Digital and remote clinical trial designs have plenty to offer in terms of cost and efficiency, but data handling and other concerns suggest there's still work to be done, according to experts at the American Heart Association Scientific Sessions 2019.

Janssen, researchers discuss evolving digital trial challenges alongside launch of remote, 1,900-person drug study

By Dave Muoio
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Photo courtesy of Janssen Pharmaceutical Companies. From left to right: panel moderator Patrick Wayte, Dr. C. Michael Gibson and Dr. Paul Stoffels.

Due to the promises of lower costs, simple scaling and greater patient engagement, digital technologies are all but an inevitability for the drug trials of tomorrow, according to experts from pharma and the clinical research community speaking this weekend at the American Heart Association Scientific Sessions in Philadelphia.

These comments were accompanied by the official kickoff of CHIEF-HF, Janssen Pharmaceutical Companies of Johnson & Johnson’s latest clinical trial that it says will be “the first-ever completely decentralized, mobile, indication-seeking clinical study.”

Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure (CHIEF-HF)

According to Janssen, the new CHIEF-HF trial will include no in-person clinical visits and instead rely on virtual communications and data collection via a smartphone app and wearable sensors. The nine-month effort aims to enroll roughly 1,900 US adults with chronic heart failure regardless of Type 2 diabetes status.

In the first of two study phases, these participants will be randomly assigned to receive the study drug canagliflozin or placebo in a 1:1 ratio. After three months, participants will be informed of which treatment they had been receiving, and will be given a choice whether or not they want to continue to switch therapies.

All the while, participants will be reporting their conditions through clinical questions provided via study app. These data will be combined with logs of their physical activity such as daily steps and stairs climbed, which will be recorded using a wearable device and delivered through the connected smartphone app.

“Our mission at Janssen is to bring transformational innovation to improve the lives of patients around the world. The CHIEF-HF study embodies that mission by combining new cutting-edge ways of doing clinical research, in a group of patients with a high unmet medical need, testing a well-studied medicine — canagliflozin,” Dr. Paul Burton, VP of medical affairs and internal medicine at Janssen Scientific Affairs, said in a statement. “Additionally, CHIEF-HF is focused on the patient experience, returning their own data to them in a staged manner that allows them to understand how treatment and lifestyle choices affect their health.”

The data from this study will be used to support a Phase 3 clinical program for canagliflozin, according to Janssen.

Digital trials can reduce burdens for pharma

Clinical trials — especially those in Phase 3 or beyond — have an overabundance of moving parts and logistical considerations that can quickly ramp up costs. Divorcing the process from physical interactions between participants and study staff can have a major impact on the final price tag.

“Very soon, digital tools will become part of clinical trials in many different disease areas [because] the cost of clinical trials is so high,” Dr. Paul Stoffels, vice chairman of the executive committee and chief scientific officer at J&J, said at the conference. “If you have to have 300,000 people in an outcomes clinical trial, the cost used to be hundreds of millions if not billions of dollars. Now it’s doable, and it very quickly will change the entire field. Virtual recruitment and inclusion, people being able to be treated at home, digital consultations — that will all help to do faster and simpler trials.”

And these new trial designs certainly aren’t limited to the largest, most expensive trials, said Dr. C. Michael Gibson, founder of the PERFUSE academic research organization at Beth Israel Deaconess that’s contributing to J&J and Apple’s HEARTLINE Study, another digital effort that was announced earlier this year.

Rather, more efficient digital trials can make their mark by generating enough data in the earlier stages of drug development to better understand whether or not an expanded effort is even necessary.

“I do think in Phase 1, Phase 2, these will be valuable tools as well,” Gibson said in response to Stoffels. “You’re trying to gather enormous amounts of data … and, say in heart failure, you’ll be able to look at how often a person is upright, or how long are they walking, what’s their gait speed. It’s like you’re doing a six-minute walk [test] all the time, and that will help you identify very quickly the most viable candidates, and allow you to fail quickly and fail cheaply before you go to Phase 3.”

Alongside facilitating easier communication, digital trial designs can also provide researchers the ability to monitor adherence to the study therapy in real time. And in the case of HEARTLINE and the newly announced CHIEF-HF, teams are incorporating digital engagement strategies directly into the study apps and devices themselves. Gibson said that both of these factors go a long way in convincing the payer and clinical communities of the value new, successful treatments can bring to care.

“The new P value is price. You really have to show value now,” he said. “I think the critical thing for engagement is showing that they are very valuable for healthcare — and then there will be the uptake. Then they will be distributed either by healthcare systems or advised by physicians. The outcome data is going to be very important to making this happen.”

Benefits also reach patients and providers

Stoffels and Gibson were quick to emphasize that the fruits of digital clinical trials won’t be enjoyed by the healthcare industry alone. First and foremost, the massive increase in clinical data generation coupled with machine learning and other analysis technologies could play a major role in transforming care from mitigation to anticipation.

“That is the next phase: not just saying ‘you have an irregular heart rhythm right now,’” Gibson said. “I think some of the more forward-looking attempts are to say ‘Based on the RR [ECG wave peak] variability, based upon the QT dispersion, etc., we predict that you’re going to have an arrhythmia. Right now we’re in the detection phase, but using all the big data that we have, we’re going to be able to predict those outcomes.”   

Further, more efficient clinical trials mean that effective new treatments will get into the hands of patients more quickly to improve their care. Meanwhile, Stoffels noted, the low-burden outreach and treatment delivery capabilities enabled by these technologies will also expand the total number of patients able to receive both experimental and proven treatments.

“I think the big win is going to be more people having access to better healthcare,” he said. “If you look around the globe and see everywhere the availability of healthcare resources and the healthcare system, everywhere in the world it is overburdened. Having the digital world come in to help people vet patients better without having to physically go into a healthcare system [will be very helpful]. More healthcare for better people with better outcomes — I think that’s going to be the big win, and it’s going to be very measurable in the number of people treated.”

These engagement-heavy approaches enable more than consistent adherence — they also include opportunities for patients and their support systems to become active participants in their care.

“I do think it’s hard to argue the value of empowering patients,” Gibson said. “The patients are entering their own data, they can access their own data — they’re not turning it over to Big Brother and have no access. We’re engaging their families so if they have an irregular heart rhythm, they can designate three family members who will know so they can get appropriate care.

“It’s not a one-way street of collecting the data,” Gibson continued. “It’s a bidirectional flow where you’re not just collecting data, you’re trying to influence behavior. … And so it’s more than a watch; it’s [also] the app that goes with it to modify behavior.”

Data handling, engagement and ‘the worried well’ are still challenges

On the subject of data, the past week’s headlines has been yet another reminder that the average consumer is either unaware or unhappy with how large healthcare institutions and tech companies are handling their personal data.

Stoffels and Gibson both admitted that poor handling of sensitive information is a major risk to the proliferation of digital research. The former stressed that reckless sharing of EHRs or other records between vendors will likely rub hospitals and other stakeholders the wrong way, and could likely lead to monetization, data gating or other overbearing systems that will harm effective healthcare data use in the long run.

For Gibson, it was all about individual privacy and the risk of medical identify theft.

“If someone knows your birthdate, gender and zip code, there’s a 95% probability they can reidentify you,” Gibson said. “And thus the trial we’re doing, the HEARTLINE Study, all the names will be removed, birthdates are removed, everything is being done to make sure privacy is really safeguarded and there’s a low risk of an adversary reidentifying a patient. We need to balance the very bright future with the possibilities of some of these risks, but I think we’re trying to strike the right balance with these kinds of studies.”

Another longstanding concern among the clinical community is the rise of the “worried well,” driven by an abundance of consumer-grade self-monitoring tools such as the Apple Watch’s atrial fibrillation detection feature. Here, Gibson recalled a past project involving a novel implantable diagnostic device that had some anticipating unnecessary hospital visits and higher costs, but in reality led to a reduction in false cases and an increase in silent heart attack detections.

But these positive outcomes may not always be the case, Stoffels said, so it’s vital that companies releasing high-engagement consumer health products make certain that the tool is working as intended before things get out of hand.

“If there’s not enough specificity in the diagnosis, that you have a lot of people coming into the healthcare system and overburdening the healthcare system,” Stoffels said. “You have to have very good sensitivity, but also good specificity, of what you try to diagnose to not have a rush of very many worried people — and that’s in all areas, not just cardiovascular. You have to be very careful that if you use these tools to mobilize people for their health that they are well treated.”

Digital clinical trials can be a boon when it comes to enrollment, coordination and other standard tasks for researchers, but that doesn’t mean these programs aren’t introducing researchers to new burdens as well.

Speaking in another session, Lora Burke, a professor at the University of Pittsburgh’s School of Nursing with decades of research on behavioral medicine, said that remote check-ins have by and large been beneficial for her ongoing study of more than 400 participants. However, it has also made her team more cognizant of issues like study dropout and continuous monitoring workloads.

“You may think [remote trials are easier], but it’s intensive work and it’s 24-7 data coming into you all the time across many behaviors,” she said during the conference. “And it’s engagement — I cannot emphasize engagement enough. You need to pay attention and you need to monitor, because you will lose people so quickly. Everybody thinks technology is the easy way, but it’s only a tool. We have to work around using that technology and engagement … is where the biggest gap is. Keep that in mind: test everything well, know what the people like, what’s user friendly, what works for them, and then test that in a trial. It’s not the easiest route, but it’s exciting … the time of people coming into research centers is outdated.”