The clinical trial landscape continues to undergo rapid transformation, spurred by shifting industry paradigms and evolving regulatory guidance, among other factors. With the pressures and restrictions imposed by COVID-19 now (mostly) behind us, how will ongoing trends like decentralization prompt life sciences organizations to further adapt to changing patient and site needs in medical research? What areas of disease-specific research will continue to grow, and will we see a renewed focus placed on diversity and inclusion?
We asked 11 of Signant’s in-house subject matter experts to share their thoughts on current industry trends as well as offer any predictions and aspirations they have about the present and future of clinical trial design and conduct. The resulting insights, summarized below, span a wide range of topics from protocol design to COA implementation and administration, equity and inclusion, disease-specific considerations, and increased adoption of artificial intelligence, machine learning, and other advanced technologies.
Read their insights below and delve into more detail with these and other Signant experts in our Clinical Viewpoints series.
Stephan Bart, SR MD CPI
In light of the pandemic, the clinical trial landscape has changed in several important ways and as a result, medicine is changing too. A recurring theme carried forward from the pandemic is health equity. For example, we saw disparities in the incidence of severe disease and access to the highest levels of care, both related to health inequities. Therefore, any discussion about where we are headed must be about health equity.
Similarly, in clinical trials, we need to include a wider spectrum of gender and race in patient and volunteer populations, but relative distrust remains that industry must continue to work to overcome. In addition, I think decentralized clinical trials, or DCTs (although I don’t like the term much), and the technology underpinning them are making it easier for patients and volunteers to participate in trials. DCTs have certainly helped industry conduct and expedite large-scale COVID-19 vaccine studies as well. Going forward, using technology such as Signant’s eCOA and telemedicine solutions will be the norm and we are well-poised to deliver them.
Another side effect of DCTs worth exploring, since all activities do not have to be centered around site visits, should be understanding and caring for sites’ needs. The Principal Investigator is still responsible for safety oversight and sites are responsible for the quality of the data, but they’re further removed from patients in DCT.
Finally, the pandemic also sidelined other important research while resources were focused on the more imminent threat. For example, there was a push to develop a more universal influenza vaccine that would cover a broader array of flu types. Currently, seasonal influenza vaccines rely on data gathered by the World Health Organization during a given season, and this can cause deficiencies in the effectiveness of the seasonal vaccine’s creation if other strains develop after the collection or mutations occur. Now, there are some new and promising opportunities for mRNA vaccines since this technology has been fully approved for SARS-COV-2. This year and next, I think we will see increased interest and a resurgence of activity around RSV and influenza vaccine research, among other targeted diseases.
Manuela Bossi, PhD
Generally, I think all stakeholders in clinical trials have become more cautious, and in parallel, there is a greater focus on adherence. For instance, investigators may want to evaluate new, potentially challenging treatments. At the same time, patients are more exposed to information about clinical trials through various information sources, potentially making them both more informed and more critical. This is where patient engagement solutions might be useful: we can use these tools to convey information about study risks and requirements, ensuring patients are well-informed and adherent to the protocol throughout the duration of a study. We should also seek ways to engage sites meaningfully to reduce burdens without compromising study operations.
Next, decentralized trials have changed how trials are planned and delivered, but the basic approach has not – we must ensure that we apply the right solution at the right time and in the right setting, rather than using technology just for technology’s sake. For example, sponsors/CROs may be more inclined to design and conduct more traditional trials if they perceive limitations in terms of technology solutions or resourcing. However, technology can still play an important role in trial optimization. Signant takes a science-led, consultative approach to all trials by advising and guiding sponsors/CROs on the best approach, which may not necessarily require our technology solutions but could involve other services.
Finally, looking at therapeutic- and indication-specific areas, I expect a sustained interest in CNS and especially Alzheimer’s disease trials, with increased emphasis on how eCOA can and should fit in those protocols. Oncology will also remain one of the hot research areas, with a renewed focus on patient centricity, in line with the general trend across trials.
Bill Byrom, PhD
Oncology COA strategy will adapt to meet regulatory requirements on the inclusion of patient-reported outcomes according to recent draft FDA guidance. We will see simple site-based collection of PROM data being replaced with more frequent at-home measurement to get a better picture of the impact of the disease and its treatment. This will be associated with careful consideration around how to reduce assessment completion burdens for trial patients, including the use of BYOD and computerized adaptive testing. We’ll also see an increased use of sensors and wearables to capture sleep and physical activity data during treatment cycles that will help us better understand and passively measure the impact of treatment. These methods are just another way of collecting clinical outcome assessment data that will deliver deeper insights in a non-obtrusive way.
Dan DeBonis
We’ll start to see an increased use of AI and how data derived from AI can be applied to clinical trials. We have clearer guidance now from regulators on how passive data collection can be utilized across trials for multiple therapeutic areas, enabling us to personalize how we collect data by using voice and activity rather than a rating scale.
Within neuroscience specifically, we’ll certainly see more investments in the Alzheimer’s disease space, especially following the Eisai trial results and industry-wide consensus that their drug is effective. There have been overwhelmingly successful trials for disease modifiers, and recent opportunities have shown that we can run high-quality trials.
In terms of decentralization, the trend will refocus on trial optimization by integrating the positive impact of decentralized trials conducted during COVID-19, as well as mature products that are easily adopted, into trial designs to make them run more efficiently. The way we approach diversity in clinical trials is also changing, which will impact how we think about Signant’s own solutions and how we can help customers achieve their diversity goals or design trials to be more inclusive.
Todd Everhart, MD
On the clinical side, we’re going to see an increased use of remote patient monitoring for chronic disease management. Particularly in the U.S., primary care physicians can utilize telemedicine and other remote monitoring tools to identify problems early before they worsen and help keep patients out of the hospital. Managing diseases like chronic obstructive pulmonary disease and congestive heart failure outside of the clinic has become easier with such technologies, which were already being used before COVID-19 but became more common during and after the pandemic.
In the research arena, we must continue exploring ways to facilitate the increased use of sensors and wearables. The ability to monitor sleep quality, vital signs, blood sugar, and more through connected devices will increase our capability to conduct remote patient monitoring. When the clinical world evolves, the research world must make sure it doesn’t fall behind.
And now that the pressures of COVID-19 have been removed, we’ll have to rethink decentralized trials and further refine our definition of decentralization. We should reconsider how we design trials moving forward, what parts of decentralization work, and what parts create more problems than they solve.
Lew Fredane, MD
The COVID-19 pandemic helped accelerate the adaptation and migration of clinical outcome assessments for remote administration, but there are still some challenges that new and emerging technology may soon be able to address as it matures.
For example, the UPDRS scale used in Parkinson’s disease clinical trials requires examination elements for which we can utilize technologies like video conferencing, wearable devices and sensors, computers, and telemedicine, as well as artificial intelligence and machine learning to administer and score assessments, monitor patients, and interpret data.
However, it is not so simple to set this up and create that experience in patients’ homes versus in clinics. We need to ensure resources can be brought inside patients’ homes and that people are trained to set it up and administer tests correctly. It is also difficult to gauge concepts such as rigidity of limbs by observation alone – clinicians have to have a feel.
Signant is actively participating in developing the future by collaborating with technology partners and industry. On the near horizon, we see the ability to measure tremors and other Parkinson’s disease symptoms using computer applications, virtual reality, artificial intelligence, and machine learning to identify and quantify changes. In other cases, we may be able to use different or modified scales as our understanding of the disease advances, with the goal to detect early disease and follow the evidence of progression or improvement.
A trend from the regulatory standpoint also emphasizes the inclusion of more patient-reported outcome measures. After all, just because we can make one objective aspect more detectable, does it improve a patient’s quality of life?
Alexandra Kalpadakis-Smith, PhD
Establishing adequate representation from diverse patient populations is critical to ensure that the data generated in a clinical trial are reflective of the population that will be using the drug under investigation if approved. However, the underrepresentation of ethnic and racial subgroups in clinical trials is a longstanding problem for our industry. Last April, the FDA issued draft guidance for developing plans to improve the enrollment of patients from underrepresented racial and ethnic populations in clinical trials. The draft guidance calls for a “Race and Ethnicity Diversity Plan” for every trial that requires sponsors, CROs, and sites to adapt the way they approach trial design and execution. This year, I expect that drug developers will strive to recruit and retain more diverse patient populations. With declining average rates of enrollment across industry, this poses a significant challenge for our customers and drug developers in general – they will have to be creative with enrollment strategies to remove barriers to participation. Intelligent use of technology is just one piece of the puzzle. In order to increase representation, it will be important to engage community organizations and patient advocacy groups as well as adapt clinical trial designs to promote inclusivity .
Moving forward post-pandemic, the industry will also take a more flexible approach to decentralization. The decision to decentralize elements of a trial is multifactorial – it depends on the patient population, the objectives, and the clinical assessments, and it’s not always black or white. There are cases where moving trial activities away from brick-and-mortar sites to the patients’ homes or to telemedicine platforms is beneficial to the trial’s objectives while successfully reducing patient and site burdens, but there are other cases where such an approach may not be optimal. We are already seeing many of our clients opt for flexibility in data capture, incorporating both remote and at-site elements in their protocols and intelligently leveraging technological tools. I expect this to continue throughout 2023.
Alan Kott, MUDr
The fast evolution of machine learning algorithms and methods will enable them to be adopted as standard parts of data quality surveillance to help predict quality concerns in clinical trials.
David Miller, MD
I have been studying Alzheimer’s disease for more than 18 years and no new drugs have been approved in that time. In fact, the failure rate in dementia trials is greater than 99%. However, just in the last year, we’ve seen accelerated approvals for two new Alzheimer’s treatments – aducanemab and lecanemab. What I am hoping to see on the heels of these is full regulatory approval of at least one of these therapeutics. First, these new treatments create the opportunity for patients and caregivers to access new and helpful medication. They also help to advance the field because there are a number of target mechanisms that are evaluated in Alzheimer’s and other dementias that offer the potential, pending full regulatory approval of one or both of these new treatments, to develop combination therapies such as monoclonal antibodies against amyloids. We’re also starting to see increased exploration into non-amyloid, non-tau mechanisms. It has been gratifying to work on trials like these that help to move the needle.
Another area of interest to me is early detection and identification of neuropsychiatric symptoms. At some point in dementia, patients will have one or more behavioral symptoms which tend to accelerate the progression from mild cognitive impairment to dementia. If we can successfully treat some of these behavioral symptoms, could this reduce progression? We are starting to look at pre-clinical dementia more often using newer biomarkers that indicate early signs of dementia, even though a person may be cognitively intact.
There are also some interesting advancements in terms of applying technology in Alzheimer’s and other dementia trials. For example, the pandemic has helped accelerate the adaptation and migration of outcome measures for electronic administration, and we’re also seeing some interesting applications of actigraphy and voice/speech monitoring which can help provide objective and potentially more frequent measures of symptom progression and severity.
Graciela Racaro
All clinical trials are centered on data, and Signant is a trusted partner for data collection and evidence generation to support the development of novel therapies. As we continue developing and applying technology in clinical trials at a rapid pace, it is important that we are mindful of the burden on patients and clinical sites.
For example, for all the opportunities afforded by increased technology adoption in clinical trials, clinical research sites access several systems with different logins just for one trial, while they may be running many clinical trials in parallel. In addition, clinical trial patients may be asked to record data through different applications on different devices while in pain or feeling sick. How can we standardize and improve their experience? How can we simplify the design and facilitate the use of technology with end users in mind? By addressing these challenges, we can also improve compliance – that’s an area we definitely need to focus on. We can do better, and we need to do more in terms of simplifying participation for clinical sites and patients as well as caregivers.
Recent FDA guidance establishes the need for patient input into drug development. Consulting with patients and/or patient organizations during drug development can help to ensure that patients’ perspectives are captured. The views of patients (or of their caregivers/parents) can be valuable throughout all phases of drug development. Involving them more in trial designs also relates to improving the patient experience. By increasing patient involvement and leveraging a strong, experienced clinical team with therapeutic-area knowledge like ours at Signant, our customers can develop better protocol designs and apply improved data capture and analysis strategies.
The industry is also talking about decentralized clinical trials, an area that continues to evolve. The combination of telemedicine, mobile solutions and in-person visits can reduce long clinical trial visits and the need to travel. The strong patient-doctor relationship is preserved, improving patient retention and compliance while the time on site is mainly spent on those assessments that can only be performed at the clinical site. There is no “one solution fits all” approach – it comes down to each individual protocol design and finding the right approach for the specific disease and patient population. Again, sites and patients must be involved with trial design decisions.
Another consideration is improving patient diversity in clinical trials. All applicable populations must be well-represented in the drug development phases. Ideally, representation in clinical trials should reflect who is going to be prescribed that medication.
We are at the frontlines contributing to the advancement of clinical research. Signant has the most comprehensive solution suite in the industry, complemented by our global scale and scientific expertise. With these resources, we are well-positioned to collaborate with the industry to optimize the experience for patients, caregivers, and sites who are all partners in the future of clinical research.
Gary Sachs, MD
I’m very interested to see the outcomes of current psychedelic trials and confirmation of clinical research approaches related to effective, safe methodology. A lot of special methods are now under consideration but should be made to be more practical so that psychedelic therapeutic options can become available to a larger, more diverse population. These trials will probably be a template for future psychedelic trials, and I think we’ll find that traditional methods are more appropriate than new, fancier techniques.
We’ll also see an increased use of AI in clinical trials, particularly with speech and facial recognition. These are niche areas, especially since they could help provide eligibility criteria for future mood disorder or Parkinson’s disease trials and allow researchers to quantify tremors or identify dementia using voice analysis. These kinds of things are not part of the routine clinical trial package, but we will see it used more often.
Looking Ahead
It’s clear from these key thought leaders and others across the industry that technology is a permanent fixture in clinical development, proven to improve participant experiences and enable research continuity in the face of unprecedented disruptions like a global pandemic. However, our experts emphasize that technology cannot necessarily solve all the challenges inherent in today’s clinical development landscape. To make strides in medical science, all industry stakeholders – from sponsors to technology solution providers to regulators, patients, caregivers, and everyone in between – must collaborate to continue adapting best practices for clinical research design and trial conduct that ensure successful, life-improving breakthroughs that will benefit as many people as possible.