The Digital Platform and Its Emerging Role in Decentralized Clinical Trials.

Decentralized clinical trials (DCTs) are becoming increasingly popular. Digital clinical trial platforms are software environments where users complete designated clinical trial tasks, providing investigators and trial participants with efficient tools to support trial activities and streamline trial processes. In particular, digital platforms with a modular architecture lend themselves to DCTs, where individual trial activities can correspond to specific platform modules. While design features can allow users to customize their platform experience, the real strengths of digital platforms for DCTs are enabling centralized data capture and remote monitoring of trial participants and in using digital technologies to streamline workflows and improve trial management. When selecting a platform for use in a DCT, sponsors and investigators must consider the specific trial requirements. All digital platforms are limited in their functionality and technical capabilities. Integrating additional functional modules into a central platform may solve these challenges, but few commercial platforms are open to integrating third-party components. The lack of common data standardization protocols for clinical trials will likely limit the development of one-size-fits-all digital platforms for DCTs. This viewpoint summarizes the current role of digital platforms in supporting decentralized trial activities, including a discussion of the potential benefits and challenges of digital platforms for investigators and participants. We will highlight the role of the digital platform in the development of DCTs and emphasize where existing technology is functionally limiting. Finally, we will discuss the concept of the ideal fully integrated and unified DCT and the obstacles developers must address before it can be realized.

Learning from remote decentralised clinical trial experiences: A qualitative analysis of interviews with trial personnel, patient representatives and other stakeholders.

AIMS: The aim of the study was to identify actionable learning points from stakeholders in remote decentralised clinical trials (RDCTs) to inform their future design and conduct. METHODS: Semistructured interviews were carried out with a purposive sample of stakeholders, including senior managers, trial managers, technology experts, principal investigators, clinical investigators, research scientists, research nurses, vendors, patient representatives and project assistants. The interview data were coded using a thematic approach, identifying similarities, differences and clustering to generate descriptive themes. Further refinement of themes was guided by empirical phenomenology, grounding explanation in the meanings that interviewees gave to their experiences. RESULTS: Forty-eight stakeholders were interviewed. Actionable learning points were generated from the thematic analysis. Patient involvement and participant engagement were seen as critical to the success of RDCTs where in-person contact is minimal or nonexistent. Involving patients in identifying the research question, creating recruitment materials, apps and websites, and providing ongoing feedback to trial participants were regarded as facilitating recruitment and engagement. Building strong relationships early with trial partners was thought to support RDCT conduct. Multiple modes of capturing information, including patient-reported outcomes (PROs) and routinely collected data, were felt to contribute to data completeness. However, RDCTs may transfer trial activity burden onto participants and remote-working research staff, therefore additional support may be needed. CONCLUSION: RDCTs will continue to face challenges in implementing novel technologies. However, maximising patient and partner involvement, reducing participant and staff burden, and simplifying how participants and staff interact with the RDCT may facilitate their implementation.

A systematic review of methods used to conduct decentralised clinical trials.

AIMS: To evaluate, using quantitative and qualitative approaches, published data on the design and conduct of decentralised clinical trials (DCTs). METHODS: We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, ProQuest Dissertations and Theses, ClinicalTrials.gov, OpenGrey and Google Scholar for publications reporting, discussing, or evaluating decentralised clinical research methods. Reports of randomised clinical trials using decentralised methods were included in a focused quantitative analysis with a primary outcome of number of randomised participants. All publications discussing or evaluating DCTs were included in a wider qualitative analysis to identify advantages, disadvantages, facilitators, barriers and stakeholder opinions of decentralised clinical trials. Quantitative data were summarised using descriptive statistics, and qualitative data analysed using a thematic approach. RESULTS: Initial searches identified 19 704 articles. After removal of duplicates, 18 553 were screened, resulting in 237 eligible for full-text assessment. Forty-five trials were included in the quantitative analysis; 117 documents were included in the qualitative analysis. Trials were widely heterogeneous in design and reporting, precluding meta-analysis of the effect of DCT methods on the primary recruitment outcome. Qualitative analysis formulated 4 broad themes: value, burden, safety and equity. Participant and stakeholder experiences of DCTs were incompletely represented. CONCLUSION: DCTs are developing rapidly. However, there is insufficient evidence to confirm which methods are most effective in trial recruitment, retention, or overall cost. The identified advantages, disadvantages, facilitators and barriers should inform the development of DCT methods. We recommend further research on how DCTs are experienced and perceived by participants and stakeholders to maximise potential benefits.

Sex Differences in Behavior and Molecular Pathology in the 5XFAD Model.

BACKGROUND: The prevalence of Alzheimer's disease (AD) is greater in women compared to men, but the reasons for this remain unknown. This sex difference has been widely neglected in experimental studies using transgenic mouse models of AD. OBJECTIVE: Here, we studied behavior and molecular pathology of 5-month-old 5XFAD mice, which express mutated human amyloid precursor protein and presenilin-1 on a C57BL/6J background, versus their wild-type littermate controls, to compare both sex- and genotype-dependent differences. METHODS: A novel behavioral paradigm was utilized (OF-NO-SI), comprising activity measures (Open Field, OF) arena, followed by Novel Object exploration (NO) and Social Interaction (SI) of a sex-matched conspecific. Each segment consisted of two repeated trials to assess between-trial habituation. Subsequently, brain pathology (amyloid load, stress response and inflammation markers, synaptic integrity, trophic support) was assessed using qPCR and western blotting. RESULTS: Female 5XFAD mice had higher levels of human APP and amyloid-ß and heightened inflammation versus males. These markers correlated with hyperactivity observed in both sexes, yet only female 5XFAD mice presented with subtle deficits in object and social exploration. Male animals had higher expression of stress markers and neurotrophic factors irrespective of genotype, this correlated with cognitive performance. CONCLUSION: The impact of sex on AD-relevant phenotypes is in line with human data and emphasizes the necessity of appropriate study design and reporting. Differential molecular profiles observed in male versus female mice offer insights into possible protective mechanisms, and hence treatment strategies.

A secondary qualitative analysis of stakeholder views about participant recruitment, retention, and adherence in decentralised clinical trials (DCTs).

BACKGROUND: Decentralised clinical trials (DCTs) are clinical trials where all or most trial activities occur in or near participants' homes instead of hospitals or research sites. While more convenient for participants, DCTs may offer limited opportunities to build trust with investigators and trial teams. This qualitative analysis explored DCT stakeholder views to inform strategies for maximising participant recruitment, retention, and adherence. METHODS: A secondary analysis of original interview transcripts focused on participant engagement: recruitment, retention, and adherence. Semi-structured interviews were conducted with a purposive sample of stakeholders, including trial managers and administrators, investigators, nurses, vendors, and patient representatives. Interview data were coded using a thematic approach to generate descriptive themes. RESULTS: Forty-eight stakeholders were interviewed. Three components of participant engagement in DCTs were identified: identifying and attracting potential participants, retaining participants and encouraging adherence, and involvement of patients and the public. Interviewees believed that a potential participant's beliefs about research value and their trust in the research team strongly influenced the likelihood of taking part in a DCT. Early involvement of patients was identified as one way to gauge participant priorities. However, perceived burden was seen as a barrier to recruitment. Factors influencing retention and adherence were related to the same underlying motivators that drove recruitment: personal values, circumstances, and burden. Being part of a DCT should not conflict with the original motivations to participate. CONCLUSION: Recruitment, retention, and adherence in DCTs are driven by factors that have previously been found to affect conventional clinical trials. Increasing patient and public involvement can address many of these factors. In contrast to conventional trials, DCTs are perceived as requiring greater emphasis on communication, and contact, to engender trust between participants and researchers despite a relative lack of in-person interaction.

Self-reported pregnancy and access to primary health care among sexually experienced New Zealand high school students.

PURPOSE: To determine the prevalence of self-reported pregnancy among sexually experienced high school students, and the association between teenage pregnancy and access to primary health care. METHODS: Between March and October 2007, 96 high schools throughout New Zealand participated in Youth'07, a cross-sectional Health and Wellbeing survey. The dataset included 2,620 (1,217 females and 1,403 males) year 9 through 13 students who reported ever having sexual intercourse and responded to a question about whether they had ever been pregnant or ever caused a pregnancy. RESULTS: Nationwide, 10.6% of sexually experienced high school students self-reported that they had been pregnant (11.6%) or caused a pregnancy (9.9%). Maori (15.3%) and Pacific Island (14.1%) students had the highest self-reports of pregnancy. Foregone health care was reported by 24.2% of sexually experienced students. Students who self-reported pregnancy reported greater difficulty accessing health care (41.7% vs. 20.6%; odds ratio: 2.6); however, when they accessed care, the majority received confidential care (67.4%) as compared with pregnancy-inexperienced peers (51.6%). Concern about privacy was the most common reason for not accessing health care. Other barriers included uncertainty about how to access care and lack of transportation (all p values < .05). CONCLUSIONS: Self-reported pregnancy among sexually active high school students in New Zealand is high and ethnic disparities exist. Being pregnant or causing a pregnancy is associated with difficulty accessing health care. Further research is needed to identify drivers for ethnic differences and determine what the cause-and-effect relationship between teenage pregnancy and access to health care looks like.