Patient Voices in Oncology: Integrating Efficacy, Tolerability and Treatment Experience

In recent years, the development of oncology therapies has advanced significantly, with the availability of new modalities and increased efficacy offering patients a range of options to consider when deciding on their treatment. While treatments focus mostly on symptoms and functional limitations, their tolerability and the burden of side effects play a critical role in shaping a patient’s overall experience, particularly as many regimens have shifted from fixed-term to long-term ⁽¹⁾. Moreover, clinicians alone cannot assess if a treatment is tolerable, as only patients can describe what they are willing to endure, often in relation to the severity of their disease. This scenario raises two questions – “What makes a new drug efficient from the patient's perspective??” and “How patients determine whether a treatment is tolerable?”

The role of Patient Reported Outcomes (PROs) in Oncology trials has evolved from providing supportive exploratory data to serving as a central component of the comprehensive assessment of patients’ symptoms, functioning, and well-being ⁽²⁾. For example, PRO instruments have been used as secondary endpoints in the clinical trials submitted to the FDA in support of the recent approval of four drugs, Blenrep, Imdelltra, Romvimza and Itovebi, with PRO data included in the final labels.

As the role of PRO outcomes continues to expand, a range of regulatory and international frameworks have been developed to guide their robust and consistent use in clinical research.

EMA and FDA: From a regulatory standpoint, the importance of collecting PRO data is well established and supported by clear recommendations from the European Medicine Agency (EMA) ⁽³⁾ and the Food and Drug Administration (FDA) ⁽⁴⁾ that outline regulatory expectations for the validity and quality of PRO data collected in clinical studies. For oncology trials, this is reflected in the EMA ^{(5, 6)} and FDA ⁽⁷⁾ guidelines, both of which emphasize the value of incorporating the patient’s viewpoint on their health and treatment experience. In particular, the FDA’s disease-specific industry guidance - Core Patient-Reported Outcomes in Cancer Clinical trials guidance ⁽⁷⁾ - recommends that PRO endpoints in cancer trials focus on five key concepts:

• Disease-related symptoms
• Symptomatic adverse events
• Overall side effect impact 
• Physical function 
• Role function 

Another key initiative is the FDA’s Project Patient Voice ⁽⁸⁾, hosted by the Oncology Center of Excellence, which provides publicly available summaries of patient-reported symptom data from completed clinical trials. This initiative gives patients, clinicians, and researchers access to a more complete picture of the treatment experience, helping to contextualize clinical data with the patient’s perspective.

Other international efforts: In addition, international efforts have been made to develop recommendations that ensure the collection of high-quality PRO data, including, but not limited to, the Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objective Recommendations (OPTIMISE-ROR), the Standard Protocol Items: Recommendations for International Trials (SPIRIT)-PRO Extension, the Consolidated Standards of Reporting Trials (CONSORT)-PRO, and the Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials – Innovative Medicines Initiative (SISAQOL-IMI) ^(9,2).

Collectively, these PRO-focused regulatory frameworks reinforce the importance of systematically capturing patients lived experiences with treatment, reflecting not only the clinical benefits but also the treatment’s tolerability. Tolerability is defined by the International Council for Harmonisation as “the degree to which overt adverse effects can be tolerated by the subject.” ⁽¹⁰⁾ This  definition has been further expanded by the Friends of Cancer Research ⁽¹¹⁾ to encompass “the degree to which symptomatic and non-symptomatic adverse events associated with the product’s administration affect the ability or desire of the patient to adhere to the dose or intensity of therapy,” also adding that “A complete understanding of tolerability should include direct measurement from the patient on how they are feeling and functioning while on treatment.” As such, tolerability should be viewed as a multidimensional measure that considers not only treatment effectiveness and burden, but also patients’ perceptions of risk and benefits, their strategies for managing side effects and the resulting impact on health-related quality of life. 

Understanding tolerability through PROs can help reveal nuances that clinical toxicity grading can miss, such as persistent symptoms that affect patients’ ability to work, rest, or perform simple daily tasks.

However, although tolerability is a central concept in oncology trials, its assessment remains limited by methodological gaps, including the lack of specific measures. From a regulatory perspective, the FDA suggests specific PRO instruments to assess four of the five key concepts outlined in its oncology-specific guidance ⁽⁷⁾ : 

• the PRO-CTCAE for capturing symptomatic adverse events
• the FACT GP5 item and the EORTC Q168 question for assessing the overall side effects impact 
• the EORTC-QLQ C30 and the PROMIS Physical Function item bank for evaluating physical and role function). 

Together, these tools highlight important aspects of patients’ experiences with their treatment but the extent to which they fully capture the multidimensional nature of treatment tolerability should be investigated. These and other challenges were discussed in a recent commentary by Byrom and Peipert, 2026 ⁽¹²⁾.

On the other hand, approved drugs in oncology have already set a precent for claiming tools that support the assessment of tolerability, with PRO-CTCAE mentioned in the Blenrep label, approved for multiple myeloma, and the FACT-GP5 mentioned in Retevmo label, for thyroid neoplasms treatment, demonstrating how regulatory recommendations are being translated into actionable evidence.

Moreover, a study from Wintner et al., 2026 , demonstrated that integrating clinician-assessed treatment-related side effects collected using CTCAE with patient-reported data from the EORTC-QLQ-C30 and selected EORTC Item Library items significantly improved the inter-rater reliability among clinicians, thereby enhancing the consistency and overall value of the adverse events reported in a randomized oncology trial, emphasizing  the added value of PRO data in the comprehensive evaluation of a new drug treatment. ⁽¹³⁾ 

While PROs bring the patient’s experience to the forefront by capturing how they feel and function during treatment, evaluating the quality of the care they receive could further enhance our understanding of the overall treatment journey. Patient-Reported Experience Measures (PREMs) could complement PROs by providing insights into how care is delivered in clinical settings ⁽¹⁴⁾. These measures support the evaluation of health care quality by capturing key aspects of patients’ experiences, such as communication with health care professionals, shared decision-making, and care coordination. In oncology, two PREMs have recently been developed: the Patient-Reported Experience Measure item bank (PREM-item bank) ⁽¹⁴⁾ and the Patient-reported Experience Measure-Cancer (PREM-C) ⁽¹⁵⁾. Together, the synergistic use of PROs and PREMs can provide a comprehensive understanding of the value of a new treatment on both patients’ health outcomes and their overall care experience. 

These findings highlight significant progress in integrating the patient voice into oncology but also reveal the potential need for improvements in how tolerability is currently measured. Strengthening tolerability assessments will require more comprehensive strategies, such as combining PROs, PREMs or considering qualitative approaches to better engage patients in their treatment experience, ultimately enabling more informed, patient-centred treatment decisions. 

Mapi Research Trust and ICON have developed comprehensive evidence-based platforms designed to aid sponsors in navigating the complexity of outcome assessment and fit-for-purpose tool selection. Through ePROVIDE, a centralized COA database, sponsors can identify, review, and implement appropriate clinical outcome assessment tools in oncology, supported by structured COA licensing and linguistic validation processes. Contact us for support with your clinical trials strategy today.

Thank you to Francesca De Giorgio, Céline Desvignes-Gleizes, Antoniya Andonova and John Kealy for their contributions to this article.

References

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