Patient-Reported Outcomes in Clinical Trials of Rare Diseases

The science of measuring patient-reported outcomes (PROs) has advanced substantially in recent decades, allowing evaluation of how patients feel and function in clinical research. Assessment of the patient experience in populations with rare diseases can be successfully achieved using PRO measures when careful planning and rigorous methods are employed. A number of challenges exist when designing and implementing PRO analyses in rare disease contexts, including heterogeneity of outcomes, availability of suitable measures, recruitment, and selection of appropriate data collection methods. Strategies to address these exist and have been employed in past clinical research, particularly in pediatric populations. PRO assessments in rare disease clinical trials have been particularly successful through partnerships between investigators, PRO methodologists, and patient organizations. The overall goal of PRO measurement is to understand the patient experience and it provides an essential part of evaluating the impact of disease and treatment.     

Provider perceptions of the value of same-day,electronic patient-reported measures for use in clinical HIV care

Strong evidence suggests that patient-reported outcomes (PROs) aid in managing chronic conditions, reduce omissions in care, and improve patient–provider communication. However, provider acceptability of PROs and their use in clinical HIV care is not well known. We interviewed providers (n?=?27) from four geographically diverse HIV and community care clinics in the US that have integrated PROs into routine HIV care, querying perceived value, challenges, and use of PRO data. Perceived benefits included the ability of PROs to identify less-observable behaviors and conditions, particularly suicidal ideation, depression, and substance use; usefulness in agenda setting prior to a visit; and reduction of social desirability bias in patient–provider communication. Challenges included initial flow integration issues and ease of interpretation of PRO feedback. Providers value same-day, electronic patient-reported measures for use in clinical HIV care with the condition that PROs are (1) tailored to be the most clinically relevant to their population; (2) well integrated into clinic flow; and (3) easy to interpret, highlighting chief patient concerns and changes over time.     

Do PRO Measures Function the Same Way for all Individuals With Heart Failure?

Women diagnosed with heart failure report worse quality of life than men on patient-reported outcome (PRO) measures. An inherent assumption of PRO measures in heart failure is that women and men interpret questions about quality of life the same way. If this is not the case, the risk then becomes that the PRO scores cannot be used for valid comparison or to combine outcomes by subgroups of the population. Inability to compare subgroups validly is a broad issue and has implications for clinical trials, and it also has specific and important implications for identifying and beginning to address health inequities. We describe this threat to validity (the psychometric term is differential item functioning), why it is so important in heart-failure outcomes, the research that has been conducted thus far in this area, the gaps that remain, and what we can do to avoid this threat to validity. PROs bring unique information to clinical decision making, and the validity of PRO measures is key to interpreting differences in heart failure outcomes.     

Selbst-Monitoring bei entzündlich-rheumatischen Erkrankungen

Background

Active involvement of patients in their care has led to better treatment and outcomes. Tight control concepts emphasize the need for regular assessments including patients’ active involvement by self-monitoring.

Methods

The literature was screened with respect to published experiences of self-monitoring of rheumatoid arthritis and spondyloarthritides. The use of “patient-reported outcome” (PRO) instruments can facilitate self-monitoring. Potentially applicable PROs and their correlations to clinical parameters as well as modern data acquisition modes are presented.

Results

Some experiences for self-monitoring have been reported. Recommendations from national and international professional rheumatology societies do not yet consider self-monitoring; however, PROs might be used for self-monitoring but instructions for patients on “how to deal with self-monitored PRO values” are missing.

Conclusion

Self-monitoring of inflammatory rheumatic diseases seems feasible. Further evaluation studies are warranted to guarantee an optimized direct patient involvement in their management beyond outpatient care in hospitals and private practices so that they can thus contribute to a better outcome.     

Patient-reported outcomes in acute myeloid leukemia: Where are we now?

Outcomes for acute myeloid leukemia remain poor, and treatment decisions must consider not just quantity, but also quality of life (QOL). We conducted a systematic review of studies in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that incorporated patient-reported outcome (PRO) measures. PubMed and PsycINFO were searched for articles published from January 2000 through June 2016. Forty-one were relevant for our review with more published in recent years. There was considerable inter-study heterogeneity in which instruments were used, and many studies employed multiple (often overlapping) instruments. Longitudinal studies in particular suffered from both high attrition rates due to disease-related mortality as well as waning compliance with questionnaire completion. There remain significant challenges to incorporation of PROs into leukemia trials. Despite these limitations, however, well-implemented PROs can provide important information beyond objective response outcomes and highlight areas of focus for clinicians caring for patients and for future research endeavors.     

Quality of Life and Other Patient-Reported Outcomes Across the Life Span Among People With Fontan Palliation

Traditional congenital heart disease (CHD) outcomes include mortality (survival to adulthood and life expectancy) as well as cardiac and noncardiac morbidity. Strategies to identify and manage sequelae have primarily focused on objective data obtained though invasive and noninvasive diagnostic approaches. In contrast, patient-reported outcomes (PROs) provide subjective information, using standardized measures, about patients’ health and well-being as reported directly by patients, without interpretation, interference, or assumptions made by clinicians or others. Selection of PRO measures entails thoughtful consideration of who the individuals being surveyed are, why assessment is occurring (eg, what are the domains of interest; clinical vs research), and what processes are in place for acquisition, administration, interpretation, and response. In this review, we focus on 3 domains of PROs for pediatric and adult patients with Fontan physiology: physical health status, psychological functioning, and quality of life. Infants, children, adolescents, and adults with CHD face a spectrum of challenges that might influence PROs across the life span. In general, patients with Fontan palliation tend to have lower physical health status, experience more psychological distress, and have equivalent or reduced quality of life compared with healthy peers. Herein, we provide an overview of PROs among people with Fontan circulation as a group, yet simultaneously emphasize that the optimal way to understand the experiences of any individual patient is to ask and listen. We also offer clinical and research initiatives to improve the adoption and utility of PROs in CHD settings, which show commitment to capturing, understanding, and responding to the patient voice.     

Patient-reported outcome measures and patient engagement in heart failure clinical trials: multi-stakeholder perspectives

There are many consequences of heart failure (HF), including symptoms, impaired health-related quality of life (HRQoL), and physical and social limitations (functional status). These have a substantial impact on patients' lives, yet are not routinely captured in clinical trials. Patient-reported outcomes (PROs) can quantify patients' experiences of their disease and its treatment. Steps can be taken to improve the use of PROs in HF trials, in regulatory and payer decisions, and in patient care. Importantly, PRO measures (PROMs) must be developed with involvement of patients, family members, and caregivers from diverse demographic groups and communities. PRO data collection should become more routine not only in clinical trials but also in clinical practice. This may be facilitated by the use of digital tools and interdisciplinary patient advocacy efforts. There is a need for standardization, not only of the PROM instruments, but also in procedures for analysis, interpretation and reporting PRO data. More work needs to be done to determine the degree of change that is important to patients and that is associated with increased risks of clinical events. This ‘minimal clinically important difference’ requires further research to determine thresholds for different PROMs, to assess consistency across trial populations, and to define standards for improvement that warrant regulatory and reimbursement approvals. PROs are a vital part of patient care and drug development, and more work should be done to ensure that these measures are both reflective of the patient experience and that they are more widely employed.     

Measuring patient-reported outcomes in haemophilia clinical research

Summary.  Patient-reported outcome (PRO) measures have been used to assess quality of life and health state preferences from the patient's perspective. However, they have not been fully utilized in haemophilia clinical practice and research. A series of meetings were convened to review and document the state of the art in PROs relevant to haemophilia. Experts developed a process for selection of measures and identified published measures of health-related quality of life (HRQoL) relevant to patients with haemophilia. These were synthesized and reviewed. Patient preference measures were also identified and reviewed. Although the majority of measures were developed for and validated in adults, several measures were identified for use in paediatric populations. This paper recommends an approach to the selection of PROs for application in haemophilia clinical research and practice and identifies several potential measures relevant for application in haemophilia clinical research and practice.     

“What Is the Right Decision for Me?” Integrating Patient Perspectives Through Shared Decision-Making for Valvular Heart Disease Therapy

Innovations in the treatment of valvular heart disease have transformed treatment options for people with valvular heart disease. In this rapidly evolving environment, the integration of patients’ perspectives is essential to close the potential gap between what can be done and what patients want. Shared decision-making (SDM) and the measurement of patient-reported outcomes (PROs) are two strategies that are in keeping with this aim and gaining significant momentum in clinical practice, research, and health policy. SDM is a process that involves an individualised, intentional, and bidirectional exchange among patients, family, and health care providers that integrates patients’ preferences, values, and priorities to reach a high-quality consensus treatment decision. SDM is widely endorsed by international valvular heart disease guidelines and increasingly integrated in health policy. Patient decision aids are evidence-based tools that facilitate SDM. The measurement of PROs—an umbrella term that refers to the standardised reporting of symptoms, health status, and other domains of health-related quality of life—provides unique data that come directly from patients to inform clinical practice and augment the reporting of quality of care. Sensitive and validated instruments are available to capture generic, dimensional, and disease-specific PROs in patients with valvular heart disease. The integration of PROs in clinical care presents significant opportunities to help guide treatment decision and monitor health status. The integration of patients’ perspectives promotes the shift to patient-centred care and optimal outcomes, and contributes to transforming the way we care for patients with valvular heart disease.     

Outcomes and Pelvic Floor Interventions: Can We Predict?

An evolving trend in reporting outcomes after pelvic floor interventions is focusing increasingly on patient-reported outcomes as assessments of pelvic floor conditions and of results after intervention. Efforts have been made to scientifically validate patient-reported outcomes instruments and to standardize their use in clinical research. Additionally, guidelines have been published recommending minimum requirements for incorporating patient-reported outcomes in peer-reviewed publications. Although an increasing number of publications are incorporating patient-reported outcomes, how these data are being used remains unclear, as many studies are not using patient-reported outcomes data as primary end points or in definitions of cure. More widespread adoption of standardized outcomes measures will better ensure more quality clinical research as well as comparability between studies.     

Assessment of outcome in clinical trials of gout--a review of current measures

There has been renewed interest in the treatment of gout with recent reported intervention studies of new agents such as etoricoxib, febuxostat and pegylated-uricase. However, these studies have highlighted the relative paucity of validated outcome measures with which to judge efficacy. This review outlines the published information regarding which endpoints have been measured in randomized clinical trials, what should be measured, what tools or instruments are available for this and the technical properties of such instruments. It highlights recent work that validates measures of tophi, radiographic damage and patient-reported outcomes. The absence of a valid definition of gout-flare or how flare reduction defines response is problematic; this forms the basis for a current ACR-EULAR sponsored project.     

Using Patient-Reported Outcomes toAssess Healthcare Quality: Toward Better Measurement of Patient-Centered Care in Cardiovascular Disease

Patient-reported outcomes (PROs) are elicited directly from patients so they can describe their overall health status, including their symptoms, function, and quality of life. While commonly used as end points in clinical trials, PROs can play an important role in routine clinical care, population health management, and as a means for quantifying the quality of patient care. In this review, we propose that PROs be used to improve patient-centered care in the treatment of cardiovascular diseases given their importance to patients and society and their ability to improve doctor- provider communication. Furthermore, given the current variability in patients’ health status across different clinics and the fact that PROs can be improved by titrating therapy, we contend that PROs have a key opportunity to serve as measures of healthcare quality.     

Patient-reported outcome I: measuring what matters in musculoskeletal care

Patients have an important role to play in communicating the impact of disease and the effectiveness of health care. Well-developed patient-reported outcome measures (PROMs) can provide a clinically relevant and scientifically rigorous resource for including the patient perspective in decisions about health care and subsequent evaluation. This article will introduce readers to the field of health outcome assessment, and specifically to patient-reported outcome measures (PROMs). The reasons for measuring health, different types of PROMs and potential applications will be discussed. A second article will present important information for users of PROMs to consider when selecting and using PROMs in research, routine practice or quality assurance.     

Patient‐reported outcomes in bariatric surgery: a systematic review of standards of reporting

Bariatric surgery is increasingly being used to treat severe obesity, but little is known about its impact on patient‐reported outcomes (PROs). For PRO data to influence practice, well‐designed and reported studies are required. A systematic review identified prospective bariatric surgery studies that used validated PRO measures. Risk of bias in randomized controlled trials (RCTs) was assessed, and papers were examined for reporting of (i) who completed PRO measures; (ii) missing PRO data and (iii) clinical interpretation of PRO data. Studies meeting all criteria were classified as robust. Eighty‐six studies were identified. Of the eight RCTs, risk of bias was high in one and unclear in seven. Sixty‐eight different PRO measures were identified, with the Short Form (SF)‐36 questionnaire most commonly used. Forty‐one (48%) studies explicitly stated measures were completed by patients, 63 (73%) documented missing PRO data and 50 (58%) interpreted PRO data clinically. Twenty‐six (30%) met all criteria. Although many bariatric surgery studies assess PROs, study design and reporting is often poor, limiting data interpretation and synthesis. Well‐designed studies that include agreed PRO measures are needed with reporting to include integration with clinical outcomes to inform practice.     

Cross‐cultural adaptation and linguistic validation of age‐group‐specific haemophilia patient‐reported outcome (PRO) instruments for patients and parents

Currently, haemophilia care aims to provide the best possible quality of life for individuals living with this chronic disease. Many factors are known to influence treatment adherence, including treatment satisfaction. Health‐related quality of life (HRQoL) and treatment satisfaction are, therefore, important outcomes in clinical trials and clinical practice. As individuals' perception of their well‐being often differs from that of their physician, it is recommended that self‐report instruments are used to assess patient‐reported outcomes (PROs). The way that the impact of haemophilia is perceived by the patient and their family can be different, so it is important to assess how parents perceive the impact on their children. A series of PRO instruments have been developed, adapted to different age groups and parents of patients with haemophilia. To allow the instruments to be used internationally, culturally adapted and linguistically validated translations have been developed; some instruments have been translated into 61 languages. Here, we report the process used for cultural adaptation of the Haemo‐QoL, Haem‐A‐QoL and Hemo‐Sat into 28 languages. Equivalent concepts for 22 items that were difficult to adapt culturally for particular languages were identified and classed as semantic/conceptual (17 items), cultural (three items), idiomatic (one item), and grammatical (one item) problems. This has resulted in linguistically validated versions of these instruments, which can be used to assess HRQoL and treatment satisfaction in clinical trials and clinical practice. They will provide new insights into areas of haemophilia that remain poorly understood today.     

Are all outcomes in chronic heart failure rated equally? An argument for a patient-centred approach to outcome assessment

Chronic heart failure (CHF) is a multi-dimensional and complex syndrome. Outcome measures are important for determining both the efficacy and quality of care and capturing the patient’s perspective in evaluating the outcomes of health care delivery. Capturing the patient’s perspective via patient-reported outcomes is increasingly important; however, including objective measures such as mortality would provide more complete account of outcomes important to patients. Currently, no single measure for CHF outcomes captures all dimensions of the quality of care from the patient’s perspective. To describe the role of outcome measures in CHF from the perspective of patients, a structured literature review was undertaken. This review discusses the concepts and methodological issues related to measurement of CHF outcomes. Outcome assessment at the level of the patient, provider and health care system were identified as being important. The perspectives of all stakeholders should be considered when developing an outcomes measurement suite to inform CHF health care. This paper recommends that choice of outcome measures should depend on their ability to provide a comprehensive, comparable, meaningful and accurate assessment that are important to patient.     

Systematic review: symptom assessment using patient-reported outcomes in gastroesophageal reflux disease and dyspepsia

Abstract

Objective. The importance of symptom assessment using patient-reported outcomes (PROs) is becoming increasingly recognized in the management of upper gastrointestinal (GI) disease. The authors aimed to review systematically the methodological aspects of PRO instrument development and use in the GERD or dyspepsia literature, and to assess these instruments' properties in light of the Food and Drug Administration's (FDA) guidance. Material and methods. Systematic PubMed and Embase searches (using terms based on the FDA guidance) identified studies that reported methodological aspects in developing or using PRO instruments for GERD or dyspepsia symptom measurement. Results. Ten studies were identified (six systematically and four from citation lists). Studies reported the development or use of a relevant PRO instrument, with a focus on methodological aspects that the FDA guidance describes as important for patient understanding. Studies demonstrated heterogeneity of recall periods, symptoms and response options. Two studies demonstrated that a lack of consistent vocabulary may contribute to discrepancy in symptom reporting between investigators and patients. Two studies indicated that symptoms must be described in a manner that is relevant to patients. One study described the development of a PRO instrument separately in two languages, acknowledging linguistic and cultural differences between populations. One study demonstrated changes in symptom severity based on the recall period. Conclusions. There is considerable heterogeneity in the methodology used to develop PRO instruments for upper GI disease. Adherence to best practices in PRO development and validation may improve the quality and utility of these measures, leading to improved communication in clinical practice.     

Time for a new era in the evaluation of targeted therapies for patients with chronic myeloid leukemia: inclusion of quality of life and other patient-reported outcomes

Health-related quality of life (HRQOL) and other patient-reported outcomes (PROs) might be crucial in comparing effectiveness of treatments as they could provide invaluable information to better inform clinical decision-making. This is particularly true in the era of targeted therapies (TT). A systematic review was undertaken on all studies with CML patients published from 1980 to 2010 and including a PRO evaluation. Out of 619 articles scrutinized, 15 met eligibility criteria and no study was published before 1995. Six dealt mainly with interferon-based therapies, 7 with bone marrow transplantation and only 2 evaluated PROs in the context of TT. No disease-specific, validated PRO instrument for these patients was found. The main evidence being that Imatinib provides clear advantage in terms of HRQOL over interferon-based treatments. There is lack of data concerning PROs in patients treated with current TT. Documenting HRQOL and side effects of CML treatments, from the patients' perspective is needed to evaluate overall treatment effectiveness and net clinical benefit of newer therapeutic strategies.     

Value of patient self-assessment in the diagnosis and monitoring of post-thrombotic syndrome: the Patient-Tracked Symptoms questionnaire

The post-thrombotic syndrome (PTS) is a frequent and burdensome disease, but no gold standard test exists to diagnose it. The value of patient-reported outcomes (PROs) in recording transient signs/symptoms, thereby possibly improving diagnosis/monitoring and subsequent clinical care in some diseases, is increasingly being recognized. For example, PROs have been successfully used in cancer, rheumatoid arthritis, and endometriosis. In this context, we describe a patient-reported questionnaire (the Patient-Tracked Symptoms questionnaire) that contains questions on the presence of signs/symptoms of PTS. This questionnaire has face validity and was successfully used in the Home-LITE trial. It could prove valuable in monitoring patient symptoms, especially in home-based patients who do not have regular contact with hospital clinicians. Patients who report symptoms can then undergo follow-up assessment by health care professionals at their next clinic visit. The Patient-Tracked Symptoms questionnaire could help clinicians to recognize the PTS early, enabling them to initiate treatment promptly.