How remote patient monitoring technology can impact decentralized clinical trials

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Already 100 years ago (see photo of the cover of Radio News, April 1924), the concept of “decentralized care” seemed very close. Several key elements had to evolve over the last century to make this a reality: sensors (remote patient monitoring), telecommunications infrastructure (the Internet), science, and perhaps most importantly, adherence. medical communities and patients. . The COVID-19 pandemic has dramatically accelerated the latter, to the point where we have to ask ourselves: what’s next? What have we learned and how are we moving forward pragmatically?

Depending on how we define them, decentralized clinical trials (DCTs) are nothing new – the concept and early trials with a decentralized design drastically predated COVID 19. Clinical research pioneer Craig Lipset cites feasibility study over the Internet from 2003 and a Boston University patent for “Trials over the Internet” in 2007. But they are still not a singularly defined entity, which has led to some confusion around nomenclature (virtual? hybrid ?combinations?without site?) and execution.

Recently, the Clinical Trials Transformation Initiative (CTTI) tips defined DCT as trials “in which some or all of the assessments or study visits are conducted at locations other than the investigator’s site”. Here we focus specifically on a portion of this wide spectrum: how technology can enable participation, reducing the burden on participants and providing better data. We believe this aligns well with efforts to provide broader access to a more diverse population, which is encouraged by recent FDA Recommendations.

In part, pharmaceutical companies and CROs can conduct viable decentralized drug development trials due to the advent of remote patient monitoring technology, wearable sensors, and electronically collected data such as ePROs, but also through more patient-centric real-world data. to concentrate. The way these trials are established, conducted and validated has evolved significantly under the pressure of the COVID-19 pandemic. The question now is what will happen next? What have we learned (both before and after COVID) and how can we put it into practice? How do the benefits of participant burden and cohort diversity balance with the endpoints needed to establish the safety and efficacy of new drugs? What elements of study design, enabling technology, and next-generation data management are needed to benefit all stakeholders, including patients, researchers, sponsors, and society?

Patient perspective

Starting with the positives on the patient side, many aspects of clinical trials can be done remotely which, when done right, increases convenience, accessibility and diversity. Medical-grade remote patient monitoring (RPM) devices and digital technology can make it easier to get high-quality data, but turning that data into clinical trial metrics is a high bar. More importantly, the foundation must first be established, which is necessary for regulatory approvals and, ultimately, buy-in from the pharmaceutical industry.

As anyone who has spent hours in the digital “customer support loops” for their mobile carrier can attest, decentralized processes need to be simple, effective and efficient in order to ensure patient buy-in. We have heard of subjects who are motivated but unable to participate in drug trials due to travel burden. DCT capabilities such as RPM devices can allow them to participate. These medical devices, mainly portable devices, must be designed for patient comfort, reuse and self-service. Depending on the trial, the participant group could be tech-savvy millennials, or it could be an older demographic that is much less tech-savvy and/or dependent on a carer. Trial participants may represent a wide range of demographics as we seek to expand the diversity of participants for various studies.

The pandemic has forced some populations to quickly adapt to various forms of digital healthcare, including telemedicine. This is a positive development, but it is not enough. There is an opportunity to further capitalize on this uptake by driving participation in decentralized trials and expanding to previously underserved populations. This requires recognizing problems and developing solutions to ensure that the progress made so far is not transitory and accelerates the development of more patient-centric medicines.

Pharmaceutical point of view

Instead of just throwing the technology at the problem, digital healthcare companies and pharmaceutical companies need to seek more deliberate application of wearable and digital technologies. There is a tension between patient burden and convenience, and the ability to piece together the precise and statistically significant endpoints for safety and efficacy that are ultimately needed for regulatory approvals. An effective DCT requires the ability to remotely monitor patients and obtain accurate data that meets both clinical criteria and those required for FDA approval.

One of the main advantages that DCT can offer using the technology is the ability to collect data in the “real world” at a biologically determined rate. This requires rethinking how we have historically defined endpoints and looking towards more functionl results that are more meaningful than the results of a one-time evaluation in the laboratory or by a doctor. Even the definition of a “fever” evolves as we better understand individual and circadian variations. It is clear that not all parameters can or should be measured at home. For example, diagnostic imaging or biopsies will not be performed in someone’s living room. But the key is decisive functional parameters that can be obtained from a patient performing daily activities that correlate with scan or biopsy results, and that provide a more granular picture of disease progression.

The successful implementation of a DCT trial is not necessarily entirely virtual. We believe hybrid approaches that incorporate remote functionality, convenient locations, and conventional methods are here to stay for the foreseeable future. Sleep is an illustrative case study. Clinical sleep studies are said to be an accurate measure of how well no one sleeps. People tend to sleep better at home, so data derived from a trial conducted with remote technology is less burdensome for subjects, more representative, and can be done at night over time, establishing patterns and derives from analyzable data. That said, sleep studies in a local sleep lab can sometimes yield valuable insights with technology that isn’t easily deployable at home. As another example, in examining the endpoints of an arthritis study, does the change in range of motion 90 days after the start of treatment reflect efficacy as much as data on the way a patient actually moves? In the real world, when not observed by a doctor. It can be the difference between a singular objective finding and the evaluation of a drug’s effectiveness by the subject’s practical function. The ability to record continuous data provides a longitudinal view of a patient instead of snapshots. Researchers can assess a patient’s progress in which each subject is their own control instead of comparing patient A with patient B for an actual analysis of applicable status and trends. This new, richer and more objective data will only be beneficial if we have the ability to structure and adequately analyze the different information flows to reap the benefits of a decentralized model.

Potential for change

With a decentralized model, a new approach to trial endpoints is needed. The recently published project FDA Guidelines regarding digital health technology and RPM for clinical investigations specifically states that new endpoints must be justified and that the method of assessing a patient’s response must be “well-defined and reliable”. This can pose a challenge to RPM and the data streams it produces. Those conducting a study want to be sure that the parameters will meet the necessary standards of safety and efficacy, and therefore approvals.

Remote patient monitoring technologies are an important tool in the DCT arsenal. They contribute to the proverbial win-win – having the cake, eating it too and not putting on the extra pounds:

  1. reduce the burden on patients, which will expand access,
  2. better and more objective data that connects clinical research to the real world; and
  3. faster recruitment, better retention, greater patient diversity, and cheaper trials that allow for more attempts to achieve the desired goal.

The pandemic has provided a glimpse of what is possible when pharma, (medical) technology, CROs and regulators work together with a sense of urgency against a common threat. To be successful in reducing urgent unmet medical needs, this spirit of cooperation must continue. This is the only way to develop trials that are situational, relevant to patients and integrated into their lives, and not the other way around.

Tony FantanaManager, Emerging Technologies Strategy – Clinical Design, Delivery and Analytics, Eli Lilly and Company

Arthur Combs, MD is a clinician, serial entrepreneur, and thought leader in wearable technology and digital biomarkers. He is a consultant to many companies, especially those commercializing new non-invasive or digital technologies.

Jiang LiFounder and CE, VivaLNK

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