The International Clinical Trial Day 2023 is shining a spotlight on Decentralised Clinical Trials: Challenges and Opportunities, prompting us to reflect on how the clinical trials industry has evolved over time. Clinical research is a fast-paced environment, demanding adaptability to keep up with the ever-changing landscape. As someone who entered the industry in 2008, I’ve witnessed remarkable transformations as sponsors, CROs, CRAs, data management, and sites have had to embrace change to meet the demands of our times.
2008 – 2012: The Paper Trial (Simple Yet Slow)
Let’s take a trip back in time when everything was delightfully simple (and frustratingly slow!). The protocols were concise and easy to comprehend. Those investigator meetings were quite the event, spanning a few days in international locations, allowing the whole team to gather and bond. During site initiation visits, the focus was on face-to-face interactions and thorough training. The delegation of authority (DoA) log was a compact list of about five tasks, spread among a few staff members. The investigational product (IP) had its place in a trusty on-site cupboard (thankfully lockable!), complete with a manual thermometer. The vigilant CRA reminded the staff to check the temperature at least once a day. Administering the IP and carrying out direct observation therapy were done in person. Sometimes, protocols required the site staff to spin off samples in a centrifuge, using uncalibrated pipettes that didn’t have any graduation marks. Ah, the good old days!
Typically, a study had a single informed consent form (ICF), the main one that had to be obtained. The CRA made regular visits to the site, engaging in the meticulous task of 100% source data verification (SDV). The case report form (CRF) was a mountain of paper, often in triplicate. After reviewing it, the CRA would tear off the second page, taking it back to the CRO office for filing, while the third copy went to the central data management team for their review. It would take a week or two before the site received an email with a data clarification form (DCF) for each query. The site staff would diligently answer the queries by hand on the form, sending it back and filing it in the CRF folder. To wrap things up, the CRA would hold exit meetings with the Principal Investigator (PI) and the team after each visit, and subsequently send a follow-up letter and report.
2013 – 2018: The Electronic Trial (Embracing Technology)
Fast forward a few years, and the life sciences industry began envisioning a different approach to clinical trials. The rise of technology, including electronic data capturing (EDC), paved the way for the first electronic clinical trial systems. This period witnessed the pioneering introduction of electronic clinical outcome assessments (eCOA) and electronic informed consent (eConsent). Goodbye paper, hello electronic systems!
The protocols grew more complex, involving sub-studies and added manuals of operating procedures (MOOPs). As a result, multiple informed consent forms with various approved versions became the norm. Precision tasks, arising from intricate protocol procedures and additional lab manuals, found their place in the expanded DoA log, appropriately assigned to staff members based on their qualifications and competency training records. IP storage and management shifted to registered pharmacies, overseen by registered pharmacists. A 24/7 centrally monitored, annually calibrated temperature monitoring system, compliant with 21 CFR Part 11, ensured the IP’s safety. Monitoring techniques also experienced a transformation, with the traditional 100% SDV CRA being replaced by risk-based monitoring (FDA guidelines released in 2013), not visiting the site frequently but the sites now using electronic case report forms (eCRF) to enter data from the source, and central monitors picking up risks such as protocol deviations, low adverse event reporting, or multiple serious adverse events (SAEs) to trigger an onsite visit. This shift to electronic risk-based monitoring led to the update of ICH GCP E6 revision 1, focusing on the sponsor’s section. A new section on quality management was introduced, emphasizing the need for upfront risk analysis and a monitoring plan that justifies the sponsor’s chosen approach (onsite, risk-based, or a combination of both). The implementation of a “quality management system” became a requirement, spanning from trial design to trial conduct to close-out.
The purpose of risk-based monitoring was to enable clinical research organizations to predict and manage risks at an early stage. This approach allowed monitoring resources to be prioritized based on risk and need, rather than adhering strictly to the traditional 100% SDV approach. As a result, sites and CRAs had to adapt to the new paradigm where data review took place off-site, and the use of electronic systems facilitated raising queries and resolving discrepancies. These changes led to faster processes and trials with quicker data turnaround times and a more proactive approach overall.
2019 – 2023: Decentralized Trials/Remote Trials
The significance of risk-based monitoring increased further since 2019, as the clinical trial management landscape faced disruptions and delays caused by the COVID-19 pandemic. Once again, the industry had to adapt, this time to the new normal of “remote” site visits. Video calls became the primary means of connecting and communicating, while documents were scanned for off-site review and data verification.
Now, one year after the COVID-19 pandemic, the era of decentralization appears to be fully realized. A late 2020 survey conducted by Oracle Life Sciences indicated that 76% of surveyed trial organizations were investing in decentralized clinical trials (DCTs). According to the FDA, decentralized clinical trials are executed through telemedicine and mobile/local healthcare providers, utilizing processes and technologies that differ from the traditional clinical trial model. These trials are conducted remotely, with patients remaining at home for the majority of the trial duration. Interactions with sites occur through software, phone applications, and connected devices, enabling critical trial data exchange and face-to-face connections with investigators using technology.
In contrast to traditional clinical trials that required patients to visit a facility for screening, consenting, and enrollment, decentralized trials offer more options for remote interactions. Many touchpoints, including screenings, consent, enrollment, and data collection, can be conducted remotely using technology. This flexibility in trial design allows for a diverse range of data collection methods in DCTs, such as electronic patient-reported outcomes (ePROs), wearable devices, telemedicine, electronic health records (EHRs), and mobile health (mHealth) apps. By collecting data remotely, DCTs reduce the burden on participants and increase study participation rates.
While decentralized trials offer several advantages, including improved access to trials and better participant retention, there are challenges to overcome. Training site staff and participants in using technology and providing tools can be demanding, and the cost of tools and data access remains high. It is crucial to address these challenges and continue exploring innovative solutions as we look to the future.
2024 and Beyond: Artificial Intelligence Trials?
As we contemplate the future, it becomes evident that the rise of artificial intelligence (AI), digital CRAs, and machine learning is transforming the field of clinical research in profound ways. The impact of AI on clinical research is highlighted in Jeff Parke’s newly released book, “From Paper to Pixels – The Rise of the Digital CRA.” This new era of “telemedicine” brings forth fresh challenges for home health CRAs, including data security and privacy concerns. The combination of AI and wearable devices can potentially monitor patients remotely, detect adverse events, and predict potential risks in real-time.
With the advancements in AI, we can expect automated data extraction, predictive analytics, and enhanced site selection processes. AI algorithms can analyze vast amounts of clinical data, identify patterns, and generate insights, enabling more precise patient recruitment, protocol design, and data monitoring. Moreover, AI can play a vital role in identifying potential safety signals and adverse events, improving signal detection and patient safety.
As technology continues to evolve, it is imperative for all stakeholders in clinical trials, including sponsors, CROs, sites, regulators, and patients, to adapt and embrace the opportunities that arise. The future holds exciting possibilities as we strive to enhance efficiency, accessibility, and patient-centricity in clinical research. The evolution of clinical trials from the “paper trial” era to the current era of decentralized trials reflects the industry’s continuous efforts to embrace technological advancements and adapt to changing circumstances.
The journey from paper-based processes to electronic systems has streamlined operations, increased data accuracy, and reduced timelines. The introduction of risk-based monitoring has optimized resource allocation and improved overall trial quality. And now, with the emergence of decentralized trials, we are witnessing a shift towards patient-centricity and improved accessibility.
Looking ahead, the integration of AI, telemedicine, and wearable devices promises further advancements in clinical research. The ability to collect and analyze real-time data, coupled with predictive analytics, will revolutionize patient recruitment, safety monitoring, and trial management. This future holds tremendous potential for driving innovation, improving patient outcomes, and accelerating the development of life-changing therapies.
At TASK Research Academy, we are dedicated to staying at the forefront of these advancements and shaping the future of clinical research. Our team of experienced professionals is committed to conducting cutting-edge trials, embracing technology, and prioritizing patient-centric approaches. We believe in the power of collaboration and strive to forge partnerships with industry leaders, research institutions, and patient advocacy groups to drive meaningful change.
As the clinical trials landscape continues to evolve, it is an exciting time to be part of the industry. Embracing technological innovations and adopting patient-centric approaches will undoubtedly shape the future of clinical research, leading to more efficient, inclusive, and impactful trials.