By Deborah Borfitz 

October 18, 2022 | Digitalization and the changing regulatory landscape, shared space between routine clinical care and research, the increased complexity of clinical trials in decentralized settings, and practical challenges in providing patient-centric solutions were the focal points of a plenary keynote panel discussion at the recent Summit for Clinical Ops Executives Europe (SCOPE Europe) in Barcelona, Spain. Moderator Marina Malikova, Ph.D., associate professor and executive director of surgical translational research, operations and compliance at Boston University School of Medicine, kicked off the conversation with the observation that the pandemic has “pushed” the adoption of digital technologies and innovation in general.  

One major trend with digitalization is how best to engage and listen to patients, and use their perspectives to improve drug development, according to Rajesh Ghosh, head of digital safety and decision support at Genentech. Another is about digitizing many of the workflows in clinical trials, including those using augmented reality tools in the informed consent process. 

Moving forward, digital devices used in trials to continuously monitor patients will create an explosion of data, he adds. It will be critical for study sponsors to have methods and tools for gaining meaningful insights from this information “about the trial, about the condition, about when to intervene, when to step back and when to listen.”   

As was repeatedly heard throughout the conference, it is important to understand what works for patients and incorporate those learnings into study designs with more efficient and user-friendly digital solutions tailored to the needs of individuals, says Malikova. The U.S. Food and Drug Administration has already issued several guidelines around the use of digital technologies but regulators in general are “still forming their opinion” with most documents existing as a draft. 

Adoption of digital technologies, while beneficial to trials, also means more work for sites, says Angela La Ronde, relationship director at Greenphire. “I think there is a responsibility on us ... to think about automating and integrating technologies to help reduce that [burden].”  

Sites are always looking for “one-click” solutions, concurs Malikova. With each new study phase and trial, sites inevitably must familiarize themselves with a new electronic data capture system and set of digital devices with no “knowledge continuity” in the transition. “So, it is exciting to have all these tools, but integration is key.” 

Clinical trials are often conducted in a shared space at a hospital or embedded with a specific clinical service rather than at a specialized facility, says Malikova in pivoting to the next discussion point. Over the past two years, she adds, the pandemic has caused widespread burnout of personnel driven by understaffing in the face of back-to-normal levels of patient flow, as well as difficulties in turnaround and management of the physical space. 

Contracts and budgets therefore need to include space- and time-related allocations, Malikova says. On vascular studies at Boston University Medical Center, for example, this might cover the budgeted time of a vascular technologist in doing exams and the pathologists in learning a new digital platform outside of their regular business hours.  

Additionally, Malikova advises sites to cross-check their clinical trial agreement, informed consent requirements, and allocations in study budgets in terms of space as well as transportation of participants to various facilities. Sponsors will often pay for infusions and study drugs, she adds, but patients may be unhappy to learn they have a copayment for something they assumed would be free of charge as part of the trial. 

In the U.S., Medicare coverage will usually offset costs for a qualified clinical trial, says Malikova. But that is not necessarily the case elsewhere in the world. 

Patient Centricity 

It might be helpful to ask patients about their clinical trial experiences with and without the deployment of digital technologies, says Rosanne Janssen, postdoctoral researcher in pharmaceutical sciences at KU Leuven, a Belgium research university. Consideration also needs to be given to how their feedback will be incorporated into study protocols, and in a way that aligns with what is most useful to patients. In Belgium, this information might logically be gleaned from an analysis of entries they are already making in a patient diary even for routine hospital visits.  

For some patients, the need may be to avoid travel to study sites by doing visits via telemedicine, says Malikova. Currently, insurers will reimburse hospitals for the cost so the trial sponsor doesn’t have to pay, but it is uncertain how long this might be the case. 

Digital tools effectively add a new element to a clinical trial, namely the user experience, according to Mohanad Fors, head of global commercial digital innovation at Almirall LLC. To patients, traditional consent forms look “scary ... [as if] I am already selling all of my organs.” Audio-guided video tours through the consent process are an appealing alternative. 

Sponsors today tend to focus more on digitizing clinical trials rather than getting to their “ultimate endpoints” with digital tools, says For. It makes sense to track the reaction of patients to the new cinematic-style approach to informed consent, for instance, to formally assess the benefit to participants as well as sites.  

Study designs also need to incorporate patient diversity and socioeconomic aspects when digital solutions are being leveraged, adds Malikova. This requires monitoring participants’ need for and response to patient-centric solutions. 

Growing Commonalities 

Digital clinical trials need to be thought of as “transformational,” says Ghosh in answering a concern about how the available tools have all been innovations produced in siloes. Only by “connecting the dots” across platforms can sponsors get to the why of an outcome and not just the existence of one—e.g., the site quickly responded to an alert from a digital device and the response was in line with what the protocol demanded. This would also make it possible to differentiate between two patients experiencing shortness of breath where one is sitting on the couch and the other is running up a flight of stairs and doing it in real time.  

Ghosh points out an emerging “osmosis” between clinical care and research, citing real-world studies and single-arm trials or those with a standard-of-care comparator arm. “We will increasingly see this kind of transformation where we cross-pollinate ideas from clinical care into research and vice versa,” he predicts. 

Janssen says she favors development of a structured framework for sharing user experience data across multiple stakeholders as it relates to both clinical trials and treatments. The European Medicines Agency, through its DARWIN (Data Analysis and Real World Interrogation Network) project, is already enabling data-sharing in the context of real-world evidence about diseases, populations and the uses and performance of medicines. DARWIN will connect to an initiative promoting better exchange and access to different types of health data.   

Clinical trials and mainstream clinical care face the same challenges and have embraced the same opportunities, says Malikova, referencing several articles about the use of electronic health record data for research (including The Lancet Digital Health, DOI: 10.1016/S2589-7500(22)00151-0). Adoption will be much faster in Europe because of its more federated, centralized approach to healthcare recordkeeping. 

Engaging patients for their feedback, whether through clinical trials or routine care, will aid in the design of more cost-efficient protocols that can also be more effectively executed, Malikova says. “Different perspectives from different stakeholders matter ... we are not going to find immediate solutions but at least we can vocalize some concerns or look for some innovative approaches to take us one step further.” 

Diversity Goals 

As to the question of whether decentralized clinical trials might inadvertently inhibit or prevent marginalized individuals from participating, Malikova says the issue bears exploring. Fixing any problems starts with understanding the root causes that might create barriers for underprivileged populations. 

Boston University Medical Center has successfully partnered with Greenphire to address some of the barriers by ensuring participants receive payments in near-real time upon completion of study visits and procedures, she says. Other options are to add allowances for meals and transportation into protocols given that they could improve study recruitment and retention rates and help sponsors meet their diversity goals.  

In his closing comments, Ghosh emphasizes the role that can be played by a “willing ecosystem ... where we can collaborate while we are still competing.” He adds that there is no one-size-fits-all company or solution, so a collaborative approach is necessary to meet patient expectations and study goals. “I don’t think decentralization should only be about mobile nursing; it should also be about extending to geographical regions, rural areas, [and] community practices, which are outside the scope of clinical trials today ... [but] will truly increase the diversity of trials.”  

Real-world evidence could assist with the selection criteria for trial participation, says Janssen, in addition to more stakeholder views and multiple concerted actions. This would also improve the generalizability of study findings to populations who ultimately will be using the treatment. 

Prompted by a question regarding case studies of solutions relevant to both clinical research and healthcare, Malikova shares that she was fortunate enough in her lifetime to see the trials-to-clinic transition of Apligraf, a cell-based product now on the formulary as a standard-of-care product for chronic wound care. It is used to treat diabetic foot ulcers and venous leg ulcers and currently the only good therapeutic option outside of clinical trials.  

In his final thoughts, Fors says it is crucial to start looking at clinical trials as a product that needs to “be commercialized ... to be nicer” by making studies easier for patients and physicians to understand and participate in—and to also thank participants when they decide to sign up. That would increase diversity and improve recruitment generally. 

Malikova, in her conclusion, notes that there is room for more routine adoption of digital technologies in everyday clinical care, particularly under reimbursement schemas factoring in rates of reoperations, readmissions, and reinterventions, as well as the feedback of patients. Something to think about as the intersection of clinical trials and routine healthcare is under construction, she says.