Catherine Foley

Patient-Reported Outcomes in Metastatic Breast Cancer: A Review of Industry-Sponsored Clinical Trials

Introduction Patient-reported outcome (PRO) measures serve to capture vital patient information not otherwise obtained by primary study endpoints. This paper examines how PROs are utilized as endpoints in industry-sponsored metastatic breast cancer clinical trials. Methods A search was conducted in the clinicaltrials.gov web site for trials involving common treatments for metastatic breast cancer. Thirty-eight clinical trials were identified which included a PRO endpoint in the study, and data were extracted and summarized. Results Overall, 17 unique PRO questionnaires and 14 concepts of measurement were identified as secondary or exploratory endpoints. The Functional Assessment of Cancer Therapy—Breast was the most frequently utilized questionnaire, commonly implemented to assess quality of life. The EORTC QLQ-C30 was also frequently used to measure quality of life or pain. Conclusion This review shares insights into the role of PROs in trials for metastatic breast cancer from which treatment developers and other stakeholders can enhance successful implementation of the patient voice into future trials.

Clinical Trial Patient-reported Outcomes Data: Going Beyond the Label in Oncology

PURPOSE Patient-reported outcome (PRO) data are increasingly being implemented in oncology clinical trial research to evaluate treatment benefit, such as disease-related symptoms, treatment-related adverse events, and health-related quality of life impacts. However, only a small amount of PRO data collected is used to support labeling claims, leaving a substantial amount of data that could be shared by sponsors to further convey treatment benefit from the patient perspective. METHODS This paper describes how pharmaceutical sponsors can realize the value of PRO data derived from oncology trials with regard to the following stakeholders: payers, health care providers (HCPs), and patient advocacy groups. Further, ideas are presented for integrating PRO data and implementing PRO assessments within oncology, by stakeholder type. Finally, a summary is provided to describe how PRO data can benefit the patient by facilitating better, more symptom-focused care and enhancing treatment decisions. FINDINGS With the goal of motivating further use of PRO assessments in oncology, we present examples of how payers utilize PRO data to inform reimbursement decisions (eg, PRO data inform decisions made by Germany׳s Institute for Quality and Efficiency in Health Care and the United Kingdom׳s National Institute for Health and Care Excellence); how communication of results with patient advocacy groups can lead to a better understanding of what is important to patients; and how HCPs can use PRO instruments to inform patient treatment decisions through real-world application. IMPLICATIONS Integrating PRO data can enhance health care by allowing the patients voice to carry beyond regulatory decisions and into those made by payers and HCPs, which are crucial to quality care and assessing the value of care. Utilizing PRO assessments and communicating results to key stakeholders in the oncology space can allow sponsors to report treatment benefit and, more importantly, can provide valuable insight into the patient treatment experience.

Development of a Symptom-Focused Patient-Reported Outcome Measure for Functional Dyspepsia: The Functional Dyspepsia Symptom Diary (FDSD)

Objectives:The Functional Dyspepsia Symptom Diary (FDSD) was developed to address the lack of symptom-focused, patient-reported outcome (PRO) measures designed for use in functional dyspepsia (FD) patients and meeting Food and Drug Administration recommendations for PRO instrument development.Methods:Concept elicitation interviews were conducted with FD participants to identify symptoms important and relevant to FD patients. A preliminary version of the FDSD was constructed, then completed by FD participants on an electronic device in cognitive interviews to evaluate the readability, comprehensibility, relevance, and comprehensiveness of the FDSD, and to preliminarily evaluate its measurement properties.Results:During concept elicitation interviews, 45 participants spontaneously reported 19 symptom concepts. Of those, seven symptoms were selected for assessment by the eight-item FDSD. Cognitive interviews with 57 participants confirmed that participants were able to comprehend and provide meaningful responses to the FDSD, and that the handheld electronic FDSD format was suitable for use in the target population. Scores of the FDSD were well-distributed among response options, item discrimination indices suggested that the FDSD items differentiate among patients with varying degrees of FD severity, and inter-item correlations suggested that no items of the FDSD were capturing redundant information. Internal consistency estimates (0.87) and construct-related validity estimates using known-groups methods were within acceptable ranges.Conclusions:The FDSD is a content-valid PRO measure, with preliminary psychometric evidence providing support for the FDSD’s items and total score. Further psychometric evaluations are recommended to more fully test the FDSD’s score performance and other measurement properties in the target patient population.

Development and initial psychometric evaluation of patient-reported outcome questionnaires to evaluate the symptoms and impact of hidradenitis suppurativa

Abstract Background: Two patient-reported outcome (PRO) questionnaires, the Hidradenitis Suppurativa Symptom Assessment (HSSA) and Hidradenitis Suppurativa Impact Assessment (HSIA), were developed to measure signs, symptoms and impacts of HS in treatment efficacy studies. Methods: In accordance with FDA guidelines and published best practices, four stages of research were conducted to create the questionnaires: concept elicitation, questionnaire construction, content evaluation and psychometric evaluation. Results: Subjects (N = 20) who participated in the concept elicitation stage reported 15 unique HS-related signs and symptoms and 51 impacts. Following this, eight sign and symptom concepts and 21 impacts were selected for construction of the HSSA and HSIA, respectively. During content evaluation, cognitive debriefing interviews with HS subjects (N = 20) confirmed subjects could read, comprehend and meaningfully respond to both questionnaires. Modifications made after this stage of work resulted in a nine-item HSSA and a 17-item HSIA. The HSSA and HSIA were subsequently entered into a US-based observational study (N = 40), and the scores produced by each were found to be reliable, construct valid, and able to distinguish among clinically distinct groups. Conclusions: The HSSA and HSIA are content-valid, HS-specific, PRO questionnaires with demonstrated ability to generate reliable, valid scores when administered to patients with HS in a research setting.

Patient-reported outcomes for US oncology labeling: review and discussion of score interpretation and analysis methods

This paper describes ways to approach the conceptual and practical challenges associated with interpreting the clinical meaning of scores produced by patient reported outcome (PRO) questionnaires, particularly when used to inform efficacy decisions for regulatory approval for oncology products. Score interpretation estimates are not inherent to PRO questionnaires per se, instead, vary dependent upon sample and study design characteristics. Scores from PRO measures can be interpreted at the individual and group level, and each carries its own set of statistics for evaluating differences. Oncology researchers have a variety of methods and data analytic strategies available to support their score interpretation needs, which should be considered in the context of their a priori knowledge of the target patient population, the hypothesized effects of treatment, the study design and assessment schedule, and the inferences and decisions to be made from the PRO data.

The use of patient-reported outcomes in advanced breast cancer clinical trials: a review of the published literature

Abstract Objective: As a means to measure quantifiable signs, symptoms, and impacts of a disease or its treatment, patient-reported outcome (PRO) instruments can be applied to numerous settings, including use in drug development to support labeling claims. This research summarizes the use of PROs in trials for 16 commonly used regulatory approved treatments for advanced or metastatic breast cancer. Methods: For each treatment (n = 16), a literature search was conducted in MEDLINE, Embase, and PsycINFO. The primary criterion for selection was the report of studies that used PROs to evaluate treatment benefit and/or toxicity in advanced or metastatic breast cancer. From this, a sub-set of articles for each treatment were selected for full-text review where PRO-related information was extracted and summarized. Results: The searches yielded 1727 publications. Following abstract review, 1702 were excluded because they failed to meet criteria, or were duplicates or less relevant for PRO information reported. Thus, 25 articles were reviewed in detail for this evaluation. Eleven PRO instruments were identified from these publications. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core (EORTC QLQ-C30) was utilized the most frequently (n = 13, 52.0%). Most publications reported PROs positioned as secondary endpoints (n = 20, 80.0%); described some of the statistical analyses applied to PRO data (n = 21, 84.0%); and specified PRO results (n = 23, 92.0%). Conclusions: While several of the publications provided some information on how PROs were utilized, many did not describe details for PRO administration, scoring, analyses, and results interpretation. While it is encouraging that PROs are often used in clinical trials for patients with metastatic breast cancer, they are not commonly used to support endpoints that establish the basis for label claims. Because they yield direct insight into the patient experience of a condition, PROs may be used to provide a more comprehensive perspective of the benefits and risks from treatment.

Adalimumab Alleviates Skin Pain in Patients with Moderate to Severe Hidradenitis Suppurativa: Secondary Efficacy Results from the PIONEER I and PIONEER II Randomized Controlled Trials

To the Editor: Skin pain among patients with hidradenitis suppurativa (HS) is prevalent, severe, and a recommended target for treatment. Adalimumab has been approved for moderate-to-severe HS in the United States and Europe on the basis of the PIONEER I and II studies. This letter describes the results of the secondary analyses pertaining to pain reduction during treatment with adalimumab. Both institutional review boardeapproved studies were global, multisite, randomized, double-blind, placebo-controlled, parallel-group clinical trials conducted from 2011 to 2014. In all, 307 and 326 adults with moderate-to-severe HS were randomized to adalimumab, 40 mg every week, or 0.8 mL of

Development and psychometric evaluation of the self-assessment of psoriasis symptoms (SAPS) – clinical trial and the SAPS – real world patient-reported outcomes

Abstract Objective: The Self-Assessment of Psoriasis Symptoms – Clinical Trials (SAPS-CT) and SAPS – Real World (SAPS-RW) were simultaneously created to assess the experience of plaque psoriasis in two unique contexts. Methods: Qualitative and quantitative research was conducted in four phases namely concept elicitation, questionnaire construction, content evaluation and psychometric evaluation. Results: Following concept elicitation, 18 concepts were selected to inform questionnaire construction of the SAPS-CT and SAPS-RW. To accommodate each context of use, the SAPS-CT asks respondents to rate the target symptom ‘at its worst’ in the 24 h prior to assessment, while the SAPS-RW asks respondents to rate the target symptom “on average” in the 7 days prior to assessment. Cognitive debriefing confirmed that patients could comprehend and provide meaningful responses to both versions and, after minor modifications, resulted in 11-item questionnaires administered in an observational study (N = 200). Results from the observational study informed further item reduction (SAPS-RW to six items and SAPS-CT to nine items) and demonstrated that scores from each were reliable (Cronbach’s α > 0.90, test–retest intraclass correlation coefficient >0.70), construct valid and able to differentiate among clinically distinct groups. Conclusion: The SAPS-CT and SAPS-RW are content-valid PRO questionnaires capable of producing psychometrically sound scores when administered chronic to plaque psoriasis patients.

Psychometric evaluation of the Rheumatoid Arthritis Symptom Questionnaire (RASQ) in an observational study

Abstract Objective: To describe the psychometric performance of the scores produced by the Rheumatoid Arthritis Symptom Questionnaire (RASQ), a new patient-reported outcome (PRO) questionnaire developed to assess the signs and symptoms of rheumatoid arthritis (RA). Methods: Adult subjects with clinically confirmed RA completed a set of questionnaires (including the RASQ) at an initial study visit (Day 1), and then completed the RASQ and the Patient Global Impression of Change (PGI-C) on their own on Day 8. Demographic and health data were summarized using descriptive statistics, and psychometric analyses were conducted, including: acceptability, item and scale distribution, reliability (internal consistency and test–re-test reliability), and construct-related validity (convergent validity and known-groups methods). Results: In total, 200 subjects (females = 61.5%; white = 72.0%; and age [mean] = 60.7 years) with RA were recruited across the US and included in the analysis. There were no missing data recorded for the RASQ, and scores were well distributed for both timepoints. The RASQ Total Symptom Score surpassed the threshold (α ≥ 0.70) for internal consistency at Day 1 (α = 0.967) and test–re-test score reliability (intra-class correlation coefficient [ICC] > 0.70) (ICC = 0.960). Convergent validity analyses demonstrated that the RASQ items and Total Symptom Score had high correlations (convergent validity) with other PRO questionnaires. Known-groups methods demonstrated that the RASQ (Total Symptom Score and all single items) can differentiate between clinically distinct groups. Conclusions: The RASQ is capable of producing psychometrically sound scores when administered to adults with RA.

Patient-reported outcomes in advanced breast cancer: inside the label and approval documents

ABSTRACT Patient-reported outcome (PRO) measures are used in clinical research and practice for the assessment of disease-related symptoms and impacts as well as treatment-related side effects, from the patient perspective. However, a systematic examination of the role of PROs in metastatic breast cancer treatment approvals is lacking. A review of FDA labels and historical drug approval documents for metastatic breast cancer treatments was conducted to determine how PROs had been used or pursued to support labeling claims. In the historical drug approval documents, PROs were often being implemented by sponsors, and regulatory reviewers noted several issues limiting their suitability to support label claims. The findings suggest there is much room for improvement in how sponsors develop, implement, and report PRO measurement strategies as part of drug approval.