Digitally Enabled, Patient‐Centric Clinical Trials: Shifting the Drug Development Paradigm

Abstract

The rapidly advancing field of digital health technologies provides a great opportunity to radically transform the way clinical trials are conducted and to shift the clinical trial paradigm from a site-centric to a patientcentric model. Merck & Co., Inc.'s (Kenilworth, NJ, USA) digitally-enabled clinical trial initiative is focused on introduction of digital technologies into the clinical trial paradigm to reduce patient burden, improve drug adherence, provide a means of more closely engaging with the patient, and enable higher quality, faster, and Accepted Article This article is protected by copyright. All rights reserved more frequent data collection. This paper will describe the following four key areas of focus from Merck & Co., Inc.'s (Kenilworth, NJ, USA) digitally-enabled clinical trials initiative, along with corresponding enabling technologies: (1) use of technologies that can monitor and improve drug adherence (smart dosing), (2) collection of pharmacokinetic, pharmacodynamic, and biomarker samples in an outpatient setting (patientcentric sampling), (3) use of digital devices to collect and measure physiological and behavioral data (digital biomarkers), and (4) use of data platforms that integrate digital data streams, visualize data in real-time, and provide a means of greater patient engagement during the trial (digital platform). Furthermore, this paper will discuss the synergistic power in implementation of these approaches jointly within a trial to enable better understanding of adherence, safety, efficacy, pharmacokinetics, pharmacodynamics, and corresponding exposure-response relationships of investigational therapies as well as reduced patient burden for clinical trial participation. Obstacle and challenges to adoption and full realization of the vision of patient-centric, digitally-enabled trials will also be discussed.

Predictors of Research Subject retention - Repetitive non-adherence or socioeconomic factors: Insights from a urological clinical trial

“…We agree with acknowledging and addressing the barriers up front, to prevent non-adherence in a patient centric manner. 22 Dockendorf et al advocated the use of digital health technologies comprising of smart dosing, outpatient sampling and digital monitoring to increase subject retention with reduced burden on patients. 22 However, further research will be required to identify common barriers and solutions encountered in real-time during clinical trial activity.…”

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“…In late phase trials, site visits are greatly diminished and opportunities to collect biological samples are minimal. Remote sampling or mobile phlebotomy could be very powerful for pharmacokinetics, pharmacodynamics or safety monitoring in this paradigm [ 37 , 38 ]. Remote collection of samples for viral shedding could be powerful for vaccine development.…”

“…We should use technology to develop patient centric sampling that is less invasive, less painful and more convenient for patients. These approaches can be combined with decentralized trials to enable innovative virtual trials [ 35 , 53 , 54 ]. The bioanalytical community will need to develop and validate assays that enable remote sample collection.…”

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“…Another obstacle in the implementation of the microsampling to the TDM process arises from the difference between capillary samples and traditional TDM samples e.g., serum or plasma derived from the venous blood. To confirm that concentration data obtained from the alternative microsampling approach is equivalent with traditional samples, bridging studies that overcome analytical and physiological issues need to be included into the validation process [ 9 , 57 , 58 ]. Small sample volume and complex matrix demand analytical method development to focus on extraction procedures and selection of sensitive analytical methods.…”