Over the last half a century or so, clinical research has progressively shifted from a somewhat paternalistic focus on physiological or surrogate endpoints such as biomarkers or imaging, toward the inclusion of patient-centered outcomes that explore an individual’s lived experiences of their illness and treatment.
Key Takeaways
- Shift toward patient-centered outcomes. Clinical research has evolved from focusing solely on physiological metrics to incorporating patient-reported outcomes that better reflect patients' lived experiences and daily functioning.
- Tension between accessibility and data integrity. While modern web and app design emphasize accessibility and flexibility, ePROM systems have historically prioritized strict standardization to preserve data integrity, creating tensions around adopting accessibility features like scalable text or screen orientation changes.
- Call for harmonization. As concerns about electronic vs. paper data comparability fade, the field is increasingly open to integrating accessibility standards into eCOA systems, with a growing recognition that true patient-centric trials must be inclusive of individuals with diverse needs and abilities.
This transition reflects a recognition that traditional clinical metrics, while objective and quantifiable, may not fully represent how patients feel or function in their daily lives. A significant change in a biomarker may not translate to a meaningful change in a patient’s real-world experience.
This shift in emphasis to the importance of understanding the patient experience was driven by the FDA’s Guidance for Industry: Patient-Reported Outcome Measures,1 which outlined the use of patient-reported outcomes (PROs) in supporting labeling claims, and the development of standardized outcome measures through initiatives such as the NIH’s Patient-Reported Outcomes Measurement Information System (PROMIS).2
In parallel, the International Council for Harmonization’s guidelines began emphasizing the importance of patient input in trial design, and the establishment of the Patient-Centered Outcomes Research Institute in 2010 further institutionalized the importance of patient experience in comparative effectiveness research. Collectively, these efforts have facilitated a reorientation in clinical research toward outcomes that matter most to patients.
Alongside these developments, over the last decade there has been a move away from paper to electronic capture of clinical outcome assessment (COA) data in clinical trials, due to benefits predominately revolving around improved data quality and, arguably, patient preference. These electronic COA (eCOA) systems are widely used across all geographies and phases of clinical research and have become integral to the successful execution of modern clinical trials. Typically deployed via an app on a smartphone provisioned to participants in a trial, or, increasingly, on apps or web browsers on a participant’s own device, there has been much talk in the eCOA industry of the importance of good usability and patient-centered design in order to reduce the burden on participants interacting with these systems in clinical trials.
Outside clinical research, general app and web-design best practices have long prioritized the accessibility and usability of these systems for the widest range of users. The history of web and app accessibility standards, particularly the Web Content Accessibility Guidelines (WCAG), reflects a global effort to ensure that digital content is usable by everyone, including people with disabilities.
Emerging from the broader push for civil rights, WCAG was developed by the World Wide Web Consortium to provide consistent, testable guidelines for accessible web design. Since its first iteration in 1999, WCAG has evolved in response to technological advances and user needs, particularly to support mobile access, impaired vision users, and those with cognitive disabilities. The most recent version, WCAG 2.2 (2023) continues this trajectory by addressing issues such as touch target size and accessible authentication. These standards are now essential for enabling equitable access to information, services, and participation in digital life and often form the basis of legal enforcement of compliance to the same.
This is not the case with eCOA, despite the purported importance of diversity and inclusivity of clinical trial populations. Integrating these practices into eCOA systems presents unique challenges. Ironically, the very same 2009 FDA guidance, which set the scene for the rise of PROs, also contained a statement that also set the scene for decades of repetitive research and conservatism in how PROs were implemented on eCOA systems.
Specifically, FDA stated that “Examples of changes that can alter the way that patients respond to the same set of questions include changing an instrument from paper to electronic format” and went on to suggest additional testing was recommended to demonstrate patients would not rate their experiences differently across different modes of data capture.
This guidance was solidified with the release of the 2009 ISPOR ePRO Good Research Practices Task Force report,3 which described the methods by which one might demonstrate this comparability.
This led to a lingering concern about the comparability of different modes of data capture in clinical research (e.g., paper vs. electronic, or between different modes of electronic data capture such as tablet and smartphone), and a focus on minimizing variability between modes by, for example, limiting to a single item and response option per screen. While this concern is finally fading in light of decades of research showing minimal impact on questionnaire integrity,4 arguably the issue has stifled the broad adoption of accessibility standards in ePROM systems due to the variability in presentation they may introduce, for example, allowing patients to set their own font size.
Comparing Web Content Accessibility Guidelines (WCAG 2.2)5 with electronic PROM (ePROM) design best practices6 suggests that, while many of the WCAG guidelines can be applied to ePROM systems today without concerns for questionnaire integrity, tensions remain between the accessibility success criteria and ePROM best practices concerning changing content size and device orientation.
A recent preprint7 by Mowlem and O’Donohoe highlighted the key considerations and tensions that arise:
The fundamental goal of best practices:
- Web/app best practices: Prioritize accessibility and usability for the broadest range of users, including those with disabilities, through principles like scalable text, flexible layouts, device orientation options, and compatibility with assistive technologies.
- ePROM best practices: Historically focus on maintaining the measurement integrity of validated questionnaires when moving from paper to electronic formats i.e. a “faithful migration.” The goal has been to minimize changes in layout, wording, and structure to preserve data comparability.
Specific tensions:
Content size and layout flexibility
- Web/app best practice: Allow users to enlarge text and adjust layouts for better readability.
- ePROM concern: Changes in visual presentation (such as increased font size or layout shift) may unintentionally influence how individuals interpret questions, potentially affecting response validity.
Device orientation
- Web/app best practice: Enable flexible orientation (portrait or landscape) to suit user preferences and accessibility needs.
- ePROM concern: Preserving a consistent presentation format across clinical trial participants is prioritized to avoid introducing variation that could impact measurement consistency.
Customization vs. standardization
- Web/app best practice: Personalization and device/browser accessibility tools are encouraged.
- ePROM concern: Standardization has been preferred to ensure all participants interact with the same layout of the measure, minimizing potential sources of bias.
The electronic data capture field has shown a trend towards flexibility and growing comfort with variability in how patients interact with their study tasks, and the time is ripe for a move towards harmonizing accessibility with validated data capture tools.
The goal is to eventually reach a point where accessibility best practices are ePRO best practices are aligned—making clinical trials more inclusive and representative, especially for people with impairments.
To make clinical trials meaningfully patient-centric and ensure we are making them accessible to all possible patients, not just a subset, it is essential that existing web and app accessibility best practices are integrated into eCOA systems.
While some standards can be adopted today, significant industry inertia remains to be overcome, and there are outstanding questions to address before best practices can be more meaningfully embraced.
However, with the transition away from concerns about comparability, the life sciences industry has demonstrated it can learn and adapt, and with patients’ best interests at heart, we are confident meaningful progress will be made in the coming years.
Paul O’Donohoe is Senior Director, eCOA Product and Science, at Medidata; and Florence Mowlem, PhD, is Chief Scientific Officer at uMotif
References
1. FDA, Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (December 2009). https://www.fda.gov/media/77832/download
2. Cella, D; Yount, S.; Rothrock, N.; et al. The Patient-Reported Outcomes Measurement Information System (PROMIS): Progress of an NIH Roadmap Cooperative Group During its First Two Years. Med Care. 2007. 45 (5 Suppl 1), S3-S11. https://pubmed.ncbi.nlm.nih.gov/17443116/
3. Coons, S.J.; Gwaltney, C.J.; Hays, R.D.; et al. Recommendations on Evidence Needed to Support Measurement Equivalence Between Electronic and Paper-Based Patient-Reported Outcome (PRO) Measures: ISPOR ePRO Good Research Practices Task Force Report. Value Health. 2009. 12 (4), 419-429. https://pubmed.ncbi.nlm.nih.gov/19900250/
4. O'Donohoe, P.; Reasner, D.S.; Kovacs, S.M.; et al. Updated Recommendations on Evidence Needed to Support Measurement Comparability Among Modes of Data Collection for Patient-Reported Outcome Measures: A Good Practices Report of an ISPOR Task Force. Value Health. 2023. 26 (5), 623-633. https://pubmed.ncbi.nlm.nih.gov/37121630/
5. Web Content Accessibility Guidelines (WCAG) 2.2. W3C. December 12, 2024. https://www.w3.org/TR/WCAG22/
6. Mowlem, F.D.; Elash, C.A.; Dumais, K.M.; et al. Best Practices for the Electronic Implementation and Migration of Patient-Reported Outcome Measures. Value Health. 2024. 27 (1), 79-94. https://www.valueinhealthjournal.com/article/S1098-3015(23)06153-3/fulltext
7. Mowlem, F.D.; O'Donohoe, P. Accessible Data Collection Methods in Clinical Trials: Do Current Best Practices for the Implementation of Electronic Patient-Reported Outcome Measures (ePROMs) Meet Accessibility Standards? Sciety. https://sciety.org/articles/activity/10.21203/rs.3.rs-5741400/v1
