Modernizing Patient-Reported Outcomes: Bridging the Gap Between Legacy Measures and Contemporary Healthcare

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Patient-reported outcomes (PROs) have long served as an essential tool for understanding how patients experience their diseases and treatments. From clinical trials to real-world applications, PROs are central to evaluating the effectiveness of interventions and ensuring that treatments align with patients' lived experiences. However, as our understanding of diseases continues to grow, and healthcare evolves with advancements in early disease detection and a deeper understanding of disease progression, the relevance and applicability of many existing PRO measures are increasingly questioned.

It is essential for clinical trial sponsors, researchers, and stakeholders to explore how PROs can evolve in parallel with these advancements to ensure they remain scientifically robust, patient-centric, and aligned with contemporary healthcare practices. In the context of clinical trials, this evolution is particularly important as accurate, meaningful, and relevant data are critical in assessing the effectiveness and safety of new drug therapies.

The importance of PRO selection

A key challenge in clinical trial design is the careful selection of PROs that are appropriate for the patient population and disease being studied. While traditional PRO measures have proven valuable in the past, failing to account for new disease knowledge, treatment modalities, and evolving patient demographics during the design phase can lead to significant issues. The use of traditional questionnaires, whilst guaranteeing the psychometric properties of the scales (these are usually validated scales), may result in skewed data by failing to capture the full scope of a patient’s experience and may not accurately reflect current disease progression and treatment effects.

“To fight against my colorectal cancer, I consented to join a clinical trial where I had been asked to complete a 42-page questionnaire at home, including parts that were really not relevant for me,” says K.M., a 40-year-old patient partnering with Kayentis and bringing insights to better understand how to improve our solution to fit patient needs. The questionnaire had several sections that were not applicable to this patient’s condition, meaning that the patient had to repeatedly refer back and forth to determine how to respond. This example underscores the challenges that arise when inappropriate PRO instruments are used. This can create compliance issues, as patients may find such instruments difficult to understand or burdensome to complete. K.M. also noted that the questionnaire was designed in 1985 and specifically focused on the menopause, which was not applicable to this patient, and included questions that were no longer relevant given the advancements in the understanding of the patient’s condition. Using such outdated measures can lead to skewed data that do not capture the true impact of the disease or treatment, overlooking the evolving nature of medical knowledge and patient care, thereby reducing the overall reliability and applicability of the trial results.

When selecting PROs for a given trial, careful consideration of the disease stage, patient characteristics, and treatment setting is critical. A lack of specific methodological precision during the design phase can contribute to significant gaps in data collection and reduce the reliability of results,¹ particularly in trials involving pediatric or geriatric groups.

Tailoring PROs to specific patient populations

Although the clinical trial endpoints drive the selection of PROs for a comprehensive clinical outcome assessment (COA) strategy, a consideration of the patient population is important to ensure that the selected PROs are appropriate.

For example, in trials involving young children, PROs that have not been validated for specific age groups or diseases may lead to insufficient or non-representative data. In such cases, it is crucial to consider age-appropriate pediatric versions of PROs, use proxy versions where caregivers or clinicians report on behalf of the child, and include observer-reported outcomes (ObsROs) when a caregiver’s perspective on the child’s health is necessary.

In rare diseases there is often a lack of validated age-specific PROs for the pediatric population, or in some cases, even proxy versions, making it necessary to use adult versions to capture the child’s perspective.² However, using adult versions may not provide a complete or accurate picture of the child’s experience. Moreover, there is a lack of disease-specific PROs, prompting the use of generic instruments³ such as those designated for quality-of-life assessment, which can fail to fully capture the unique perspectives of patients with these conditions. Instrument development, which is lacking in the rare disease field, should focus on creating new versions of PROs that reflect the full spectrum of disease experiences, especially for conditions where proxy responses are necessary or where early disease detection has led to more complex or varied patient outcomes.

Modern research practices, including the use of digital technologies, can help ensure that these instruments capture more meaningful, representative, and nuanced data.

The role of electronic data collection in PRO modernization

The introduction of electronic data collection tools has revolutionized the administration of PROs and patient engagement. Electronic platforms allow for greater flexibility in adapting PRO questionnaires based on previous patient responses or responses collected through alternative methods, such as observer or clinician-reported outcomes.⁴

These adaptations can make PROs more dynamic, allowing them to remain relevant to the patient’s condition and treatment journey.

• One example is the use of triggers that allow only the most relevant questions to be displayed, based on the patient’s previous responses. For instance, if a patient reports a particular symptom, the relevant follow-up questions can explore that issue in more depth.
• Another example is the use of additional questionnaires to collect basic patient information at the beginning of the trial—such as age, gender, and disease stage—which can then be used to update all subsequent questionnaires for that patient to ensure that they remain appropriate and aligned with the patient’s specific profile.

The level of customization provided by electronic systems increases the relevance and usability of PROs, ensuring that patients are not overwhelmed by irrelevant questions or data points.

While these systems allow patient insights to be captured, unlocking the full potential of patients will require integrating such systems earlier and more deeply into the trial design and process.

Including patient representatives in the design and modification of PROs

Modernizing PRO strategies is not just about updating tools and measures, but also about listening to patients and ensuring their voices are heard throughout the entire process.

Their input can be valuable at different steps:

• During the selection of appropriate PRO instruments, to make sure the PROs chosen for a given trial are fit for purpose and will measure what matters most to patients.
• During the creation and development of questionnaires. While patient involvement in the validation of these instruments is important, co-creation goes a step further by directly incorporating patients' lived experiences to ensure the measures are intuitive and truly reflective of the challenges faced by patients. Through co-development, patients can offer their perspective on the types of questions that matter most and how these should be framed.

For instance, in rare diseases where the history and progression of the disease can vary greatly between individuals, it can be challenging to develop standardized PRO measures.³ In these cases, collaboration between patients and clinicians is crucial. Patients, who have a deeper understanding of their condition and the impact of treatment, can provide key insights into which symptoms and experiences should be measured. Clinicians, with their medical expertise, can help contextualize these experiences and guide the development of questionnaires that capture both the clinical and personal aspects of the disease.

This collaboration ensures that the resulting PROs are not only clinically relevant but also resonate with patients' daily experiences and challenges, making the tools more accurate and meaningful.

The goal is to reduce the patient burden while maximizing the utility of the data collected, an outcome that can only be achieved by tailoring the experience to individual patients' needs and preferences.

As clinical trials continue to evolve alongside advancements in disease knowledge, early detection, and patient care, the tools used to measure patient experiences must also adapt. Modernizing PROs is not just about embracing new technologies, but also ensuring that patient voices are integral to the process of trial design and data collection. Incorporating real-time electronic modifications and actively engaging patients in the co-creation of PRO instruments ensures that clinical trials remain both scientifically rigorous and patient-centric. By adopting these strategies, sponsors can lead the way in creating clinical trials that not only meet rigorous scientific standards, but also uphold the needs and experiences of the patients they aim to benefit, ultimately ensuring compliance and maximizing the success of therapeutic interventions.

Anna Dudalyan, implementation project manager, clinical operations department, Kayentis

References

1. Mercieca-Bebber R, Palmer MJ, Brundage M, et al.Design, implementation and reporting strategies to reduce the instance and impact of missing patient-reported outcome (PRO) data: a systematic review. BMJ Open. 2016;6(6):e010938
doi: 10.1136/bmjopen-2015-010938. PMID: 27311907; PMCID: PMC4916640

2. U.S. Department of Health and Human Services. (2009). Guidance for industry: Patient-reported outcome measures: Use in medical product development to support labeling claims. Food and Drug Administration
https://www.fda.gov/media/77832/download Accessed 1 April 2025

3. Slade, A., Isa, F., Kyte, D. et al. Patient reported outcome measures in rare diseases: a narrative review. Orphanet J Rare Dis 2018;13:61
https://doi.org/10.1186/s13023-018-0810-x

4. Mowlem FD, Elash CA, Dumais KM, et al. Best practices for the electronic implementation and migration of patient-reported outcome measures. Value in Health 2024;27(1):79-94
https://www.valueinhealthjournal.com/article/S1098-3015(23)06153-3/fulltext