Using patient-reported outcomes and health-related quality of life data in regulatory decisions on cancer treatment: highlights from an EMA-EORTC workshop

Abstract

Section snippets

Well-defined PRO research objectives

A commonly shared view across various international stakeholders was that PROs intended to provide quantitative assessment of clinical outcomes should be treated like any other endpoint that is included in the evaluation of a cancer treatment. Thus, an important first step is to clearly describe the research questions that PROs can address to support the evaluation of cancer treatments. PROs are not an outcome but a way to measure an outcome; therefore, it is important to identify in the

Role of submitted PRO data for decision making

Further optimisation in the use of PROs is necessary to fully leverage the insights patient-generated data can provide.4, 5

Support overall benefit–risk evaluation

PROs can quantify symptoms and functional aspects of how patients experience and respond to their treatment and can complement traditional clinical endpoints such as overall survival, progression-free survival, and tumour response measures. PRO data can reflect treatment efficacy (ie, improvement in disease-related symptoms) or harms (ie, emergence of symptomatic adverse events and their impact on functioning). By incorporating these additional outcomes into clinical trials, a more holistic

Further characterise tolerability

One research objective that is relevant across early phase and late phase clinical cancer trials is to characterise safety and tolerability. It has been proposed that a complete understanding of tolerability should include direct measurement from the patient on how they are feeling and functioning when on treatment.⁶ For example, patient-reported symptomatic adverse events can complement standard safety reporting by clinicians. Understanding treatment tolerability can help corroborate or refine

Product information and label

A common goal for commercial sponsors is to use PROs to support medicines' approval, labelling, or marketing claims of treatment benefit. However, methodological issues, PRO data quality (including high rates of missing data or asymmetric missing data), and the question of what makes a clinically relevant PRO result have often prevented their inclusion in the product label (eg, EU Summary of Product Characteristics).¹ Development of PRO standards to address these methodological issues is

PROs, including HRQOL, are a crucial endpoint from the HTA's and payers' perspectives

PROs can help assess the overall value of a new treatment by considering patient-reported experiences. A crucial consideration for HTA decisions is that the data can address questions on comparative effectiveness versus standard of care. In some health-care systems, PROs also inform cost–benefit considerations of alternative treatment options and determine patient access to new treatments.¹⁰ High-quality PRO data provide crucial information for HTA evaluations, reimbursement decisions, and

PRO measures for an adequate intended use: balancing static and flexible approaches

A standard approach in the use of PROs in cancer clinical trials has been the use of validated HRQOL questionnaires (static approach).11, 12 The development of validated questionnaires focuses on rigorous approaches following a standardised methodology,¹³ including applicability across different cultures and languages.¹⁴ Important aspects are content validity (ie, measuring what matters to patients) and sound measurement properties (ie, ensuring measurement reliability).13, 14, 15 Guidance on

Standardised robust methodology and reporting

As for any other key scientific evidence, the need for robust methodology and standardised reporting has been also identified for PROs. Drug development programmes should have a clear PRO evidence strategy, broken down into a design and analysis plan that addresses the PRO objective and high-quality collected PRO data at the study level. The clear PRO evidence strategy should be accompanied by consistent reporting and visualisation of the PRO results, which focus on the benefit and harms of a

Future steps

The relevance of incorporating PROs into regulatory decision making has been recognised for a long time. Nevertheless, this workshop was developed because there remains a need to discuss methodological considerations across various international regulatory agencies and different stakeholders to understand, accommodate, and align perspectives to improve data quality from commercial sponsors when receiving applications. Although it is important to acknowledge that different stakeholders might