Technology Driving Clinical Trials -- To the Patient, For the Patient

Garun Yadav, Associate Director, Biometric FSP, Clinical Solutions, Syneos HealthWith ‘advertisements popping up on user’s screen based on their interests,' people saw a phenomenal paradigm shift to the marketing industry using new-generation technologies. Predictive and prescriptive modeling, the new buzz words, is the strategy of advertising products they are most likely to buy to customers based on their interests and searches. Furthermore, technology drove the industry toward improving efficiency with improved operating costs and never-matched customer-centricity. Multiple industries latched on to this exciting future of unending possibilities with the technology. One industry that was a pinch late in reacting to this fourth industrial revolution was the one that touches a living being the most, that is, Clinical Research. With spending a decade and around US$2.6 billion in investments on bringing a new drug to market, the Clinical Research industry has galactical opportunities to optimize costs, shorten timelines, and engage patients. However, it would be unfair to leave out that it is an extraordinarily regulated industry involving human lives. The past half a decade has been exciting for the Pharma sector; albeit a little late, the industry, its regulators, and investors have endorsed the unmatched potential of technology in the Clinical Research domain. Tech giants, including Microsoft, Google, and Tencent, have invested a record $11B+ last year in 38+ digital healthcare start-ups. These investments are distributed fairly into a spread of domains, with maximum towards Data Management and Analytics, Genomics, Wearables, Clinical Research, Remote Patient Monitoring, and Telemedicine (CBInsights). Not only new tech investors but also pharmaceutical sponsors have invested heavily in technology and new partnerships to catalyze the digital transformation. Top 10 pharma companies have contributed to 129+ digital health investments and 8+ acquisitions of digital health companies in the last 5+ years, with an accumulated investment of more than 4 Billion dollars (HelathXL). Clinical Research industry too has been the forefront drivers of digital transformation, with mHealth, Artificial Intelligence, Blockchain, Electronic Health Records, Real World Evidence, Data Science, and Data democratization being the buzz words and the most gazed topics in industry conferences across the globe. Overall, these developments have paved a way for a launching platform for digital innovation in Clinical Research. Two enduring outcomes of digital healthcare are ‘Virtual Trials’ and ‘Patient Centricity’ that are stirring and taking clinical trials ‘To The Patient, For The Patient’.

To The Patient; Virtual Clinical Trials:

Debatably first coined in 2003, as Internet-based/Remote trials, Virtual Trials are new-generation trials that allow a patient to participate in a clinical study without visiting a clinic to complete outlined protocol procedures. What is referred to as ‘Virtual Trials’ here is currently being defined using multiple terms including decentralized trials, remote trials, direct-to-patient trials, and hybrid trials based on the exposure of technology at the patient's end and clinical intervention. Major breakthrough came in 2011 with a Pfizer’s fully virtual trial on tolterodine. Consecutively, the top 10 pharmas have embraced the use of technology in driving the clinical trials virtually as compared to their traditional alternatives. The industry has progressed in bringing trials to patients' home using powered technologies with central virtual coordinating centers. By using the new-world technologies, virtual trials have demonstrated promise of reducing or even eliminating the clinical site visits and improving the patients' experience. The use of digital health, including mobile health applications, wearable devices-sensors, digital biomarkers, integrated data platforms, real-world evidence, and electronic health records, has brought in new trends in the process. A few of the process outcomes of digital transformation are noted below:

Physical to eRecruitment: Digital application- and social media platform-driven trial advertising and patient connect, engagement, education, and onboarding as compared to traditional, local, face to face recruitment. For example, Facebook, Yahoo Health, PatientLikeMe.

Paper to eConsent: Automated applications/tools to create and communicate clinical trial planned procedures in detail to the patients as well as feasibility to provide electronic consent on fingertips using tablet/smartphone moving away from the traditional at-site deportment. For example, FDA MyStudies, MedrioeConsent, MedidataeConsent

Paper to eCOA/ePRO: Electronic diaries/applications where trial patients record their live trial data about their health outcomes such as disease status, adverse events, or any other outcomes electronically instead of on paper. For example, ERT, YPrime, TrialMax, LumenisePRO, Clincapture.

Paper/Manual to eSource: Digitization of source data capturing process using electronic medium instead of recording source data manually and later transferring the data to an online database. It supports contemporaneous and original data, with promoting real-time entry and removing transcription error and duplication. For example, Electronic Health Records, Glucose Monitor, Smart Pill, Remote Chemistry, Ambient Sensors, Electronic lab records.

Clinic to Telemedicine: Video, e-mail, and online shared space interactions between patients and doctors / home care nurses, with higher levels of health-related quality of life and home care satisfaction, and fewer inpatient admissions, hospital stays, and outpatient and emergency room visits as compared to traditional on-site examinations. For example, MDLive, Lemonaid, LiveHealth, Doctor on Demand, Amwell.

Clinic to Wearables/Sensors: Vital patient data collection using sensors and devices directly, moving away from the physical site visits and recording data manually and later transferring the data to an online database.
For example, ACTi Graph, Fitbit, Apple Watch.

Clinic to Remote Monitoring: Centralized verification of trial data using mobile and/or central monitoring applications with improved efficiency and cost, substituting the prolonged on-site visits by a study monitors from the coordinating centers. For example, Promeditec, Florence, Veeva, Electronic Medical Records, File Share.

Cloud/IoT Data Integration and Analysis: Data acquisition, storage, aggregation, and analysis using IoT connected devices and Cloud based CDM/CTMS and analysis systems, moving away from non-interoperable legacy enterprise systems. Data at single platform in the form of big data, provides opportunity to apply principles of Artificial Intelligence and Data Science. For Example: Accenture Life Sciences Cloud, Amazon Web Services, Oracle Clinical One, Google Cloud.

Moving from traditional to digital methods has notable advantages, as noted below:

• Patient-Centric: Flexibility, Less Travel, Comfortable Space, More Engagement, Improved Patient Reach.

• Reduced Time and Cost: Reduced operating costs, Reduced number of sites, Reduced monitoring travel time, and cost.

• Improved Data Collection: Real-time and increased frequency of data collection with possibly more accuracy.

• Happy research team: Virtual trials clearly can make the data collection simpler and improved patient participation, thus, benefiting the research team.

As with other digital transformations, digital healthcare has its own challenges of moving from traditional to virtual platforms, including concerns about patient care and safety, regulatory compliance, fear of technology failure, complex therapeutic area/protocols, complex procedures of certain diseases such as biopsies, high-imaging machines such as MRI, process re-engineering, data integration from innumerous sources, data privacy and accuracy, technology trainings and appropriate handling of petabytes of data. Conversely, experience with new-age technologies in the past with demonstrated success in relatively less complex therapeutic areas/indication/designs show that the Virtual Trials are the future. Few classic examples worth mentioning here are SANOFI’s post-marketing surveillance complete virtual trial VERKKO using a wireless glucometer to monitor glucose, J&J’s Heartline study using APPLE Watch ECG application and APPLE’s health App, Janssen’s innovative trial using real-world data used for patient enrollment and daily living assessments being collected using an Actigraph watch; USFDA’s approval for a treatment delivery system combining a drug with an ingestible digital tracking system for schizophrenia, Roche’s study Floodlight, evaluating endpoint questionnaires with tailored remote monitoring smartphone and wearable, all these trials used novel mobile clinical trial platforms, wearables, and new-gen digital technologies. Numerous other observational studies and experiences demonstrate that the industry did move steadily to adapt to the new normal.

To this self-paced adoption, ‘COVID-19’ brought opportunities in disruption. The crisis has driven a surge of interest in virtual clinical trials, with the much-needed fuel from the policy release on March 8 2020 by the USFDA. Although there is no universal dashboard to track new virtual trials, the number of studies have risen exponentially since the virus outbreak, accelerating a long-simmering trend that could forever change the face of Clinical Research. As per an industry leader, "It would have taken us at least 5 years to generate the adoption that we’ve seen over a matter of 60-90 days.” In this rapidly evolving technology-driven world, with the above noted experiences, advantages as well as challenges, some trials could continue to traditional approach, especially therapeutic areas like Oncology, few could use hybrid approach using a mix of traditional and technology-based approach, and a few could be completely virtual, for example, Dermatology and Infection (COVID-19) studies. Overall, these technologies and trial experiences are driving the much-required change in the customer space, that is, trials ‘To the Patients.'

For the Patient; Patient Centricity:

The success of a clinical trial is highly dependent on effective patient recruitment and engagement. Patient recruitment and retention in clinical trials have long been a barrier for the industry. Recruitment rates, even for therapeutic areas with the highest patient availability, remain hindered in the low single digits. With 49% of participants drop out before completion in traditional clinical trials and 80% of clinical trials failing to meet their initial patient enrollment, many trials are getting delayed and even canceled. With such low numbers of patient enrollment and engagement, it was important to bring ‘Patient-Centric Trials’. Analyzing the data of cancelled/delayed trials and route causes behind the delays, industry acknowledged that, it needs to leverage technology to enhance the experience of patients and clinical trials need to be more patient oriented, need to reach more wide patient audience and possibly driven by patients. New healthcare strategies and the current age technology have been a game-changer in empowering the much-needed Patient Centricity in clinical trials.

• Social Media/Sponsor Applications: With record internet users across the world, including patients, social media/platforms have emerged as a great medium to engage needful patients and make them aware of diseases, trials, drug efficiencies and adverse effects. These platforms have been a one-stop shop for the industry for collaboration and communication, to hear the voice of the patients as well as for patients to learn and choose their clinical trials. These mediums show promises of reaching to a wider patient population.

• Smartphones/Mobile Applications: Mobile technology uses in Clinical Research has opened a hall of opportunities. Whether it is the pre-screening questionnaire, sharing trial-related information or eligibility information, or signing e-Consent, patients can now complete these tiresome processes on their fingertips from the comfort of their home. Voice, text, and video messages have provided a much-required boost for effective connectivity with patients, trial status updates as well as uninterrupted engagement.

• Electronic Patient-Reported Outcome/Electronic Clinical Outcome Assessment (ePRO/eCOA) Tools: ePRO/eCOA tools have facilitated the real-time recording of patients' clinical trial outcomes, which has helped in reducing the burden, non-compliance and turnaround time and also has helped in enhancing the data quality. Real-time capturing of outcome has helped in safety monitoring, immediate treatment, and needed protocol adjustments helping in increasing patient safety and monitoring.

• Wearables/Sensors/Virtual Trials: Virtual trials as whole, reduces the patient burden of travel to site, in some cases long distances, to a centralized site on a regular basis and instead create virtual sites in a patient’s home. Additionally, wearables/sensors release the burden of tracking and recording the trial procedures. Collectively providing patients the comfort of home treatment.

In addition to technology, industry strategies too are a driving factor in personalizing the clinical trial experience for patients. Whether its developing patient friendly websites, new digital health strategy, patient centric roles, asking for patients input to the trial or developing data science solutions to ease patient burden during trials, new healthcare strategies are focused on improved patient participation, retention in studies and providing increased convenience to the primary customer. Cumulative outcomes of technology and sponsor’s efforts, are helping the primary customer to be in the center of the process and trials to be ‘For The Patients’.

The Conclusion:

Overall, looking at promising outcomes like virtual trials and patient centricity, digital technologies have the potential to completely transform the entire clinical research process. With the never seen investments pouring in, regulatory bodies endorsement, the most recent technology push with USFDA Launching Digital Health Center of Excellence and proven proof of concept of early adopters at disposal, its only forward to go in utilizing and optimizing the use of technology in clinical research. The day will not be far when we will see the first approved medicine of a 100% virtual trial that would serve as the benchmark for future evaluation of technology driven trials.