The deployment and adoption of electronic patient-reported outcomes (ePRO) in clinical trials has increased significantly during, and since, the COVID-19 pandemic, given the many documented benefits of using electronic modalities to capture PRO data. As eDiaries have become more common, some well-established challenges still exist in their design and implementation. Continued raised awareness of key challenges by subject matter experts (SMEs) aims to encourage an industry change in the way sponsors plan and approach the inclusion of eDiaries. With that in mind, we have documented two early-stage challenges – protocol interpretation and planning and eDiary design – that need to be addressed. 

Challenge one: Protocol interpretation and planning
One of the earliest and most important design challenges when implementing eDiaries is ascertaining exactly what data are required to be captured and when. Homegrown eDiaries rely upon the interpretation of trial protocols by vendors and SME teams from the sponsor or clinical research organizations (CROs). Protocols often do not include the level of detail necessary to begin eDiary build activities immediately. This is in stark contrast to validated questionnaires, the datapoints of which are mostly fixed, with little to no interpretation required.

Experienced eCOA teams from vendors and CROs can work with varying levels of initial direction to produce an eDiary that meets the needs of the study. However, the amount of design to be delegated by the sponsor should be defined from the outset. Design versus development of an instrument should be considered during this phase and scientific resources should be added, if needed. Furthermore, scientific input ensures diary questions are written with a lay audience and, ideally, the specific participant population in mind.

The development of an eDiary must therefore begin with consultation among the various stakeholders. While electronic clinical outcome assessment (eCOA) experts from CROs and technology vendors can catalyze discussions and decision-making, having the right sponsor stakeholders involved at an early stage is essential. This ideally includes representatives from medical and statistical departments, as well as data management and/or eCOA specialists. This early alignment of the study teams helps to avoid costly rework, late eDiary iterations and delays and/or compromises further down the line.

Currently, sponsors can provide eCOA vendors with an incomplete list of variables to be collected, an initial draft of the diary workflow as a starting point or a diary used on another of their studies. When a diary designed for use on paper is used as a starting point, the migration to electronic administration must be given due consideration and explained to the sponsor team. This part of the process is well understood today and, most commonly, results in the revision of paper-specific words such as “tick” to words better suited for electronic use, such as “select” or “tap.”

Most vendors start with an iterative design process taking the first primitive draft into an electronic format. The number of iterations from first to final version can be numerous and sponsors often underestimate the time input required from them at this crucial stage of design.

Next, eCOA SMEs and vendors must find areas of the protocol that might be relevant for eCOA instruments, including:

• Any indicators of eligibility assessment fed by eCOA completion
• Any indicators of alerts or notifications that must inform patients and sites
• Any indicators of comparisons of scores
• Indicators that phases/periods of the study change what the patient will do
• Cohort or country-specific nuances 
• Any indicators that eCOA compliance will feed continuation in the study

These elements need to be discussed and turned into project parameters and specifications. These discussions are documented and form the template from which eCOA vendors will build. 

How should you address? Here are three recommendations for sponsors:
1.     Consider eDiary content early and appoint a scientific team to assist in its development, with input from the medical and biostats teams.
2.     Define eCOA calculations, eligibility and alerts in the protocol, and, if possible, add the draft eDiary to the protocol as an annex.
3.     Be available during the two- to four-week design phase of the eCOA system.
 
Challenge two: eDiary design
While interpretation of the protocol defines what is captured by the eDiary, the design phase focuses on how it’s done. 

Considerations around basic best practices are important at an early stage of design. Limited screen scrolling per page helps prevent participants from missing questions or feeling overwhelmed by text. Branching logic can reduce the number of redundant questions or screens the participant has to address, as well as affording the opportunity to present different cohorts, study periods or age groups with different question sets.

Incorporating different study periods or pediatric age groups can lead to further design-related challenges. In longer trials, consideration must be given to whether pediatric patients receive the same diary form, or move to one designed for the next age group as they progress through the trial. Similarly, if different study periods utilize different eDiary forms, the functionality and programming logic of entering, leaving or switching between them must be designed in conjunction with the vendor and CRO.

One of the most important design principals is the avoidance of free text. Free text is almost impossible to codify and therefore analyze. It is also burdensome for patients to enter, taking far longer to record than multi-select or radio options. In multi-country studies translating free text into one language can also add to the cost and complexity of the trial for little overall benefit. There are also ethical considerations here. For instance, data should not be requested from patients if of little or no use to the study. 

Many diaries designed for use on paper included sections for free text, for example to record comments on possible symptoms or to give explanations as to why a dose was not administered. If diaries designed for paper are provided as a basis for the eDiary, these free text questions should be updated where possible. SMEs often will explain the risks around un-codable and un-analyzable free-text data to sponsor teams.

While these challenges and others can make eDiary development appear complex, using the right CRO and vendor partner can help to overcome them and realize the benefits of using electronic diary forms. It’s important to partner with a CRO that has true subject matter expertise in eCOA design and implementation to ensure proper bridging of the study team with the eCOA vendor.

How should you address? Here are five recommendations:

1.     Source an eCOA vendor that offers a product with features and capabilities that fit with the complexity of the study design, considering alerts, calculations, branching, eligibility, etc. 
2.     Design a system where patient engagement can be achieved to ensure a high quality of data and high compliance.
3.     Think early about free text options, prepare and provide code lists or remove free text questions of little value.
4.     Define the availability of eDiaries and alerts.
5.     Define what happens when patients move into a new age group or a new period during the study. 

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