The value of decentralized clinical trials: Inclusion, accessibility, and innovation.

In this Review, we explore the transformative potential of decentralized clinical trials (DCTs) in addressing the limitations of traditional randomized controlled trials (RCTs). We highlight the merits of DCTs fostering greater inclusivity, efficiency, and adaptability. We emphasize the challenges of RCTs, including limited participant diversity and logistical barriers, geographical constraints, and mistrust in research institutions, showing how DCTs are preferred in addressing these challenges by utilizing remote digital technologies and community providers to enable broader, more inclusive participation. Furthermore, we underscore the potential of DCTs for democratizing clinical research. We also stress the importance of addressing unresolved challenges, including data security and privacy, remote patient monitoring, and regulatory variations. Research is needed to devise standardized protocols to streamline DCT processes, explore its long-term impacts on patient outcomes, and overcome challenges through equitable stakeholder engagement.

Recruitment in Appalachian, Rural and Older Adult Populations in an Artificial Intelligence World: Study Using Human-Mediated Follow-Up.

BACKGROUND: Participant recruitment in rural and hard-to-reach (HTR) populations can present unique challenges. These challenges are further exacerbated by the need for low-cost recruiting, which often leads to use of web-based recruitment methods (eg, email, social media). Despite these challenges, recruitment strategy statistics that support effective enrollment strategies for underserved and HTR populations are underreported. This study highlights how a recruitment strategy that uses email in combination with follow-up, mostly phone calls and email reminders, produced a higher-than-expected enrollment rate that includes a diversity of participants from rural, Appalachian populations in older age brackets and reports recruitment and demographic statistics within a subset of HTR populations. OBJECTIVE: This study aims to provide evidence that a recruitment strategy that uses a combination of email, telephonic, and follow-up recruitment strategies increases recruitment rates in various HTR populations, specifically in rural, older, and Appalachian populations. METHODS: We evaluated the overall enrollment rate of 1 recruitment arm of a larger study that aims to understand the relationship between genetics and substance use disorders. We evaluated the enrolled population's characteristics to determine recruitment success of a combined email and follow-up recruitment strategy, and the enrollment rate of HTR populations. These characteristics included (1) enrollment rate before versus after follow-up; (2) zip code and county of enrollee to determine rural or urban and Appalachian status; (3) age to verify recruitment in all eligible age brackets; and (4) sex distribution among age brackets and rural or urban status. RESULTS: The email and follow-up arm of the study had a 17.4% enrollment rate. Of the enrolled participants, 76.3% (4602/6030) lived in rural counties and 23.7% (1428/6030) lived in urban counties in Pennsylvania. In addition, of patients enrolled, 98.7% (5956/6030) were from Appalachian counties and 1.3% (76/6030) were from non-Appalachian counties. Patients from rural Appalachia made up 76.2% (4603/6030) of the total rural population. Enrolled patients represented all eligible age brackets from ages 20 to 75 years, with the 60-70 years age bracket having the most enrollees. Females made up 72.5% (4371/6030) of the enrolled population and males made up 27.5% (1659/6030) of the population. CONCLUSIONS: Results indicate that a web-based recruitment method with participant follow-up, such as a phone call and email follow-up, increases enrollment numbers more than web-based methods alone for rural, Appalachian, and older populations. Adding a humanizing component, such as a live person phone call, may be a key element needed to establish trust and encourage patients from underserved and rural areas to enroll in studies via web-based recruitment methods. Supporting statistics on this recruitment strategy should help researchers identify whether this strategy may be useful in future studies and HTR populations.

Using Short-Form Videos to Get Clinical Trial Newcomers to Sign Up: Message-Testing Experiment.

BACKGROUND: Recruiting participants for clinical trials poses challenges. Major barriers to participation include psychological factors (eg, fear and mistrust) and logistical constraints (eg, transportation, cost, and scheduling). The strategic design of clinical trial messaging can help overcome these barriers. While strategic communication can be done through various channels (eg, recruitment advertisements), health care providers on the internet have been found to be key sources for communicating clinical trial information to US adults in the social media era. OBJECTIVE: This study aims to examine how communication source (ie, medical doctors and peers) and message framing of TikTok videos (ie, psychological and logistical framing) influence clinical trial-related attitudes, perceptions, and sign-up behaviors under the guidance of the integrated behavioral model. METHODS: This study used a 2 (source: doctor vs peer) × 2 (framing: psychological vs logistical) between-participant factorial design web-based experiment targeting adults in the United States who had never participated in clinical trials (ie, newcomers). A Qualtrics panel was used to recruit and compensate the study respondents (n=561). Participants viewed short-form videos with doctors or peers, using psychological or logistical framing. The main outcome measures included perceived source credibility, self-efficacy, attitude toward clinical trial participation, behavioral intention, and sign-up behavior. Structural equation modeling was used to analyze the direct and indirect effects of message factors on the outcome variables. Source (doctor=1; peer=0) and framing (psychological=1; logistical=0) were dummy-coded. RESULTS: Doctor-featured messages led to greater perceived source credibility (ß=.31, P<.001), leading to greater self-efficacy (95% CI 0.13-0.30), which in turn enhanced behavioral intention (95% CI 0.12-0.29) and clinical trial sign-up behavior (95% CI 0.02-0.04). Logistical barrier-framed messages led to greater self-efficacy (ß=-.09, P=.02), resulting in higher intention to participate in clinical trials (95% CI -0.38 to -0.03) and improved sign-up behavior (95% CI -0.06 to -0.004). Logistical barrier-framed messages were also directly associated with an increased likelihood of signing up for a clinical trial (ß=-.08, P=.03). The model accounted for 21% of the variance in clinical trial sign-up behavior. Attitude did not significantly affect behavioral intention in this study (ß=.08, P=.14), and psychological and logistical barrier-framed messages did not significantly differ in attitudes toward clinical trial participation (ß=-.04, P=.09). CONCLUSIONS: These findings advance our understanding of how people process popular message characteristics in short-form videos and lend practical guidance for communicators. We encourage medical professionals to consider short-form video sites (eg, TikTok and Instagram Reels) as effective tools for discussing clinical trials and participation opportunities. Specifically, featuring doctors discussing efforts to reduce logistical barriers is recommended. Our measuring of actual behavior as an outcome is a rare and noteworthy contribution to this research.

Rapid qualitative analysis of recruitment obstacles in the FORVAD (Posterior Cervical Foraminotomy surgery versus Anterior Cervical Discectomy surgery in the treatment of cervical brachialgia) randomised, controlled trial.

BACKGROUND: The number of surgical trials is increasing but such trials can be complex to deliver and pose specific challenges. A multi-centre, Phase III, RCT comparing Posterior Cervical Foraminotomy versus Anterior Cervical Discectomy and Fusion in the Treatment of Cervical Brachialgia (FORVAD Trial) was unable to recruit to target. A rapid qualitative study was conducted during trial closedown to understand the experiences of healthcare professionals who participated in the FORVAD Trial, with the aim of informing future research in this area. METHODS: Semi-structured interviews were conducted with 18 healthcare professionals who had participated in the FORVAD Trial. Interviews explored participants' experiences of the FORVAD trial. A rapid qualitative analysis was conducted, informed by Normalisation Process Theory. RESULTS: Four main themes were generated in the data analysis: (1) individual vs. community equipoise; (2) trial set-up and delivery; (3) identifying and approaching patients; and (4) timing of randomisation. The objectives of the FORVAD trial made sense to participants and they supported the idea that there was clinical or collective equipoise regarding the two FORVAD interventions; however, many surgeons had treatment preferences and lacked individual equipoise. The site which had most recruitment success had adopted a more structured process for identification and recruitment of patients, whereas other sites that adopted more "ad hoc" screening strategies struggled to identify patients. Randomisation on the day of surgery caused both medico-legal and practical concerns at some sites. CONCLUSIONS: Organisation and implementation of a surgical trial in neurosurgery is complex and presents many challenges. Sites often reported low recruitment and discussed the logistical issues of conducting a complex surgical RCT. Future trials in neurosurgery may need to offer more flexibility and time during set-up to maximise opportunities for larger recruitment numbers. Rapid qualitative analysis informed by Normalisation Process Theory was able to quickly identify key issues with trial implementation so rapid qualitative analysis may be a useful approach for teams conducting qualitative research in trials. TRIAL REGISTRATION: ISRCTN, ISRCTN reference: 10,133,661. Registered 23rd November 2018.

Patient and public involvement and engagement in the ASCEND PLUS trial: reflections from the design of a streamlined and decentralised clinical trial.

INTRODUCTION: ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK. The trial's innovative design includes a decentralised direct-to-participant invitation, recruitment, and follow-up model, relying on self-completion of online forms or telephone or video calls with research nurses, with no physical sites. Extensive patient and public involvement and engagement (PPIE) was essential to the design and conduct of ASCEND PLUS. AIM: To report the process and conduct of PPIE activity in ASCEND PLUS, evaluate effects on trial design, reflect critically on successes and aspects that could have been improved, and identify themes and learning relevant to implementation of PPIE in future trials. METHODS: PPIE activity was coordinated centrally and included six PPIE focus groups and creation of an ASCEND PLUS public advisory group (PAG) during the design phase. Recruitment to these groups was carefully considered to ensure diversity and inclusion, largely consisting of adults living with type 2 diabetes from across the UK. Two members of the PAG also joined the trial Steering Committee. Steering Committee meetings, focus groups, and PAG meetings were conducted online, with two hybrid workshops to discuss PPIE activity and aspects of the trial. RESULTS: PPIE activity was critical to shaping the design and conduct of ASCEND PLUS. Key examples included supporting choice for participants to either complete the screening/consent process independently online, or during a telephone or video call interview with a research nurse. A concise 'initial information leaflet' was developed to be sent with the initial invitations, with the 'full' information leaflet sent later to those interested in joining the trial. The PAG reviewed the content and format of participant- and public-facing materials, including written documents, online screening forms, animated videos, and the trial website, to aid clarity and accessibility, and provided input into the choice of instruments to assess quality of life. CONCLUSIONS: PPIE is integral in ASCEND PLUS and will continue throughout the trial. This involvement has been critical to optimising the trial design, successfully obtaining regulatory and ethical approval, and conducting the trial.

Using Natural Language Processing on Expert Panel Discussions to Gain Insights for Recruitment, Retention and Intervention Adherence for Online Social Support Interventions on a Stage II-III Clinical Trial Among Hispanic and African American Dementia Caregivers.

We applied natural language processing (NLP) to a corpus extracted from 4 hours of expert panel discussion transcripts to determine the sustainability of a Stage II-III clinical trial of online social support interventions for Hispanic and African American dementia caregivers. Prominent topics included Technology/hard to reach populations, Training younger populations, Building trust, Privacy and security issues, Simplification of screening questions and recruitment procedures, Understanding participants' needs, Planning strategies and logistics, Potential recruitment places, Adjusting intervention size downwards to engage elderly participants, Targeting different generations, Internet-based interventions by age range, and Providing step-by-step instructions and an overview of the entire research process during recruitment. The application of NLP to qualitative data on a dementia caregiving clinical trial provides useful insights for recruitment, retention, and adherence to guidelines for such interventions serving Hispanic and African American dementia caregivers.

A Precision Oncology Platform to Support Genotype-Tailored Therapy Selection.

There is a critical need for a streamlined process to identify genotype-matched individuals eligible for enrollment into clinical trials and/or targeted therapies, as current methodologies face challenges in integrating diverse molecular data sources. We have developed a precision oncology platform to assist molecular tumor boards and community oncologists in reviewing patients' phenotypes, evaluating related knowledge, and identifying genotype-matched therapies.

Patient Selection Is the Key for Successful Video Appointments: Lessons Learned from the COVID-19 Pandemic.

The use of video appointments (VAs) increased significantly during the COVID-19 pandemic. This study investigated the evolution of VA utilisation in Finland using data from two surveys conducted in 2021 (40 responses) and 2023 (30 responses). Our primary aim was to identify patient groups best suited for VAs. Respondents were either neurologists or neurologists-in-training. Our findings suggest that patients with epilepsy or headaches are most suitable for VAs. VAs were primarily used for follow-up visits during both survey periods, but their application for first visits decreased from 68.20% in 2021 to 27.80% in 2023. Healthcare professionals' concerns about data protection have diminished over time, but there is still need for enhanced training in the use of remote applications. Future research should focus on validating the cost-effectiveness, data security and timeliness of VAs.

Recruitment, retention and reporting of variables related to ethnic diversity in randomised controlled trials: an umbrella review.

OBJECTIVE: This umbrella review synthesises evidence on the methods used to recruit and retain ethnically diverse participants and report and analyse variables related to ethnic diversity in randomised controlled trials. DESIGN: Umbrella review. DATA SOURCES: Ovid MEDLINE, Ovid Embase, CINAHL, PsycINFO and Cochrane and Campbell Libraries for review papers published between 1 January 2010 and 13 May 2024. ELIGIBILITY CRITERIA: English language systematic reviews focusing on inclusion and reporting of ethnicity variables. Methodological quality was assessed using the AMSTAR 2 tool. RESULTS: Sixty-two systematic reviews were included. Findings point to limited representation and reporting of ethnic diversity in trials. Recruitment strategies commonly reported by the reviews were community engagement, advertisement, face-to-face recruitment, cultural targeting, clinical referral, community presentation, use of technology, incentives and research partnership with communities. Retention strategies highlighted by the reviews included frequent follow-ups on participants to check how they are doing in the study, provision of incentives, use of tailored approaches and culturally appropriate interventions. The findings point to a limited focus on the analysis of variables relevant to ethnic diversity in trials even when they are reported in trials. CONCLUSION: Significant improvements are required in enhancing the recruitment and retention of ethnically diverse participants in trials as well as analysis and reporting of variables relating to diversity in clinical trials. PROSPERO REGISTRATION NUMBER: CRD42022325241.

Patient selection for arterial procedures in office-based laboratories: A systematic review.

A dramatic increase in the number of vascular procedures performed in the office-based laboratory setting has been observed since 2008, when the Centers for Medicare and Medicaid Services increased reimbursement for procedures performed in the ambulatory setting. We sought to evaluate the appropriateness of arterial intervention in the office-based laboratory and patient selection. This systematic review was conducted with a search of Google Scholar and PubMed using the following search terms: office-based lab, outpatient, angioplasty, patient selection, arterial, and appropriateness. More than 500 publications were screened and 14 publications related to the topic were selected. The existing literature that examined patient selection for intervention in the outpatient setting, rates of complications after outpatient procedures, and short-term data on the safety and efficacy of these procedures is discussed. Gaps were identified in current knowledge about the long-term outcomes of peripheral arterial interventions performed in the office-based laboratory setting, as well as existing guidelines for the management of patients with peripheral arterial disease.

Recruiting transgender men in the Southeastern United States for genital microbiome research: Lessons learned.

BACKGROUND: Transgender men (TGM) are underrepresented in genital microbiome research. Our prospective study in Birmingham, AL investigated genital microbiota changes over time in TGM initiating testosterone, including the development of incident bacterial vaginosis (iBV). Here, we present lessons learned from recruitment challenges encountered during the conduct of this study. METHODS: Inclusion criteria were assigned female sex at birth, TGM or non-binary identity, age ≥18 years, interested in injectable testosterone but willing to wait 7 days after enrollment before starting, and engaged with a testosterone-prescribing provider. Exclusion criteria were recent antibiotic use, HIV/STI infection, current vaginal infection, pregnancy, or past 6 months testosterone use. Recruitment initiatives included community advertisements via flyers, social media posts, and referrals from local gender health clinics. RESULTS: Between February 2022 and October 2023, 61 individuals contacted the study, 17 (27.9%) completed an in-person screening visit, and 10 (58.8%) of those screened were enrolled. The primary reasons for individuals failing study screening were having limited access to testosterone-prescribing providers, already being on testosterone, being unwilling to wait 7 days to initiate testosterone therapy, or desiring the use of topical testosterone. Engagement of non-White TGM was also minimal. CONCLUSION: Despite robust study inquiry by TGM, screening and enrollment challenges were faced including engagement by TGM not yet in care and specific study eligibility criteria. Excitement among TGM for research representation should be leveraged in future work by engaging transgender community stakeholders at the inception of study development, particularly regarding feasibility of study inclusion and exclusion criteria, as well as recruitment of TGM of color. These results also highlight the need for more clinical resources for prescribing gender-affirming hormone therapy, especially in the Southeastern US.

Engagement in rapid public health research among young people from underserved communities: maximising opportunities and overcoming barriers.

BACKGROUND: Inclusion in public health research of young people from low-income households and those from minority ethnic groups remains low. It is recognised that there is a need to change the way in which research is conducted so that it becomes more inclusive. The aim of this work was to identify novel and innovative ways to maximise recruitment and inclusion of diverse participants when doing co-production within very short time frames for emergency responses. METHOD: We conducted interviews with young people from low-income and minority ethnic backgrounds, and members or leaders of groups or organisations supporting or representing young people from underserved communities. RESULTS: A total of 42 participants took part in an interview. This included 30 young people from low income or minority ethnic backgrounds and 12 community leaders/service providers. Of the 30 young people, 26 participants identified as female and 12 participants identified as being from a minority ethnic background. Participants discussed a number of interrelated barriers to research involvement and identified ways in which barriers may be reduced. Prejudice and discrimination experienced by young people from underserved communities has led to substantial mistrust of educational and governmental establishments. Rigid and unfamiliar research practices further limit the involvement of young people. Four themes were identified as ways of supporting involvement, including: making opportunities available for young people, adaptations to research governance, understanding and acknowledging challenges faced by young people, and ensuring reciprocal benefits. CONCLUSION: This research explored barriers to engagement in rapid public health co-production. Working with communities to co-produce rapid recruitment and research procedures to suit the needs and the context in which young people live is necessary.

Recruiting Persons With Dementia: A Systematic Review of Facilitators, Barriers, and Strategies.

Study recruitment of persons with dementia is challenging. We aimed to assess facilitators, barriers, and strategies to identify and approach persons with dementia for recruitment to dementia care studies. We systematically searched MEDLINE/PubMed, CINAHL, Web of Science, and other sources (ORRCA [Online Resource for Research in Clinical triAls]; pertinent evidence syntheses; citation searching) and narratively summarised the results (PROSPERO CRD42022342600). Facilitators and barriers consisted of "characteristics of participants, researchers, clinical contact persons", "study characteristics", and "communication with participants". The highest number of participants were recruited by study information in electronic and print formats, as well as by networking and collaboration. Advertisements proved to be the most expensive way of recruitment. There is limited evidence on the impact of recruitment strategies to identify persons with dementia for recruitment to dementia care studies. Our analysis of facilitators and barriers may inform research teams in designing strategies to identify persons with dementia for recruitment purposes.

Appropriateness of care in superficial venous disease.

Chronic superficial venous disease, including superficial venous insufficiency, superficial venous thrombosis, and aneurysms, are prevalent conditions that affect millions of individuals worldwide. With chronic venous insufficiency specifically, the advent of office-based minimally invasive procedures in recent decades has significantly expanded access to outpatient treatment. However, as venous insufficiency is rarely life- or limb-threatening, the clinical diagnosis, diagnostic evaluation, and treatment indications should be considered carefully when recommending elective intervention. Appropriateness of care guidelines intend to aid providers and patients in the decision-making process, based on the available evidence in the scientific literature, to select the best care for the patient when treating their superficial venous disease.

Appropriateness of care: Deep venous procedures.

In the past decade, technologies to treat venous pathologies have increased dramatically, to the benefit of an often underserved and overlooked population of patients with venous disease. However, given the rapid release of various technologies, including venous-dedicated stents and thrombectomy devices across varied venous pathologies, evidence-based guidelines have been slow to develop. When discussing appropriateness of care, one needs to consider optimal patient selection, technical approach, medical management, and surveillance protocols, to name a few. All of which, in the venous space, are currently widely varied in practice. The future of deep venous work is limitless, but multicenter, randomized controlled trials are needed to optimally treat patients with venous disease.

Appropriateness guidelines for inferior vena cava filter utilization: A contemporary review.

Concern regarding the exponential increase in optional utilization of inferior vena cava filters (IVCFs) in the early 2000s with a persistent low retrieval rate nationwide has resulted in increased scrutiny regarding clinical application of IVCFs. IVCFs are used in a variety of clinical scenarios, ranging from thromboembolic protection in patients with deep venous thrombosis and contraindication to anticoagulation to prophylactic deployment in multitrauma and critically ill patients. Evidence supporting IVCFs as mechanical thromboembolic protection in certain clinical scenarios has been established through evidenced-based guidelines. As an adjunct to evidence-based guidelines, appropriateness criteria to address specific clinical scenarios and facilitate clinical decision making when considering placement of an IVCF have been developed. In this review, current evidence-based and appropriateness guidelines are summarized.

Decision making in the frail vascular surgery patient: A scoping review.

Increasing evidence highlights the adverse impact of frailty and reduced physiologic reserve on surgical outcomes. Therefore, identification of frailty is essential for older adults being evaluated for vascular surgery procedures. Numerous frailty assessment tools are available to quantify the level of frailty and assist in preoperative decision making for these older patients. This review evaluates traditional and novel frailty metrics for their scientific validation, limitations, and clinical utility in vascular surgery decision-making.

Appropriateness of care in complex fenestrated-branched aortic endografting.

Fenestrated and branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms is increasingly replacing open repair as the primary modality of treatment. Mid- and long-term results are encouraging and support its use in the correct settings. Nevertheless, appropriateness of indication for treatment, patient selection, and surgeon and hospital performance has not been clearly evaluated and reviewed. The objective of this review article was to identify areas in which appropriateness of care is relevant and can be optimized when considering treatment of patients with fenestrated and branched endovascular repair for complex abdominal and thoracoabdominal aortic aneurysms.

Appropriate Use Criteria Committees: The professional society role in the development and implementation of Appropriate Use Criteria.

Vascular surgeons have the ability to manage and intervene on numerous vascular diseases of both the arterial and venous systems. With the growing number of interventions available as endovascular technology evolves, it is important to determine when a procedure is safely indicated for a vascular surgery patient. Appropriate Use Criteria (AUC) offer synthesized clinical information and practice standards that can aid clinicians in making these management decisions. Professional societies, such as the Society for Vascular Surgery, bring experts in the field together to collaborate and create AUC for various vascular diseases and interventions. It is essential to publish these criteria in peer-reviewed journals, as well as make them available on public websites so the information is available to vascular surgeons and interventionalists from other specialties who also treat patients with vascular disease. Cardiology, interventional radiology, and interventional nephrology are some other specialties that perform procedures for vascular disease, and vascular interventions by nonsurgeon specialists continue to increase. The Society for Vascular Surgery has published AUC on intermittent claudication, carotid disease, and abdominal aneurysm management. These are intended to guide practice, but also have highlighted areas for improvement that would allow for more universal implementation of AUC in vascular patient care across medical specialties. Increased intersocietal participation and perhaps inclusion of government and other payer participation will allow professional society-sponsored AUC to evolve, resulting in coordinated, appropriate care for vascular surgery patients.

Appropriate management of the small abdominal aortic aneurysm.

There is variation in the management of small aneurysms in the United States today, with some surgeons moving forward with elective repair and others practice ongoing surveillance. Literature exists to suggest that small aneurysms are repaired at a higher rate than should be considered acceptable, and this represents a deviation from current standards of care. To best understand the optimal care of this patient population, this article aims to evaluate the current management of small aneurysms, review contemporary guidelines and the literature behind them, and assess the appropriateness of surgical management of small aneurysms.