A patient-reported outcome or PRO is a questionnaire used in a clinical trial or a clinical setting, where the responses are collected directly from the patient.
The term PRO should not be confused with patient-based outcomes. The latter implies that questionnaire covers issues of specific concern to the patient. However, patient-reported implies only that the patient provides the information. This information may, or may not, be of concern to the patient. The term PROs is synonymous with the increasing use of the term patient reported outcome measures (PROMs).
PRO is an umbrella term that covers a whole range of potential types of measurement but is used specifically to refer to self-reports by the patient. PRO data may be collected via self-administered questionnaires completed by the patient themselves or via interviews. The latter will only qualify as a PRO where the interviewer is gaining the patient's views, not where the interviewer uses patient responses to make a professional assessment or judgment of the impact of the patient's condition. Thus, PROs are a means of gathering patient rather than clinical or other views on outcomes. This patients' perspective can play an important role in drug approval.
A well-designed PRO questionnaire should assess either a single underlying characteristic or, where it addresses multiple characteristics, should be a number of scales that each address a single characteristic. These measurement "characteristics" are termed constructs and the questionnaires used to collect them, termed instruments, measures, scales or tools.
A questionnaire that measures a single construct is described as unidimensional. Items (questions) in a unidimensional questionnaire can be added to provide a single scale score. However, it cannot be assumed that a questionnaire is unidimensional simply because the author intended it to be. This must be demonstrated empirically (for example, by confirmatory factor analysis or Rasch analysis). A questionnaire that measures multiple constructs is termed multi-dimensional. A multi-dimensional questionnaire is used to provide a profile of scores; that is, each scale is scored and reported separately. It is possible to create an overall (single summary) score from a multi-dimensional measure using factor analysis or preference-based methods but some may see this as akin to adding apples and oranges together.
Questionnaires may be generic (designed to be used in any disease population and cover a broad aspect of the construct measured) or condition-targeted (developed specifically to measure those aspects of outcome that are of importance for a people with a particular medical condition).
The most commonly used PRO questionnaires assess one of the following constructs:
- Symptoms (impairments) and other aspects of well-being
- Functioning (disability)
- Health status
- General health perceptions
- Quality of life (QoL)
- Health related quality of life (HRQoL)
- Reports and Ratings of health care.
Measures of symptoms may focus on a range of impairments or on a specific impairment such as depression or pain. Measures of functioning assess activities such as personal care, activities of daily living and locomotor activities. Health-related quality of life instruments are generally multi-dimensional questionnaires assessing a combination of aspects of impairments and/or disability and reflect a patient's health status. In contrast, QoL goes beyond impairment and disability by asking about the patient's ability to fulfill their needs and also about their emotional response to their restrictions.
A new generation of short and easy-to-use tools to monitor patient outcomes on a regular basis has been recently proposed. These tools are quick, effective, and easy to understand, as they allow patients to evaluate their health status and experience in a semi-structured way and accordingly aggregate input data, while automatically tracking their physio-emotional sensitivity. As part of the National Institute of Health's Roadmap Initiative, the Patient-Reported Outcomes Measurement Information System (PROMIS) uses modern advances in psychometrics such as Item Response Theory (IRT) and Computerized Adaptive Testing (CAT) to create highly reliable and validated measurement tools.
Validation and quality assessment
It is essential that a PRO instrument satisfy certain development, psychometric and scaling standards if it is to provide useful information. Specifically, measures should have a sound theoretical basis and should be relevant to the patient group with which they are to be used. They should also be reliable and valid (including responsive to underlying change) and the structure of the scale (whether it possesses a single or multiple domains) should have been thoroughly tested using appropriate methodology in order to justify the use of scale or summary scores.
These standards must be maintained throughout every target language population. In order to ensure that developmental standards are consistent in translated versions of a PRO instrument, the translated instrument undergoes a process known as Linguistic validation in which the preliminary translation is adapted to reflect cultural and linguistic differences between diverse target populations.
Many of the common generic PRO tools assess health-related quality of life or patient evaluations of health care. For example, the SF-36 Health Survey, SF-12 Health Survey, Profile, the Nottingham Health Profile, the Health Utilities Index, the Quality of Well-Being Scale, the EuroQol (EQ-5D), and the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey instruments are PRO instruments.
Condition-targeted tools may capture any of the constructs listed above, depending on the purpose for which they were designed. Examples include the Adult Asthma Quality of Life Questionnaire (AQLQ), the Kidney Disease Quality of Life Instrument, National Eye Institute Visual Functioning Questionnaire, Epilepsy Surgery Inventory, Migraine Specific Quality of Life (MSQOL), the Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) and the Seattle Angina Questionnaire (SAQ), to name a few.
PROMs in the NHS
Since 1 April 2009 all providers of care funded by the National Health Service (NHS) in England have been required to provide Patient-Reported Outcome Measures (PROMs) in four elective surgical procedures: hip replacement, knee replacement, varicose vein surgery and hernia surgery.,. Patients are asked to complete a questionnaire before undergoing the surgical procedure; a follow-up questionnaire is then sent to the patient some weeks or months later. Patient participation is, however, not compulsory.
In December 2013 a team from the London School of Hygiene and Tropical Medicine reviewed the first 3 years of NHS PROMs data which captured responses from more than 50,000 patients who underwent groin hernia repair, varicose vein surgery or hip or knee replacements. They found “no grounds to suggest we should start cutting the amount of surgery we are doing.”
Patient-reported Outcomes in Drug Licensing and Label Claims
Patient-reported outcomes are important in a regulatory context. The US Food and Drug Adminstration (FDA) has issued formal Guidance to Industry on PROs in label claims  and the European Medicines Agency (EMA) has produced a reflection paper on HRQoL. Increasing numbers of regulatory submissions for new drugs provide PRO data to support claims. DeMuro et al. (2013) have reviewed drug approvals for the years 2006 - 2010. They showed that of 75 drugs approved by both agencies, 35 (47%) had at last one PRO-related claim approved by the EMA compared to 14 (19%) for the FDA. The FDA was more likely to approve claims for symptom reduction, while the EMA approved relatively more claims for improvement in functioning or HrQoL.
- Electronic patient-reported outcome
- Patient diary
- Clinical trial protocol
- Clinical data acquisition
- Case report form
- Data clarification form
- Electronic data capture
- Clinical research associate (CRA)
- Drug development
- Linguistic validation
- Marquis P, Caron M, Emery M-P, et al. (2011). "The Role of Health-Related Quality of Life Data in the Drug Approval Processes in the US and Europe: A Review of Guidance Documents and Authorizations of Medicinal Products from 2006 to 2010". Pharm Med 25 (3): 147–60. doi:10.1007/bf03256856.
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- "Patient Reported Outcomes Measures (PROMs)". NHS Information Centre. Retrieved 1 September 2012.
- "Guidance on the routine collection of Patient Reported Outcome Measures (PROMs)". Department of Health, England. Retrieved 1 September 2012.
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- "Guidance for Industry. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims". U.S. Department of Health and Human Services. Retrieved 6 August 2014.
- "REFLECTION PAPER ON THE REGULATORY GUIDANCE FOR THE USE OF HEALTHRELATED QUALITY OF LIFE (HRQL) MEASURES IN THE EVALUATION OF MEDICINAL PRODUCTS". European Medicines Agency. Retrieved 6 August 2014.
- DeMuro C, Clark M, Doward L, Evans E, Mordin M, & Gnanasakthy A (2013). "Assessment of PRO label claims granted by the FDA as compared to the EMA (2006-2010)". Value in health 16 (8): 1150–5. doi:10.1016/j.jval.2013.08.2293.
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- EuroQol Group (EQ-5D)
- Patient Reported Outcomes Measurement Information System
- Medical Outcomes Trust
- Health Surveys
- Mapi Research Trust (non-profit organization involved in Patient-Centered Outcomes)
- ProQolid (Patient-Reported Outcome & Quality of Life Instruments Database)
- PROLabels(Database on Patient-Reported Outcome claims in marketing authorizations)
- Vector Psychometric Group, LLC: PRO consulting, development, and delivery systems
- Open Research Exchange: PatientsLikeMe