Why ePRO Matters

Electronic Participant Reported Outcomes (ePRO), one type of electronic Clinical Outcome Assessment (eCOA), have become increasingly important in clinical trials. They address many of the challenges associated with traditional paper diaries, such as missing pages, retrospective data entry, and errors introduced when information is recorded after the fact. Beyond reducing these issues, ePRO systems foster clear communication and consistent reporting of outcomes between participants and study teams.

If you’re building your own ePRO instrument, take a look at our article on statistical validation.

Simplifying Patient Engagement

At S‑cubed Biometrics, we strive to make data collection straightforward, dependable, and easy for everyone involved. This is especially true for ePRO, which is why we use OpenClinica Participate. This module allows participants to enter their information via a simple link on a device they already use, a Bring Your Own Device (BYOD) approach. There are no apps to download and no need for the costly provision or management of standalone devices. For sponsors, this simplifies study setup and delivery. For participants, it reduces barriers to participation and increases compliance.

Real-Time Data Capture and Visibility

The Participate module integrates immediately and directly with the clinical database, commonly known as the EDC. By capturing data in real time and making it readily available, data management and clinical teams gain immediate visibility of participant reported information within the EDC. This timely access supports appropriate oversight of incoming data and helps identify potential issues early, strengthening participant safety. Automated reminders also encourage participant engagement without adding burden to site staff.

To support study start up and downstream approvals, our Data Management team produces PDF representations of unique eDiary screens at an early stage. These materials can be used during protocol development, ethics review, and regulatory submissions, helping to ensure diary requirements are clearly defined, feasible for participants, and approved prior to build.

Ensuring Quality from the First Entry

Our Data Management team plays a central role in the setup of ePRO and its seamless integration with the EDC. They design and configure eDiary forms to be intuitive for participants, while ensuring that study specific visit schedules and diary windows allow appropriate flexibility for real world scenarios. Built in validation checks help reduce incomplete or inconsistent entries, supporting cleaner data from the outset.

Throughout the study, our Data Managers closely monitor incoming ePRO data, respond quickly to issues, and ensure that data entering the database is accurate, complete, and ready for analysis. If the ePRO platform is the vehicle, our Data Managers are the specialists keeping it running reliably from start to finish.

By combining rapid eDiary build timelines, full EDC integration, and a BYOD delivery model, S-cubed Biometrics offers a cost efficient ePRO solution that delivers high data quality, promotes participant engagement, and contributes to efficient study delivery.

When Clinical Endpoints Aren’t Enough

For many indications there are clear objective clinical endpoints, such as changes in antibody levels, tumour size and chemistry or haematology lab parameters, which can be utilized to measure the efficacy of a new treatment. However, for a number of indications the endpoints of primary interest are concerned with the individual’s impression of how the treatment is affecting them, whether that be in evaluating symptoms such as pain or itching, or evaluating how the treatment impacts a patient’s day-to-day life. These are all typically measured via Patient Reported Outcomes (PROs). Careful design and analysis are critical for these types of endpoints, often benefiting from specialist statistical expertise early in development.

PROs take a wide variety of forms from the SF-36 used to measure quality of life, and the C-SSRS used to ascertain the presence and severity of suicidal ideation, to the single question Patient Global Impression of Severity (PGI-S) or Change (PGI-C). While there are a lot of questionnaires available, often it is difficult to identify one that accurately or completely reflects the evaluation of the disease or symptom of interest and the decision could be made to develop a new questionnaire to better capture this.

Regulatory Expectations for PROs

The FDA guidelines on the use of PROs to support claims for a medical product state that ‘A PRO instrument, like physician-based instruments, should be shown to measure the concept it is intended to measure, and the FDA will review the evidence that a particular PRO instrument measures the concept claimed.’

As part of meeting these requirements, any new instrument used in the evaluation of products should be formally validated and shown to provide a reliable and consistent measure of the concept of interest.

Building Validated PROs with Patients as Priority

It is recommended that PRO instrument development and validation involve the patients, through interviews and focus groups, to help inform the language of the questions and the ease of use of the PRO instrument. Statistics can also be useful in the development of these instruments and can be used to help define the optimum recall period, identify redundant questions, or classify domains within the instrument.

The Role of Statistics

The next stages of PRO development rely heavily on statistics to examine the reliability and validity of the PRO instrument, and evaluate its ability to detect change. If these elements cannot be demonstrated satisfactorily, the PRO instrument will not be accepted as an endpoint.

Reliability and Consistency

It is important to evaluate the stability of responses over time when no changes are expected, to ensure that the instrument provides a reliable result. Similarly, if the instrument consists of multiple questions it is important that the responses within a questionnaire are consistent when multiple questions are intended to measure the same concept.

Validity

Additional considerations are whether the responses to the new instrument are consistently related to other instruments used in the field of interest and whether the relationship is as expected. This could be looking at the overall instrument, or domains within the instrument. Examining responses in known groups (which can be defined clinically or via a different validated PRO) can be used to look at whether the response differs between the groups as expected.

Change

Assessment of the ability to detect change focuses on evaluating the ability of the instrument to measure any degree of change when a known change in the concept of interest has occurred. The minimally important clinical difference (MCID) can be identified using anchor-based methods and instruments for which an MCID has already been established.

How We Can Help

If you are considering developing a new PRO instrument or are already using one which has not been validated, we can help. We have experience with the various statistical aspects of PRO validation, in both the design of studies (observational and interventional) and the methods that can be used to demonstrate the validity of the PRO instrument and ensure that it will be acceptable for use as a key endpoint in your studies.