Today is Clinical Trials Day 2021 — a day for recognizing the importance of clinical research in protecting and improving global health. The day has taken on even greater significance this year in light of the recent one-year anniversary of the start of the COVID-19 pandemic and all of the changes the clinical trials industry has seen since early 2020.
Xtalks is committed to supporting trials by serving as a provider of free educational content in the form of webinars, articles and job listings to help those in the industry stay up to date and advance their careers in the field. Amid the alarmist headlines posted by other media outlets, Xtalks has remained balanced in its reporting of COVID-19 clinical trial results and safety data.
Some of the main themes in the clinical trials space during the past year include the widespread adoption of decentralized trials (DCT), leveraging modern, digital technologies, increased patient inclusion and diversity and a greater positive perception of clinical trials among the general public.
Clinical Trials Day 2021: The Year of COVID-19
Last year’s celebrations came just over a month after the World Health Organization (WHO) officially declared the COVID-19 outbreak as a pandemic. As physicians’ offices and primary care centers sought to limit the number of people passing through their doors — turning instead to telehealth wherever possible — almost all realms of healthcare and medical research, including clinical trials, were affected, with many temporarily halting new patient recruitment and dosing.
As the efforts to develop a vaccine against SARS-CoV-2 intensified, clinical research groups found themselves designing trials to evaluate them under the confines of tighter timelines. Though clinical researchers recognize the importance of any trial they run — from new therapeutics for pediatric cancers to pioneering gene therapies for rare diseases — the trials underway for COVID-19 vaccines and treatments were part of an unprecedented emergency response of global significance.
“At an early stage during this pandemic, it quickly became apparent that to end this global crisis we don’t just need COVID-19 vaccines, we also need to ensure that everyone in the world has access to them,” said Dr. Seth Berkley, CEO of Gavi, the Vaccine Alliance, the organization that’s co-leading the COVAX Facility to ensure equitable access of the COVID-19 vaccines to all countries around the world regardless of wealth.
According to the NIH’s clinicaltrials.gov, there are currently 5,706 clinical trials for COVID-19 registered in the database. The fight against COVID-19 has not only been led by vaccines, but also a need for effective treatments. Industry, academic centers and hospital institutions were all part of massive efforts to design, repurpose and test different treatment strategies to treat and manage COVID-19.
COVID-19 Challenges for Clinical Researchers
The past year was a challenging one for clinical trials as the pandemic situation put into jeopardy the development of timely treatments for patients. Sites grappled with continued lockdowns that limited access for both patients and practitioners. In many cases, remote and virtual trials were largely able to fill in the gaps.
However, some trials were easier to shift to virtual models than others. For example, oncology and rare disease trials were amongst the most affected by the pandemic.
Dr. Kazem Kazempour, President and CEO, Amarex Clinical Research, an NSF International company, told Xtalks that the disruption to oncology clinical trials was a major concern because of the great medical need for new therapies for patients with terminal illnesses. He explains how due to COVID-19, patient enrollment decreased, delayed or missed visits increased and the likelihood of incomplete patient data increased. In addition, trials with intravenous administration of therapies were a challenge to adjust for, and data collection, verification, query generation and resolution were all delayed.
To help maintain high operational performance, technologies such as telemedicine, remote patient access and other digital tools were used to ensure the preservation of trial integrity and quality.
“Clinical research is a risk-averse industry. We like orderly studies that meticulously follow protocols and regimens. That was all thrown out the window during the pandemic leaving many researchers unsure of what to do,” says Nico O’Kuinghttons, VP of Clinical Trials, Tissue Analytics, a company focused on leveraging digital and AI technologies for wound care treatments.
In light of the disarray, the challenge was to adapt trial processes that would maintain the integrity of the trial to enable success. Questions such as how could existing data be used with new incoming data, for example, were concerns for in-progress/active trials. Trials that were already ongoing had to adapt especially fast, which encouraged researchers to make decisions quickly. Dr. Kazempour says this allowed them to be more open to alternatives like virtual and decentralized trials as they could help keep research projects going.
Many agree that adapting ongoing trials was one of the biggest challenges. Dr. Matthew Roe, Chief Medical Officer for Verana Health, explains how many of the trials that were in progress at the onset of the pandemic relied heavily on human resources. Trial sites suddenly had to decide whether it was safe to continue conducting in-person trial visits for existing participants and for enrolling new participants, and if it not, enrollment had to be suspended for some time while remote follow-up visits were implemented for those already enrolled.
And it wasn’t just trial participants. Trial sponsors faced the same issue with trial monitors who could no longer visit sites and had to manage everything virtually, explains Dr. Roe. This included reviewing source documents at participating sites and re-directing investigational drugs to patients’ homes from clinical sites. Therefore, the greatest challenge initially was to switch over to remote operations and manage the logistics so patients could continue to participate in trials and get the investigational therapies, along with continued management of trial procedures with a high degree of quality.
“There was a lot of messiness in the first several months, but eventually the clinical trials industry was able to continue just like the delivery of healthcare continued but with appropriate safety measures in place,” says Dr. Roe.
Improvements in Public Perception of Clinical Trials
As newly developed COVID-19 vaccines started entering large-scale clinical trials in the summer and fall of 2020, the world was watching with eyes peeled. The unprecedented situation brought about an unprecedented focus on clinical trials. With concerns of safety riding high given the speed at which the vaccines were being developed, interest in how clinical trials are conducted, what endpoints are and how regulatory agencies evaluate trial data became mainstream topics of discussion.
And the discussion transcended COVID-19. COVID-19 vaccine trials helped many consumers become more familiar with the role and importance of research in general, says O’Kuinghttons. “There were stories in mainstream media about research into hyperbaric oxygen chambers, [the] way severe wounds are treated and other novel therapies to treat COVID.”
Conversations about clinical trials and novel therapies were constantly in the news and people began to sit up and take notice of the value of the research process.
Moreover, and most importantly, says O’Kuinghttons, is that the increased mainstream interest in clinical trials helped make people more willing to participate in trials in the future.
In fact, Dr. Roe told Xtalks that in his opinion, the public’s perception and trust of clinical trials has markedly improved during the pandemic.
He says inclusion and diversity were key to the success of the COVID-19 vaccine trials as, “everyday citizens across many countries volunteered to participate in large numbers, so the altruism of diverse populations for participating in these trials was a strong glimmer of hope during the throes of the COVID-19 pandemic.”
John Reites, CEO, THREAD, a company that offers a comprehensive DCT platform, told Xtalks that due to widespread coverage of COVID-19 vaccine clinical trials, more people know about clinical trials and their benefits now.
“We see a positive response from participants to clinical research when they are educated about the clinical development process, why it is important and why patient safety is the driver of long timelines for medicines,” he says.
And it is the hope of patients and the clinical trials community that the rapid development of COVID-19 vaccines could be mirrored and serve as a template for the more expeditious development of innovative therapies and potential cures for other diseases. With the right blend of resources, motivation and participation, COVID-19 demonstrated how robust clinical trials can be conducted with great success.
Shift to Decentralized Clinical Trials
The COVID-19 pandemic spurred an unexpected and unintended shift to virtual or DCTs. Due to the pandemic, many clinical centers running trials were forced to halt trial operations, causing many of them to be brought to a standstill or some to even be scrapped altogether. Patients could no longer visit centers to provide important biological samples or be administered a given treatment.
Adapting to the new normal of the past pandemic year has been key to survival in many industries, and clinical trials were no different. This led the industry to quickly adapt to remote or decentralized trials.
Fortunately, DCTs were not a new concept. Over the past several years, there has been a steadily increasing trend towards the adoption of DCTs or hybrid trial models, with the latter incorporating a mix of traditional on-site and at-home, virtual approaches. For example, in a hybrid vaccine trial, a patient may visit a site to be administered a vaccine dose but monitoring and follow-ups are then conducted remotely.
A decentralized trial incorporates a variety of solutions that include digital tools for obtaining consent data, options for home visits by health care providers, direct-to-patient drug distribution, remote monitoring and diagnostics and the use of local labs and imaging centers. Decentralized trials use novel technologies and strategies to offer patients options for participating in trials outside of traditional clinical settings to improve convenience and access. As such, they offer a more patient-centric approach by reducing time, cost and physical burdens on the patient and their caregivers with respect to factors such as traveling to sites or taking time off work or personal time to participate in trials.
“We learned a common theme [during the pandemic], that the patient experience is essential to being able to implement a successfully enrolling trial, in all circumstances,” says Tom Lemberg, founder and CEO of Curebase, a company that offers a decentralized clinical research solution through software technology.
While some trial vendors, CROs and clinical centers had already been adopting or testing virtual trial models pre-pandemic, others had not been doing so quite as rigorously, perhaps out of reluctancy or simply not having had the chance or resources to “trial” them. However, the pandemic brought about both the opportunity and necessity to do so for many in the industry.
In fact, according to a survey conducted by Informa Pharma Intelligence on behalf of Oracle Health Sciences, 76 percent of survey respondents noted that the pandemic accelerated their adoption of decentralized clinical trial methods. Interestingly, the same percentage reported at least some of their trials had already been decentralized while 38 percent revealed that more than half were decentralized. Despite this, respondents remain concerned about decentralized trial data collection and quality, as well as regulatory guidance.
Patient-Centricity: Inclusion and Diversity
As part of the greater focus on patient-centricity that comes with decentralized trials, off-site trials offer greater opportunities for patient inclusion and diversity. Decentralized trials can expand the pool of participants geographically, allowing enrolment of patients outside of local site areas, and also in terms of physical abilities by offering greater flexibility, accessibility and convenience through at-home trial options.
“Decentralized clinical trials present a major shift to modernize research by expanding access to trials as a viable care option for more diverse populations than ever before,” says Reites.
Like Reites, Dr. Roe says the positive benefit and response of an increasingly industry-wide focus on inclusivity and diversity within clinical trials was manifested in the development of COVID-19 vaccines, explaining it is precisely why vaccine developers “were able to rapidly conduct trials for COVID-19 vaccine candidates, recruiting tens of thousands of participants for the trials around the world in record time.”
Reites says the pandemic helped fuel the recognition that it is key to provide a hybrid decentralized approach with flexibility to adapt to any therapeutic area and patient population.
Clinical Trial Technology
Key to the success of decentralized and remote trial models is the incorporation of digital technologies that enable faster and more convenient means for healthcare providers to connect and communicate with patients and collect data.
Follow-up appointments are conducted remotely through telemedicine or digital communication platforms. A major area of consideration and concern has been ensuring quality data capture. Technologies such as electronic data capture (EDC) systems allow for rapid recording, transfer and sharing of data, real-time edits and checks and rapid analysis with built-in analysis tools to generate quality, robust data. Data integrity is key to a successful trial.
Additionally, new technologies are enabling innovative ways to capture and assess data. For example, O’Kuinghttons explains how the pandemic has put the value of digital and mobile technologies at the forefront in wound care research.
“Wound care researchers have seen firsthand how smartphones can be used to send images of wounds and to keep participants engaged in the research process. Virtual trials made it easier for participants who couldn’t travel because of lockdowns to remain enrolled in clinical trials. The use of smartphones helped researchers remain more connected with their participants and to answer questions, educate and keep them involved, more so even than before the pandemic.”
While he acknowledges that virtual and mobile technologies can’t completely replace the need for in-person visits, he says they can serve as an important adjunct.
He also encourages researchers to look at mobile and digital technologies and decentralized clinical trials “not as a contingency plan in the event of future lockdowns but as tools to be leveraged to bring value to the research process, especially when it comes to patient enrollment and engagement.”
Clinical Trials Day 2021: Trials of the Future
While the overarching theme of the past year has seemingly been trials going virtual or decentralized, the patient as the primary focus of clinical research is one thing that did not change.
Pandemic-driven remote trials widened options for patients and ensured ongoing trials were not disrupted. In addition, COVID-19 also allowed trial sponsors to innovate decentralized trials in light of needed change and adaptation. Customers were quick to adopt telemedicine, home-care and real-world study designs leveraging a patient’s own care provider.
Much was learned from the experience of the past year and moving forward, experts are confident that many of the positives gleaned from it will be retained to help enhance and innovate trials of the future.
Dr. Roe believes the biggest lesson learned is that trials can be conducted in a much more efficient and streamlined fashion, particularly with respect to trial follow-up visits and procedures. “If a patient enrolls in a clinical trial, we have learned that they can routinely have follow-up visits or blood drawn done directly from their home rather than making time-consuming in-person visits to the enrolling trial site.”
In addition, clinical operations groups that oversee the conduct of trials have learned that most trial start-up procedures and monitoring can also be done remotely to protect their employees while still ensuring high quality in trial conduct processes.
The pandemic in essence provided the conditions for a real-world case study of the widespread adoption of decentralized trials.
Of course, some trials are better suited to adopt hybrid or fully decentralized models than others. Overall, though, many in the industry believe that decentralized trials, and continued innovations to trials, are here to stay.
The pandemic led to a heavy reliance on remote data collection, and this change is expected to continue after the pandemic because it is efficient, cost-effective, allows for greater patient privacy, decreases missed visits and is convenient for patients, caregivers and providers.
“Sponsors are now applying these methods to actually power complex pivotal studies in ways that would not have been possible pre-pandemic, and this approach is almost certainly here to stay,” says Lemberg.
Dr. Kazempour hopes that the advances to clinical research that 2020 brought will continue beyond the pandemic, allowing for faster, more efficient trials while still maintaining patient safety and scientific integrity.
There have also been many changes on the regulatory side in the past year. Regulators, sponsors, CROs and others involved in the clinical trial process learned how to adapt quickly and accelerate processes to get approvals faster, while learning to maintain data integrity and patient safety. Development of COVID-19 vaccines and therapies have demonstrated that regulatory authorities can move quickly and efficiently, when necessary, to review trial protocols and regulatory submissions.
“The FDA made a huge effort to streamline all of their processes as quickly as possible and the agency thus deserves tremendous credit for those accomplishments. Trial efficiency has dramatically improved during the pandemic, and we hope that these developments will usher in a new era in clinical trials,” says Roe.
The pandemic may indeed have been the catalyst that the clinical trials space needed for the more widespread acceptance and adoption of decentralized trials. This Clinical Trials Day 2021 is about recognizing the tremendous hurdles overcome by clinical researchers in the past year, and reflecting on how those lessons can be used to improve this important aspect of drug development in the future.
As we enter what is hopefully the final stretch of the pandemic, the industry is expected to retain many of the positive changes that came with adaptations and innovations to trials, changes that benefit both patients and practitioners. The hope is that the increased convenience, inclusion, efficiencies and reduced costs associated with new decentralized trial models and digital technologies will help foster accelerated development and approval of therapies in the post-pandemic era.