Traditionally, clinical trials have emphasized objective clinical measures and laboratory data. While these are crucial, they often fail to capture an essential aspect – the trial participants personal experience.

Patient-reported outcomes (PROs) have become an increasingly important element of clinical trials, providing insights into the effects of treatment on symptoms, side effects, daily functioning and quality of life from the patient’s perspective, and consequently providing insights with which we can amplify the voice of the patients. Providing trial data beyond the standard clinical outcomes such as disease response, biomarkers, clinician-reported symptoms and adverse events, PROs enhance our understanding of the patients’ experience [1].

Despite the growing use of PROs, the extent to which these observations are reported in registries and scientific publications is variable, with positive outcomes being more likely to be covered [1,2]. Trials that prioritise PROs as key secondary or even primary endpoints aim to capture patients' perspectives, complementing clinical outcome measures. This approach ensures that the research aligns with what matters most to patients – how their condition affects their daily life – it also provides regulators and clinicians with a more complete picture of a treatment’s impact. After all, patients are more than just data points; their experiences and burden of the disease varies significantly from person to person.

Ultimately PROs capture a broad range of patient insights, from pain severity and treatment satisfaction to overall quality of life [3]. Although PROs are measured more frequently in later-phase trials, there is also a strong argument for their inclusion in early-phase studies where they may be valuable in informing dose selection and optimising drug development strategies [4]. Clearly, PROs should be seen as playing a crucial role throughout the clinical drug development process.

Ensuring high-value PRO reporting starts with defining the PROs clearly in the protocol. Researchers must use appropriate methods to collect and analyse PROs, including validated questionnaires and procedures to ensure data accuracy and reliability. Validation confirms that a questionnaire captures what it intends to and that its findings among trial participants accurately represents patients experience outside the trial [5]. Regulatory agencies emphasise the importance of validated PROs in collecting relevant and robust data, especially in cases where disease-specific questionnaires have been designed by the Sponsor [6]. Both the FDA and EMA have produced PRO guidelines [7,8], and the FDA also recently published a guideline specific to the inclusion of PROs in cancer trials [9]. Data on PROs can support regulatory submissions and the FDA can grant PRO-related labelling to a product, especially if PROs were included as primary trial endpoints and the trials followed a robust (i.e., randomised, double blind, placebo controlled) design [7,10]. The SPIRIT Statement on protocol design for interventional trials also provides guidance for writing protocols in which PROs are a primary or key secondary outcome. Statement on protocol design for interventional trials [11,12]. In addition, a PRO version of the National Cancer Institute's Common Terminology Criteria for Adverse Events is available, facilitating patient reporting of side effects [13].

As research shifts toward patient-centred metrics, the robust reporting of PROs must lie within in the clinical study report (CSR). In addition to giving appropriate consideration to the PRO data, the CSR discussion should put the PRO data into context, explaining whether or not it translates into a meaningful impact on the patient experience. For example, an enhanced quality of life or a reduction in fatigue would be extremely important for patients with cancer, even if overall survival was not affected. In other therapeutic areas, improved patient satisfaction with a new formulation will most likely translate into better treatment compliance.

With the requirement for timely clinical trial reporting and the advent of lay summaries, the inclusion of PROs gives patients more insight into the potential impacts of a pre-registration clinical trial, helping patients make informed decisions about whether they should take part. A well-presented PRO data in the CSR feeds into a high-quality lay summary, ensuring that clear and meaningful information is available. With patient well-being at the core of healthcare, PRO measures are vital tools to help ensure healthcare policy makers are aware of the outcomes that are most consequential for patients [6]. Incorporating PRO measures into clinical care promotes patient-centred care by accurately reflecting patients’ experiences [14]. Ultimately, PRO data can inform treatment guidelines and influence drug approvals [3,15].

To summarise, PROs add an important dimension to clinical trial reporting by giving patients a more prominent role, highlighting their experiences alongside key components of the clinical trial protocol.

References

1. Blackstone EC, et al. Timely Reporting of Patient-Reported Outcomes in Cancer Clinical Trials: An Ethical Imperative. J Clin Oncol. 2025:JCO2402021. doi: 10.1200/JCO-24-02021.
2. Rivera SC, et al. The impact of patient-reported outcome (PRO) data from clinical trials: a systematic review and critical analysis. Health Qual Life Outcomes. 2019;17(1):156. doi: 10.1186/s12955-019-1220-z.
3. Weldring T, Smith SM. Patient-Reported Outcomes (PROs) and Patient-Reported Outcome Measures (PROMs). Health Serv Insights. 2013;6:61-68. doi: 10.4137/HSI.S11093.
4. Navas C, et al. The Role of Patient-Reported Outcomes to Measure Treatment Satisfaction in Drug Development. Patient. 2024;17(6):603-617. doi: 10.1007/s40271-024-00702-w.
5. Ranganathan P, et al. Designing and validating a research questionnaire - Part 2. Perspect Clin Res 2024;15:42-5. doi: 10.4103/picr.picr_318_23.
6. Johnston BC, et al. Chapter 18: Patient-reported outcomes [last updated October 2019]. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.5. Cochrane, 2024. Available from www.training.cochrane.org/handbook. Direct link to chapter: https://training.cochrane.org/handbook/current/chapter-18
7. FDA Guidance for Industry. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. December 2009.
8. EMA/CHMP/292464/2014. Appendix 2 to the guideline on the evaluation of anticancer medicinal products in man: The use of patient-reported outcome (PRO) measures in oncology studies. 01-Apr-2016.
9. FDA Guidance for Industry. Core Patient-Reported Outcomes in Cancer Clinical Trials. October 2024.
10. Gnanasakthy A, et al. Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014). J Clin Oncol. 2016 Jun 1;34(16):1928-34. doi: 10.1200/JCO.2015.63.6480.
11. Calvert M, et al. Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension. JAMA. 2018;319(5):483-494. doi: 10.1001/jama.2017.21903.
12. Calvert M, et al. SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials. BMJ Open. 2021;11(6):e045105. doi: 10.1136/bmjopen-2020-045105.
13. Basch E, et al. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst. 2014;106(9):dju244. doi: 10.1093/jnci/dju244.
14. Anderson M, et al. Understanding factors impacting patient-reported outcome measures integration in routine clinical practice: an umbrella review. Qual Life Res. 2024 Oct;33(10):2611-2629. doi: 10.1007/s11136-024-03728-7.
15. Gnanasakthy A, et al. Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014). J Clin Oncol. 2016 Jun 1;34(16):1928-34. doi: 10.1200/JCO.2015.63.6480.