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The phytocannabinoid cannabinol (CBN) has a potential mechanism of action as an alternative sleep aid but there is minimal evidence to support its effectiveness. The aim of this randomized, double-blind, placebo-controlled study was to assess the safety and effects of three formulations of a hemp-derived CBN sleep aid, TruCBN™ [25 mg (n = 206), 50 mg (n = 205), 100 mg (n = 203)], on sleep quality (PROMIS Sleep Disturbance 8A), relative to placebo (n = 204). The effectiveness and safety of these formulations relative to 4 mg of melatonin (n = 202) was assessed. Exploratory measures were stress (PROMIS Stress 4A), anxiety (Anxiety 4A), pain (PROMIS™ PEG), and well-being (WHO 5). All groups and the 4 mg melatonin group experienced significant improvement in sleep quality relative to the placebo group with no significant differences between any group and the melatonin group. Participants taking 100 mg showed a larger decrease in stress compared to the placebo group. There were no significant differences in anxiety, pain, well-being, or the frequency of side effects between any group and the placebo group. There was no significant difference in improvements in sleep quality between any of the treatment groups and the 4 mg melatonin group. Orally ingested CBN, at 25 mg, 50 mg, and 100 mg, is a safe and effective alternative for the improvement of sleep.

This study describes decentralized recruitment and enrollment for a COVID-19 treatment trial, while comparing 5 primary recruitment methods: search engine ads, paid advertising within a national testing company, paid advertising within a regional testing company, electronic health record messages, and word of mouth. These are compared across patient demographics, efficiency, and cost. Clinical Trials Registration NCT04510194. [ABSTRACT FROM AUTHOR]

Aim: Patients with cancer experience various forms of psychological distress, including depressive symptoms, which can impact quality of life, elevate morbidity risk, and increase medical costs. Psychotherapy and pharmacotherapy are effective for reducing depressive symptoms among patients with cancer, but most patients prefer psychotherapy. This study aimed to develop an efficient and effective smartphone psychotherapy component to address depressive symptom. Methods: This was a decentralized, parallel‐group, multicenter, open, individually randomized, fully factorial trial. Patients aged ≥20 years with cancer were randomized by the presence/absence of three cognitive‐behavioral therapy (CBT) skills (behavioral activation [BA], assertiveness training [AT], and problem‐solving [PS]) on a smartphone app. All participants received psychoeducation (PE). The primary outcome was change in the patient health questionnaire‐9 (PHQ‐9) total score between baseline and week 8. Secondary outcomes included anxiety. Results: In total, 359 participants were randomized. Primary outcome data at week 8 were obtained for 355 participants (99%). The week 8 PHQ‐9 total score was significantly reduced from baseline for all participants by −1.41 points (95% confidence interval [CI] −1.89, −0.92), but between‐group differences in change scores were not significant (BA: −0.04, 95% CI −0.75, 0.67; AT: −0.16, 95% CI −0.87, 0.55; PS: −0.19, 95% CI −0.90, 0.52). Conclusion: As the presence of any of the three intervention components did not contribute to a significant additive reduction of depressive symptoms, we cannot make evidence‐based recommendations regarding the use of specific smartphone psychotherapy. [ABSTRACT FROM AUTHOR]

Aims: Insights into the current practice of direct‐to‐participant (DtP) supply of investigational medicinal product (IMP) in the context of clinical trials conducted in Europe are needed, as regulations are unharmonized. This study is set out to explore how DtP IMP supply has been employed in Europe and what the advantages and disadvantages and barriers and facilitators of its implementation are. Methods: We conducted semi‐structured interviews with representatives from sponsor companies, courier services and site study staff involved in the IMP dispensing and delivery process in Europe. Interviews were conducted between May and November 2021, and data were analysed following thematic analysis. Results: Sixteen respondents participated in one of the 12 interviews. Respondents had experience with different models of DtP IMP supply including shipment from the investigative site, a central pharmacy (a depot under the control of a pharmacist) and a local pharmacy—aiming to reduce trial participation burden. The respondents indicated that investigative site‐to‐participant shipment is not affected by regulatory barriers, but could burden site staff. Shipment from central locations was considered most efficient, but possible regulatory barriers related to maintaining participants' privacy and investigator oversight were identified. The respondents indicated that the involvement of local pharmacies to dispense IMP can be considered when the IMP is authorized. Conclusions: Several DtP IMP supply models are implemented in clinical trials conducted in Europe. In this study, three main DtP IMP models were identified, which can be referenced when describing these approaches for regulatory approval. [ABSTRACT FROM AUTHOR]

The phytocannabinoid cannabinol (CBN) has a potential mechanism of action as an alternative sleep aid but there is minimal evidence to support its effectiveness. The aim of this randomized, double-blind, placebo-controlled study was to assess the safety and effects of three formulations of a hemp-derived CBN sleep aid, TruCBN™ [25 mg (n = 206), 50 mg (n = 205), 100 mg (n = 203)], on sleep quality (PROMIS Sleep Disturbance 8A), relative to placebo (n = 204). The effectiveness and safety of these formulations relative to 4 mg of melatonin (n = 202) was assessed. Exploratory measures were stress (PROMIS Stress 4A), anxiety (Anxiety 4A), pain (PROMIS™ PEG), and well-being (WHO 5). All groups and the 4 mg melatonin group experienced significant improvement in sleep quality relative to the placebo group with no significant differences between any group and the melatonin group. Participants taking 100 mg showed a larger decrease in stress compared to the placebo group. There were no significant differences in anxiety, pain, well-being, or the frequency of side effects between any group and the placebo group. There was no significant difference in improvements in sleep quality between any of the treatment groups and the 4 mg melatonin group. Orally ingested CBN, at 25 mg, 50 mg, and 100 mg, is a safe and effective alternative for the improvement of sleep.

Abstract Introduction: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety. Methods: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites. Results: We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites. Conclusion: The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

Connected health technology is playing an increasingly important role in healthcare. The power, complexity, functionality, and accessibility of connected health technologies are increasing rapidly, showing promise for improved and more equitable healthcare outcomes. They are integral to the lifecycle of medical products, from discovery and development to manufacturing and ultimately to the patient. The spectrum of integration between medical products and digital technologies ranges from non-drug specific solutions for supporting adherence or patient monitoring, which may or may not require regulatory approval, to digital therapeutics and software-containing combination products, which make claims supported by clinical evidence. The exponential increase and rapid evolution of connected health technologies – and the accompanying possibilities for innovative healthcare interventions, delivery systems, and clinical trial designs – pose new and complicated regulatory challenges. Currently, connected health may involve the use of regulated medical devices, including software as a medical device, or consumer products, such as wearables or apps, that fall under regulatory discretion. In this paper we examine how connected health technologies intersect with the development and lifecycle of medical products, how they are impacted by existing regulatory frameworks in the US, EU, and China, and propose future focus areas of activity.

Introduction/Background Atopic dermatitis (AD) is a chronic, relapsing, remitting, pruritic inflammatory skin disease that often manifests in sensitive regions, including the facial/neck region. Although topical therapies are the mainstay of treatment, AD localized to the facial/neck region can be challenging to treat. Thus, there is a need for effective topical therapies for the treatment of facial/neck AD. Objectives Here we describe results from a randomized, double-blind, vehicle-controlled decentralized phase 2 study evaluating the efficacy and safety of 1.5% ruxolitinib cream in adolescent and adult patients with facial and/or neck AD (NCT05127421). Methods Eligible patients aged 12–70 years with AD for ≥6 months, an Investigator's Global Assessment (IGA) score of 2 or 3 (overall and in the facial/neck region excluding the scalp), and ≤20% affected total body surface area (BSA; with ≥0.5% on the facial/neck region) were randomized 2:1 to apply twice-daily 1.5% ruxolitinib cream or vehicle continuously for 4 weeks (vehicle-controlled [VC] period). After Week 4, patients (regardless of initial randomization group) with no safety concerns applied ruxolitinib cream (open label) as needed for 4 weeks. Efficacy was assessed by a dermatologist/central reader using digital photographs captured by a mobile healthcare provider. The primary endpoint was the proportion of patients who achieved ≥75% improvement in Eczema Area and Severity Index (EASI-75) in the head/neck region at Week 4. Secondary endpoints included the proportion of patients who achieved overall EASI-75 and safety (frequency and severity of treatment-emergent adverse events [TEAEs]). Exploratory endpoints included the proportion of patients who achieved an IGA score of 0/1 or IGA treatment success (IGA-TS; IGA score of 0/1 with ≥2-point improvement from baseline) in the facial/neck region and overall. Patients with missing values were imputed as nonresponders for the primary endpoint. Results Overall, 77 patients were randomized (1.5% ruxolitinib cream, n=54; vehicle, n=23); 66 patients (85.7%) completed the VC period. The median age was 38.0 years (range, 17–66 y), 80.5% of patients were female, and 44.2% were Black. At baseline, mean (SD) overall and head/neck EASI scores were 4.0 (2.5) and 1.2 (0.7), respectively. Mean (SD) overall and head/neck BSA were 5.4% (4.0%) and 2.1% (1.3%), and 67.5% and 64.9% of patients had overall and facial/neck IGA scores of 3, respectively. A greater proportion of patients randomized to ruxolitinib cream vs vehicle achieved head/neck EASI-75 at Week 4 (37.0% [20/54] vs 17.4% [4/23], respectively); however, this difference was not statistically significant (P =0.091). The proportion of patients who achieved overall EASI-75 was similar between treatment groups at Week 4 (ruxolitinib cream, 29.2% [14/48]; vehicle, 33.3% [6/18]). At Week 4, more patients who applied ruxolitinib cream vs vehicle achieved facial/neck IGA-TS (41.7% [20/48] vs 11.1% [2/18], respectively) and overall IGA-TS (29.2% [14/48] vs 11.1% [2/18]) as well as a facial/neck IGA score of 0/1 (58.3% [28/48] vs 16.7% [3/18]). EASI-75 and IGA-TS improvements (overall and facial/neck) continued through Week 8 among patients who applied ruxolitinib cream from Day 1. During the VC period, TEAEs were reported in 6 patients (11.1%) who applied ruxolitinib cream vs 5 patients (21.7%) who applied vehicle. Application-site reactions were infrequent during the VC period (ruxolitinib cream, 1.9% [n=1]; vehicle, 8.7% [n=2]), and none were reported during the open-label period. No serious TEAEs or discontinuations due to TEAEs were reported among patients who applied ruxolitinib cream. Conclusions In this phase 2 decentralized study evaluating twice-daily ruxolitinib cream for the treatment of facial and/or neck AD, more patients who applied ruxolitinib cream vs vehicle achieved head/neck EASI-75 and facial/neck IGA-TS. Ruxolitinib cream was well tolerated with no serious TEAEs. [ABSTRACT FROM AUTHOR]

Clinical trials are an essential source of high-quality evidence for the assessment of efficacy and safety of healthcare interventions. Nowadays the main criticality of the traditional clinical trial model is perhaps the need to improve patient selection and management, in terms of initial identification, recruitment and retention. Digital technology offers operational solutions that can facilitate many of the activities involved in clinical investigation. Decentralized Clinical Trials (DCTs) could be a new option that provides for the use of remote instruments/methods/activities in the different stages of a clinical trial, so that a range of procedures (such as informed consent, medical visits, administration of a drug or use of a medical device, measurement of clinical parameters, diagnostic testing etc.) can be moved from the research hospital to the patient’s home. Also in Italy the interest in DCTs is progressively growing, and thanks to their potential benefits DCTs can lead to significant advantages not only for patients, but also for the National Health Service and for the country as a whole. It is important that this interest should act as a stimulus, prompting timely initiatives in order to promote and regulate this new methodology for conduct of clinical trials to avoid the risk that, while other countries will be actively involved in the promotion and leading of DCTs, Italy will be selected only as “control arm”.

The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.

Patient recruitment, diversity, and retention continue to impede successful and representative clinical studies. This systematic review aims to assess the impact of decentralized methods on recruitment, retention, and diversity in recent clinical studies. A systematic search of literature reporting on recruitment in decentralized clinical studies was performed. Studies were reviewed for those reporting the primary outcome of recruitment in decentralized clinical trials, observational studies, or those covering the topic of clinical trials. Secondary outcomes included retention, participant diversity, and participant satisfaction. This systematic search returned 13 studies highlighting the role of decentralized methods impacting participant recruitment, retention, and diversity in clinical studies. Eleven reported improved recruitment using decentralized methods. Seven of these reported improvements directly compared to traditional methods. Seven studies reported positive retention outcomes, with four directly comparing decentralized methods with traditional methods. Six studies were reported to have trended toward increased diversity in the demographics of the sample population, including race or geographic location. Related reviews have stated a lack of published comparable data to determine if decentralized clinical methods improved recruitment and retention. Results suggest this review addresses such a gap, providing data on how decentralized methods such as virtual visits can positively impact recruitment and retention.

The International Rare Diseases Research Consortium (IRDiRC) Telehealth (TH) Task Force explored the use of TH for improving diagnosis, care, research, and education for rare diseases (RDs). The Task Force reviewed related literature published from January 2017 to August 2023, and identified various models and implementation strategies of TH for RD. The Task Force highlighted the reported value and benefits of using TH for RDs, along with the limitations and opportunities. The number of publications sharply increased since 2021, coinciding with the onset of the COVID-19 pandemic, which forced the rapid adoption of TH in many healthcare settings. One of the major benefits of TH for RDs lies in its capacity to surmount geographical barriers, which helps in overcoming the constraints posed by limited numbers and geographical dispersion of specialists. This was evident during the pandemic when TH was used to maintain a level of continued medical care and research when face-to-face visits were severely restricted. TH, through which clinical research can be decentralized, can also facilitate and enhance RD research by decreasing burden, expanding access, and enhancing efficiency. This will be especially beneficial when coupled with the adoption of digital health technologies, such as mobile health (mHealth) and wearable devices for remote monitoring (i.e., surveillance of outpatient data transmitted through devices), along with big data solutions. TH has also been shown to be an effective means for RD education and peer mentoring, enabling local health care providers (HCPs) to care for RD patients, which indirectly ensures that RD patients get the expertise and multidisciplinary care they need. However, limitations and weaknesses associated with using TH for RD care and research were also identified, including the inability to perform physical examinations and build relationships with HCPs. Therefore, TH has been recommended as a complement to, rather than substitute for, face-to-face consultations. There is also a concern that TH may lead to an amplification of health disparities and inequities related to social determinants of health for those with RDs due to lack of access to TH technologies, inadequate digital literacy, and geographical, socio-cultural, and linguistic barriers. Finally, the Task Force also discussed evidence and knowledge gaps that will benefit from future research efforts to help advance and expand the use of TH for RD care, research, and education., (Copyright © 2024. Published by Elsevier Masson SAS.)

BackgroundThe need for a new style of clinical trials, called decentralized clinical trials (DCTs), has been increasing as they do not depend on physical visits to clinical sites. DCTs are expected to provide a new opportunity to patients who cannot participate in a clinical trial due to geographical and time limitations. For the adoption of DCTs, it is essential that medical devices with Internet of Medical Things (IoMT) and Internet of Health Things (IoHT) based technologies are developed and commercially adopted. In this study, we aimed to identify the regulatory considerations when IoMT/IoHT-based technologies are used in DCTs or products developed using DCTs.MethodTo understand the study and development field of IoMT/IoHT comprehensively and panoramically, relevant papers published in Web of Science were searched online. Subsequently, a citation network was obtained and characterized as a cluster using a text mining method to identify IoMT/IoHT-based technologies expected to be utilized in DCTs or products developed using DCTs.Result and DiscussionUpon analysis of the top 15 clusters and subsequent 51 sub-clusters, we identified the therapeutic areas (psychology, neurology) and IoMT/IoHT-based technologies (telemedicine, remote monitoring, and virtual reality) that are expected to be used in DCTs. We also identified several considerations based on the current regulatory guidance.ConclusionIoMT/IoHT-based technologies that are expected to be used or products developed using DCTs and key considerations made when they are used in DCTs were identified. The considerations could encourage conducting DCTs using IoMT/IoHT-based technologies.

Fear of cancer recurrence (FCR) is a common and distressing condition among adolescents and young adults (AYAs). This study aims to investigate the efficacy of digital interventions, including distress screening-based information provision and smartphone problem-solving therapy, on common psychological distress, especially FCR, in AYA patients with cancer. Participants will be 224 AYA outpatients with cancer aged 15-39 years who will be randomly assigned to either an 8-week smartphone-based intervention or a waitlist control group. This intervention includes smartphone-based distress screening, information provision, and psychotherapy (problem-solving therapy). The primary endpoint will be the Fear of Cancer Recurrence Inventory-Short Form score at week 8. This study will be conducted as a fully decentralized, randomized, and multicenter trial. The study protocol was approved by the Institutional Review Board of Nagoya City University on 19 April 2024 (ID: 46-23-0005). Trial registration: UMIN-CTR: UMIN000054583., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study aims to evaluate the effect of an adaptive nutritional and educational intervention for patients on hemodialysis (HD) in a routine care setting, using real-world data from electronic health records., Methods: Decentralized clinical trial of seven HD facilities recruited patients who have been on HD for over 3 months (N = 153) for an 8-week adaptive intervention protocol. Patients were divided into four groups: (1) control (2) education intervention (3) meal intervention (4) education and meal interventions. Educational contents were digitally delivered via mobile phones and premade meals tailored on laboratory findings were home-delivered. Changes in serum electrolytes and malnutrition inflammation score (MIS) were analyzed., Results: Meal intervention statistically significantly stabilized serum phosphorus level (β = -0.81 mg/dL, 95% confidence interval = [-1.40, -0.22]) at week 8, with increased likelihood of being within target serum value range (odds ratio = 1.21, 95% confidence interval = [1.04, 1.40]). Meal group showed better nutritional status (MIS = 3.65) than the education group (MIS = 5.10) at week 8 (adjusted p < .05). No significant changes were observed in serum potassium level, depression, and self-efficacy., Conclusion: It was demonstrated that an adaptive meal intervention in a real-world care setting may benefit serum phosphorus control and nutritional status of patients on HD, without negative effect on depression levels or self-efficacy. More work is needed to develop an effective educational intervention., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT's are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment., Competing Interests: The fluvoxamine placebo tablets were donated by the Apotex pharmacy. The ivermectin placebo and active tablets were donated by the Edenbridge pharmacy. The funders had no influence on the design or conduct of the trial and were not involved in data collection or analysis, writing of the manuscript, or decision to submit for publication. The authors assume responsibility for trial fidelity and the accuracy and completeness of the data and analyses., (© The Author(s) 2023.)

Patient recruitment, diversity, and retention continue to impede successful and representative clinical studies. This systematic review aims to assess the impact of decentralized methods on recruitment, retention, and diversity in recent clinical studies. A systematic search of literature reporting on recruitment in decentralized clinical studies was performed. Studies were reviewed for those reporting the primary outcome of recruitment in decentralized clinical trials, observational studies, or those covering the topic of clinical trials. Secondary outcomes included retention, participant diversity, and participant satisfaction. This systematic search returned 13 studies highlighting the role of decentralized methods impacting participant recruitment, retention, and diversity in clinical studies. Eleven reported improved recruitment using decentralized methods. Seven of these reported improvements directly compared to traditional methods. Seven studies reported positive retention outcomes, with four directly comparing decentralized methods with traditional methods. Six studies were reported to have trended toward increased diversity in the demographics of the sample population, including race or geographic location. Related reviews have stated a lack of published comparable data to determine if decentralized clinical methods improved recruitment and retention. Results suggest this review addresses such a gap, providing data on how decentralized methods such as virtual visits can positively impact recruitment and retention., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2023.)

Connected health technology is playing an increasingly important role in healthcare. The power, complexity, functionality, and accessibility of connected health technologies are increasing rapidly, showing promise for improved and more equitable healthcare outcomes. They are integral to the lifecycle of medical products, from discovery and development to manufacturing and ultimately to the patient. The spectrum of integration between medical products and digital technologies ranges from non-drug specific solutions for supporting adherence or patient monitoring, which may or may not require regulatory approval, to digital therapeutics and software-containing combination products, which make claims supported by clinical evidence. The exponential increase and rapid evolution of connected health technologies - and the accompanying possibilities for innovative healthcare interventions, delivery systems, and clinical trial designs - pose new and complicated regulatory challenges. Currently, connected health may involve the use of regulated medical devices, including software as a medical device, or consumer products, such as wearables or apps, that fall under regulatory discretion. In this paper we examine how connected health technologies intersect with the development and lifecycle of medical products, how they are impacted by existing regulatory frameworks in the US, EU, and China, and propose future focus areas of activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Awad, Aljuburi, Lumsden, Mpandzou and Marinus.)

Background: By eliminating the requirement for participants to make frequent visits to research sites, mobile phone applications ("apps") may help to decentralize clinical trials. Apps may also be an effective mechanism for capturing patient-reported outcomes and other endpoints, helping to optimize patient care during and outside of clinical trials., Objectives: We report on the usability of Digital BioMarkers for Clinical Impact (DigiBioMarC™ (DBM)), a novel smartphone-based app used by cancer patients in conjunction with a wearable device (Apple Watch®). DBM is designed to collect patient-reported outcomes and record physical functions., Methods: In a fully decentralized "bring-your-own-device" smartphone study, we enrolled 54 cancer patient and caregiver dyads from Kaiser Permanente Northern California (KPNC) from October 2020 through March 2021. Patients used the app for at least 28 days, completed weekly questionnaires about their symptoms, physical functions, and mood, and performed timed physical tasks. Usability was determined through a subset of the Mobile App Rating Scale (MARS), the full System Usability Scale (SUS), the Net Promoter Score (NPS), and semi-structured interviews., Results: We obtained usability survey data from 50 of 54 patients. Median responses to the selected MARS questions and the mean SUS scores indicated above average usability. The NPS from the semi-structured interviews at the end of the study was 24, indicating a favorable score., Conclusions: Cancer patients reported above average usability for the DBM app. Qualitative analyses indicated that the app was easy to use and helpful. Future work will emphasize implementing further patient recommendations and evaluating the app's clinical efficacy in multiple settings., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: IOG, SWD, and RY are employed by Medable Inc., which developed the DBM app with funding from the National Institutes of Health through the Small Business Innovation Research program with the National Cancer Institute. SJF is subcontracted to work with Medable to analyze the study data., (© The Author(s) 2023.)

Background: Retaining participants in clinical trials is an established challenge. Currently, the industry is moving to a technology-mediated, decentralized model for running trials. The shift presents an opportunity for technology design to aid the participant experience and promote retention; however, there are many open questions regarding how this can be best supported. We advocate the adoption of a stronger theoretical position to improve the quality of design decisions for clinical trial technology to promote participant engagement., Objective: This study aimed to identify and analyze the types of retention strategies used in published clinical trials that successfully retain participants., Methods: A systematic scoping review was carried out on 6 electronic databases for articles published from 1990 to September 2020, namely CINAHL, The Cochrane Library, EBSCO, Embase, PsycINFO, and PubMed, using the concepts "retention," "strategy," "clinal trial," and "clinical research." This was followed by an analysis of the included articles through the lens of self-determination theory, an evidence-based theory of human motivation., Results: A total of 26 articles were included in this review. The motivational strategies identified in the clinical trials in our sample were categorized into 8 themes: autonomy; competence; relatedness; controlled motivation; branding, communication material, and marketing literature; contact, tracking, and scheduling methods and data collection; convenience to contribute to data collection; and organizational competence. The trials used a wide range of motivational strategies. Notably, the trials often relied on controlled motivation interventions and underused strategies to support intrinsic motivation. Moreover, traditional clinical trials relied heavily on human interaction and "relatedness" to support motivation and retention, which may cause problems in the move to technology-led decentralized trials. We found inconsistency in the data-reporting methods and that motivational theory-based approaches were not evident in strategy design., Conclusions: This study offers direction and a framework to guide digital technology design decisions for future decentralized clinical trials to enhance participant retention during clinical trials. This research defines previous clinical trial retention strategies in terms of participant motivation, identifies motivational strategies, and offers a rationale for selecting strategies that will improve retention. It emphasizes the benefits of using theoretical frameworks to analyze strategic approaches and aid decision-making to improve the quality of technology design decisions., (©Eoin Gamble, Conor Linehan, Ciara Heavin. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 13.04.2023.)

Background: Clinical trials often suffer from recruitment barriers and poor adherence, which increases costs and affects trial outcomes., Objective: To investigate the feasibility of Decentralized Clinical Trial (DCT) design elements to recruit, enroll, and engage patients with type 2 diabetes mellitus (T2DM)., Methods: Patients with T2DM were recruited through a pharmacy and online recruitment using advert on Facebook, to 3 weeks monitoring of glucose and behaviometric parameters. Subjects recruited online could either complete an informed consent conversation in the pharmacy or through live video call managed by the study app.A continuous glucose monitoring (CGM) device to collect glucose data, and a hybrid smartwatch to monitor heart rate, track activity and sleep pattern were delivered by postal service to the participants' home address. The devices were connected to a study specific app on the participant's smartphone also capturing GPS data and questionnaire answers., Results: Twenty-six subjects (3 pharmacy, 23 online) with T2DM were recruited, 85% preferred online informed consent conversation. All participants were able to self-apply the CGM device, use the smartwatch, and download the app. GPS location was captured more than 100 times for each participant, and more than 90% completed all 3 questionnaires. All the participants felt safe with the informed consent process and they felt confident in participating from home. Three participants dropped-out during the study period leaving a retention rate at 87%., Conclusions: Use of DCT design elements to conduct a T2DM study is feasible regarding recruitment, data collection from various electronic devices, and participant engagement.

Background: The need for a new style of clinical trials, called decentralized clinical trials (DCTs), has been increasing as they do not depend on physical visits to clinical sites. DCTs are expected to provide a new opportunity to patients who cannot participate in a clinical trial due to geographical and time limitations. For the adoption of DCTs, it is essential that medical devices with Internet of Medical Things (IoMT) and Internet of Health Things (IoHT) based technologies are developed and commercially adopted. In this study, we aimed to identify the regulatory considerations when IoMT/IoHT-based technologies are used in DCTs or products developed using DCTs., Method: To understand the study and development field of IoMT/IoHT comprehensively and panoramically, relevant papers published in Web of Science were searched online. Subsequently, a citation network was obtained and characterized as a cluster using a text mining method to identify IoMT/IoHT-based technologies expected to be utilized in DCTs or products developed using DCTs., Result and Discussion: Upon analysis of the top 15 clusters and subsequent 51 sub-clusters, we identified the therapeutic areas (psychology, neurology) and IoMT/IoHT-based technologies (telemedicine, remote monitoring, and virtual reality) that are expected to be used in DCTs. We also identified several considerations based on the current regulatory guidance., Conclusion: IoMT/IoHT-based technologies that are expected to be used or products developed using DCTs and key considerations made when they are used in DCTs were identified. The considerations could encourage conducting DCTs using IoMT/IoHT-based technologies., Competing Interests: TS was employed by Astellas Pharma Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sato, Ishimaru, Takata, Sasaki and Shikano.)

Clinical trials are slow and costly, built around the research centers that study local participants. Building clinical trials around patients in their homes and community through remote visits and monitoring could enhance recruitment and increase convenience for participants. This study evaluated different trial settings, a decentralized arm via telemedicine center (virtual study conduct), a conventional arm via health clinic (onsite study conduct) and a mixed model arm. Acute low-back pain patients (20-65 years) were recruited to this non-interventional trial in Switzerland. The study consisted of a screening period and a 2-week data collection period using direct data capture (eSource), electronic informed consent form (eICF), electronic diary (eDiary) and wearable actigraphy sensor. A higher number of patients were enrolled in the decentralized arm (N = 18) compared to the conventional arm (N = 5) and none in the mixed model arm. The decentralized arm consisted of a diverse population with increased participation from rural areas. In the decentralized arm 89% of enrolled patients completed the study compared to 60% in the conventional arm. All the patients reported satisfaction with the use of eICF, eDiary and remote visits; whereas patients reported a lower level of satisfaction with the wearable sensor. The decentralized setting was operationally feasible and well accepted by patients. Faster recruitment and improved access to patients was observed in the decentralized arm. This study supports broader adoption of the decentralized model in clinical trials, though further investigations in larger interventional trials are needed to confirm the benefits from this patient-centric approach.