Cari Kniola
Senior Director, Corporate Strategy

May 25, 2021

If the adoptability of decentralized clinical trials were based solely on the amount it is in industry headlines, there would be no question that we have landed a virtual home run. However, as with any potential change, when looking at the big picture of what decentralizing a clinical trial entails one has to balance the risks and benefits. There is no doubt that this is making the industry re-think how we approach clinical trials and can serve as a benefit to patients. Below we discuss some of the risks and benefits that are introduced with decentralized clinical trials.

Benefit of Decentralized Clinical Trials: Patient Centricity

Overwhelmingly we are seeing how decentralization is making clinical trials more patient-friendly. We live in a society where most people have fully packed schedules. Add in an illness, and patients are looking at unscheduled time off work, issues with childcare, transportation, and potentially catastrophic medical expenses. When given the option of enrolling in a clinical trial – which has historically involved more to fit into a schedule, more time off work, more figuring out transportation – how many patients don’t enroll because they simply cannot fit any more into their lives?

Finding ways to incorporate aspects of decentralization into a trial can remove, or at least reduce, that barrier for patients. As we discussed in our first blog article on decentralized trials, most studies are hybrid studies, with varying degrees of virtual aspects. If a study has eight visits and four of those virtual, that is four less times a patient has to travel to a site. With 22% of patients taking over an hour each way to get to a study clinic, that has a big impact. If done via home health visits, nurses can typically work around patient schedules. If collected via a patient wearable or ePro, a patient may not have to worry about changing their day-to-day routine at all.

Decentralization shows efforts to make the trial fit the patient, instead of making the patient fit the clinical trial. In a study done in 2018 (yes, we were talking about this before COVID!) that compared trial enrollment in a conventional study arm vs. a decentralized arm, the decentralized arm enrolled over 300% more patients. When looking at patient retention in the same study, 89% of the decentralized arm completed the study vs. 60% of the conventional arm. With low patient recruitment and high drop-out rates being the top killers of a clinical study, focusing on patient centricity could greatly impact study outcomes.

Risk of Decentralized Clinical Trials: Validated Remote Assessments

Validated remote assessments are available and their numbers are growing. Digital Medicine Society’s (DiMe) Library of Digital Endpoints increased the number of unique digital endpoints from 34 to 166 from mid-2019 through the end of 2020. However, as of early 2021, they had yet to see a new medical product approved on the basis of a digital clinical endpoint. They had also not seen a digital endpoint appear more than once, reflecting a lack of common digital approaches.

The current technology environment surrounding decentralized trials feels a bit like the Wild West. Companies are running their horses as fast as they can to get out front, but rather than work together to find a safe trail to the coast, they are each blazing independent paths. Clinical research is not known for a ‘seat of the pants’ approach to conducting clinical studies. So how can we find some cohesion in the rush for decentralized gold?

DiMe is working to help with that as well, and introduced The Playbook, an industry guide for how to select and develop digital clinical measures. The FDA has a Clinical Outcome Assessment Qualification Program, which currently has seven digital outcome assessments qualified. FDA also has a Biomarker Qualification Program, and while there are a number of submissions, none of them appear to be digital biomarkers. Even though FDA qualification is not a requirement for the use of a digital endpoint in a clinical trial, let’s not pretend that it wouldn’t feel a lot more warm and fuzzy to use one that was.

What does this mean for those looking to incorporate digital endpoints into their clinical trial? Keep meeting with FDA. Even before the decentralized clinical trial rush it has always been best practice to have a pre-submission meeting with the FDA to make sure you are on the right track, whether you are working on a drug or device trial. With the incorporation of decentralization in the mix, this becomes even more critical to make sure that the digital endpoint the study is banking on will meet FDA expectations.

Benefit of Decentralized Clinical Trials: Data Based in Reality

The patient centricity benefits noted above not only benefit the patient, they benefit the clinical trial data. By providing an opportunity for a more diverse patient population and geographic area to enroll in a clinical study, the data captured will represent more of the ‘big picture’. While some may see that as a risk, by not gathering data across diverse populations there could be not only safety issues missed, but also potential treatment benefits. In particular for large observational studies, having such a wide range of data could prove invaluable.

In site-based visits, studies capture patient data at one time point on one day, and possibly on only one day out of a whole month, depending on visit frequency. With technologies such as ePROs or wearables, clinical studies can capture data in more real time. With something like an ePRO symptom diary, patients can capture a change in symptoms or maybe even a potential AE on the day it happens, rather than forgetting about it by the time their next visit comes around. With patient wearables, data points like heart rate, activity, even glucose monitoring can be captured each and every day. Picking the clinical trial technology used in a study will depend a lot on the patients being enrolled. Do you want to give a study population of elderly patients a wearable that requires a significant amount of technological know-how to use? Probably not.

Speaking of data, you better make sure it’s secure.  As with any technology, the more it is embraced in clinical trials the more data security risk there is. Mapping where the data flows each step of the way and identifying any protection gaps will be critical, and will take collaboration with all technologies involved in the study.

Risk of Decentralized Clinical Trials: Budget Impact

COVID-19 forced ongoing clinical trials to either find a way to go virtual or shut down. When facing shutting down a trial that may be ‘this close’ to completion, the benefit of decentralization far outweighed the cost. Now it appears, however, that that the decentralization we were forced to implement during COVID will become the new normal for clinical research going forward. The boon in technology and uptick in talk of adding home study visits and telehealth demonstrates that many companies out there are banking on this being the case. Technology is fun, but it isn’t free. Home study visits are very convenient for the patient, but nurses get paid by the hour.

The cost will not only be with the individual vendors and their technologies or services. It will take increased resources, either internally at a sponsor or with a CRO, to manage the multiple vendors and troubleshoot issues as they arise. And they will arise. Risk based quality management (RBQM) has increased its presence in the limelight along with clinical trial decentralization, and that is no coincidence. Adding decentralization to a trial adds on another level of risk, both to data and patient safety. For example, if a study requires daily monitoring of heartrate and activity via a patient wearable, what happens if the patient loses it? Or if it malfunctions? If a patient is having IP shipped directly to their home and it has to be refrigerated, what happens if the electricity goes out? Or what if the IP doesn’t arrive in time for the home study nurse to administer it? What happens if there is a data security issue? Not only do the individual aspects of decentralization have their own costs, the mitigations if something should go awry will have their own budgetary impacts.

There are potential costs outside of vendor budgets as well. Sites have their own concerns about decentralization. Some of the top site concerns of SCRS’ Impact Assessment of DCTs  after concerns about quality and patient safety were that less study sites would be needed, less study personnel would be needed, and that study-related systems would become more complex. A standard study probably has at least three systems for which site personnel will need to train on, troubleshoot, and remember passwords. If a site is running just five studies, that in itself is 15 systems. If each of those studies added just three more technologies – say eConsent, ePRO, and a wearable – that is another 15 technologies. That means a site that is only running 5 studies would potentially have 30 different systems to manage. Now throw in having them train patients on using their technology. And let’s toss in a couple home study visits, which have nurses they know nothing about now added to their delegation log and technically their site’s responsibility. These additional efforts are translated into increased study coordinator time on investigator grants.

The Big Picture

Assessing risks and benefits of a decentralized clinical trial is a critical step in determining if it is right for your study. These represent a sampling of considerations that will be ongoing as we work out this new phase of clinical research. In many cases the benefits will outweigh the risks and decentralization will be a perfect fit. In other situations, after evaluation of all the possibilities, it may be that going virtual will not be in the cards for your study.

In the final installation of this series, we will discuss steps to take to determine if decentralization is right for your clinical trial.