PATIENT-REPORTED OUTCOMES

Integrating the patient’s voice into clinical settings

While patient-reported outcomes (PROs) are now an integral part of many phase III trials, their incorporation into routine clinical practice is hampered by economic and time pressures among healthcare professionals. However, with the advent of electronic-based questionnaires, current boundaries are likely to be stretched.

When we look at cancer treatments today we should not just focus on that they are clinically effective and sustainable but also on how they are perceived by patients. In the last few decades, growing attention to disease-related aspects that could not otherwise be captured by objective clinical measurements has resulted in patient-reported outcomes (PROs) with the aim to get doctors closer to patients and better understand their experience with the disease and its treatments.


It has been proved that physicians can often underestimate the impact of a particular side-effect on a patient’s life. In oncology, for example, chronic grade 1 nausea would probably not seem to a doctor to be a particularly noteworthy side-effect. However, patients find it extremely difficult to function with this constant low level of nausea and it can really interfere with their quality of life (QoL). And the reverse is also true, as highlighted by Nadia Harbeck from the University of Munich, Germany. She said, “For instance, on paper, objective assessment of the CDK 4/6 inhibitors reveals a high degree of grade 3/4 neutropenic toxicity, which might be expected to result in poor patient acceptability. However, PROs show that because this is a manageable side-effect it does not actually have an impact on patient quality of life.”


Having already been used for a long time in clinical trials to assess QoL and health-related QoL, the importance of PROs has grown to such an extent that phase III trials are now generally required to include a PRO measure and they are also a particularly important element of health technology assessments. Described as enabling the doctor to hear the patient voice at a greater volume, PROs have the true potential to get doctors closer to patients.


“As doctors, we try our best to meet the patient’s needs, but we must realise that we cannot do this without the patient’s input,” said Emiliano Calvo who leads the Early Phase Clinical Drug Development in Oncology, international programme at START Madrid Group, Spain, at Centro Integral Oncológico Clara Campal (CIOCC). PROs are also a more reliable and accurate way of gauging a patient’s health than simply talking with them. “Patients may forget, or be too embarrassed, to tell the doctor about a side-effect they had several weeks ago. But if it is recorded on a PRO, it can be used to modify management, if necessary,” continued Calvo.


Despite the many benefits of formal questionnaires, their use is still sparse. While most doctors are not against their use as a concept, in fact, the logistics of implementing PROs in daily practice may represent a major limitation. “Oncologists want to spend their time helping the patient. They already do not have enough time to discuss the results of diagnostic tests, treatment options, side-effects, etc. with patients, and so it is difficult for them to see how PROs can be incorporated into their daily practice,” said Calvo. Some physicians may feel that PROs provide no extra information over what can be obtained during the usual work-up and monitoring of the patient. This lack of awareness regarding the additional value of PROs needs to be addressed through education and training.


A lack of standardised tools also hinders the use of PROs in clinical practice. “Can you imagine how difficult it would be to assess and compare efficacy and toxicity if clinicians worldwide did not use the same standardised scales to measure anti-tumour activity and side-effects?” said Calvo. “This is the situation with PROs.” Choosing which PRO to administer can also deter doctors from using them. PROs cover a wide range of parameters – including symptoms, mood, QoL, physical function and distress – and selecting the most appropriate one to use in any setting can be confusing. Although the advice is to individualise choice according to the patient’s needs, this can be a hard task.


Electronic PROs may help doctors to overcome major barriers to their use. However, these barriers seem to apply mainly to the relatively outdated paper-based PROs, a format which is unlikely to be fully integrated into clinical practice. The introduction of electronic PROs (ePROs), which are digitally-based and can be used by patients remotely, has also come with the promise to change the face of PROs in clinical care. By using these tools to record outcomes on a regular basis, patients’ cumulative experiences can be stored digitally and then be discussed with the doctor at the next visit.


Studies have shown that by enabling management to be individualised to the patient, these ePROs can actually improve survival in patients with metastatic cancer (JAMA. 2017 Jul 11;318(2):197–198; LBA9006 Journal of Clinical Oncology 34, no. 18_suppl). “They allow patients to feel that their care is continuous and they help doctors to build a better chronological picture of how patients are coping with their disease and its treatment,” said Harbeck. The integration of ePROs into clinical practice will take time and will require a change of mindset on the part of healthcare practitioners. “Some doctors may be concerned that by using ePROs they may be legally obliged to continuously monitor a patient’s health and may be liable to legal redress if they fail to do so. This issue can be addressed by requiring patients to formally agree that an ePRO is to be used only as a tool for them to prepare themselves for their next visit with the doctor.

Putting the patient at the centre of care

Friedrich Stiefel, University of Lausanne, Switzerland

“Since the implementation of PROs combined with patient-centred interventions has already been shown to be associated with better health-related QoL, with fewer hospitalisations and even increased survival compared with standard care, these data collections and evaluations should be highly encouraged. How critically patient-reported data are needed becomes even more evident, as it has been demonstrated that clinicians miss about half of their patients’ symptoms during treatment.”


Karin Jordan

University of Heidelberg, Germany

“PROs collected via validated measures are an important and valuable means of determining if cancer treatments and procedures help rather than harming patients. The benefits of novel therapies expressed as progression-free survival or modest overall survival, which may excite clinical scientists, are often of little or no real value to patients experiencing the burdens of treatment-related side-effects. Quality not just quantity of life must be measured.”


Dame Lesley Fallowfield

University of Sussex, Brighton, UK

“The value of PROs lies in their nature; they come directly from the patient and represent his or her health status perception. We know that clinicians might underestimate the incidence of symptoms, therefore PROs need to be included in clinical decision-making. Moreover, to develop patient-centred care we need to further engage patients in the development of care. PROs, ideally combined with patient-reported experiences, could enhance such initiatives.”


Manuela Eicher

University of Lausanne, Switzerland