Evaluation and Modification of a Shared Decision-Making Tool for Peanut Allergy Management.

PURPOSE OF REVIEW: Based on shared decision-making (SDM) principles, a decision aid was previously developed to help patients, their caregivers, and physicians decide which peanut allergy management approach best suits them. This study refined the decision aid's content to better reflect patients' and caregivers' lived experience. RECENT FINDINGS: Current standard of care for peanut allergy is avoidance, although peanut oral immunotherapy has been approved by the Food and Drug Administration for use in patients 4-17 years old. An advisory board of allergy therapy experts (n = 3) and patient advocates (n = 3) informed modifications to the decision aid. The revised tool underwent cognitive debriefing interviews (CDIs) among adolescents (12-17 years old) with peanut allergy and caregivers of patients 4-17 years old with peanut allergy to evaluate its relevance, understandability, and usefulness. The 20 CDI participants understood the information presented in the SDM tool and reported it was important and relevant. Some revisions were made based on participant feedback. Results support content validity of the Peanut Allergy Treatment SDM Tool.

Validation of the novel Eosinophilic Esophagitis Impact Questionnaire.

BACKGROUND: Eosinophilic esophagitis (EoE) has a detrimental effect on health-related quality of life (HRQOL). The Eosinophilic Esophagitis Impact Questionnaire (EoE-IQ) is a novel patient-reported outcome (PRO) measure assessing the impact of EoE on HRQOL. To assess suitability of the EoE-IQ, its measurement properties were evaluated. METHODS: Using baseline and week 24 data from the pivotal, randomized, placebo-controlled, multinational phase 3 R668-EE-1774 trial (NCT03633617) of dupilumab, we evaluated EoE-IQ's measurement properties (including reliability, construct and known-groups validity, and ability to detect change) and established the threshold for change in scores that can be considered clinically meaningful. RESULTS: The analysis population comprised 239 adults and adolescents with EoE. Mean age was 28.1 (standard deviation, 13.14) years; 63.6% were male, and 90.4% were White. Reliability estimates for the EoE-IQ average score exceeded acceptable thresholds for patients who were stable as indicated by ratings of Patient Global Impression of Severity (PGIS) and Change (PGIC) (intraclass correlation coefficients, 0.75 and 0.81). Construct validity correlations with other EoE-specific PRO scores were moderate at baseline (|r|= 0.44-0.60) and moderate to strong at week 24 (|r|= 0.61-0.72). In known-groups analysis, EoE-IQ average score discriminated among groups of patients at varying EoE severity levels defined by PGIS scores. A ≥ 0.6-point reduction in EoE-IQ average score (where scores range from 1 to 5, with higher scores indicating worse HRQOL) from baseline to week 24 can be considered clinically meaningful. CONCLUSIONS: The EoE-IQ's measurement properties are acceptable, making it a valid, reliable measure of the HRQOL impacts of EoE among adults and adolescents. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03633617. Registered August 14, 2018, https://clinicaltrials.gov/study/NCT03633617 .

Physician experience with once-weekly somatrogon versus once-daily rhGH regimen in pediatric patients with growth hormone deficiency: a cross-sectional survey of physicians from the global phase 3 study.

Introduction: The standard of care for pediatric growth hormone deficiency (pGHD) is once-daily recombinant human growth hormone (rhGH). Somatrogon, a long-acting rhGH, requires less frequent, once-weekly, dosing. We describe physicians' preference for, experiences, and satisfaction with once-weekly somatrogon vs once-daily rhGH. Methods: English-speaking investigators from somatrogon's global phase III study (NCT02968004) with prior experience using once-daily rhGH were included. Participants answered an online survey containing 14 closed- and open-ended items. Results: Twenty-four pediatric endocrinologists (41.7% men; 79.2% practiced at public/private hospitals) from 12 countries with 25.8 ± 12.0 years' experience treating pGHD completed the survey. In terms of the time and effort required to explain device instructions, injection regimen, procedure for missed injection, and address patients'/caregivers' concerns, a similar proportion of physicians chose once-weekly somatrogon and once-daily rhGH; 62.5% physicians indicated that once-daily rhGH required greater effort to monitor adherence. Overall, 75% preferred once-weekly somatrogon over once-daily rhGH, 79.2% considered once-weekly somatrogon to be more convenient and less burdensome, and 83.3% were likely to prescribe somatrogon in the future. Overall, 50% felt that once-weekly somatrogon was more beneficial to patients, while 50% chose "No difference". Most physicians (62.5%) felt both regimens were equally likely to support positive long-term growth outcomes and reduce healthcare utilization. More physicians were "very satisfied" with once-weekly somatrogon (62.5%) than with once-daily rhGH (16.7%). Reduced injection frequency, patient and caregiver burden, increased convenience, and improved adherence were reasons for these choices. Conclusion: Physicians had a positive experience with, and perception of, treating pGHD with once-weekly somatrogon.

Experience of switching from a daily to a less frequent administration of injection treatments.

BACKGROUND: Daily injections of recombinant human growth hormone are the standard of care to treat growth failure due to pediatric growth hormone deficiency (GHD). While effective, daily injections are burdensome and can compromise adherence. In recent years, novel injection treatments requiring less frequent administration for growth hormone deficiency (GHD) have been developed. A targeted, pragmatic literature review was conducted to summarize and document the patient experience of moving from daily to less frequent injections, with a specific focus on changing from daily to weekly injection treatments in pediatric GHD (pGHD). OBJECTIVE: Explore and describe the patient experience when switching from a daily to a less frequent injection schedule for GHD. METHODS: Targeted literature searches were conducted to identify literature describing the patient experience of moving from a daily to weekly injection in GHD. Supplementary searches were conducted to identify literature describing the patient experience of moving from daily to less frequent injection regimens in other medical conditions. RESULTS: Across searches, 1,691 abstracts were reviewed and 13 articles were included in the final analysis. These publications reported that patients moving to less frequent injections across a variety of conditions, including GHD, experienced increased convenience and satisfaction, higher adherence rates, fewer adverse events, and improved quality of life. Less frequent injections were also reported to be at least as efficacious as daily treatments. CONCLUSIONS: Less frequent injections in GHD and as other conditions are less burdensome, positively benefit patients, and result in improved adherence that may lead to improved clinical outcomes. Clinicians may consider weekly regimens as an effective alternative for patients, in particular in pGHD, especially when missed injections can negatively impact treatment outcomes. More research is needed to better understand the real-world benefits of injectable therapies that require less frequent administration (e.g., weekly versus daily).

Novel Questionnaires for Assessing Signs and Symptoms of Eosinophilic Esophagitis in Children.

BACKGROUND: Pediatric patients with eosinophilic esophagitis (EoE) experience heterogeneous symptoms and the patient's age may preclude reliable self-report of symptoms. OBJECTIVE: The goal of this study was to develop a patient-reported outcome and an observer-reported outcome questionnaire to evaluate the signs and symptoms of EoE in pediatric patients (≥1 to <12 y of age) in a clinical trial setting. METHODS: A concept-focused literature review, expert advice meetings, and concept elicitation interviews with pediatric EoE patients and their caregivers were conducted to identify disease-related signs and symptoms. Instructions, items, and response options were drafted. Cognitive debriefing interviews were conducted to evaluate children's and caregivers' ability to understand and respond to the questionnaires and to evaluate the comprehensiveness of the concepts measured. RESULTS: Results from the literature review, expert advice meetings (n = 6), and concept elicitation interviews (n = 24) informed the development of the Pediatric Eosinophilic Esophagitis Sign/Symptom Questionnaire intended for use by patients (PESQ-P) with EoE 8 years or older to younger than 12 years and an observer-reported outcome questionnaire planned for use by caregivers of patients (PESQ-C) 1 year old or older to younger than 12 years. Both questionnaires measure the same concepts; the PESQ-P assesses the frequency, duration, and/or severity of symptoms and the PESQ-C assesses the presence/absence of the signs/symptoms. The cognitive debriefing interviews (n = 17) demonstrated that participants were able to comprehend and complete the questionnaires as intended. CONCLUSIONS: This study provides evidence of the content validity of 2 novel questionnaires, PESQ-P and PESQ-C, designed to evaluate the symptom experience of pediatric EoE patients in a clinical trial setting.

Reliability, validity and important difference estimates for the NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18).

Objective: To evaluate psychometric performance of the NCCN-FACT Ovarian Cancer Symptom Index-18 (NFOSI-18) in advanced ovarian cancer. Methods: Cross-sectional, observational data from patients receiving treatment for ovarian cancer. Other measures included European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core (EORTC QLQ-C30) and associated ovarian cancer module (EORTC QLQ-OV28) and Work Productivity and Activity Impairment. Internal consistency reliability, construct validity and anchor-based clinically important differences were assessed. Results: 897 patients were analyzed. Reliability was acceptable for all NFOSI-18 scores; construct validity was supported. Twelve anchors sufficiently correlated with NFOSI-18 scores and suggested clinically important differences: NFOSI-18 total score (5-7), disease-related symptoms - physical (3-4), disease-related symptoms - emotional (1), treatment side effects (2) and functional well-being (1-2). Conclusions: Results provide evidence of reliability and validity of NFOSI-18 scores. Generated CIDs will help improve interpretation of between-group treatment differences in clinical trials.

Lay abstract The National Comprehensive Cancer Network Functional Assessment of Cancer Therapy ­ Ovarian Cancer Symptom Index-18 (NFOSI-18) is a questionnaire assessing the health of patients with ovarian cancer. When using such questionnaires, it is important to evidence that they produce consistent scores (referred to as reliability) and are aligned with other assessments of health (referred to as construct validity). It is also important to set guidelines on what constitutes a clinically important difference in scores, so clinicians and researchers can judge how effective new treatments are. This study analyzed data from 897 patients with advanced ovarian cancer, providing evidence of reliability and construct validity. Guidelines for clinically important differences were also provided. The findings support continued use of the NFOSI-18.

A novel patient-reported outcomes instrument assessing the side effects of peanut oral immunotherapy.

BACKGROUND: Patients treated with peanut oral immunotherapy (OIT) may experience adverse reactions, particularly during up-dosing. OBJECTIVE: To develop the Side Effects of Peanut Oral Immunotherapy Diary (SEPOD), an electronic questionnaire assessing the daily side effects of peanut OIT in clinical trials. METHODS: Content and design of the SEPOD were informed by empirical literature review and meetings with 3 allergy-immunology experts. Interviews to confirm content and inform revisions were conducted in 24 pediatric patients with peanut allergy (14 treated with peanut OIT) aged 6 to 17 years; children aged 6 to 11 years were interviewed with their caregiver. RESULTS: The SEPOD was drafted after literature review and expert interviews; the initial measurement approach comprised 2 SEPOD versions, a patient-reported outcome (PRO) version for children aged 12 to 17 years, and a caregiver-administered PRO version for children aged 6 to 11 years with instructions for caregiver questionnaire administration. Pediatric patients were expected to respond independently on both versions. Patient interviews indicated that some younger children (ie, aged 6-8 years) had difficulty understanding questions, even when reading aloud; therefore, a caregiver-administered outcome version, identical in content to the caregiver-administered PRO version, was developed for this age group. The final electronic SEPOD covered 23 peanut OIT side effects within the following 7 domains: gastrointestinal, dermatologic, itching, nasal, and respiratory, swelling (eyelid or periorbital, lip, tongue, and throat), pain (tongue, mouth, and throat), and dizziness. CONCLUSION: This study yielded the SEPOD, a new clinical outcome assessment instrument with various methods of administration that can be used to assess the side effects of peanut OIT experienced by pediatric patients in a clinical trial setting.

Development and content validation of the Pediatric Oral Medicines Acceptability Questionnaires (P-OMAQ): patient-reported and caregiver-reported outcome measures.

BACKGROUND: Evolving regulatory guidelines recommend routine assessment of the acceptability of pediatric oral medicines throughout clinical development processes. However, such assessment is problematic owing to a lack of standard methods or criteria that define acceptability for children and their caregivers. This research aimed to identify the attributes of acceptability for targeted oral formulation types that are important to children, and to develop content-valid patient- and caregiver-reported outcome acceptability measures for use in the context of clinical drug development. METHODS: A concept-focused literature review and two advisory panel meetings involving researchers, clinicians, and measurement scientists were conducted to identify acceptability attributes that may be relevant to children taking targeted oral medicine formulations. The Pediatric Oral Medicines Acceptability Questionnaires (P-OMAQs), including patient (P-OMAQ-P) and caregiver (P-OMAQ-C) versions, were drafted to assess these attributes. Qualitative concept elicitation (CE) and cognitive debriefing (CD) patient and caregiver interviews were conducted to confirm key acceptability attribute concepts for measurement and to evaluate patient and caregiver ability to understand and respond to the questions. RESULTS: A full-text review of 40 articles identified 24 acceptability attributes that were categorized into 10 overarching domains and organized into a preliminary conceptual model. Feedback from the advisory panel refined the preliminary model. In total, 14 attributes were reported during the CE phase of the interviews (n = 23 pediatric patients, n = 13 caregivers); six attributes were included in the final model. The draft P-OMAQ was refined over four waves of CD interviews (n = 31 pediatric patients, n = 48 caregivers). The final version of the P-OMAQ-P is a 12-item questionnaire designed for young people aged 8-17 years. The P-OMAQ-C is a 19-item questionnaire designed for adult caregivers of young people aged 6 months to 17 years. There are two versions of each questionnaire: one with a 24-h recall period and one with a 7-day recall period. All items are answered on a 5-point numerical rating scale. CONCLUSIONS: This research supports the content validity of the patient and caregiver versions of the P-OMAQ. Both questionnaires appropriately assess the acceptability of oral medicine formulations from the perspective of pediatric patients and their caregivers.

Factors Driving Patient Preferences for Growth Hormone Deficiency (GHD) Injection Regimen and Injection Device Features: A Discrete Choice Experiment.

INTRODUCTION: The daily injection burden of recombinant human growth hormone (r-hGH) replacement therapy to treat growth hormone deficiency (GHD) may reduce compliance and limit treatment benefit. Research is needed to evaluate patient preferences for GHD injection regimen and device features. OBJECTIVE: Quantitatively evaluate factors driving preferences for r-hGH injection regimen and device features among pediatric (3-17 years, and caregivers) and adult (≥25 years) patients with GHD using a discrete choice experiment (DCE) approach. METHODS: The DCE was part of a broader, cross-sectional observational field study to develop clinical outcome assessments (COAs) that assess the experience of patients taking r-hGH injections. Following ethics approval, discrete choice data were collected through an online questionnaire from consented participants recruited from eight sites in the United States. Participants were presented with 20 choice tasks, each comprising different combinations of two profiles. Participants were then shown the same set of three hypothetical device and injection profiles (ie, storage, preparation, injection type device, maintenance, dose setting, injection schedule) and asked whether they would choose each profile over their current device and schedule. Choice-based conjoint analyses were used to estimate the marginal utilities and values for treatment attributes. Subject preferences were estimated at individual and aggregate levels. RESULTS: Two hundred and twenty-four participants completed the DCE (n=75 adults, n=79 adolescent/caregiver dyads, n=70 child/caregiver dyads). Injection schedule was the strongest predictor of choice for the total sample and each patient group. Less frequent injection schedules were more likely to be chosen by participants. A "ready to use" injection was preferred, with no preference for auto-injector versus needle-free device. Most participants would choose the hypothetical injection devices and less frequent dosing over their current daily administered device schedule. CONCLUSION: Patients prefer a less frequent injection regimen for treating GHD. Addressing patient preferences may improve compliance, adherence, and ultimately, clinical outcomes.

Development and Psychometric Evaluation of the Life Interference Questionnaire for Growth Hormone Deficiency (LIQ-GHD) to Assess Growth Hormone Injection Burden in Children and Adults.

BACKGROUND: Current recombinant human growth hormone (r-hGH) replacement therapy involves long-term daily subcutaneous injections to treat growth hormone deficiency (GHD) in children and adults. Daily r-hGH injections can be burdensome, often resulting in poor treatment compliance. Clinical outcome assessments (COAs) can capture the burden of these injections from the patient (and caregiver) perspective and may demonstrate the benefit of a less-frequent r-hGH injection regimen, which may ultimately improve treatment compliance and long-term outcomes. OBJECTIVE: To address this knowledge gap, qualitative research was conducted to inform the development of a new Life Interference Questionnaire for Growth Hormone Deficiency (LIQ-GHD), designed to measure the experiences of patients taking r-hGH GHD injections. A second objective was to evaluate the hypothesized factor structure and preliminary performance of the LIQ-GHD in a cross-sectional observational study. METHODS: An empirical literature review and expert advice meetings were conducted to inform development of the draft LIQ-GHD (pediatric and adult versions). In-person concept elicitation and cognitive debriefing interviews were conducted with GHD patients (and patient dyads including caregivers) to explore and confirm concept coverage and evaluate respondents' ability to understand the questionnaire. The draft LIQ-GHD was then tested in a cross-sectional field study involving pediatric and adult patients receiving daily r-hGH injections for GHD. The factor structure, reliability, and validity were analyzed for the overall sample and for pediatric, adolescent, and adult subgroups. RESULTS: Results from the literature review and input from six experts were used to develop and refine the LIQ-GHD, with content covering pen ease of use; regimen convenience; life interference due to regimen; benefit/satisfaction/willingness to continue treatment; regimen choice/preference; intent to comply with regimen; injection-related signs/symptoms; and reasons for missed injections. Twenty-one patient interviews confirmed comprehensive concept coverage and patient/caregiver comprehension of the LIQ-GHD. A total of 224 patients (n = 70 children/caregiver dyads, n = 79 adolescents/caregiver dyads, n = 75 adults) participated in the field study. While most items showed floor effects, confirmatory factor analysis fit statistics were good for the overall sample (root mean square error of approximation = 0.07, comparative fit index = 0.98) and for the full pediatric sample after dropping co-dependent questions from the model. Cronbach's alpha (α) ranged from 0.746 to 0.905 and intra-class correlation coefficients ranged from 0.761 to 0.918 for the overall sample on LIQ-GHD domains. Scores correlated as predicted with an existing criterion measure in the overall sample and LIQ-GHD domain scores distinguished known groups as expected. CONCLUSIONS: The LIQ-GHD is a new COA for the measurement of r-hGH injection treatment burden. This research provides evidence supporting its content validity, hypothesized factor structure, score reliability, and construct validity in pediatric and adult populations.

Informing a priori Sample Size Estimation in Qualitative Concept Elicitation Interview Studies for Clinical Outcome Assessment Instrument Development.

OBJECTIVE: Evidence-based recommendations for the a priori estimation of sample size are needed for qualitative concept elicitation (CE) interview studies in clinical outcome assessment (COA) instrument development. Saturation is described as the point at which no new data is expected to emerge from the conduct of additional qualitative interviews. STUDY DESIGN: A retrospective evaluation of 26 CE interview studies conducted with patients between 2006 and 2013 was completed to assess the point at which saturation of concept was achieved in each study. METHODS: For each of the 26 interview studies, saturation of symptom concepts was assessed by dividing the sample into quartiles and then comparing the number of responses elicited from the first 25% of participants to the next 25% of participants, from the first 50% of participants to the next 25% of participants, and then from the first 75% of participants to the last 25% of participants. The number of interviews required to achieve saturation was documented for each study and then summarized across studies. RESULTS: Findings indicate that 84% of symptom concepts emerged by the 10th interview, 92% emerged by the 15th interview, 97% emerged by the 20th interview, and 99% by the 25th interview. CONCLUSIONS: Results provide practical guidance for estimating the number of interviews that may be needed to achieve saturation in a qualitative CE interview study for COA instrument development; address an important gap in qualitative research for the development of COAs in the context of medical product development; and offer useful information for study design and implementation.

Quality of Care in Rheumatoid Disease from the Clinician Perspective: A Modified Delphi Panel Approach.

INTRODUCTION: To establish clinical consensus on important and relevant quality-of-care (QoC) attributes in rheumatic disease (RD) treatment that may improve treatment outcomes and guide best practices. METHODS: Twenty-three QoC attributes were identified in a literature review. Fifteen European-based clinicians were selected based on their contributions to RD guidelines, publications, and patient care. A three-round (an interview round and two web-based rounds) modified Delphi panel was conducted to reach consensus and finalize a QoC attribute list. RESULTS: In round 1 (clinician interviews), clinicians reported 52 unique QoC attributes across 14 themes, with the greatest number of attributes reported in the "treatment goals" (n = 7) and "remote monitoring" (n = 7) themes. During rounds 2 and 3, the critically important QoC attributes most frequently reported were access to care/treatment (n = 14, 93.3%), safety of treatment (round 2 n = 14, 93.3%, round 3 n = 13, 86.7%), and access to clinicians and specialists (round 2: n = 13, 86.7%, round 3: n = 14, 93.3%). The final list contained 53 QoC attributes. CONCLUSION: The study demonstrates consensus across several themes of QoC. Quality of care is a complex, multidimensional, and fluid concept that can be improved by ensuring patients have access to care, open communication between patients and clinicians, and the use of novel strategies, such as remote monitoring. Utilization of the attribute list can potentially improve the lives of patients, provide clinicians with tools to provide greater QoC, and improve the healthcare system as a whole. FUNDING: Merck & Co., Inc.

Patient-Reported Outcomes in Oncology Drug Labeling in the United States: A Framework for Navigating Early Challenges.

BACKGROUND: Despite an increased use of patient-reported outcomes (PROs) in oncology clinical trials, integrating the patient perspective into drug approval decisions and documentation has been challenging. OBJECTIVES: To review important regulatory and measurement terminology, and to provide oncology outcomes researchers and those involved with building oncology programs with tools to plan PRO data collection, particularly in relation to drug efficacy claims for drug labeling in the United States. DISCUSSION: When contemplating a PRO measurement strategy for oncology clinical trials, outcomes researchers are challenged in several ways. First, given multiple stakeholders, researchers must communicate with their scientific, commercial, and regulatory colleagues using often misunderstood terms, such as "label," "claim," "end point," "outcome," and "concept." Second, because stakeholders do not always have access to data from early-stage clinical trials and do not contribute to the target drug's profile in early development, researchers are often unable to address the most important question in building a measurement strategy: What do we want to say about our drug? To overcome these challenges, researchers can systematically develop an end point model to facilitate communication among drug development stakeholders using a common language and to link the building blocks of a PRO measurement strategy, including claims, concepts, questionnaires, and end points. We developed a model that characterizes a disease by its proximal signs and/or symptoms and increasingly distal health outcomes to provide researchers potential measurement concepts that can be instrumental in selecting PRO questionnaires for use in studies. CONCLUSION: PRO data collected in clinical trials should be used in drug development to evaluate the drug's efficacy; it is encouraging that US regulators are willing to work with drug sponsors to overcome the challenges associated with the development, implementation, and interpretation of PROs. The tools discussed in this article can facilitate the planning process for oncology researchers, as well as assist in communicating with US regulators.

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 patient's 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.

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 impact of upper facial lines and psychological impact of crow's feet lines: content validation of the Facial Line Outcomes (FLO-11) Questionnaire.

BACKGROUND: Treatments for upper facial lines (UFL), the most visible sign of aging, are of interest to patients and clinicians alike. Patient-reported outcomes (PROs) are valuable in evaluating the impact of such treatments; however, regulatory recommendations have stipulated that the patient perspective be central in developing these assessments. OBJECTIVES: (1) To evaluate the content validity of the Facial Lines Outcomes Questionnaire, a PRO instrument developed to assess upper facial line impacts, according to the regulatory guidance of the United States Food and Drug Administration and (2) assess whether it adequately measures the psychological impacts associated with crow's feet lines (CFL) (lateral canthal lines) from the patient perspective. METHODS: Two patient groups participated in face-to-face qualitative interviews. One group included patients with UFL (Group 1, n = 25 interviews), and the other included patients specifically with CFL (Group 2, n = 41 interviews). Each interview consisted of a concept elicitation and cognitive debriefing phase. RESULTS: Interviews with both groups elicited all key concepts of the instrument, including "bothered by facial lines"; "looking older"; "looking less attractive"; and looking "tired," "stressed," or "angry." Most Group 2 patients (n = 35, 85%) agreed that the instrument adequately assessed the psychological impacts associated with CFL. During cognitive debriefing, the majority of patients in both groups agreed the instrument was understandable, comprehensive, and easy to complete. CONCLUSIONS: The Facial Line Outcomes Questionnaire is an appropriate and valid tool to assess the impact of UFL and the psychological impacts associated with CFL.