Unlocking the full potential of digital endpoints for decision making: a novel modular evidence concept enabling re-use and advancing collaboration.

INTRODUCTION: Over the last decade increasing examples indicate opportunities to measure patient functioning and its relevance for clinical and regulatory decision making via endpoints collected through digital health technologies. More recently, we have seen such measures support primary study endpoints and enable smaller trials. The field is advancing fast: validation requirements have been proposed in the literature and regulators are releasing new guidances to review these endpoints. Pharmaceutical companies are embracing collaborations to develop them and working with academia and patient organizations in their development. However, the road to validation and regulatory acceptance is lengthy. The full value of digital endpoints cannot be unlocked until better collaboration and modular evidence frameworks are developed enabling re-use of evidence and repurposing of digital endpoints. AREAS COVERED: This paper proposes a solution by presenting a novel modular evidence framework -the Digital Evidence Ecosystem and Protocols (DEEP)- enabling repurposing of measurement solutions, re-use of evidence, application of standards and also facilitates collaboration with health technology assessment bodies. EXPERT OPINION: The integration of digital endpoints in healthcare, essential for personalized and remote care, requires harmonization and transparency. The proposed novel stack model offers a modular approach, fostering collaboration and expediting the adoption in patient care.

Digital Health Technologies in Clinical Trials: An Ontology-Driven Analysis to Inform Digital Sustainability Policies.

BACKGROUND: Digital health technologies (DHTs) can facilitate the execution of de-centralized trials that can offer opportunities to reduce the burden on participants, collect outcome data in a real-world setting, and potentially make trial populations more diverse and inclusive. However, DHTs can also be a significant source of electronic waste (e-waste). In recognition of the potential health and environmental impact from DHT use in trials, private and public institutions have recently launched initiatives to help measure and manage this e-waste. But in order to develop sound e-waste management policies, it will be necessary to first estimate the current volume of e-waste that results from the use of DHTs in trials. MATERIALS AND METHODS: A Web Ontology Language (OWL)-compliant ontology of DHTs was created using a list of 500 DHT device names derived from a mixture of public and private sources. The U.S. clinical trials registry, ClinicalTrials.gov, was then queried to identify and classify trials using any of the devices in the ontology. The ClinicalTrials.gov records from this search were then analyzed to characterize the volume and properties of trials using DHTs, as well as estimating the total volume of individual DHT units that have been provisioned (or are planned to be provisioned) for clinical research. RESULTS: Our ontology-driven search identified 2326 unique clinical trials with a reported "actual" enrollment of 200,947 participants and a "planned" enrollment of an additional 4,094,748 participants. The most-used class of DHTs in our ontology was "wearables," (1852 trials), largely driven by the use of smart watches and other wrist-worn sensors (estimated to involve 149,391 provisioned devices). The most-used subtype of DHTs in trials was "subcutaneous" devices (367 trials), driven by the prevalent use and testing of glucose monitors (estimated to involve 17,666 provisioned devices). CONCLUSION: Thousands of trials, involving hundreds of thousands of devices, have already been completed, and many more trials (potentially involving millions more devices) are planned. Despite the great opportunities that are afforded by DHTs to the clinical trial enterprise, if the industry lacks the ability to track DHT use with sufficient resolution, the result is likely to be a great deal of e-waste. A new ontology of DHTs, combined with rigorous data science methods like those described in this paper, can be used to provide better information across the industry, and in turn, help create a more sustainable and equitable clinical trials enterprise.

Adenoma Detection Rate and Risk for Interval Postcolonoscopy Colorectal Cancer in Fecal Immunochemical Test-Based Screening : A Population-Based Cohort Study.

BACKGROUND: The adenoma detection rate (ADR) is an essential quality indicator for endoscopists performing colonoscopies for colorectal cancer (CRC) screening as it is associated with postcolonoscopy CRCs (PCCRCs). Currently, data on ADRs of endoscopists performing colonoscopies in fecal immunochemical testing (FIT)-based screening, the most common screening method, are scarce. Also, the association between the ADR and PCCRC has not been demonstrated in this setting. OBJECTIVE: To evaluate the association between the ADR and PCCRC risk in colonoscopies done after a positive FIT result. DESIGN: Population-based cohort. SETTING: Dutch, FIT-based, CRC screening program. PARTICIPANTS: Patients undergoing colonoscopy, done by accredited endoscopists, after a positive FIT result. MEASUREMENTS: Quality indicator performance and PCCRC incidence for colonoscopies in FIT-positive screenees were assessed. The PCCRCs were classified as interval, a cancer detected before recommended surveillance, or noninterval. The association between ADR and interval PCCRC was evaluated with a multivariable Cox regression model and PCCRC incidence was determined for different ADRs. RESULTS: 362 endoscopists performed 116 360 colonoscopies with a median ADR of 67%. In total, 209 interval PCCRCs were identified. The ADR was associated with interval PCCRC, with an adjusted hazard ratio of 0.95 (95% CI, 0.92 to 0.97) per 1% increase in ADR. For every 1000 patients undergoing colonoscopy, the expected number of interval PCCRC diagnoses after 5 years was approximately 2 for endoscopists with ADRs of 70%, compared with more than 2.5, almost 3.5, and more than 4.5 for endoscopists with ADRs of 65%, 60%, and 55%, respectively. LIMITATION: The relative short duration of follow-up (median, 52 months) could be considered a limitation. CONCLUSION: The ADR of endoscopists is inversely associated with the risk for interval PCCRC in FIT-positive colonoscopies. Endoscopists performing colonoscopy in FIT-based screening should aim for markedly higher ADRs compared with primary colonoscopy. PRIMARY FUNDING SOURCE: None.

User experience with a voice-enabled smartphone app to collect patient-reported outcomes in rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic disease, requiring frequent patient-provider interaction and self-monitoring. We developed a novel mobile health smartphone app with a voice-enabled feature to help patients virtually track disease activity and ask general questions about RA. METHODS: With a user-centered design (UCD) approach, we developed a voice-enabled app (VEA) which was then tested in two focus groups of patients (n=8) and one with providers (n=4). Voice enablement and a question and answer (Q & A) library function were previously requested by patients. Based on focus group feedback, the VEA was refined and tested with 26 patients for 56 days. The VEA asked patients to fill in daily patient-reported outcomes (PROs) and complete the trial with a satisfaction survey. RESULTS: Of the 26 patients in the VEA trial, 77% were female and 50% were aged 55 and older. Adherence to daily PROs during the 56-day trial was 66%, with <1% of PROs completed using the voice-enabled feature. PROMIS short forms and RADAI-5 PROs remained stable. Of the 22 satisfaction survey respondents, 86% were satisfied with their overall experience with the app and 18.5% were satisfied with voice enablement. The voice assistant had an 86% success rate at understanding and answering interactions regarding surveys and a 44% success rate regarding Q & A interactions. CONCLUSIONS: We developed a novel VEA through a UCD framework and conducted pilot testing. Adherence was moderate and RADAI-5 and PROMIS measures were stable. Based on satisfaction results, PROs may not be the best use of voice enablement technology.

Harnessing Real-World Evidence for the Development of Novel Cancer Therapies.

Resourcing real-world evidence (RWE) is becoming an increasingly important asset in developing novel therapies for cancer. In this article, an overview of the benefits and challenges of using these data is provided. Through several case examples we highlight future applications and potential.

Clinical Course of Nodular Regenerative Hyperplasia in Thiopurine Treated Inflammatory Bowel Disease Patients.

Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD).1 It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown.2 The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.