Emerging technologies and industry enablers of future drug trial designs in a decentralized world

Source: Healthcare Weekly

Almost everything went online due to the COVID-19 pandemic, from remote collaboration with coworkers to ordering groceries and conducting online classes. But unlike other industries that have responded rapidly to COVID-19, clinical trials have been slower to adapt. One thing the pandemic has done however, is significantly catalyze and accelerate the adoption of decentralized clinical trials (DCTs).

• Travel restrictions and lockdown conditions prevented CRA (clinical research associates) visits and patient participation in clinical trials. These challenges have led to difficulties in meeting protocol-specific procedures, diagnostic testing and protocol-scheduled visits. The limited availability of ancillary services at sites, such as radiology, also led to challenges with sites where some of these departments were simply non-functional.
• Because historically, clinical trials have been designed and conducted with a site investigator-centric approach with RCTs (randomized clinical trials) optimized for an analog world, these have been costly, laborious and time-consuming. Trial participants had to travel to study sites on episodic schedules dictated by the operational convenience of the investigators and study teams, rather than based on the disease’s natural history or patient preferences, thus leading to exclusion from studies.
• Clinical trials became increasingly difficult to ensure continuity and integrity, especially long-term studies; plus, there has been increasing pressure on the researchers for real-time oversight and data sharing. Patient safety became a major concern in a way that hadn’t never been before. The clinical studies faced delays and suspensions as a result, with many patients seeing the trials as inconvenient, or too much of a burden. With no real way to respond to the pandemic, many clinical trials were temporarily paused or abandoned altogether.

Catalyzing and accelerating decentralized clinical trials

With COVID-19 making the operational feasibility of clinical trials more challenging, this breeds the new age of decentralized clinical trials (DCTs). Digital health technologies (DHTs), such as wearables, smart devices, environmental sensors and low-risk, consumer-grade devices, are catalyzing the transition from centralized to remote settings in DCTs, with a remote-first paradigm. DHTs enable multi-site reporting of trial-related activities, communication, inclusion, diversity, consent, enrollment, and retention for a study.

The traditional clinical trial models that involve in-person visits by patients prohibit participation from otherwise willing patients as the majority of them live more than two hours away from the research site, nearly half of the participants find it difficult to stay enrolled due to poor health, while 85% of trials fail to recruit patients on time due to logistical and other issues. Convenience is increasingly critical to patient enrollment and retention.

A paradigm shift in clinical research activities

The shift of clinical trial activities closer to patients has been enabled due to evolving technologies such as Software as a Service (SaaS), wearables, and mHealth. Features like remote electronic informed consent, remote patient monitoring, electronic clinical outcomes assessments (eCOAs) and end-to-end digital tools have enabled more procedures to occur away from research sites.

Patient-centric, decentralized trial designs are critical to mitigate concerns of patients, such as replacing in-person visits with clinical-grade videoconferencing, telemedicine, and visiting home nurses. Decentralized trials need to provide high-quality logistical and technical support and optimize the patient-investigator experience. Hybrid trial designs and maturity tools, such as novel sensors, voice and video, remote monitoring, alternative sites, will increasingly be validated by regulators, establishing standards for their broader use.

Considerations and challenges for decentralized trials

Investigators and researchers looking to deploy remote and decentralized trial designs face some inherent challenges such as:

• The technology used for decentralized trials should be easy to use and intuitive to learn. It should allow the study to fit seamlessly into the patient’s daily routines and should be accessible to them from any device they are familiar with, like smartphones, laptops, desktop computers or iPads.
• The tools and processes should have been thoroughly tested and the study team should be aware of any potential pitfalls requiring mitigation.
• The HCPs (healthcare professionals) should be able to visit multiple patients on the same day while maintaining high standards of care.
• Elimination of some site visits should be facilitated by the tool to reduce the logistics burden on the participants, wherever patient travel is essential.
• The study team should be accessible to seeing patients at their time and location of convenience, especially the elderly or first-timers.
• Finding new technology vendors who could conduct trials in a timely and compliant manner.
• The vendor should be able to deliver medications and medical supplies equipment safely and legally.

Modular and flexible SaaS solution to address patient needs

COVID-19 has been one instance where deviations from standard operating procedures (SOPs) may have occurred. But it is important for a study to identify and address these deviations to remain complaint. This will mitigate any risks of data integrity, regulations and patient safety. Some of these challenges will not go away with COVID-19 and will only increase over time.

The patient-centric approach of DCTs can address various patient needs that often go unmet in traditional study designs. A modular and flexible SaaS solution provides unique opportunities to move toward a new patient- and site-centric paradigm. R&D (research and development) teams and therapeutic-area leaders can leverage the capabilities of SaaS eClinical cloud solutions to deploy across portfolios.

Bridging the gap for efficiencies and effectiveness

Where on-site monitoring was once a regulatory requirement, there is now a greater emphasis on moving away from 100% SDV (source data verification) as regulators understand that sponsors need to look for efficiencies and effectiveness in the drug development process. Remote monitoring, combined with risk-based monitoring, facilitates remote source data verification (rSDV) by a specialist team. rSDV is conducted by site teams sharing redacted copies of trial-related source documents, video review of records, and provisioning authorized, read-only access to electronic medical records (EMRs) for finite periods.

Prerequisites and factors that limit faster DCT tech adoption

Some of the key prerequisites for decentralized trials and virtual healthcare are:

• The ideal solution should be a single and cohesive platform which is capable of collecting, reviewing and analyzing unstructured trial data.
• It should be able to track study progress against the key indicators, even for the most complex trials.
• The system should allow for immediate aggregation, visualization and streamlining site and review team interactionswith a clear interface.
• It should enable multiple-site studies with centralized monitoring dashboard.
• The application should have intelligent workflows for better collaboration among study teams.
• Upload of lab reports, medical records and visit documents in real-time should be possible.
• It should have patient eDiaries, questionnaires and two-way communication capabilities by video, audio, SMS, and email.
• The tool should have capabilities for long-term follow-up studies in a virtual environment.
• The platform should be easy to set up, and conduct studies of any scale, size or duration, with or without patient travel involved.
• The solution should be user-friendly, scalable, modular, flexible and adaptable that works for sponsors and researchers.

Paving the way for the trials of the future

Trials of the future will have improved speed and accuracy, and regulators will be recommending pushing for remote monitoring for the continuance of trials without leaving their homes. As per a Pharmafile study, 85% of trials failed to finish on time as of 2016, impacting trial study sponsors by up to $8 million per day. Drug-based interventional DCTs increased from 7% CAGR (compound annual growth rate) in 2014 to 77% in 2020 after the onset of COVID-19, as per a ZS’s DCT database, referencing data from more than 1,000 trials. Horizontal and vertical integrations among technology solutions would only increase the demand for end-to-end clinical study solutions to deliver DCTs.

Workflows, milestones, patient-reported outcomes and other study-related activities can all be automated and tracked on a study calendar on a robust SaaS study solution. Documents can be reviewed and routed based on policies to reach the right persons, and lab report uploads can happen in seconds, not hours and days. Systems that allow for secure document collaboration, FDA (US Food and Drug Administration) compliant eSigning and FDA 21 CFR Part 11 (Code of Federal Regulations) signing makes monitoring convenient, easy and quick.

Ensuring trial participant’s privacy

DHTs process data on a trial participant’s device, significantly broadening the possibilities of more data, frequently and continuously, and enhance trial participant’s engagement and privacy to an extent not possible with manual workflows. There are significant benefits of digitizing and streamlining clinical trial study processes. Industry-leading SaaS-based DCT solutions can overcome functional silos and allow sponsors to establish consistent processes to facilitate scaling and multi-site remote testing.

DCTs and DHTs are here to stay

DCTs, enabled by DHTs will accelerate the pace of clinical research while protecting the users. The combination of DCT and DHT technologies allows for heterogeneous and continuous data collection in real-world settings, enabling better evaluation of the novel medical intervention, and determination of the safety and efficacy of an investigational medical product. Time saving and cost saving by a modular and flexible SaaS solution that enables a speedier and more accurate clinical trial, one which is also available on a per participant subscription basis, means sponsors, CROs (contract research organization), researchers and academicians may bring more therapies to patients more cost-effectively, quicker, and with improved access and efficiency.

Decentralized clinical trials meet patients where they are

Decentralized technologies allow research teams to build research sites where patients are, not just where trial sites or healthcare facilities are located, thus allowing the teams to have a more diverse, inclusive and representative participating population, and achieve wider and reliable industry-wide goals. Meeting people where they are makes it easier to enroll participants who meet a study trial’s criteria. Decentralization allows for hyper-local trials, allowing research teams to move where diverse, minorities, underprivileged and underrepresented population feels most comfortable and likely to participate.

The promise of SaaS solutions in transforming the trial and healthcare industry

With a modular SaaS solution, study teams with diverse clinical development pipelines can tailor their activities to specific demographics, endpoints and interventional modalities. The use of a modular and SaaS-based flexible study trial solution also ensures that monitoring obligations are fulfilled, protocols are deployed correctly, and trials are conducted as per good clinical practices (GCPs). If you are the sponsor designing a study protocol, it will be good to embrace a tried and trusted SaaS solution that generates reliable clinical evidence, maximizes compliance, walks the talk of patient-centricity, maximizes diversity, equity and inclusion, reduces the logistical burden on the participants and study teams, and accelerates patient recruitment and retention. For more information, visit www.jeevatrials.com.

LEADERSHIP AND BIOS

Harsha Rajasimha, Ph.D., Founder and CEO

Dr. Rajasimha is the founder and CEO of the decentralized clinical trials software company, Jeeva Clinical Trials Inc., based in Virginia. He is a precision medicine data scientist-turned social entrepreneur on a mission to accelerate human-centric clinical research through technology innovation and global advocacy. He is the founder and chairman of the humanitarian non-profit Indo US Organization for Rare Diseases. Earlier, he served as cofounder and co-chair of the Organization for Rare Diseases in India from 2013 – 2019. He is academically affiliated as a faculty in the School of Systems Biology at George Mason University in Fairfax, VA since 2012.

Prior to founding Jeeva, Harsha was leading the healthcare and life science R&D practice at NTTDATA Services, a global top 7 consulting company. He was Vice President of business development at Strand Life Sciences where he led the commercial launch of next-generation sequencing based genetic testing panels for rare diseases and Cancer. Earlier, he was a Sr.

Director of Bioinformatics and Translational Research at Dovel Technologies, a Virginia based health IT company, where he covered academic and US Federal Government contracts, advised FDA on the STARLIMS implementation program at their office of regulatory affairs.

Dr. Rajasimha has over a decade of experience working on various interdisciplinary projects involving genomics and big data as a consultant for clients including National Cancer Institute, National Eye Institute, Georgetown University, and Genome International Corporation. His research has focused on the genomics and systems biology of diseases including cancer, infectious diseases, neuro-muscular diseases, and retinal degenerative diseases. He completed his M.S. in Computer Science and Ph.D. in Genetics, Bioinformatics and Computational Biology at Virginia Tech, where he developed and applied reusable simulation models of mitochondrial DNA heteroplasmy dynamics to study various diseases.”