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BackgroundDesigning and conducting randomized controlled trials is not possible for some institutions and researchers due to their associated costs and personnel requirements. Advances in telehealth for patient care and clinical trial methods adaptations were hastened due to the coronavirus 2019 pandemic. We conducted subject recruitment, screening, informed consent, study product distribution, and data collection remotely using Research Electronic Data Capture (REDCap) and other readily available applications for a prospective randomized clinical trial on vitamin D3 supplementation to prevent influenza-like illness in healthcare workers.ObjectivesTo describe how to efficiently and cost-effectively conduct a randomized clinical trial using remote and semi-automated methods.MethodsA previously described prospective, controlled, trial in healthcare workers at a tertiary university hospital that used Zelen’s design to facilitate enrollment is used as a model. A random group of healthcare workers were invited to participate in the study through email. Following an automated process, interested individuals could schedule a HIPAA compliant, video-facilitated consent interview. Following e-consenting, participants received vitamin D3 supplementation bottles by mail and electronic surveys via email. Adherence to the study intervention was monitored through survey data review and vitamin D3 safety was monitored via real-time automated warnings to study staff if any symptoms, health changes, hospitalizations, or pregnancies were reported on monthly surveys.ResultsA small study staff of 10 team members were able to screen 406 subjects and enroll 299 subjects over a 3-month period using completely remote methods. Adherence to vitamin D3 supplementation was high (87%) over 9 months. Survey data completeness was 98.5% over 9 months. Participants and study staff scored the system usability 93.8% and 90%, respectively. The automated and remote methods allowed the study maintenance period to be managed by a small study team staff of 2 members while safety monitoring was conducted by 3-4 team members.ConclusionsThe remote and automated methods developed to conduct a randomized controlled trial produced efficient subject recruitment with excellent study product adherence and data completeness. These methods can significantly minimize costs and time without sacrificing safety or quality, thereby offering greater equity in scientific research. We share our XML file for researchers to use as a template for learning purposes or designing their own clinical trials.Trial RegistrationNCT04596657

ImportanceVitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers.ObjectiveThe aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers.DesignWe conducted an open label, randomized clinical trial wherein a random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare workers served as passive controls. All healthcare workers were required to self-monitor and report to employee health for COVID-19 testing when experiencing symptoms of ILI. COVID-19 test results were retrieved.SettingThe trial was conducted at a tertiary university hospital.ParticipantsOut of 7,600 healthcare workers, two groups of 4,708 and 2,892 subjects were pre-randomized to the vitamin D3 intervention and passive control groups, respectively. Out of 4,708 intervention subjects approached, 299 with no history of hypercalcemia or nephrolithiasis were enrolled. Subjects who completed at least 2 months of supplementation to ensure adequate vitamin D levels were included in the analysis (n=255).InterventionDaily oral vitamin D3 gel capsules at 5000 IU for 9 months.Main Outcome and MeasureThe primary analysis compared the incidence rate of all ILI, while secondary analyses examined incidence rates of COVID-19 ILI and non-COVID-19 ILI. Incidence rates were compared between the vitamin D and control groups.ResultsBetween October 2020 and November 2021, 255 healthcare workers (age 47±12 years, 199 women) completed at least two months of vitamin D3 supplementation. Five subjects were withdrawn due to adverse effects. The control group consisted of 2,827 workers. Vitamin D3 5000 IU supplementation was associated with lower risk of ILI (incidence rate difference: - 1.7×10-4/person-day, 95%-CI: -3.0×10-4 to -3.3×10-5/person-day, P = 0.015) and a lower incidence rate for non-COVID-19 ILI (incidence rate difference: -1.3×10-4/person-day, 95%-CI - 2.5×10-4 to -7.1×10-6 /person-day, P = 0.038). COVID-19 ILI incidence was not statistically different (incidence rate difference: -4.2×10-5/person-day, 95%-CI: -10.0×10-5 to 1.5×10-5/person-day, P = 0.152). An intention-to-treat analysis could not be performed due to low enrollment in the pre-randomized intervention group.Conclusion and RelevanceDaily supplementation with 5000 IU vitamin D3 reduces influenza-like illness in healthcare workers.Trial RegistrationClinicaltrials.gov, NCT04596657Key PointsQuestionCan 5,000 IU of daily vitamin D3 prevent influenza-like illness in healthcare workers?FindingsIn this randomized controlled trial, 5,000 IU of once daily vitamin D3 over a 9-month period revealed that vitamin D3 supplementation was associated with a statistically significant lower risk of influenza-like illness (incidence rate difference -1.7 × 10-4 / person-day, 95%-CI - 3.0 × 10-4 to -3.3 × 10-5 / person-day, P = 0.0147).MeaningDaily supplementation with 5,000 IU vitamin D3 reduces influenza-like illness in healthcare workers.

Vitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers. The aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers. We conducted a prospective, controlled trial at a tertiary university hospital. A random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare system workers served as controls. All healthcare workers were required to self-monitor and report to employee health for COVID-19 testing when experiencing symptoms of ILI. COVID-19 test results were retrieved. Incidence rates were compared between the vitamin D and control groups. Workers in the intervention group were included in the analysis if they completed at least 2 months of supplementation to ensure adequate vitamin D levels. The primary analysis compared the incidence rate of all ILI, while secondary analyses examined incidence rates of COVID-19 ILI and non-COVID-19 ILI. Between October 2020 and November 2021, 255 healthcare workers (age 47 ± 12 years, 199 women) completed at least two months of vitamin D3 supplementation. The control group consisted of 2827 workers. Vitamin D3 5000 IU supplementation was associated with a lower risk of ILI (incidence rate difference: −1.7 × 10−4/person-day, 95%-CI: −3.0 × 10−4 to −3.3 × 10−5/person-day, p = 0.015) and a lower incidence rate for non-COVID-19 ILI (incidence rate difference: −1.3 × 10−4/person-day, 95%-CI −2.5 × 10−4 to −7.1 × 10−6/person-day, p = 0.038). COVID-19 ILI incidence was not statistically different (incidence rate difference: −4.2 × 10−5/person-day, 95%-CI: −10.0 × 10−5 to 1.5 × 10−5/person-day, p = 0.152). Daily supplementation with 5000 IU vitamin D3 reduces influenza-like illness in healthcare workers.

Objectives To present a meta-analysis of the efficacy and safety data of two recently completed Phase II studies examining a novel alprostadil topical cream for the treatment of erectile dysfunction (ED). Methods Patients (n = 303) with ED of at least 3 months’ duration were randomized to receive placebo or 50, 100, 200, or 300 μg alprostadil in two nearly identical 11-dose, multicenter, at-home studies of a novel topical cream containing alprostadil and a proprietary skin permeation enhancer. The primary efficacy endpoint was the change in erectile function domain score from baseline to the final visit. Secondary endpoints included changes in scores for questions 3 and 4 of the International Index of Erectile Function and standard diary analyses. Safety was assessed by analysis of adverse events, changes in laboratory test results, and physical examination findings. Results The mean baseline parameters for the erectile function score, ED history, and secondary diagnoses suggested no significant differences among the treatment groups. The changes from baseline to the final visit erectile function scores were 0.98 ± 0.84, 3.4 ± 1.3, 3.4 ± 0.88 (P