Top of mind for Rob Church, a pharmaceutical and biotechnology regulatory law expert at US firm, Hogan Lovells, is the future of clinical studies, particularly in light of the decentralized clinical trial (DCT) trend seen over the past year.
The pandemic has been the catalyst in speeding up the wider adoption of DCTs, with sponsors using electronic remote informed consent, remote outcomes assessments, and, in some cases, remote administration of a study drug, and home health visits by clinical study staff, he told us
Technologies that support the decentralized process have also been benefiting from this shift.
Smart phones, wearables, artificial intelligence (AI), machine learning, cloud computing and blood self-collection devices are some of the tools enabling DCTs.
And there is already a clear indication that the US Food and Drug Administration (FDA) plans to adopt certain electronic tools going forward, said Church, who leads the clinical trials working group at Hogan Lovells.
“Many of our clients, both on the pharma side as well as on the service industry side, are trying to come to terms with what standards these digital technologies or devices, whether they are wearables or apps, need to comply with before they are used in studies. This is a real area of interest for the industry right now but also something the FDA is paying attention to.”
The legal specialist has also been tracking the US regulator’s interest in evaluating the running of trials during the pandemic, the quality of the data, whether any studies suffered during the course of the interruptions related to COVID-19, and whether any integrity problems arose.
“I do think that since the FDA started going down this road and started seeing the benefits of permitting more flexibility, in having more decentralization in trials, it has made it harder for the agency to go back at this point. I believe it is in everyone’s interest to permit this kind of greater flexibility, not just for the sponsors but also for the patients, for the clinical sites, and even for the FDA. For years, the agency has been pushing for ways to speed up clinical trials, bring down the cost, enable more studies to be conducted where needed and I think these tools may all help to facilitate that.”
The CRO perspective
Australian contract research organization, Avance Clinical, agrees there is no going back now on the DCT trend.
Its CEO, Yvonne Lungershausen, shared insights on the future of DCTs, the technology and patient factors that will determine success in this regard, during the Oracle Health Sciences Connect conference earlier this month.
The CRO uses eClincial technologies to support clients wanting DCTs or a site-based approach while still leveraging advance technology including ePro, eSource and eConsent.
She noted considerable benefits to DCT's including:
- Reducing the scheduling and travel burden on patients - providing care from the comfort of the patient's home.
- Connecting patients to trials on a global scale - patients that were otherwise inaccessible under more traditional trial protocols are now available.
Though there can be, of course, some downsides to the DCT approach in relation to human-to-human contact and continuity of patient care, or challenges related to investigational product distribution to more remote destinations, and oversight of compliance and study procedures in the patient's home, noted the CRO.
Remote technologies such as video conferencing can remove some of the hurdles though around patient care, stressed Church.
“Certainly where there needs to be an in-person assessment of a patient, if that individual needs to physically be in the clinic, to undergo certain tests and analyses, and to have access to the diagnostic equipment in a hospital, obviously a patient needs to be there for that. However, if it is more to check in on the patient, to see how they are feeling, then we see subjective outcomes assessments are facilitating that,” he said.
Another tendency that he has observed in the course of the past year has been the increasing use of home health nurses to make clinical site visits. “This is fairly new. It had been done before but in a limited way. The pandemic has seen much more rapid adoption of that now. It may add a little bit of additional expense to a clinical trial to have a home health practitioner visit a trial participant in their house but it certainly can help the patient.”
Boosting trial diversity
Moreover, the legal specialist noted an interesting convergence between some of the tools being used during the pandemic just to keep trials going and other FDA initiatives carried out in the past couple of years – efforts to increase the level of diversity in clinical trials and finding ways of gathering reliable, real world data for studies.
There is a growing industry focus today on ensuring trial participants reflect the racial and genetic diversity of the ultimate users of the product under study, arising out of both the moral imperative and the need to ensure a more robust dataset. There has been a lot of emphasis on this aspect during the COVID-19 vaccine trials, said Church.
A study published in JAMA Network Open of demographics of a decade’s worth of vaccine clinical trials found Black Americans, Latinos, American Indians, and Alaskan Natives, as well as people age 65 and older, were underrepresented as participants within studies.
One of the causes of a lack of diversity in trials can be issues around access to those medical facilities conducting the studies. “If a study sponsor is trying to ensure a more diverse population for its trial but does not have any sites in those areas where it is seeking out that diversity, it makes it difficult to get those patients enrolled. There is also the cost factor involved in patients getting back and forth to a clinical site.
“So, suddenly, if a sponsor can start carrying out many aspects of a trial remotely and is not demanding participants come to an institution every other week, it does open up the possibility of enrolling people that historically may not have made it into a study. That is one benefit from some of the decentralized tools we are seeing being rolled out right now.”
There are inherent risks with DCTs and the FDA is mindful of potential threats in terms of its remit to protect patients and ensure the quality and the integrity of the data, he said.
“If you have a patient that is not being seen at a hospital or a clinic and is going through remote monitoring, you can limit the risk trough using proper procedures, but there is always a possibility that a patient starts to have some kind of adverse effect that goes undetected. A sponsor has to be mindful of that and make sure the right tools are in place to appropriately monitor the patients.
“And, on the data integrity side, it is interesting to think about all these new technologies, the ways of gathering data through smart phones and wearables, but those tools can present a myriad of opportunities for data to be mishandled, corrupted and not tracked accurately. It does, in the near term, pose challenges for drug companies to make sure that they are building and using systems that are not only compliant with standards but, more broadly, are performing the way they were intended to.”
During the last year, the DCT approach was used to keep studies that had already started on track; it meant not having to pause such work. “Now that we are hopefully making it towards the end of the pandemic, or at least seeing the light at the end of the tunnel, it will be interesting to keep an eye on such developments, to see if the DCT process speeds up trials. I think it will have to but whether there is data right now to support that premise or not, I haven’t seen it.
“I don’t think there is any way that the clock is going to be turned back. I am working with a number of companies right now that are looking at very interesting novel study designs, to collect data, not conventional trials but studies being conducted under FDA’s investigational new drug application regulations, where this decentralized technology such as wearables or video conferencing, is allowing them to undertake such work.
“Whether the DCT process ultimately speeds up the clinical trial enterprise, or just provides greater flexibility, is able to bring in a more diverse patient population and reduce the number of in person monitoring visits or possibly reduce expenses a little, I think all of those factors remain to be seen a little further into the future.”
DCT enabling technology can include:
- Wearable devices; these are demonstrating enormous potential whether worn as a wrist strap or an adhesive patch on the body. AI-embedded capabilities allow these devices to measure a patient's heart rate or metabolism remotely. Linked to the cloud through secure networks, clinicians can receive and analyze the data real-time.
- Video calling and electronic reminders can improve patient compliance in trials - prompting participants to take their medication at the right time or to record in their electronic diary.
- Technologies are being developed also to allow patient-centric sampling - self-collection of specimens - with devices that require the use of a lancet and finger prick whereas others do not, making clinical trials even more convenient.
Source: Avance Clinical