Efforts to Optimize Clinical Trial Management by Revising Deviation Reports and Classifying Deviation Cases for Efficient Clinical Trial Quality Improvement at Asahikawa Medical University Hospital.

Face-to-face communication during on-site monitoring is important for clinical trial quality assurance. However, with the coronavirus disease early 2020 pandemic, medical institutions placed restrictions on hospital visits to secure their medical systems. Asahikawa Medical University Hospital similarly established restrictions on outpatient and inpatient visits and legal restrictions on outside vendors. Therefore, the frequency of on-site monitoring of clinical trials conducted at our hospital was reduced. Since there was no sign of convergence at the infection units even after 2 years, we investigated the frequency of on-site monitoring and the frequency of clinical trial deviations in the review of the system. In addition, although a clinical trial deviation report form (previous form)was prepared in the fiscal year 2019, there were many free descriptions, and many deviation reports were difficult to understand. Similarly, there were cases where deviations were not recorded on the deviation report form but only on article records (source documents), such as electronic medical records after consultation with the sponsor, and deviations were not recorded in a uniform format. Thus, the hospital experienced difficulty tabulating and classifying the number of deviation occurrences. Based on this experience, this report describes the progress of revising the clinical trial deviation report, clarifying the items to be included in the report, and establishing a system to clarify the process related to clinical trial deviation occurrences.Copyright: © 2023 the Japanese Society of Clinical Pharmacology and Therapeutics (JSCPT).

If you build it, will they come? Acceptability, feasibility, and uptake of TMS-based treatment for pediatric Tourette Syndrome

Background: Transcranial magnetic stimulation (TMS) treatment holds promise for pediatric neurological and psychiatric illnesses, but little is known about the acceptability, feasibility, and uptake of experimental TMS intervention in pediatric populations. The current study aimed to identify successful recruitment strategies and participation barriers in the CBIT+TMS Trial, an ongoing clinical trial testing TMS augmentation of behavior therapy for Tourette Syndrome in 12-21 year olds. Method(s): Participation involves 10 daily treatment sessions over two weeks plus pre/post neuroimaging and clinical assessments through 3-month follow-up. Recruitment data from November 2020 - August 2022 were examined for recruitment status, recruitment source, and reason for ineligibility or non-participation. Result(s): N = 171 individuals expressed interest in participation. Of these, 53% declined or passively declined participation, 45% completed phone screening, 19% were deemed ineligible, and 18% enrolled. The most successful recruitment strategies were community flyering, sharing information through a patient support organization, and provider referrals. The most commonly stated reasons for declining participation were related to time commitment and the need to travel to in-person appointments. Notably, participation was greatest during summer months. All enrolled participants have been retained through follow-up visits. Conclusion(s): TMS treatment is of interest to youth and parents in the TS community. As a comparison, a prior TS therapy trial screened =6 youth/month across three sites (Piacentini et al., 2010), whereas our single site is screening =4 youth/month. Stated reasons for declining participation related to schedule and travel feasibility rather than concerns about TMS. This recruitment period overlapped with the COVID-19 pandemic, which likely heightened these particular barriers. Future pediatric TMS research should include efforts to maximize efficacy within protocol schedules that are feasible for youth. Continued examination of factors contributing to pediatric TMS interest and uptake can help inform developmentally sensitive intervention and clinical trial protocols. Research Category and Technology and Methods Clinical Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Tourette, Clinical Trial, Pediatric, FeasibilityCopyright © 2023

The effect of vitamin D and magnesium supplementation on clinical symptoms and serum inflammatory and oxidative stress markers in patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This study aims to evaluate the effect of vitamin D and magnesium supplementation on clinical symptoms and serum inflammatory and oxidative stress markers in patients with COVID-19. TRIAL DESIGN: This study is a 4-arm randomized, double-blind, placebo-controlled clinical trial with a factorial design and the intervention period is 3 weeks. PARTICIPANTS: This study is conducted on COVID-19 patients admitted to the Shahid Mohammadi hospital in Bandar Abbas, Iran, who are eligible for inclusion in the study. Patients are included only if they meet all of the following criteria: (1) aged from 18 to 65 years old; (2) confirmation of COVID-19 by RT-PCR test; (3) completing informed consent; (4) passing less than 48 h since the patient's hospitalization; (5) no skin or gastrointestinal allergies due to taking multivitamin supplements, vitamin D, and magnesium; and (6) having more than 30 breaths per minute and less than 93% oxygen saturation in room air and sea level. Patients are excluded if they have any of the following conditions: (1) pregnancy or lactation; (2) taking a daily multivitamin or take a vitamin D or magnesium supplement in the last month; (3) participating in other clinical trials; (4) renal failure or dialysis, severe liver disease or cirrhosis; (5) known diagnosis of hypercalcemia; (6) discharging from the hospital less than 24 h after the start of the intervention; (7) history of kidney stones in the last year; (8) transfer the patient to the ICU; (9) baseline vitamin D levels above 80 ng/ml; (10) baseline magnesium levels above 2.6 mg/dl; and (11) unwillingness of the patient to continue the study. INTERVENTION AND COMPARATOR: Participants will be randomly allocated to one of the four following groups: (A) vitamin D (two 50,000 IU capsules at the beginning of the study, two 50,000 IU capsules on the 4th day, one 50,000 IU capsule on the 11th day, and one 50,000 IU capsule on the 17th day) and magnesium supplement (300 mg/day); (B) vitamin D capsule and magnesium placebo; (C) magnesium supplement and vitamin D placebo; and (D) vitamin D placebo and magnesium placebo. MAIN OUTCOMES: The resolution of clinical symptoms (fever, dry cough, shortness of breath, headache, myalgia, oxygen saturation, and mortality rate) and interpretation of laboratory assays (CRP, MDA, TAC, WBC, neutrophils count, lymphocytes count, ratio of neutrophils to lymphocytes, levels of 25 hydroxyvitamin D and magnesium) will be assessed in the study groups. RANDOMIZATION: A computer-generated block randomization list is used for randomization. BLINDING (MASKING): Investigators and patients are blinded to group allocation and treatment. A double-blind design is achieved using matched placebos. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 104 eligible patients are randomized into four groups of 26 subjects (1:1:1:1 allocation ratio). DISCUSSION: With the rapid prevalence of COVID-19 in recent years, more attention has been paid to effective dietary supplementation to improve clinical symptoms and biochemical parameters in these patients. To our knowledge, this is the first study to evaluate the effects of vitamin D supplementation in combination with magnesium or alone with respect to this infectious disease. The findings of the current RCT will provide evidence regarding the effectiveness of dietary supplementation strategies to improve COVID-19 outcomes. TRIAL STATUS: Ethical approval of the first version of the study protocol was obtained from the medical ethics committee of Hormozgan University of Medical Sciences, Bandar Abbas, Iran on May 30, 2021 (IR.HUMS.REC.1400.085). Currently, the recruitment phase is ongoing since August 23, 2021, and is anticipated to be complete by the end of August 2022. TRIAL REGISTRATION: The study protocol was registered in the Iranian Registry of Clinical Trials ( https://www.irct.ir ; IRCT20210702051763N1) on August 14, 2021. https://www.irct.ir/trial/57413 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Reduction of Daily Moderate Alcohol Intake Predicted to Decrease Fibrosis Stage in Patients with Nonalcoholic Steatohepatitis

Background: Several recently completed clinical trials in NASH patients have included fibrosis stage reductions in 20-30% of the patients in placebo cohorts(a,b,c). The mechanisms driving these reductions have not yet been identified. Reductions of alcohol intake could be influential, as moderate alcohol intake has been shown to enhance hepatic de novo lipogenesis (d). Moreover, alcohol consumption is common in populations worldwide and has increased in some populations during the COVID-19 pandemic (e,f). NASH clinical trial protocols do not exclude moderate alcohol consumers (20-30 g/d, equivalent to 1.5-2 standard drinks/d). A quantitative systems pharmacology (QSP) model, NAFLDsym (g), was employed to test the hypothesis that reductions in daily moderate alcohol intake could reduce liver lipid burden, lipotoxicity, and fibrosis stage in NASH patients. Method(s): NASH SimCohorts (n=50;liver fat = 22+/-7%, ALT = 48+/-10 U/L, fibrosis stage 3) regularly consuming 30 g/d alcohol were used to simulate reductions in daily alcohol intake. Baseline alcohol administration was simulated as two 15 g drinks over one hour, coincident with the dinner meal. GastroPlus was used to simulate the rate of hepatic metabolism. Consistent with previous reports, 20% of the metabolized alcohol was able to contribute to hepatic de novo lipogenesis in the simulations (d,h). Reductions of alcohol intake to 15 g/d or 0 g/d were simulated for 52weeks in the SimCohorts, with changes in liver fat, plasma ALT, and fibrosis stage predicted. Result(s): Decreased alcohol intake elicited fibrosis stage reductions, with a greater frequency of patients with an improved fibrosis stage in the 0 g/d vs. 15 g/d simulations. Twentyfour-hour average de novo lipogenesis was predicted to decline 56+/-8% and 30+/-5% in the 0 g/d or 15 g/d simulations. Liver fat was predicted to decrease 5+/-3% and 1+/-1% and ALT decreased 10 +/-7 % and 1+/-1% when alcohol intake was reduced to 0 or 15 g/d, respectively. Conclusion(s): Reductions in moderate alcohol intake for NASH patients who are regular consumers may lead to improvements in fibrosis stage due to decreased de novo lipogenesis. This behavioral adjustment may influence the frequency of observed fibrosis stage reductions in clinical trials whether on placebo or treatment, particularly in studies conducted in regions with a higher prevalence of moderate alcohol consumption. a Newsome 2021 b Francque 2022 c Harrison 2022 d Siler 1999 e Holmes 2017 f Pelham 2022 g Siler 2022 h Lundquist 1962.

The 5-Cog paradigm to improve detection of cognitive impairment and dementia: clinical trial protocol.

Cognitive impairment related to dementia is under-diagnosed in primary care despite availability of numerous cognitive assessment tools; under-diagnosis is more prevalent for members of racial and ethnic minority groups. Clinical decision-support systems may improve rates of primary care providers responding to positive cognitive assessments with appropriate follow-up. The 5-Cog study is a randomized controlled trial in 1200 predominantly Black and Hispanic older adults from an urban underserved community who are presenting to primary care with cognitive concerns. The study will validate a novel 5-minute cognitive assessment coupled with an electronic medical record-embedded decision tree to overcome the barriers of current cognitive assessment paradigms in primary care and facilitate improved dementia care.

Dementia is common, though under-recognized, in older adults (OAs). Primary care providers (PCPs) miss opportunities to help patients and their families manage the disease because of failure to, or delay to, make an appropriate diagnosis. Black and Hispanic OAs are more likely than White OAs to experience delayed diagnosis. Most available memory tests are too long for practical use by PCPs, and are ill suited to patients of diverse language, cultural and educational backgrounds. Studies have shown that even when patients test positive for dementia in primary care, PCPs often do not take follow-up action. Our improved memory test, the 5-Cog, is brief (5 min), not biased by language issues (uses pictures and symbols instead of words), and simple (doesn't require expensive technology and complex staff training). The 5-Cog is paired with a clinical decision support tool, providing tailored recommendations directly into the patient's medical record, and making it easier for PCPs to take appropriate action. This study will evaluate whether the 5-Cog paradigm results in improved dementia care.

Reports of clinical trial protocols of coronavirus disease 2019: A systematic review

Background: To examine the outcomes heterogeneity of clinical trial protocols of coronavirus disease 2019 (COVID-19) to prioritize the establishment of a core outcome set. Methods: Databases of the International Committee of Medical Journal Editors - accepted clinical trial registry platforms were searched on February 14, 2020 and May 31, 2020. Randomized controlled trials and non-randomized controlled trials of COVID-19 were considered. Patient condition was classified as common, severe, or critical. Interventions included traditional Chinese medicine and Western medicine. We excluded trials that involved discharged patients, psychological intervention, and complications of COVID-19. The general information and outcomes, outcome measurement instruments, and measurement times were extracted. The results were analyzed by descriptive analysis. Results: In all, 19 registry platforms were searched. A total of 97 protocols were selected from among 160 protocols for the first search. For protocols of traditional Chinese medicine clinical trials, 76 outcomes from 16 outcome domains were reported, and almost half (34/76, 44.74%) of the outcomes were reported only once;the most frequently reported outcome was time taken for severe acute respiratory syndrome coronavirus 2 RNA to become negative. Twenty-seven (27/76, 35.53%) outcomes provided one or more outcome measurement instruments. Ten outcomes provided one or more measurement time frame. For protocols of Western medicine clinical trials, 126 outcomes from 17 outcome domains were reported;almost half (62/126, 49.21%) of the outcomes were reported only once;the most frequently reported outcome was proportion of patients with negative severe acute respiratory syndrome coronavirus 2. Twenty-seven outcomes provided one or more outcome measurement instruments. Forty (40/126, 31.75%) outcomes provided one or more measurement time frame. There were > 40 duplicated outcomes between the clinical trials protocols of traditional Chinese medicine and western medicine protocols. All of them were included in the Delphi survey when developing core outcome set for COVID-19. A total of 1,027 protocols were selected from 2,741 protocols for the second search. Forty-two new outcomes and 47 new outcome measurement instruments were reported. Conclusion: Outcome reporting in clinical trial protocols of COVID-19 is inconsistent. Thus, establishing a core outcome set is necessary for diagnosis and management.

Protocol of a randomized controlled trial investigating the effectiveness of Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS).

RATIONALE: To address unmet needs, electronic messages to support person-centered goal attainment and secondary prevention may avoid hospital presentations/readmissions after stroke, but evidence is limited. HYPOTHESIS: Compared to control participants, there will be a 10% lower proportion of intervention participants who represent to hospital (emergency/admission) within 90 days of randomization. METHODS AND DESIGN: Multicenter, double-blind, randomized controlled trial with intention-to-treat analysis. The intervention group receives 12 weeks of personalized, goal-centered, and administrative electronic messages, while the control group only receive administrative messages. The trial includes a process evaluation, assessment of treatment fidelity, and an economic evaluation. Participants: Confirmed stroke (modified Rankin Score: 0-4), aged ≥18 years with internet/mobile phone access, discharged directly home from hospital. Randomization: 1:1 computer-generated, stratified by age and baseline disability. Outcomes assessments: Collected at 90 days and 12 months following randomization. OUTCOMES: Primary outcomes include hospital emergency presentations/admissions within 90 days of randomization. Secondary outcomes include goal attainment, self-efficacy, mood, unmet needs, disability, quality-of-life, recurrent stroke/cardiovascular events/deaths at 90 days and 12 months, and death and cost-effectiveness at 12 months. Sample size: To test our primary hypothesis, we estimated a sample size of 890 participants (445 per group) with 80% power and two-tailed significance threshold of α = 0.05. Given uncertainty for the effect size of this novel intervention, the sample size will be adaptively re-estimated when outcomes for n = 668 are obtained, with maximum sample capped at 1100. DISCUSSION: We will provide new evidence on the potential effectiveness, implementation, and cost-effectiveness of a tailored eHealth intervention for survivors of stroke.

A SMARTTT approach to Treating Tobacco use disorder in persons with HIV (SMARTTT): Rationale and design for a hybrid type 1 effectiveness-implementation study.

BACKGROUND: Tobacco use disorder is a leading threat to the health of persons with HIV (PWH) on antiretroviral treatment and identifying optimal treatment approaches to promote abstinence is critical. We describe the rationale, aims, and design for a new study, "A SMART Approach to Treating Tobacco Use Disorder in Persons with HIV (SMARTTT)," a sequential multiple assignment randomized trial. METHODS: In HIV clinics within three health systems in the northeastern United States, PWH with tobacco use disorder are randomized to nicotine replacement therapy (NRT) with or without contingency management (NRT vs. NRT + CM). Participants with response (defined as exhaled carbon monoxide (eCO)-confirmed smoking abstinence at week 12), continue the same treatment for another 12 weeks. Participants with non-response, are re-randomized to either switch medications from NRT to varenicline or intensify treatment to a higher CM reward schedule. Interventions are delivered by clinical pharmacists embedded in HIV clinics. The primary outcome is eCO-confirmed smoking abstinence; secondary outcomes include CD4 cell count, HIV viral load suppression, and the Veterans Aging Cohort Study (VACS) Index 2.0 score (a validated measure of morbidity and mortality based on laboratory data). Consistent with a hybrid type 1 effectiveness-implementation design and grounded in implementation science frameworks, we will conduct an implementation-focused process evaluation in parallel. Study protocol adaptations related to the COVID-19 pandemic have been made. CONCLUSIONS: SMARTTT is expected to generate novel findings regarding the impact, cost, and implementation of an adaptive clinical pharmacist-delivered intervention involving medications and CM to promote smoking abstinence among PWH. ClinicalTrials.govidentifier:NCT04490057.

Characteristics of registered clinical trials on traditional Chinese medicine for coronavirus disease 2019 (COVID-19): A scoping review.

INTRODUCTION: Traditional Chinese medicine (TCM) has been fully committed to the treatment of coronavirus disease 2019 (COVID-19) in China. An increasing number of clinical trials have been registered to evaluate the effects of TCM for COVID-19. The aim of this study was to review the existing TCM clinical trial registrations and identify potentially promising and available TCM therapies, in order to provide a reference for the global management of COVID-19. METHODS: All clinical trials on TCM for COVID-19 registered in registry platforms worldwide were searched. The data of registration temporal trend, design, objective, interventions, and relevant information were reviewed and summarized. RESULTS: 161 TCM trials were identified from three registries (January 26 to May 14 2020,). Of these, 94 (58.4%) were randomized controlled trials and 114 trials (70.8%) assessed therapeutic effects; while the remainder focused on prevention, rehabilitation, and the epidemiology of TCM syndromes. Eight trials (5.0%) had completed their recruitment. TCM interventions with potential for further evaluation in terms of prevention were moxibustion, Huoxiang Zhengqi pill and Jinye Baidu granules. For treatment of COVID-19, Qingfei Paidu decoction, Huashi Baidu decoction, Lianhua Qingwen capsules, Toujie Quwen granules and Xiyanping injection, and Xuebijing injection were to be tested for their therapeutic effects and symptoms relief. For rehabilitation, Tai Chi and Liuzijue were to be tested for improving patients' lung function. CONCLUSION: Some potentially promising TCM interventions have been identified and deserve further evaluation to establish their evidence base, particularly on populations outside of China.

Feasibility, Reliability, and Value of Remote Video-Based Trial Visits in Parkinson's Disease.

BACKGROUND: There is rising interest in remote clinical trial assessments, particularly in the setting of the COVID-19 pandemic. OBJECTIVE: To demonstrate the feasibility, reliability, and value of remote visits in a phase III clinical trial of individuals with Parkinson's disease. METHODS: We invited individuals with Parkinson's disease enrolled in a phase III clinical trial (STEADY-PD III) to enroll in a sub-study of remote video-based visits. Participants completed three remote visits over one year within four weeks of an in-person visit and completed assessments performed during the remote visit. We evaluated the ability to complete scheduled assessments remotely; agreement between remote and in-person outcome measures; and opinions of remote visits. RESULTS: We enrolled 40 participants (mean (SD) age 64.3 (10.4), 29% women), and 38 (95%) completed all remote visits. There was excellent correlation (ICC 0.81-0.87) between remote and in-person patient-reported outcomes, and moderate correlation (ICC 0.43-0.51) between remote and in-person motor assessments. On average, remote visits took around one quarter of the time of in-person visits (54 vs 190 minutes). Nearly all participants liked remote visits, and three-quarters said they would be more likely to participate in future trials if some visits could be conducted remotely. CONCLUSION: Remote visits are feasible and reliable in a phase III clinical trial of individuals with early, untreated Parkinson's disease. These visits are shorter, reduce participant burden, and enable safe conduct of research visits, which is especially important in the COVID-19 pandemic.