While clinical trial teams increasingly use electronic patient-reported outcome (ePRO) data, there still is some reliance on paper-based questionnaires and forms. However, reliance on such physical forms can negatively impact trial data, introducing inaccuracies and reducing patient satisfaction.
By contrast, use of ePRO can improve data accuracy, save time, increase security and bring about other benefits. Outsourcing-Pharma (OSP) recently checked in with leaders from contract research organization (CRO) Premier Research (PR) about how ePRO works, and the advantages such a system can provide.
OSP: Could you please provide the ‘elevator presentation’ of what ePRO actually is (and what it isn’t)?
PR: According to the FDA, a patient-reported outcome (PRO) is “any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else.”
An ePRO is this data collected by electronic methods, including computers, smartphones, or telephone systems. ePROs are typically developed as diaries or questionnaires. While ePROs are most commonly used in clinical trials, they can also be used in clinical practice.
OSP: What are the benefits of using ePRO, compared to using paper-based PROs?
PR: Compared to paper-based PROs, ePROs offer various potential benefits, such as:
- Data integrity. ePRO systems have electronic time stamps and can be configured to allow data entry only within specified time windows. These systems also enable input validation to check that patient entries are valid and complete. This may improve data integrity and compliance.
- Patient satisfaction. Studies on satisfaction and ease of use have shown that patients prefer ePRO systems over paper and that ePRO measures typically produce less missing data.
- Time-saving. ePROs are typically less time-consuming for patients than their paper counterparts. ePROs also save time for investigators, as assessment calculations are automatically made in real-time, eliminating the need to manually tally up responses and apply scores.
- Patient safety. Some ePRO systems have a data monitoring feature that allows messages to be sent directly to patients if their responses meet pre-determined levels.
- Data security. ePRO data is stored on a server, with a backup, reducing the risk of data loss.
OSP: Can you think of any misconceptions about using ePRO, and why these specific misconceptions are not a significant cause for concern?
PR: One common misconception is that incorporating ePROs or other electronic clinical outcome assessment methodologies into a clinical trial will require additional lead time.
Our experience is that developing, testing, and deploying ePROs can be performed in parallel with site selection and study start-up with no additional lead time necessary. And, in the long run, implementation of ePROs saves time in data transcription, clarification, reconciliation, and final database cleaning.
Another misconception may be that developing an ePRO system is similar to building an electronic data capture (EDC) system. In reality, ePRO design is very different because ePROs must be designed for use by a wide variety of patients who have different backgrounds and different levels of computer, language, and health literacy, so the user experience and user interface are critical for adoption and compliance.
OSP: What are some of the factors in the industry, and in the larger world, driving the migration from paper to ePRO?
PR: The FDA supports direct patient reporting, as the agency believes some treatment effects are only known to patients and may not otherwise be captured as outcomes in clinical trials. The FDA has communicated a preference for ePROs over paper-based PROs.
More broadly, an increased emphasis on patient-centricity, advances in technology, and the proliferation of smartphones have made it easier to implement ePROs.
OSP: Could you please talk about some of the ways in which use of ePRO adds convenience?
PR: Appropriate implementation of ePRO adds convenience for both patients and investigators. ePROs generally take less time for patients to complete and certain ePRO devices can even send automated reminders to patients when it’s time to make an entry or complete another study-related task. From the sponsor or investigator perspective, ePROs eliminate not only the need for secondary data entry, but also the errors that may occur when transcribing responses from paper-based assessments.
As mentioned earlier, ePROs also add efficiency because assessment calculations are performed automatically.
OSP: How does ePRO support FDA requirements regarding digitalization?
PR: Over the past 15 years, the patient perspective has become an increasingly important part of the drug development and approval process. From 2006 to 2010, the EMA and FDA collectively issued nearly 50 guidance documents that recommended the collection of patient-reported outcomes in clinical trials; ePROs play an important role in the efforts of the FDA to augment the use of PROs and to increase adoption of digitalization initiatives across the clinical trial process.
OSP: Why do you think some organizations still aren’t paperless?
PR: Not all PROs are suitable for electronic collection of data. When determining whether a paper-based PRO can be transitioned to an ePRO, it is important to consider the type of PRO measure being adapted, the target population, and the complexity of data capture and scoring requirements. If free text responses are required as part of the PRO, ePRO may not be suitable.
The transition from paper-based PROs to ePROs requires a validation process. To validate the ePRO questionnaire, sponsors need to do one of the following:
- Ensure that the data collected via paper and electronic methods are equivalent
- Account for any differences identified between the two versions
The level of evidence required to validate an ePRO measure varies depending on the amount of content and the format modifications needed to migrate the measure from paper to an electronic method.
Regulations require that investigators be responsible for controlling, maintaining, and providing access to all source documentation in the event of an FDA inspection during the conduct of a clinical trial. The use of ePROs may interfere with this responsibility if the sponsor or CRO controls ePRO source data.
OSP: How has the COVID-19 pandemic affected adoption of ePRO and other advanced technologies?
PR: The COVID-19 pandemic has accelerated much-needed change in the conduct of clinical trials, including an uptick in the adoption of ePRO and other technologies that enable remote assessment. Driven by the need to incorporate alternative approaches for working and interacting with study participants, sponsors and CROs have been leveraging technology for a range of study activities, from patient consent and consultation to PROs and site monitoring.
OSP: What else would you like to add about ePRO that we might not have touched upon in the other questions?
PR: Outside of the clinical trial landscape, pandemic-related healthcare delivery challenges have also sparked increased interest in utilizing ePROs in routine clinical practice. In the wake of the pandemic, we expect that ePROs will continue to be a valuable adjunct data collection tool in both clinical trials and the clinic.
