To the Editor,
The new European Medicines Agency (EMA) guidance on the use of patient-reported outcomes (PROs) in cancer studies is a further step toward recognition of the importance of patient perception of a disease and treatment benefits and harms [Citation1]. This guidance is likely to stimulate wider inclusion of PROs in drug development plans and in the evidence accompanying marketing authorization applications in Europe.
Decision making processes informed also by PROs are welcome. However, the situation must be monitored and rules provided, besides acknowledging and minimizing caveats in the definition, measurement and interpretation of these outcomes. A potential benefit on a given PRO, demonstrated in trials, could support a claim of superiority over other therapeutic options, making the patient-centered approach a potential marketing tool for (new) products. As stated in the guidance, careful planning is needed when PROs have to be included among the trial endpoints. This implies transparent choices on what to measure, how, and the threshold for a clinically meaningful difference. Instruments should be reliable, valid, and responsive, developed using robust and reproducible methods [Citation2] and taking account of the patients’ perspective [Citation3].
EMA’s role in backing these requirements is necessary to assess the therapeutic added value related to a better PRO (which is also important for patients).
However, this may not be enough if investigators do not fully understand how a given PRO could confirm well formulated hypotheses and are not appropriately trained on the use of instruments to collect them. To ensure correct data collection throughout a trial, time and efforts must be invested to make study participants aware of the value of the information they provide with questionnaires on the definition of the overall benefit-harm profile of a new treatment. Clinical sites should be monitored and corrective measures taken to reduce missing or invalid data, which limit the robustness of the results. Even when all these specified measures are adopted, the question of data interpretation remains. To what extent a given difference is meaningful for patients depends on several factors: setting, line of therapy, patients’ values and culture. This needs to be defined and agreed by all the stakeholders [Citation4].
PROs can contribute greatly to decision making, but only if investigators and patients’ representatives are fully engaged in the discussion about their importance at the same table.
Acknowledgments
The authors thank J. D. Baggott for editing.
Disclosure statement
None of the authors have financial or non-financial personal competing interests to be declared.
Funding
This paper was supported by institutional funds of the Mario Negri Institute.
References
- European Medicines Agency. 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. 2016. http://www.ema.europa.eu/docs/en_GB/document_library/Other/2016/04/WC500205159.pdf (accessed May 17, 2016).
- Consensus-based standards for the selection of health measurement instruments. 2010. http://www.cosmin.nl/ (accessed May 17, 2016).
- Staniszewska S, Haywood KL, Brett J, et al. Patient and public involvement in patient-reported outcome measures: evolution not revolution. Patient 2012;5:79–87.
- Revicki D, Hays RD, Cella D, et al. Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol 2008;61:102–9.