusion, and reduced resuscitative requirements compared to complete REBOA.

Deferred consent in emergency trauma research: A qualitative study assessing the healthcare professional's opinions

IntroductionSeverely injured patients are often incapacitated to provide informed consent for clinical studies. Deferred consent could facilitate unbiased enrollment in studies involving these patients. Little is known about how healthcare professionals (HCPs) perceive deferred consent and how this impacts patient enrollment. The aim of this study was to identify factors that could influence HCPs decision-making during recruitment of patients for interventional studies in (pre)hospital emergency trauma research. MethodsThis was a qualitative study in which physicians and nurses working in prehospital or in-hospital care were interviewed using a semi-structured interview guide. Interviews were audio-recorded, transcribed, and analyzed according to thematic analysis as described by Braun and Clarke. ResultsTen semi-structured interviews were conducted with six physicians and four nurses. Eight themes were identified as being relevant consent related factors influencing HCPs’ decision-making during patient recruitment in studies using deferred consent: (1) HCPs’ lack of knowledge; (2) Patients’ and proxies’ inability to be informed; (3) Practical (im)possibilities for informed consent; (4) Nature of intervention; (5) HCPs’ personal beliefs; (6) Importance of emergency care research; (7) HCPs’ trust in legal base; and (8) Communication and collaboration. ConclusionsEight consent-related factors influencing HCPs’ decision making were identified. Insufficient knowledge about consent procedures among HCPs leads to significant negative attitudes towards deferred consent.

Prediction Modelling for Gastroesophageal Variceal Bleeding in Patients With Chronic Hepatitis B Using Four-dimensional Flow MRI

Introduction and objectivesIn this study, we aim to develop a model for predicting Gastroesophageal varices (GEV) bleeding in patients with chronic hepatitis B (CHB) by utilizing hemodynamic parameters obtained through four-dimensional flow MRI (4D flow MRI). Materials and methodsThis study conducted a prospective enrollment of CHB patients suspected of GEV from October 2021 to May 2022. The severity of varices and bleeding risk were evaluated using clinical findings and upper gastrointestinal endoscopy, and patients were classified into high-risk and non-high-risk groups. The study utilized serological examination, ultrasonographic examination, and 4D flow MRI. Relevant parameters were selected through univariate and multivariate analyses, and a prediction model was established using binary logistic regression analysis. The model was combined with the Baveno Ⅵ/Ⅶ and Expanded Baveno Ⅵ/Ⅶ criteria to evaluate diagnostic efficacy and the risk of avoiding endoscopic examination. ResultsA total of 40 CHB patients were enrolled and categorized into the high-risk group (n=15) and the non-high-risk group (n=25). The spleen diameter and regurgitant fraction (R%) were independent predictors of variceal bleeding and a predictive model was established. The combination of this prediction model and the Baveno Ⅵ/Ⅶ criteria achieved high diagnostic efficiency, enabling 45.00% (18/40) of patients to be exempted from the unnecessary endoscopic procedure and the high-risk misclassification rate (0%) was less than 5%. ConclusionThe prediction model generated by 4D flow MRI has the potential to assess the likelihood of varices and can be supplemented by the Baveno VI/VII criteria to improve diagnostic accuracy in CHB patients.

Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients

BackgroundRecognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses.MethodsA prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome.ResultsThis study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384–73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045–28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48–49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25–25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48–12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09–27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798–0.934) with a sensitivity of 0.761 and specificity of 0.869.ConclusionWe established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

Ultrasound-guided superior laryngeal nerve block: a randomized comparison between parasagittal and transverse approach

BackgroundDifferent approach ultrasound-guided superior laryngeal nerve block was used to aid awake intubation, but little is known which approach was superior. We aimed to compare the parasagittal and transverse approaches for ultrasound-guided superior laryngeal nerve block in adult patients undergoing awake intubation.MethodsFifty patients with awake orotracheal intubation were randomized to receive either a parasagittal or transverse ultrasound-guided superior laryngeal nerve block. The primary outcome was patient’s quality of airway anesthesia grade during insertion of the tube into the trachea. The patients’ tube tolerance score after intubation, total procedure time, mean arterial pressure, heart rate, Ramsay sedation score at each time point, incidence of sore throat both 1 h and 24 h after extubation, and hoarseness before intubation, 1 h and 24 h after extubation were documented.ResultsPatients’ quality of airway anesthesia was significantly better in the parasagittal group than in the transverse group (median grade[IQR], 0 [0–1] vs. 1 [0–1], P = 0.036). Patients in the parasagittal approach group had better tube tolerance scores (median score [IQR],1[1–1] vs. 1 [1–1.5], P = 0.042) and shorter total procedure time (median time [IQR], 113 s [98.5–125.5] vs. 188 s [149.5–260], P < 0.001) than those in the transverse approach group. The incidence of sore throat 24 h after extubation was lower in the parasagittal group (8% vs. 36%, P = 0.041). Hoarseness occurred in more than half of the patients in parasagittal group before intubation (72% vs. 40%, P = 0.023).ConclusionsCompared to the transverse approach, the ultrasound-guided parasagittal approach showed improved efficacy in terms of the quality of airway topical anesthesia and shorter total procedure time for superior laryngeal nerve block.Trial registrationThis prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20220425-014) and registered in the Chinese Clinical Trial Registry (19/6/2022, ChiCTR2200061287) prior to patient enrollment. Written informed consent was obtained from all participants in this trial.

GIFTS: Geriatric Intensive Functional Therapy Sessions-for the older trauma patient.

Considering resources for comprehensive geriatric care, it would be beneficial for geriatric trauma patients (GTPs) and medical patients to be comanaged in one program focusing on ancillary therapeutics (AT): physical therapy, occupational therapy, speech language pathology, respiratory therapy, and sleep wake hygiene. This pilot study describes outcomes of GTPs in a hospital-wide program focused on geriatric-specific AT. Geriatric trauma patients and geriatric patients were screened by program coordinator for enrollment at one Level II trauma center from August 2021 to December 2022. Enrolled patients (EPs) were admitted to trauma or medicine floors and received repetitive AT with attention to sleep wake hygiene throughout hospitalization and compared with similar nonenrolled patients (NEPs). Excluded patients had any of the following: indication of geriatric syndrome with a fatigue, resistance, ambulation, illness, and loss of weight (FRAIL) score of 5, no frailty with a FRAIL score of 0, comfort focused plans, or arrived from skilled care. Retrospective chart review of demographics and outcomes was completed for both EPs and NEPs. A total of 224 EPs (28 trauma [TR]) were compared with 574 NEPs (148 TR). Enrolled patients showed shorter length of stay (mean, 3.8 vs. 6.1; p = 0.0001), less delirium (3.1% vs. 9.6%, p = 0.00222), less time to ambulation (13 hours vs. 39 hours, p = 0.0005), and higher likelihood to discharge home (56% vs. 27%, p < 0.0001) as compared with NEPs. The median FRAIL score was 3 for both groups. Enrolled medical patients ambulated the soonest at 11 average hours, compared with 23 hours for enrolled trauma patients and 39 hours for NEPs. There were zero delirium events among enrolled trauma patients; 25% was found among nonenrolled trauma patients ( p = 0.00288). Despite a small trauma cohort, results support feasibility to include GTPs in hospital-wide programs with geriatric-specific AT. Mobility and cognitive strategies may improve opportunities to avoid delirium, decrease length of stay, and influence more frequent disposition to home. Therapeutic/Care Management; Level III.

Cardiac stasis imaging, stroke, and silent brain infarcts in patients with nonischemic dilated cardiomyopathy.

Cardioembolic stroke is one of the most devastating complications of nonischemic dilated cardiomyopathy (NIDCM). However, in clinical trials of primary prevention, the benefits of anticoagulation are hampered by the risk of bleeding. Indices of cardiac blood stasis may account for the risk of stroke and be useful to individualize primary prevention treatments. We performed a cross-sectional study in patients with NIDCM and no history of atrial fibrillation (AF) from two sources: 1) a prospective enrollment of unselected patients with left ventricular (LV) ejection fraction <45% and 2) a retrospective identification of patients with a history of previous cardioembolic neurological event. The primary end point integrated a history of ischemic stroke or the presence intraventricular thrombus, or a silent brain infarction (SBI) by imaging. From echocardiography, we calculated blood flow inside the LV, its residence time (TR) maps, and its derived stasis indices. Of the 89 recruited patients, 18 showed a positive end point, 9 had a history of stroke or transient ischemic attack (TIA) and 9 were diagnosed with SBIs in the brain imaging. Averaged TR, [Formula: see text] performed well to identify the primary end point [AUC (95% CI) = 0.75 (0.61-0.89), P = 0.001]. When accounting only for identifying a history of stroke or TIA, AUC for [Formula: see text] was 0.92 (0.85-1.00) with odds ratio = 7.2 (2.3-22.3) per cycle, P < 0.001. These results suggest that in patients with NIDCM in sinus rhythm, stasis imaging derived from echocardiography may account for the burden of stroke.NEW & NOTEWORTHY Patients with nonischemic dilated cardiomyopathy (NIDCM) are at higher risk of stroke than their age-matched population. However, the risk of bleeding neutralizes the benefit of preventive oral anticoagulation. In this work, we show that in patients in sinus rhythm, the burden of stroke is related to intraventricular stasis metrics derived from echocardiography. Therefore, stasis metrics may be useful to personalize primary prevention anticoagulation in these patients.

Changes in Primary Care Health Services During the COVID-19 Pandemic: A Longitudinal Analysis of Data From Ontario.

The COVID-19 pandemic significantly impacted primary care, but its effect on quality of care is not well understood. We used health administrative data to understand the changes in quality-of-care measures for primary care between October 2018 and April 2022. We examined the following domains: cancer screening, chronic disease (diabetes) management, high-risk prescribing, continuity of care and capacity of primary care services. Colorectal and breast cancer screenings declined after the pandemic and had not returned to baseline by study end. In patients living with diabetes, in-person visits and up-to-date retinopathy screening rates declined after the pandemic declaration and did not return to baseline by study end, while statin prescribing remained stable. High-risk opioid prescribing decreased over time and was not affected by the pandemic. Physician continuity remained stable, though new patient enrollments decreased over the pandemic but returned to baseline by study end. Existing disparities in colorectal cancer screening by income and recent registration widened during the pandemic. In summary, COVID-19 had a variable impact on primary care, with the strongest influence on preventive and chronic disease care that was dependent on in-person visits.

AB012. A phase III randomized trial of gross total resection versus possible resection of fluid-attenuated inversion recovery (FLAIR) hyperintensity lesion on magnetic resonance image for newly diagnosed supratentorial glioblastoma (JCOG2209).

Complete resection of contrast-enhanced lesions [gross total resection (GTR)] without severe neurological deficits has been generally accepted as the goal of surgery. However, it remains unclear if additional resection of surrounding fluid-attenuated inversion recovery (FLAIR) hyper-intense lesions combined with GTR (FLAIRectomy) has survival advantage of primary glioblastoma patients. Multicenter, open-label, randomized phase III trial was commenced to confirm the superiority of FLAIRectomy to GTR alone followed by radiotherapy with concomitant and adjuvant temozolomide in terms of overall survival (OS) for primary glioblastoma IDH-wildtype patients. This trial investigates not only survival but also postoperative neurological and neurocognitive deficits in detail. We assumed a 2-year OS of 50% in the GTR arm and expected a 15% improvement in the FLAIRectomy arm. A total of 130 patients is required with a one-sided alpha of 5%, power of 70%, and will be accrued from 49 Japanese institutions in 4 years and follow-up will last 2.5 years. Patients aged 18-75 years will be registered and randomly assigned to each arm with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, proportion of National Institutes of Health stroke scale preservation, proportion of mini-mental state examination preservation and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in May 2023. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in July 2023. If FLAIRectomy is superior to GTR alone, aggressive surgery will become a standard surgical treatment for glioblastoma with resectable contrast-enhanced lesion. Registry number: jRCT1031230245. Date of registration: 19/July/2023. Date of first participant enrollment: 28/July/2023.

Patient Enrollment per Month (Accrual) in Clinical Trials Leading to the FDA Approval of New Cancer Drugs.

Insufficient patient enrollment per month (=accrual) is the leading cause of cancer trial termination. To identify and quantify factors associated with patient accrual in trials leading to the US Food and Drug Administration (FDA) approval of new cancer drugs. All anti-cancer drugs with FDA approval were identified in the Drugs@FDA database (2000-2022). Data on drug indication's background-, treatment-, disease-, and trial-related factors were collected from FDA labels, clinicaltrials.gov, and the Global Burden of Disease study. The association between patient accrual and collected variables was assessed in Poisson regression models reporting adjusted rate ratios (aRR). We identified 170 drugs with approval in 455 cancer indications on the basis of 292 randomized and 163 single-arm trials. Among randomized trials, median enrollment per month was 38 patients (interquartile range [IQR]: 26-54) for non-orphan, 21 (IQR: 15-38, aRR 0.88, p = 0.361) for common orphan, 20 (IQR: 10-35, aRR 0.73, p <0.001) for rare orphan, and 8 (IQR 6-12, aRR 0.30, p < 0.001) for ultra-rare orphan indications. Patient enrollment was positively associated with disease burden [aRR: 1.0003 per disability-adjusted life year (DALY), p < 0.001), trial sites (aRR: 1.001 per site, p < 0.001), participating countries (aRR: 1.02 per country, p < 0.001), and phase 3 vs. 1/2 trials (aRR: 1.64, p = 0.037). Enrollment was negatively associated with advanced-line vs. first-line treatments (aRR: 0.81, p = 0.010) and monotherapy vs. combination treatments (aRR: 0.80, p = 0.007). Patient enrollment per month was similar between indications with and without a biomarker (median: 27 vs. 32, aRR 0.80, p = 0.117). Patient enrollment per month was substantially lower in government-sponsored than industry-sponsored trials (median: 14 vs. 32, aRR 0.80, p = 0.209). Enrollment was not associated with randomization ratios, crossover, and study blinding. Disease incidence and disease burden alongside the number of study sites and participating countries are the main drivers of patient enrollment in clinical trials. For rare disease trials, greater financial incentives could help expedite patient enrollment. Novel trial design features, including skewed randomization, crossover, or open-label masking, did not entice patient enrollment.

Efficacy of azasetron on postoperative chronic pain after pulmonary surgery: a randomized triple-blind controlled trial

BackgroundInhibition of 5-HT3 (5-Hydroxyl Tryptamine) receptors is known to enhance morphine analgesia in animal models. We tested the efficacy of azasetron, a 5-HT3 receptor antagonist, on postoperative chronic pain after pulmonary surgery in a randomized triple-blind controlled study.MethodsA total of 250 patients who were scheduled to receive pulmonary surgery were randomized to patient-controlled analgesia (PCA) using 200 µg sufentanil with normal saline or 200 µg sufentanil with 20 mg azasetron. The numerical rating scale of pain (NRS) was recorded at baseline, postoperative day (POD) 1, 2, 3, 90, and 180. Negative binomial regression was used to identify associated factors for postoperative NRS six months after surgery.ResultsThe results showed that azasetron did not affect the primary outcomes: the incidence of postoperative chronic pain on POD90 and 180. However, azasetron decreased postoperative NRS at rest and activity on POD1, 2, and 3. Furthermore, azasetron decreased postoperative nausea and vomiting on POD1 and 2. Univariate and multivariate negative binomial regression analysis identified preoperative pain, smoking, drinking and open surgery are risk factors of chronic pain six months after surgery.ConclusionsAzasetron did not affect the incidence of chronic pain after pulmonary surgery. The presence of preoperative pain, smoking, drinking, and open surgery were found to be associated with chronic pain six months after surgery.Clinical trial registrationThe trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200060139), 20/05/2022; the site url is https://www.chictr.org.cn/.

Does the type of pharmacy used influence medication adherence? A retrospective observational study in Aotearoa, New Zealand.

Community pharmacies in New Zealand have varying ownership and operational structures. Unlike independent pharmacies, corporate and hybrid pharmacies do not charge prescription copayments. This research aimed to determine whether people receiving free prescriptions from corporate and hybrid pharmacies (via copayment waiver) have greater medication adherence than the users of independent pharmacies. A nationwide, retrospective, observational study linked 1 year of dispensing data (1/05/2022 to 30/04/2023) from the Pharmaceutical Collection to patient enrollment data using a National Health Index number to identify demographics of different pharmacy-type users. People were assigned to a particular type of pharmacy if they collected at least 70% of their prescriptions from there; if they did not meet this threshold, they were defined as mixed users. People were classified as adherent if dispensing data showed they collected their supply of medication to cover at least 80% of the study period. The sample captured 218,080 people taking at least 1 diabetes medication, with a total of 360,079 unique medications being included in the analysis. The majority, 156,893, used independent pharmacies. The type of pharmacy used was shown to be a significant predictor of adherence. Corporate and hybrid pharmacy users were 0.90 (95% CI 0.88 to 0.93) and 0.93 (95% CI 0.90 to 0.96) times as likely be adherent than the users of independent pharmacies. Mail order pharmacy users were the most likely to be adherent, whereas mixed pharmacy users were the least likely to be adherent. Our findings suggest that prescription copayments provided by corporate and hybrid pharmacies are not the most significant barrier to medication adherence. Further research may identify more efficient ways of improving medication adherence than removing prescription copayments for all.

Email recruitment for chronic pain clinical trials: results from the LAMP trial

BackgroundRecruitment for clinical trials and large-scale studies is challenging, especially for patients with complex conditions like chronic pain. Email recruitment has the potential to increase efficiency, to reduce costs, and to improve access for underrepresented patient populations. The objective of this study was to examine the effectiveness, efficiency, and equitability of email versus postal mail recruitment for the Learning to Apply Mindfulness to Pain (LAMP) study, a three-site clinical trial of mindfulness-based interventions for chronic pain.MethodsPatients with chronic pain diagnoses were recruited from three United States Department of Veterans Affairs (VA) facilities using the VA electronic health record (EHR). Recruitment materials were sent using either postal mail (n = 7986) or email (n = 19,333). Patients in the email recruitment group were also mailed introductory postcards before any emails. Mailing addresses and email addresses were obtained from the EHR. Effectiveness was measured by the response rate of patients who logged into the secure LAMP study website. Efficiency was measured by the number of days from when the recruitment materials were sent to when patients logged into the LAMP portal as well as the estimated costs of each recruitment approach. To assess equitability, we examined whether email recruitment was less effective for underrepresented populations, based on demographic information from the EHR.ResultsEffectiveness—unadjusted response rates were greater for email versus postal-mail recruitment (18.9% versus 6.3%), and adjusted response rates were over three times greater for email recruitment (RR = 3.5, 95% CI 3.1–3.8) based on a multivariable analysis controlling for age, gender, race, ethnicity, rurality, and site. Efficiency—email recruitment had a significantly lower mean response time (1 day versus 8 days) and a lower cost. Equity—email recruitment led to higher response rates for all subpopulations, including older, non-White, Hispanic, rural, and female Veterans.ConclusionsEmail recruitment is an effective, efficient, and equitable way to recruit VA patients to large-scale, chronic pain clinical trials.Trial registrationClinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.

Occult residual ovarian tissue at the time of minimally invasive risk reducing surgery in women with BRCA mutations

ObjectiveTo describe extension of ovarian tissue beyond visible and National Comprehensive Cancer Network recommended margins among patients with BRCA mutations undergoing minimally invasive risk-reducing salpingo-oophorectomy. MethodsA prospective study of patients with BRCA mutations who underwent minimally invasive risk-reducing bilateral salpingo-oophorectomy was conducted. Patient enrollment occurred between October 2021 and 2023. Tissue specimens were analyzed according to the Sectioning and Extensively Examining the Fimbriated End protocol. ResultsTwenty women with BRCA mutations were prospectively enrolled. All patients underwent minimally invasive surgery with 70% undergoing concurrent hysterectomy (n = 14). Approximately half of these procedures were performed with robotic assistance (n = 9, 45%). One patient was admitted overnight (5%); the other nineteen were discharged on the day of surgery (95%). One patient experienced a major complication and required readmission (5%). Extension of ovarian tissue beyond the visible ovary was noted on pathologic examination of six specimens (30%). In one patient this was observed on the left (17%), in three on the right (50%), and in two bilateral extension (33%) was noted. The distance ovarian stroma extended microscopically beyond the visible ovary was between 2 and 14 mm, with a median of 5 mm. Among patients with microscopic extension of ovarian tissue, the majority (n = 5, 83%) had a BRCA2 mutation. ConclusionIn women with BRCA mutations undergoing risk-reducing minimally invasive surgery, approximately one third had microscopic extension of ovarian stroma beyond the visible ovary. Current guidelines which recommend resection of at least 20 mm of tissue beyond the visible ovary are likely adequate in this population.

M147 - Assessing the Impact of Medical Expenditure Supplements Program on the Enrolling and Retention of Patients Attending Methadone Maintenance Treatment Clinics in Taiwan: An Interrupted Time Series Analysis

M147 - Assessing the Impact of Medical Expenditure Supplements Program on the Enrolling and Retention of Patients Attending Methadone Maintenance Treatment Clinics in Taiwan: An Interrupted Time Series Analysis