Even as vaccines are distributed across the country, the lingering effects of the COVID-19 pandemic remain. In the realm of clinical trials, researchers and administrators are left wondering what policies will remain in the future and what changes are here to stay.
One source of debate involves electronic clinical outcome assessment (eCOA) data collection methods. It’s important to review how the pandemic impacted data collection and what the future of clinical trials looks like.
While there have been advocates calling for the use of technology in clinical trial data collection for some time, the pandemic proved to be a necessary catalyst to drive mass adoption. Researchers scrambled to embrace decentralized trials and off-site data collection.
“Until now, oncology clinical trial design and implementation has not changed in a meaningful way in decades,” write Fatima Karzai, Ravi A. Madan and William L. Dahut, associate professor of medicine, senior clinician, and scientific director for clinical research, respectively, at the National Cancer Institute. “However, in response to the pandemic, oncologists have adopted telemedicine, community partnerships, and simplified protocols to protect patients while maintaining the integrity of studies...It has become clear that embracing these changes is imperative.”
At the start of the pandemic, the FDA produced guidelines for conducting clinical trials when patients couldn’t leave their homes. They did not want to lose trials simply because there were changes in data collection halfway through.
“The guidance acknowledges that due to challenges such as quarantines, clinical site closures, travel limitations and interruptions to supply chains, certain protocol modifications may be required and protocol deviations may be unavoidable,” write Allison Fulton, Kenneth Yood and Melissa Gertler at the law firm of SheppardMullin.
As long as trial leaders made a note of the modifications and how they could affect the trial, the research could move forward. This allowed clinical trial developers to embrace at-home visits and virtual checkups.
“Many trials have shifted from the distribution of drugs at the trial site to direct-to-patient courier services, whereby trial drugs are distributed and administered to patients in their homes, eliminating the need for at-risk patients to visit trial sites,” writes Aaron van Dorn at The Lancet. “Many in-person visits for checkups and other aspects of trials were shifted to teleconferencing services.”
These changes in appointment styles also changed how researchers collected, shared and analyzed data from the trials. Electronic data and analysis became even more important than before.
The technology was already available for researchers to embrace alternative forms of data collection. Most clinical research organizations (CROs) could use existing systems and tools.
“Fortunately, the technology now in demand has been in flight since the early 2000s,” write Hannah Yee and John Ferraro of Halloran Consulting Group. “Home visit coordination, at-home procedures (infusions, blood draws, etc.), self-report solutions, video visits, and digital endpoints surfaced long ago. Until now, the barriers were chiefly regulatory obstacles around implementation and the business case necessary to drive change management internally.”
The pandemic created an emergency that forced administrators and legislators to cut through any bureaucracy. While there may need to be some adjustments in policy and best practices in the future, this turned out to be a major leap forward in clinical trial advancement.
The use of alternative data entry modes and eCOAs provide significant opportunities for researchers. However, new solutions tend to create fresh challenges that also need to be addressed.
“While there is a chance the pandemic may not be a major factor in the outcome of clinical trials, it would certainly muddy the waters with regards to efficacy data,” says Ronald DePinho, professor and past president at MD Anderson Cancer Center in Houston.
There are multiple challenges to the data that researchers face. The first is the sheer amount of it. This happens when a patient using a wearable device or digestible device produces more data than a clinician could collect during a brief in-person meeting.
“This big data has the potential to overwhelm a study team,” says Mark Wade, global practice leader of life sciences at TransPerfect. “Data scientists will be challenged with not only the mass of data but also the disparate systems that do not have universal interoperability, and 80% of that data will be unstructured.”
Another challenge is the data from trials that were stopped during the pandemic. The benefit here, however, is that study teams can cross-reference this data and perform additional analyses where the previous researchers left off.
“Many trials are likely to shut down during the current pandemic, but this should not translate into a loss of useful data,” Deborah Plana, Andrea Arfè and Michael S. Sinha, researchers at the Harvard-MIT Center for Regulatory Science at Harvard Medical School, wrote in 2020. “Meta-analyses and methods to adjust for missing data, such as multiple imputation methods, can leverage data from discontinued trials to provide important information on the safety and effectiveness of tested therapies.”
Finally, clinical teams can also pull data from third-party sources to enhance the information they have.
“The opportunity for us to source our data electronically from Real World Data sources can be extremely powerful in terms of bringing better quality, better efficiency and lower cost into our trials,” says Craig Lipset, founder of Clinical Innovation Partners. “I think there are opportunities for Real World Data to improve our engagement with patients and studies.”
All of these data sets compound the amount of information that clinical researchers pull in trials. This can make the trials stronger and potentially drive better conclusions on the effectiveness of medications or treatments.
One of the biggest changes to clinical trials and their data collection was the use of telehealth during the pandemic lockdown periods — particularly the use of video calls, phone interviews, and patient self-reporting. Meeting with patients in these formats will likely remain, although researchers are considering how they want to move forward with these new options.
“[Clinical trial] visits occur much more frequently than what standard practice follows,” write Chadi Nabhan, Toni K. Choueiri, and Anthony R. Mato, chairman of the Precision Oncology Alliance at Caris Life Sciences, division chief of the Dana-Farber Cancer Institute, and associate professor at Memorial Sloan Kettering Cancer Center, respectively. “As such, the logistical aspects of enrollment represent major barriers to participation. These in-person visits can make it difficult for patients, increasing out-of-pocket expenses and requiring them to be absent from work, while also being particularly prohibitive for patients traveling from afar.”
Fewer people sign up for clinical trials if they need to visit a doctor frequently, especially if they have to travel for those appointments. A video call is much easier; patients just need to log on to a call from their home or local doctor’s office.
Even before the pandemic, clinical researchers were considering the preferences and needs of patients. The Center for Information and Study on Clinical Research Participation conducted a study in 2019 that asked patients whether they want to travel for a clinical trial. “While alternative clinical trial models are generally regarded as appealing when compared to the traditional model, there is no single preferred option suggesting that no one size fits all as preferences can vary widely by participant,” according to the report.
Findings included a majority of respondents that said the idea of collecting all of the data on their own at home was either very appealing or somewhat appealing. Similarly, a majority were also open to attending visits at the clinic or having nurses stop by their homes for data collection.
Still, while virtual appointments and self-reporting make clinical trials more accessible for some patients, the same can be a bigger burden for others.
“While the overall impact is to reduce barriers and burdens, for certain participants who do not have access to internet or videoconferencing or without experience utilizing such tools, [decentralized clinical trials] may pose challenges,” write Sarah Ferranti and Shine Chen Schattgen, lawyers at Epstein Becker Green and St. Jude Children's Research Hospital, respectively. “Sponsors and sites may need to consider whether they are able to assist such participants in overcoming those challenges.”
Across most medical fields, clinical researchers develop their trials with the same goal: collecting the best data while creating positive experiences for patients. With eCOA data collection, researchers can collect more data while sorting through the key points they need. A lot of data is good, but it needs to maintain high quality levels to be effective.
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