Listening to patients and what matters to them
The use of Patient Reported Outcomes (PROs) in clinical research
Clinical trials usually rate the success of a potential new treatment based on the things the research team can check or measure. For example, in trials of potential new medicines for the skin condition psoriasis, an official rating scale called the Psoriasis Area & Severity Index (PASI) is typically used to assess three things: the redness, thickness, and scaliness of the skin patches.1 A score is given to rate these three aspects before and after study treatment.
But using an approach like this by itself has limitations. Often what matters most to people with psoriasis is how disfiguring or embarrassing they perceive their skin problem to be, how it affects their self-confidence and whether having the condition stops them from doing the things they would normally do.2 In a similar way, people with life-threatening conditions like advanced cancer are sometimes mainly concerned with pain management and whether they feel comfortable and calm, rather than whether their lifespan is extended by a few more weeks or months.3
By including patient reported outcomes in clinical studies, the true value of a potential treatment – according to patients as well as to doctors – is more likely to be shown.
In recent years, researchers have come to realize that testing new treatments based on things that are meaningful and important to patients – in addition to the things that the research team can measure– may give a much more complete picture of how useful the potential new treatment truly is. Sometimes a change in a score on an established rating scale may not translate into a noticeable difference in how the person feels. These realizations have led to the development of Patient Reported Outcomes (PROs).
What are Patient Reported Outcomes (PROs)?
The US Food and Drug Administration (FDA) defines a patient-reported outcome (PRO) as “any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else.”4
The European Medicines Agency (EMA) uses a very similar definition: “A patient reported outcome (PRO) is an umbrella term that can be defined as a measurement based on a report that comes directly from the patient about the status of disease and treatment without amendment or interpretation of the patient’s response by a clinician or anyone else.”5
In order to receive these reports from patients in a way that is ‘standardized’ (i.e. in the same format for every patient in a clinical study), research teams have worked to devise detailed patient questionnaires that are valid for the condition being studied. The questionnaires focus mainly on what is known as ‘quality of life’ – i.e. how the condition and the treatment affect someone’s daily life physically, mentally, emotionally, practically and socially. Over the last two to three decades, hundreds of PRO questionnaires have been developed for many different conditions6 and they are increasingly being used in clinical trials and also to some extent in routine clinical practice.
Some questions may have ‘yes / no’ answers but in most cases patients will be asked to choose amongst a selection of answers. Each response will then be given a score and the total score calculated.7
How are PROs developed?
When developing a PRO for a particular condition, a team of healthcare professionals usually meet to discuss it. The members of the team will differ but may include specialist doctors, primary care doctors (i.e. GPs or family physicians), nurses with experience in the condition and medical statisticians (experts in the mathematical calculations needed to judge how well a treatment does in a clinical trial). These days, patients themselves – or people who work for patient support groups related to the condition – are often also invited to join PRO development teams and their inclusion is increasingly viewed as important.8
Once a PRO questionnaire has been drafted, there are a number of ways that it has to be validated (tested) in people with the relevant condition to ensure it is reliable and appropriate to use in a clinical study.8 To be useful, a PRO questionnaire also needs to be easily understood by the people who will complete it and must not take up too much time.8 Although many PRO questionnaires already exist, new ones are constantly being developed as researchers learn more about diseases, treatments and the important things to ask patients.
How are PROs used as measures in clinical trials?
There are some conditions where using PROs is obviously needed, like assessing pain in studies of potential new painkillers or assessing mood in studies of potential new treatments for depression. However, some experts now think that PROs should be included in all clinical studies, even where the main thing to judge is something only doctors can detect.9 This is because patients’ opinions, thoughts, beliefs and perceptions about their condition and the treatment being tested should always count. In the past, PROs were included in clinical studies as ‘just another thing to do’ and were not really central to the study design. However, these days, more studies are giving PROs greater importance and some are even making a PRO the main thing that is assessed (called the primary endpoint).10
What are the benefits and challenges of using PROs in clinical research?
The main difficulty with PROs is that they are not an exact science. Different people rate things differently: for example, one person’s idea of ‘the worst pain you can imagine’ might not match another person’s. The validation testing is designed to ensure this variability is accounted for but it can be challenging. Then there is the problem of incomplete questionnaires. Sometimes analyzing PRO questionnaires can also be time-consuming for study teams. But PROs are being refined and improved all the time. By including PROs in clinical studies, the true value of a potential treatment – according to patients as well as to doctors – is more likely to be shown.
- Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials Ann Rheum Dis 2005;64: ii65-ii68.
- McKenna SP, Cook SA, Whalley D et al. Development of the PSORIQoL, a psoriasis-specific measure of quality of life designed for use in clinical practice and trials. Br J Dermatol 2003; 149(2):323-31.
- Basch E, Geoghegan C, Coons SJ et al. Patient-reported outcomes in cancer drug development and US regulatory review perspectives from industry, the Food and Drug Administration and the patient. JAMA Oncol 2015; 1(3):375-379.
- Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. U.S. Department of Health and Human Services Food and Drug Administration Dec 2009. Available from: http://www.fda.gov/downloads/Drugs/.../Guidances/UCM193282.pdf
- Reflection paper on the use of Patient-Reported Outcomes. European Medicines Agency June 2014. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/06/WC500168852.pdf
- Nelson EC, Eftimovska E, Lind C et al. Patient reported outcome measures in practice. Brit Med J 2015; 350: g7818.
- FACIT.org questionnaires. Available from: http://www.facit.org/FACITOrg/Questionnaires
- Trujols J, Portella MJ, Ioseba Iraurgi I et al. Patient-reported outcome measures: are they patient-generated, patient-centred or patient-valued? J Mental Health 2013; 22(6): 555-562
- Denniston AK, Kyte D, Calvert M et al. An introduction to patient-reported outcome measures in ophthalmic research. Eye 2014; 28: 637–645.
- Calvert M, Blazeby J, Altman DG et al. Reporting of patient-reported outcomes in randomized trials: the CONSORT PRO extension. JAMA 2013; 309 (8):814-22.