How Digitalization and DCTs are Transforming the Clinical Landscape

Dr. Rajesh Jain- PharmaLex

COVID-19 shifted sentiment toward decentralized clinical trials and demonstrated that they could benefit patients and sponsors alike. Dr. Rajesh Jain of PharmaLex discusses changing sentiment and the technology behind the uptake of DCTs.

What began as a trickle a decade ago, with very small numbers of virtual trials, turned into a tsunami during the COVID-19 pandemic. With reports that patient access to trial sites fell by 80%¹ it was evident that sponsors needed to mobilize quickly to keep trials going. As a result, decentralized clinical trials (DCTs) started to take center stage.

DCTs are a key manifestation of digitalization, which itself is well-established across the pharmaceutical industry.

Digitalization has paved the way for greater R&D innovation by enabling interoperability and data sharing. In clinical trials, digitalization has made it possible for many trials, or aspects of a trial, to be conducted remotely. During the pandemic, as healthcare came under enormous pressure from COVID-19 related care and as people were forced to isolate, DCTs were often the only way to keep trials going.

Yet, even as site-based trials became operational again, many sponsors and clinical research organizations chose to continue with the DCT model in light of patient preferences. Pharmaceutical leaders at a McKinsey Clinical Operations Roundtable, held in 2020, said adapting to DCTs during the pandemic was effective in addressing patient needs.²

The two advantages of DCTs are 1) connectivity and networking and 2) real-time data sharing. The connectivity component makes the trial experience more attainable and straightforward for patients, and technology platforms connect all stakeholders involved in a trial. This is the essence of decentralization.

The second component, data sharing and data acquisition in real time, allows processes to be handled more efficiently and enables recruitment to be expanded to more patients in a wider range of geographic locations.

The Technology Behind DCTs

DCTs depend on a whole raft of different technologies. At the front end, digital solutions include a number of patient-facing platforms. These are helping to make clinical trials more patient-centric, for example with the use of e-consent, which are much easier for patients to manage than traditional paper methods. Studies have found that when well designed and patient-centric, e-consent does ensure patients are better informed³ with better consent conversion rates than paper-based trials. From the point of view of trial staff, e-consent reduces burdensome manual processes and reduces the likelihood of errors occurring.

Once the trial starts, patient engagement applications keep trial participants connected to those running the trial – the investigators and study teams, as well as their own clinicians. These tools provide reminders to the patient to take their medication, fill in a questionnaire or perform other activities such as using sensors to measure blood pressure.

The heart of any study is the collection of data from various sources – patient records, laboratory tests, questionnaires, pharmacy dispensing records and more – which traditionally has been a very manual process. The use of a data collection platform, which spans wearables, devices, digital health records, and other e-source platforms, allows trial staff to capture data in real-time. With the addition of telemedicine/patient concierge services, patients stay connected to their clinician/healthcare to support their healthcare needs throughout the trial.

Full DCTs include a third crucial element, which is the integration of technology platforms for the exchange of medical information and records. Access to an expanded healthcare network paves the way for better patient identification and enrollment and to devise innovative clinical trial designs. As an example, the Joint Research Centre (JRC) – the science and knowledge service of the European Commission – developed the Central Metadata Repository to enable the integration of data from rare disease registries across Europe.⁴ The purpose is to make data on patients with rare diseases searchable and usable for all stakeholders.

The rapid and continual evolution of technology solutions for remote data gathering and for the exchange of information – e-patient reported outcomes (ePRO)/e-clinical outcome assessments (eCOA), eConsent, telemedicine, eSource, site portals, interactive response technology (IRT), virtual scheduling solutions, wearables, EHR connections, EDC and more -- means DCTs will become easier to conduct and more broadly accepted in the coming years.

Making Virtual a Reality

During COVID-19 when patients were under home quarantine, entire studies were conducted remotely with all study procedures including patient reported data (vitals, quality of life questionnaires, medication adherence, etc.) being collected using a mobile app. The benefit of DCTs is patients can follow the protocol (taking their medication, filling in questionnaires, sending in blood pressure and other measurements) from their own homes, thereby removing or reducing the need to visit sites.

Many trials for COVID treatments were entirely digitalized, with patient reported outcomes, medication adherence management, patient monitoring, etc. all being done via an app. Using digital data collection platforms, investigators and sponsors were able to receive data on their dashboards and integration of technology platforms ensured transparency for all participants and stakeholders.

One example during the pandemic was a fully decentralized trial in atrial fibrillation patients (DeTAP), which was a single-arm virtual trial of 100 patients with AF that took place over a period of six months.⁵ Patients were recruited by various means, both traditionally and through social media, though 94 of the 100 patients enrolled was achieved from a social media drive. Medication was self-administered and patients sent their electrocardiograms (ECGs) and blood pressure (BP) measurements through apps and completed surveys and medical follow up remotely. According to study findings, adherence was high throughout the study and most participants indicated a willingness to continue.

The one area of concern for many stakeholders is data security and data authenticity. However, the right technology and processes – for example, using permissioned blockchain which provides a distributed ledger that is only accessible to users with permission – ensures the establishment of data provenance, security, privacy and auditability required for clinical trials.

While the obvious benefit of DCTs is removing the burden for patients, they also benefit the trial process itself. First, recruitment opportunities are broadened to a more diverse pool of patients. Second, DCTs offer the potential to speed up the whole process, ultimately enabling products to be brought to market more rapidly.

From a resource perspective, the clinical trial investigators can be supported by a centralized study team, comprising qualified physicians and nurses, to manage the interactions with different sites, patients, regulatory documentation management, etc. In addition, qualified study personnel such as nurses, raters and laboratory technicians, can conduct in-home visits or visits to nearby care centers in collaboration with the investigator and sites which can help to streamline the process and improve study outcomes including recruitment, retention and data quality.

Making Adjustments for DCTs

While there are clear benefits, there are also process changes involved. Since data review and analytics can be done remotely, there is a need to ensure careful oversight of remote monitoring and risk assessment and to adapt processes based on what is being seen in the trial.

Virtual trials do also require changes to the protocol design to incorporate digital components. This will influence trial applications with ethics committees or the institutional review boards (IRBs) as well as regulatory submission activities. Understandably, these changes do raise some concerns for sponsors, such as having assurance that the health authorities will accept data from wearables and the process won’t be flagged by ethics committees.

These concerns and the cautious nature of the industry explain why most sponsors still only use components of digitalization, such as e-consent technology and digital patient engagement modules, while choosing more traditional processes to manage data exchange.

Nevertheless, the mood across industry and with regulators is changing. The Food and Drug Administration and the European Medicines Agency have provided guidances to help sponsors safeguard patients, manage the integrity of their trial data and ensure they are compliant with GCP.^6,7 The FDA also established the Digital Health Center of Excellence to support the development and review of digital health technologies that are instrumental in DCTs, such as mobile health devices, Software as a Medical Device (SaMD) and wearables as a medical device.⁸

A number of initiatives are helping to support the shift to virtual trials. These include the Clinical Trials Transformation Initiative (CTTI),⁹ a collaborative program to address issues related to digital trials; and the Decentralized Trials & Research Alliance (DTRA),¹⁰ which is committed to establishing best practices to support DCTs; the Trials@ Home consortium,¹¹ which is seeking to ensure acceptance of DCTs for patients in Europe; and the #NoGoingBack movement¹² that seeks to ensure the advances made with clinical research are preserved.

The central premise of DCTs is that they hold the key to transforming clinical research by making it patient-centric and by shifting the burden of clinical trials away from the patient. As the comfort level with decentralization grows and as technology continues to support virtual trials, it is likely that DCTs will eventually become the norm.

References

1. No place like home? Stepping up the decentralization of clinical trials, McKinsey, June 2021, https://www.mckinsey.com/industries/life-sciences/our-insights/no-place-like-home-stepping-up-the-decentralization-of-clinical-trials
2. No place like home? Stepping up the decentralization of clinical trials, McKinsey, June 2021, https://www.mckinsey.com/industries/life-sciences/our-insights/no-place-like[1]home-stepping-up-the-decentralization-of-clinical-trials
3. Replacing Paper Informed Consent with Electronic Informed Consent for Research in Academic Medical Centers: A Scoping Review, May 2020, https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC7233043/
4. New user-friendly tool for European Platform on Rare Disease Registration, JRC, Feb 2022, https://joint-research-centre.ec.europa.eu/jrc-news/new-user-friendly-tool-european[1]platform-rare-disease-registration-2022-02-28_en
5. Pandemic-proof recruitment and engagement in a fully decentralized trial in atrial fibrillation patients (DeTAP), June 2022, Nature, https://www.nature.com/articles/s41746- 022-00622-9
6. Guidance on the Management of Clinical Trials During the Covid-19 (Coronavirus) Pandemic, Version 5, Oct 2022, https://health.ec.europa.eu/system/files/2022-02/ guidanceclinicaltrials_covid19_en_1.pdf
7. Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency, Aug 2021, https://www.fda.gov/regulatory-information/search-fda-guidance[1]documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19- public-health-emergency
8. FDA Launches the Digital Health Center of Excellence, Sept 2020, https://www.fda.gov/ news-events/press-announcements/fda-launches-digital-health-center-excellence
9. Clinical Trials Transformation Initiativehttps://ctti-clinicaltrials.org/
10. The Decentralized Trials & Research Alliance, https://www.dtra.org/
11. Trials@Home, https://trialsathome.com/
12. #NoGoingBack, https://www.nogoingback.health/

Rajesh Jain, MBBS, is Vice President Operations India and Global Lead Clinical Services Solutions at PharmaLex. Rajesh has spent many years in the pharmaceutical industry, working in global clinical trial management as well as in medical affairs and leading business operations. He is focused on bridging medical science and clinical operations with digital technologies for improved efficiencies and outcomes. Rajesh received his Bachelor of Medicine, Bachelor of Surgery from Grant Medical College Mumbai.

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