A patient-reported outcome or PRO is a method or 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-centered 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 PRO should also not be confused with the term "patient reported experience measures" (PREMs), which focuses more on a patient's experience versus outcomes.
The term PROs is synonymous with the increasingly used 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. Typically, PRO tools much undergo extensive validation and testing.
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 (e.g. ). 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. Classic examples of such tools and methods are noted in commonly used oncology tools, such as fact or EORTC tools.
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.
Preference based PROs can be used for the computation of a Quality-Adjusted Life Year. A preference based PRO has an algorithm attached to the PRO instrument which can 'weigh' the outcomes reported by patients according to the preferences for health outcomes of a group of individuals such as the general public or of patient groups. The purpose of this 'weighing' is to make sure that elements of health that are very important receive larger weight when computing sum scores. For example, individuals may consider problems with their mood to be more important than limitations in usual activities. Examples of generic preference-based PROs are the Health Utilities Index and the EQ-5D. Condition-targeted preference-based PROs also exist, but there are some questions regarding their comparability to generic PROs when used for the computation of Quality Adjusted Life Years.
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 AJRR
The American Joint Replacement Registry (AJRR) launched their Level III patient-reported outcome (PRO) platform in November 2015. AJRR developed the PRO platform within AJRR’s Demand Reporting & Electronic Dashboard system. Clinical staff is able to access patient data while having the ability to manage PRO surveys electronically via a secure patient portal. The AJRR Dashboard system can also pull site-specific patient reports and summary results for each PRO measure supported on the AJRR system.
AJRR collaborated with several orthopaedic organizations to identify the specific measures that AJRR should recommend and that may be used as national benchmarks. Even though specific measures are recommended, AJRR understands that some institutions may have in place a long-standing PRO data collection process. Participating hospitals are able to submit and retrieve these alternative measures, but there will not be national benchmarks available for them.
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 Administration (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
- Quality of Life in Depression Scale
- Marquis P, Caron M, Emery MP, 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.
- Bottomley, Andrew; Jones, Dave; Claassens, Lily (Feb 2009). "Patient-reported outcomes: assessment and current perspectives of the guidelines of the Food and Drug Administration and the reflection paper of the European Medicines Agency". European Journal of Cancer (Oxford, England: 1990) 45 (3): 347–353. doi:10.1016/j.ejca.2008.09.032. ISSN 1879-0852. PMID 19013787. Retrieved 2015-05-05.
- Pugliese, Patrizia; Perrone, Maria; Nisi, Enrica; Garufi, Carlo; Giannarelli, Diana; Bottomley, Andrew; Terzoli, Edmondo (2006). "An integrated psychological strategy for advanced colorectal cancer patients". Health and Quality of Life Outcomes 4: 9. doi:10.1186/1477-7525-4-9. ISSN 1477-7525. PMC 1409769. PMID 16460566. Retrieved 2015-05-05.
- Kuliś, Dagmara; Arnott, María; Greimel, Elfriede R.; Bottomley, Andrew; Koller, Michael (Jun 2011). "Trends in translation requests and arising issues regarding cultural adaptation". Expert Review of Pharmacoeconomics & Outcomes Research 11 (3): 307–314. doi:10.1586/erp.11.27. ISSN 1744-8379. PMID 21671700. Retrieved 2015-05-05.
- Bottomley, Andrew (2002). "The cancer patient and quality of life". The Oncologist 7 (2): 120–125. doi:10.1634/theoncologist.7-2-120. ISSN 1083-7159. PMID 11961195. Retrieved 2015-05-05.
- Scott, Neil W.; Fayers, Peter M.; Aaronson, Neil K.; Bottomley, Andrew; de Graeff, Alexander; Groenvold, Mogens; Koller, Michael; Petersen, Morten A.; Sprangers, Mirjam A. G. (Aug 2008). "The relationship between overall quality of life and its subdimensions was influenced by culture: analysis of an international database". Journal of Clinical Epidemiology 61 (8): 788–795. doi:10.1016/j.jclinepi.2007.08.015. ISSN 0895-4356. PMID 18359194. Retrieved 2015-05-05.
- Erik Cambria; Tim Benson; Chris Eckl; Amir Hussain (2012). "Sentic PROMs: Application of Sentic Computing to the Development of a Novel Unified Framework for Measuring Health-Care Quality". Expert Systems with Applications, Elsevier.
- Chu, Dominic; Popovic, Marko; Chow, Edward; Cella, David; Beaumont, Jennifer L.; Lam, Henry; Nguyen, Jasmine; Di Giovanni, Julia; Pulenzas, Natalie (Sep 2014). "Development, characteristics and validity of the EORTC QLQ-PR25 and the FACT-P for assessment of quality of life in prostate cancer patients". Journal of Comparative Effectiveness Research 3 (5): 523–531. doi:10.2217/cer.14.41. ISSN 2042-6313. PMID 25350803. Retrieved 2015-05-05.
- Winstanley, Julie B.; Young, Teresa E.; Boyle, Frances M.; Bergenmar, Mia; Bottomley, Andrew; Burmeister, Bryan; Campana, Luca G.; Garioch, Jennifer J.; King, Madeleine (Feb 2015). "Cross-cultural development of a quality-of-life measure for patients with melanoma: phase 3 testing of an EORTC Melanoma Module". Melanoma Research 25 (1): 47–58. doi:10.1097/CMR.0000000000000122. ISSN 1473-5636. PMID 25325247. Retrieved 2015-05-05.
- Yekaninejad, Mir S.; Ahmadzadeh, Ahmad; Mosavi, Seyed H.; Saffari, Mohsen; Pakpour, Amir H.; Tolooei, Fatemeh; Chow, Edward; Bottomley, Andrew (Feb 2014). "The reliability and validity of the Iranian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for patients with Bone Metastases: the EORTC QLQ-BM22". Expert Review of Pharmacoeconomics & Outcomes Research 14 (1): 147–156. doi:10.1586/14737167.2014.864559. ISSN 1744-8379. PMID 24328844. Retrieved 2015-05-05.
- Bottomley, Andrew; Aaronson, Neil K. (Nov 10, 2007). "International perspective on health-related quality-of-life research in cancer clinical trials: the European Organisation for Research and Treatment of Cancer experience". Journal of Clinical Oncology 25 (32): 5082–5086. doi:10.1200/JCO.2007.11.3183. ISSN 1527-7755. PMID 17991925. Retrieved 2015-05-05.
- Taphoorn, Martin J. B.; Claassens, Lily; Aaronson, Neil K.; Coens, Corneel; Mauer, Murielle; Osoba, David; Stupp, Roger; Mirimanoff, René O.; van den Bent, Martin J. (Apr 2010). "An international validation study of the EORTC brain cancer module (EORTC QLQ-BN20) for assessing health-related quality of life and symptoms in brain cancer patients". European Journal of Cancer (Oxford, England: 1990) 46 (6): 1033–1040. doi:10.1016/j.ejca.2010.01.012. ISSN 1879-0852. PMID 20181476. Retrieved 2015-05-05.
- Holzner, Bernhard; Efficace, Fabio; Basso, Umberto; Johnson, Colin D.; Aaronson, Neil K.; Arraras, Juan I.; Smith, Allan B.; Chow, Edward; Oberguggenberger, Anne S. (Mar 2013). "Cross-cultural development of an EORTC questionnaire to assess health-related quality of life in patients with testicular cancer: the EORTC QLQ-TC26". Quality of Life Research: An International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation 22 (2): 369–378. doi:10.1007/s11136-012-0147-1. ISSN 1573-2649. PMC 3576569. PMID 22407356. Retrieved 2015-05-05.
- Versteegh, Matthijs; Leunis, Annemieke; Uyl-deGroot, Carin; Stolk, Elly (May 2012). "Condition-Specific Preference-Based Measures: Benefit or Burden?". Value in Health 15 (3): 503–513. doi:10.1016/j.jval.2011.12.003. Retrieved 2015-08-04.
- Michalesko, Erik. "AJRR Launches Patient-reported Outcome Platform". ajrr.net. Retrieved 2016-02-02.
- "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.
- "What are PROMs?". NHS Choices. Retrieved 1 September 2012.
- "PROMs: Frequently asked questions". NHS Choices. Retrieved 1 September 2012.
- "PROMs show no evidence of inappropriate surgery". Health Service Journal. 9 December 2013. Retrieved 15 December 2013.
- "Guidance for Industry. Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims" (PDF). 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" (PDF). 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. PMID 24326168.
- Bradley C. Importance of differentiating health status from quality of life. Lancet 2001; 357 (9249):7-8.
- Fung CH, Hays RD. Prospects and challenges in using patient-reported outcomes in clinical practice. Quality of Life Research 2008; 17: 1297-302.
- Doward LC, McKenna SP, Defining Patient-Reported Outcomes. Value in Health 2004; 7(S1): S4-S8.
- Fayers P, Hays RD. (eds.) Assessing Quality of Life in Clinical Trials: Methods and Practice. Oxford: Oxford University Press, 2005.
- Gallagher P, Ding L, Ham HP, Schor EL, Hays RD, Cleary PD. Development of a new patient-based measure of pediatric ambulatory care. Pediatrics 2009; 124: 1348-1354.
- Hays RD, Reeve BB. Measurement and modeling of health-related quality of life. In J. Killewo, H. K. Heggenhougen & S. R. Quah (eds.), Epidemiology and Demography in Public Health (pp. 195–205). Elsevier, 2010.
- Kennedy D, CRF Designer, Canary Publications, ISBN 0-9531174-7-2
- McKenna SP, Doward LC, Integrating Patient-Reported Outcomes. Value in Health 2004; 7(S1): S9-S12.
- Patrick DL, Bergner M. Measurement of Health Status in the 1990s. Annu Rev Public Health. 1990; 11: 165-83.
- Tennant A, McKenna SP. Conceptualising and defining outcome. Br J Rheumatol 1995;34:899-900.
- Valderas JM, Alonso J. Patient reported outcome measures: a model-based classification system for research and clinical practice. Qual Life Res. 2008; 17: 1125-35.
- Wiklund I., Assessment of patient-reported outcomes in clinical trials: the example of health-related quality of life, Fundam Clin Pharmacol. 2004 Jun;18(3):351-63.
- Willke RJ, Burke LB, Erickson P., Measuring treatment impact: a review of patient-reported outcomes and other efficacy endpoints in approved product labels, Control Clin Trials. 2004 Dec;25(6):535-52.
- 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)
- University of Oxford's Clinical Outcomes Assessment (Oxford Hip Score, Oxford Knee Score)
- Information for members of Center for Medicare and Medicaid Services (CMS) regarding Oxford Hip & Knee Scores
- FREE Oxford Hip and Knee Scores for NHS and Medicare/Medicaid patients
- Vector Psychometric Group, LLC: PRO consulting, development, and delivery systems
- Open Research Exchange: PatientsLikeMe