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Electronic patient-reported outcomes (ePRO) are patient-provided information about symptoms, side effects, drug timing and other questions recorded on an electronic device during a clinical trial.
The technology used to gather ePRO can be an app that can be downloaded onto any device, such as a patient's iPhone. Many ePRO vendors also provide devices with the technology pre-loaded onto them. The basic feature of ePRO technology is the ability to record responses to trial questions, but some vendors offer the ability to take photos or videos through an ePRO app, as well, to provide additional context. The technology also includes features to help improve patient compliance, such as reminder alarms.
Another common term related to ePRO is eCOA, or electronic clinical outcome assessments. As it can be used to refer to ePRO as well as input provided by clinicians, "eCOA" can be considered an umbrella term for electronically recorded outcomes.
When shopping for a new ePRO app or device, make sure it's compatible with your other clinical trial technologies, especially your Interactive Response Technology (IRT). Many ePRO vendors also offer other clinical trial technologies, so if you're also in the market for other systems, it may be helpful to consider finding compatible products from the same company.
Other factors to consider include whether to allow patients to bring their own devices, what kind of devices to use if patients are not using their own, and what outcomes you're looking to capture.
Today, more than a quarter of clinical trials use patient-reported outcomes, digital or otherwise. With the healthcare industry's focus on patient centricity, patient-reported outcomes are an important tool for understanding the real impact of a new potential treatment on patients.
Patient-reported outcomes (PRO) are helpful for measuring quality of life outcomes from a clinical trial that can't be measured in other ways, such as pain symptoms.
"As more and more drugs are entering the market, really what we need to understand are the patient impacts and the patient profiles of those drugs," Susan Dallabrida, Vice President of eCOA Clinical Science and Consulting at eCOA company ERT, told Antidote. "The only way to begin to dissect what those profiles look like is to have some sort of daily or regular collection of those symptomatologies. That's where eCOA begins to lend itself as helpful in dissecting that next useful profile of drugs."
The first publication with "PRO" in the title came out in 1976. Since then, the inclusion of patient-reported data in publications has grown almost exponentially, with nearly 3,000 mentions in 2013.
The FDA's focus on patient-reported outcomes has also increased over the years. In 2009, the FDA released guidelines around the use of PROs to support labeling claims. The FDA also released a report on patient-reported outcomes in medical device premarket submissions and postmarket studies.
An example of this patient outcomes focus is that for oncology trials specifically, in 2014, the FDA denied a new drug application for a melanoma treatment because the trial design measured lesion response, but not assessments of patient symptoms. In 2015, the FDA issued draft guidance on non-small cell lung cancer, saying that while overall survival is still the standard endpoint of clinical benefit, future trials should also include PRO measures of tumor-related symptom benefit. These reports suggest the increasing importance of including PROs in clinical trial design.
One of the most common types of patient-reported outcomes is referred to as health-related quality of life (HRQL). This data point combines physical, social, and emotional well-being associated with the treatment of a condition. It's also a helpful measure because it's not disease-specific, so it can be asked of trial participants in a control group who do not have the condition. It also allows researchers to estimate population norms.
Health behaviors are another commonly-tracked PRO that can be informative to include in a clinical trial. These can include information on exercise, smoking, drinking, etc. and can be used to assess patients' response to health promotion interventions as well as to monitor health behaviors over time.
Considering how much of our daily lives are now conducted online, electronic patient-reported outcomes are not as common as one may think. As recently as 2014, around half of clinical trials were still using paper forms. However, the ePRO industry is slated to grow by 15% between now and 2025.
Users and vendors of ePRO cite several potential benefits for using digital tools rather than paper forms to collect patient input:
Cost savings: While using ePRO may involve up-front costs, the technology also has the cost-saving potential down the line. For example, using ePRO rather than paper can help save money on the manpower needed for data reconciliation. In a trial that uses ePRO, you may also need fewer participants to reach statistical significance. That's because common errors on paper can introduce statistical "noise" into trial results.
"If you're trying to get a drug to market, you're trying to get it to work as soon as you possibly can," said Dallabrida. "If it's not working, the goal is to stop giving it to people as soon as you possibly can. Paper will always bring noise into a signal [in a trial]."
One study on a treatment for overactive bladders, for example, found that the study's data variability was reduced by 33% when electronic forms were used instead of paper. Of course, all trials – and budgets – are different, and it's important to take a close look at your budget before making the decision to use ePRO.
Patient experience and compliance: Research suggests that patients are more compliant when using electronic devices to record outcomes rather than paper diaries.
Studies on compliance differences between paper diaries and e-diaries have been conducted for years. Researchers were inspired to run one oft-cited study when a scientist spotted a trial participant in the site's parking lot frantically filling out his paper diary before the appointment. The incident led to the coining of the term "parking lot compliance."
While "parking lot compliance" had been observed anecdotally for years, the first study tracking paper diary compliance started in 2002. In the rather crafty study, patients were given a paper binder equipped with a computer chip and light sensor that recorded when the binder was opened.
In the study, 79% of patients routinely reported entries that they had not actually made. The other group of patients was given a fully electronic diary that prompted, accepted, and confirmed entries at the required time intervals. Compliance for that group rose to almost 100%.
It appears that e-diaries are simply better suited to human nature. Alarms and push notifications help form habits, Dallabrida said. Electronic devices that are password protected can also help create more of a sense of privacy when patients enter sensitive information.
"One thing we know about humans, is that [they] would prefer to report that a value that they have is within what they would consider a social norm," said Dallabrida. Data points from weight, to finance, to blood sugar levels can all fall under the category of sensitive information that patients may alter if they know they'll be turning in a piece of paper to a doctor face-to-face. Dallabrida said that electronic diaries create more of a sense of privacy for patients, which contributes to better compliance.
Dallabrida shared more benefits of using ePRO over paper forms in a video recorded with Antidote:
Like with any clinical trial design, it's important to keep your IRB in mind when mapping out a trial that will include ePRO. While IRBs are likely looking more at the content of your trial than at the method you're using to collect patient responses, there are few factors to think of when considering how much of a burden your approach will put on patient participants.
"The IRB is looking at the content more than the delivery method," Nathan M. Lee, Vice Chairperson of Schulman IRB, an independent IRB, told Applied Clinical Trials (ACT). "That said, there may be unique circumstances when because of the subject population, it may be better to use one method over the other."
The ACT article points out that self-assessment may be less taxing on a patient experiencing allergies, for example, than an oncology or HIV patient. For those trials, you may choose to require fewer or shorter check-ins in your protocol.
Dallabrida also suggests considering the number of questions you ask a patient in one sitting. While many traditional PRO instruments include more than 30 questions, taking patients 10-12 minutes to complete, including fewer questions would allow patients to share symptom information more frequently. She notes that symptom information is best shared soon after it occurs, and as frequently as possible. Using ePRO allows for the immediate and regular collection of symptom data, so it's important to further encourage patients to share by reducing the time burden of completing the questionnaire.
Once you have a draft of your protocol prepared, you can start conversations with ePRO vendors for help with the next step. Even if your protocol isn't finalized, vendors can take what you have and create mockups of the e-diary or app for your trial, so you can start sharing feedback with their team early on in your process.
You can also enlist your vendor's help in putting together user guides for your trial. Create guides both for patients and for trial administrators so they can help answer technological questions as they come up.
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