A new perspective, published in npj Digital Medicine, has reviewed the status of digital clinical trials and described future priorities and strategies that need to be addressed to fully harness the benefits of digital methods.
Current clinical trials
Clinical trials form the most critical stage of drug development. They are a fundamental tool to assess the efficacy and safety of new drugs and medical devices. However, current operational inefficiencies, including identification and recruitment of participants, all pose challenges that hinder the conduct of research. Additionally, low clinical-trial participation is a major issue. Estimates suggest that only about 8% of cancer patients enrol in cancer trials. Issues that impact participation include travelling far to the research site and the costs of participating. All of these increase disparities in access to research and also limit the diversity of participants in clinical trials.
Digital clinical trials
The concept of digital clinical trials holds promise as a method to overcome current challenges. This approach uses technology to improve recruitment and retention, data collection and analytics. Digitisation helps to accelerate regulatory approval, which can streamline clinical trial costs and efforts. It also provides an opportunity to move more towards a patient-centred trial experience.
Experts and leaders have recognised the value of harnessing digital technology to accelerate the pace at which evidence is being generated through clinical trials. In April 2019, the United States National Institutes of Health (NIH) and the National Science Foundation (NSF) held a workshop bringing together experts in clinical trials, digital technology and digital analytics to discuss strategies to implement the use of digital technologies.
Digital technology can increase efficiency by supporting the role of investigators and study teams. For example, many trials could be done without in person visits. In addition, in some cases, participants may not have to meet the study teams.
Although digital health technologies will need more evaluation and validation before they are fully ready for use, they provide the research community with new tools that can greatly enhance the clinical trial enterprise. In addition, a fully digital trial will allow access for potential participants regardless of where they live or work. Investigators can also investigate both traditionally collected endpoints and also more novel endpoints. These endpoints could be captured in an automated fashion over extended periods of time.
Example
A recent randomised trial evaluated a 5-day course of hydroxychloroquine for asymptomatic volunteers following exposure to someone with confirmed COVID-19 infection. Participants were enrolled via traditional and social media, consented via electronic means and all data was collected electronically and published online within 90 days. Although digital trials are in their infancy, the authors note that the ability to more widely operationalise them has taken on new urgency.
Digital recruitment and retention
Recruitment, informed consent and retention of participants is a major impediment to the timely completion of clinical trials. While guidance has been issued for the use of new technologies in the informed consent process, similar guidance for recruitment is lacking. Retention in studies can be impacted by, for example, concerns regarding assignment to the placebo arm and also lack of understanding of the clinical trial process. Digital technologies could help with these issues, including more efficient participant outreach and visual formats to aid informed consent.
Disparities within clinical trials is a major issue. There are many underrepresented groups within clinical trials, including Black Americans and older adults. Solutions may vary but could include tailored communication strategies to overcome barriers, such as mistrust, as well as remote monitoring to reduce in-person visits.
Work to harness new technologies has already begun. For example, the Metastatic Breast Cancer Project, engaged participants through social media and involved online consent and bidirectional communication.
Digital health data collection
Digital data in clinical trials can take many forms, including clinical and demographic data or images collected via a smartphone. A digital biomarker is an objective measure of physiologic, pathologic, anatomic, behavioural, social or activity characteristic, and patient self-report. It can be acquired using digital technology. These biomarkers can be evaluated as an indicator of normal and pathologic processes or responses to therapeutics. Current examples include wearable sweat sensing for glucose and lactate. Most importantly, collecting data continuously could help improve detection of infrequent events or those that are situation specific. This could allow for adverse and safety events to be detected early which may impact timeliness of completion and reporting of clinical trials.
A key issue that remains, is the evaluation of these tools to ensure that they meet standards for reliability and validity. With this, digital health technology has created challenges in modernising standards for privacy, safety, ethics and regulation. Digital technology heightens the need to protect against data breaches.
Data analytics
The digital transformation presents significant opportunities to improve clinical trials (from trial matching to data collection) using real-world data. In particular, clinical trial infrastructure that utilises electronic-health records is now possible. Artificial intelligence and machine learning are also enabling the development of advanced analytic methods that can be used across different elements of digital clinical trials. For example, these methods can be used to match participants to studies, improve digital data extraction and aid in interpretation of trial findings.
Conclusions
The authors note that research into the risk and benefit of digital trials is essential. This includes research into privacy and security concerns, training protocols and the potential negative impact of technology use. Transition to digital trials will transform clinical trial research teams, with the incorporation of computer scientists and engineers. Digital tools that enable the reengineering of healthcare and clinical research are becoming increasingly available and continue to expand rapidly. The authors address that many challenges remain. However, it is evident that now is the time to support digital methods with a focus on the most effective and efficient methods.
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