Clinical Trial Optionality: Its Reality is Within Reach

Joe Dustin, Vice President and General Manager of eCOA, Medable

Industry consensus has solidified around the concept of patient-first: the idea that when clinical trials are designed with patient optionality, everyone benefits—from patients, caregivers, onsite staff, and trial sponsors to the entire population that might someday receive the treatments being tested. As a result, patient-centric innovations are being increasingly deployed to solve many of the traditional challenges associated with clinical trial participation and execution. From remote patient onboarding and consent to connected devices and televisits, patient optionality reduces the time and cost burden of in-person site visits, expands participation to previously underserved patient populations, and may even have the potential to accelerate trials.

Patient-first technologies are also embracing patients as experts in their own health. Clinical outcome assessments (COAs)—which encompass patient-reported outcomes (PROs), observer-reported outcomes (ObsROs), clinician-reported outcomes (ClinROs), and performance-related outcomes (PerfROs) that reflect how a patient feels, functions, or survives in a trial—are more personal and easier to access in their electronic form. Specifically, electronic PROs (ePROs) are growing in popularity with sponsors across a wider percentage of their clinical programs.

Advanced ePROs provide rich and accurate data that is both easy for patients to input and easy for sites to share with stakeholders—especially important as regulators are asking¹ for more patient self-reported data in trials. However, some hurdles block the path of ePRO’s widespread adoption, including user-friendliness and troubleshooting of the technologies themselves. In the name of patient centricity, the industry must work better together and clear those hurdles to allow the patient voice to be captured.

ePRO isn’t new, but progress has been slow

Required by FDA and the European Medicines Agency (EMA), COAs—again, encompassing PROs, ObsROs, ClinROs, and PerfROs—are part and parcel of clinical trials across the globe.

Because electronic data can be easily tracked and time-stamped, is confidential, and enables easy monitoring, ePROs have become an increasingly attractive option to sponsors for clinical trials—especially decentralized clinical trials (DCTs) or hybrid trials spread across communities. Some large pharmaceutical companies are using ePROs for nearly every trial and want to bring the process of building ePROs in-house for greater control and efficiency. In-house ePRO-build is a relatively new strategy. In the past, most companies considered the risks to be too high for a majority of studies and limited their use of ePRO to collect patient claims and health-related quality of life reports only.

Essentially, ePRO was only mandated when the primary endpoint was supported by patient-reported data. If those data in another trial were not tied to these critical endpoints, then it was collected on paper due to cost and complexity.

But the COVID-19 pandemic changed everything. Overnight, sponsors experienced unprecedented pressure to develop and test treatments—and they had to do it all remotely. The rise of DCTs caused ePROs to be included in more protocol designs and expand their use into therapeutic areas where the primary endpoint was not necessarily derived from patient-reported data. Bringing patient and caregiver reporting in-house is a rising trend now among sponsors and contract research organizations (CROs) because the volume has increased. The share of clinical trials using ePRO is now rapidly expanding, creating more opportunities to engage patients with an app already in their hands.

The following major clinical technology categories dominate the market today:

• Electronic data capture (EDC)
• Randomization and trial supply management (RTSM/interactive response technologies)
• Electronic clinical outcome assessments (eCOA)
• Clinical trial management systems (CTMS)
• Clinical data warehouse (CDW)

Out of these five groupings, eCOA is the only one that has not successfully transitioned to an enabled, in-house, configurable SaaS model at scale—although, this is accelerating. Technology companies are releasing new capabilities to make this a reality, and sponsors and CROs are adopting new processes, budgets, resources, and change management strategies to make it possible. The pandemic has hastened this trend and the rise of DCTs has forced new models that will shape a digital transformation across clinical operations. Grandview Research projects the ePRO market to exceed $4 billion by 2030.

The wide-reaching benefits of ePRO

The benefits of ePRO (and all eCOAs) extend far beyond a once-in-a-lifetime public health emergency. Compared to onsite paper assessments, ePRO-generated data is easy to share across all stakeholders in the drug development chain. Systems and surveys are easy to adapt, too, based on how the trial is progressing. And when ePROs are directly connected to wearable patient monitoring devices, the speed, reliability, and accuracy of data is even more significant.

Beyond measuring cures, clinical worsening, or mortality, today’s modern ePROs are asking equally important questions about patients’ quality of life. They allow for the implementation of branching the logic of questions—skip patterns, which create a custom path that varies based on a respondent’s answers and offers patients a more personalized experience. Skip-pattern functionality can also shorten the length of questionnaires, reducing patient burden. Finally, ePROs can improve patients’ willingness to answer sensitive questions² that they otherwise may not be comfortable answering.

The ePRO approach likewise elevates patient voices. For example, one of the five core aspects¹ of the patient experience that ePROs should measure, according to FDA, is “role function,” which measures the overall impact of a treatment on a patient’s ability to work and carry on with daily activities. This goes beyond sterile measurements of symptoms and side effects to ask the patient, “How is this going for you in real life?” When a drug’s side effects might outweigh its benefits, real-life impact is incredibly important for researchers.

Finally, ePROs reduce burdens on the patient. Consider a patient in an oncology trial who is suffering from fatigue and all the other effects of their disease. As opposed to requiring that patient to travel to the trial site to report their outcomes, an ePRO allows them to submit their assessment on their own time from home. The patient can probably even report from their own device, which they are already familiar with—which research³ shows most patients prefer. The comfort and flexibility of their ePRO experience means the patient is less likely to drop out of the trial, too, for improved patient retention.

Indeed, recruiting and retaining trial participants is a widely recognized hurdle in trials. Medable spoke to a member of its Patient/Caregiver Network, Katie Moureau, who shared her experience. Moureau’s eight-year-old son has Prader-Willi syndrome and has participated in several hybrid and DCTs where ePROs were used.

“Being in the rare disease community, there’s already a limited number of participants,” said Moureau. “And now throw on top of that, are patients unable to afford to travel or take off work to go the distance of far-away sites? That’s difficult for families. In a DCT, you’re able to do most, if not all, of that in your home. I think that’s going to help us move science forward and give sufferers of rare diseases more potential for their future and less burdens on their families and themselves.”

Beyond increasing patient access to trials, ePROs can also help patients and caregivers remember to report in the first place. “An ePRO app that provides reminders and well-timed prompts is really helpful,” added Moureau.

The remaining hurdles to climb

It’s clear that ePROs pose benefits, but hurdles still exist on the path to adopting them at full-scale.

For example, building ePRO applications takes too long. In a few years, the majority of ePRO-builds will be automated using libraries and templates—perhaps aided by new AI technologies—but changes need to happen now. The patient experience should improve as well as more integrations with existing software platforms become easier and more configurable, which also prevents patients from having to toggle between multiple apps for the same trial. Ultimately, the ideal solution will be one platform that unifies the trial experience, even if the capabilities stem from different applications.

The life sciences industry is learning from the plight of trial site teams who, on average, are required to use 12 to 17 different systems and logins per study. While the industry continues to work to solve this problem at the site level, this cannot happen to patients, as the negative experience could cause extra burden and increase dropouts.

The interoperability of ePRO data also has room for improvement. The Clinical Data Interchange Standards Consortium (CDISC) has already created mature standards for clinical research that are accepted by FDA and global regulatory agencies while HL7 is the accepted standard for healthcare.

The challenge is in bridging research and healthcare data together bidirectionally.

Data interoperability has two sides: sponsors and patients. Standardizing ePRO data—and all eCOA data—will help optimize data validation and conformance, as well as improve data transfer by eliminating the need for data manipulation before it is sent to external stakeholders, which helps the sponsor. Patients, however, still struggle to receive any of their data at the end of a trial. The concept of “patient data return” has only been explored by a few large sponsors, with Pfizer⁴ being one of the only to succeed. Once the industry reaches a point where patients get their study results returned to them in a standardized way, it can be added to their medical records and potentially provide more opportunities to patients to find medical solutions. Patients are also more likely to share their data to help others.

There are some initiatives in progress that offer a good model to follow. The Vulcan Accelerator,⁵ for instance, was launched in 2019 by a group of industry stakeholders to bring research and healthcare together through standardized data exchange. The initiative is testing various use cases with results expected over the next five or more years. Ultimately, success will unlock many opportunities for clinical research and patients.

Technical support is another challenge, with patients resorting to calling help desks and clinical trial administrators spending time helping patients troubleshoot. Existing ePRO solutions also require a great deal of training for sites before a trial can start, which is counterproductive to the industry’s larger effort to shorten study times.

To make ePRO successful at scale, sites say that technology must be simplified, and training streamlined⁶ so they can easily troubleshoot for their patients and avoid third-party help-desk support. Intuitive apps, easily digestible administrator and user training, as well as sandbox environments that allow for administrators to test different emergency scenarios would go a long way.

Give patients more options: It’s worth the effort

Just as consensus is growing around the importance of patient optionality in clinical trials, it is also growing around ePROs being a core part of that goal. One cannot exist without the other. Besides the data quality advantages, ePROs also elevate patients from test subjects to partners in drug research—minimizing the burden on patients and their caregivers while amplifying their voices.

Life sciences companies, and clinical research in general, cannot revert to inefficient pre-pandemic processes. Even as the economy threatens budgets, the industry can’t afford to take its eye off the progress we’ve started to make with patient-centric decentralized trials. Modern ePRO solutions offer a clear path forward. If we can successfully make ePRO a configurable, enterprise-grade solution that provides sponsors with additional flexibility, the result is digital transformation around the patient experience that also accelerates study timelines. The harder we step on the gas, the more quickly we can reach scale. It will take work—but the benefits will be more than worth the effort.

Joe Dustin, vice president and general manager of eCOA, Medable

References

1. FDA, Core Patient-Reported Outcomes in Cancer Clinical Trials (June 2021). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/core-patient-reported-outcomes-cancer-clinical-trials
2. Tourangeau, R.; Yan T. Sensitive Questions in Surveys. Psychological Bulletin. 2007. 133 (5), 859-883. https://www.researchgate.net/publication/6117379_Sensitive_Questions_in_Surveys
3. Byrom, B.; Doll, H.; Muehlhausen, W. Measurement Equivalence of Patient-Reported Outcome Measure Response Scale Types Collected Using Bring Your Own Device Compared to Paper and a Provisioned Device: Results of a Randomized Equivalence Trial. Value Health. 2018. 21 (5), 581-589. https://doi.org/10.1016/j.jval.2017.10.008
4. Returning Clinical Data to Patients. Pfizer. 2023, https://www.pfizer.com/science/clinical-trials/trial-data-and-results/data-to-patients
5. Vulcan Accelerator Home Page. https://confluence.hl7.org/display/VA/Vulcan+Accelerator+Home (accessed August 22, 2021)
6. eCOA Digital Week: An Honest Assessment of eCOAs From a Site Perspective. Medable webinar. May 17, 2023, https://www.medable.com/knowledge-center/on-demand-webinar-ecoa-digital-week-an-honest-assessment-of-ecoas-from-a-site-perspective