Patient-reported Outcome Guidance Research Articles

The Atopic Dermatitis Control Tool: Adaptation and Content Validation for Children and Caregivers of Children with Atopic Dermatitis.

The Atopic Dermatitis Control Tool (ADCT) assesses six concepts regarding patient-perceived control of atopic dermatitis (AD) in adults and adolescents with AD. This study aimed to develop two modified ADCT versions, one for children with AD aged 8-11years and another for caregivers of children with AD aged 6months to 11years. Following the US Food and Drug Administration patient-reported outcomes guidance, the ADCT was modified to produce draft Child and Caregiver ADCT versions, maintaining the original six concepts. The instruments were refined and finalized through an iterative process using input from children with AD and caregivers of children with AD via qualitative interviews. Inclusion criteria were clinician diagnosis of AD, prescription treatment use in the past 3months, and itching/scratching or rash in the past month. Interviews consisted of concept elicitation to identify perceptions of AD control and cognitive debriefing to test and refine the ADCT items. In total, 19 children (mean age 9.2years, 74% male) and 17 caregivers (mean age 36.3years, 100% female) were interviewed. During concept elicitation, children and caregivers reported similar symptoms and described the cycling and unpredictability of AD. Most participants reported that daily activities were impacted negatively by AD symptoms. The concept of AD control resonated with children and caregivers, and respondents were able to describe their experiences related to AD symptom severity. Children were unfamiliar with the term AD, so the Child ADCT version was named the Child Eczema Control Tool (ECT). Children and caregivers both reported that the instruments assessed relevant concepts, comprehensively measured AD control, and demonstrated content and face validity. The Child ECT and Caregiver ADCT were developed and qualitatively validated for assessing AD control in patients aged 6months to 11years and may offer simple ways to assess disease control and optimize treatment decisions. Video Abstract.

12481 Evaluating The Device Handling And Preference Assessment Questionnaire For Growth Hormone Deficiency: Results From Content Validation Interviews

Abstract Disclosure: J. Neergaard: Employee; Self; Novo Nordisk. S. Akhtar: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. B. Berg: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. S. Hamilton: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. E. Hildebrand: Consulting Fee; Self; Novo Nordisk. J. Medina: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. G. Ter-Borch: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. N. Rasmussen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. Background: Patient experiences with injection devices may affect treatment adherence, and hence it is important to ensure patient-reported outcomes (PRO) instruments used to assess experience are supported by evidence of validity. As part of a study that compared patient preference and ease of use between the devices used to administer Somapacitan (Sogroya®, Novo Nordisk A/S) and Somatrogon (Ngenla®, Pfizer), we assessed relevance, comprehensiveness and comprehension of a PRO instrument, the Device Handling and Preference Assessment Questionnaire (DHPAQ), in adolescent patients with growth hormone deficiency (GHD) and their caregivers. Methods: We recruited 33 adolescent patients with GHD and 37 caregivers across five sites in the US for an open label, randomized, crossover study in which participants simulated an injection with each device using an injection pad or mannequin. The DHPAQ was used to assess patients’ device preference. Two-sided statistical tests with 5% significance levels were performed using DHPAQ responses. After completing the DHPAQ, a random subgroup of 10 adolescents and 10 caregivers were offered additional compensation to participate in a cognitive interview (CI). The CIs were conducted in accordance with the US Food and Drug Administration 2022 Principles for PRO Instruments and 2009 PRO Guidance for Industry. Trained interviewers used a structured guide to evaluate questions, statements, tasks and response options in the DHPAQ. Participants’ interview responses for each question were coded and added to summary tables. These summary tables were evaluated by the study team to determine the relevance, comprehensiveness and participant comprehension of instructions, item stems and response options. Results: When asked if any questions in the DHPAQ did not seem relevant to their device experience, all 20 CI participants answered “no”. Questions on “learning how to use the device”, “selecting the correct dose” and “injecting the dose” were ranked as most relevant. Participants responses from the CIs supported perceived comprehensiveness of all DHPAQ items. All CI participants reported comprehension of all test items in the DHPAQ, and only three items did not receive a “no difficulty” response from all 20 participants. In the main study, the number of participants who preferred the somapacitan device was significantly greater than those who preferred the somatrogon device (84.3% vs 12.9%, p<0.0001). More participants found the somapacitan device easy or very easy to use compared with the somatrogon device (98.6% vs 74.3%). Conclusions: The results from the CIs indicated that the instructions, item stems and response options of the DHPAQ were relevant, comprehensive and fully comprehended by all participants. In the main study, patients with GHD and their caregivers were found to prefer the somapacitan device to the somatrogon device. Presentation: 6/2/2024

Three Novel Patient-Reported Outcome Measures to Assess the Patient Experience With Daily and Weekly HIV Oral Antiretroviral Therapy.

Patient-reported outcome measures (PROMs) can provide data on the barriers and facilitators of adherence to daily oral antiretroviral therapy (OART) regimens. We aimed to develop PROMs to understand the perspectives of people with HIV (PWH) on (1) facilitators/barriers to daily OART regimen adherence and (2) a hypothetical switch to a long-acting (LA)-OART regimen. Following the US food and drug administration patient-reported outcome guidance, targeted literature reviews and concept elicitation interviews with clinicians (n = 7) and PWH (n = 28) were conducted to develop conceptual models (CMs) of facilitators/barriers to OART regimen adherence. Three de novo PROMs were developed after an item-generation meeting. Three waves of cognitive debriefing interviews were conducted among PWH (n = 30) to demonstrate content validity and refine the PROMs. The targeted literature review identified 25 facilitators/barriers; an additional 16 facilitators/barriers were added by clinicians and PWH and represented in 2 CMs. During the item-generation meeting, the CMs were used to develop 3 de novo PROMs: (1) HIV Patient Perspective of Regimen, (2) HIV Patient Perspective of Regimen Change, and (3) HIV Drivers of Adherence Questionnaire. In the cognitive debriefing interviews, PWH corroborated the relevancy of items in the PROMs, and minor adjustments were made for clarity. Three content-valid PROMs were developed to understand the treatment experience of PWH taking daily OART and how that experience may be altered upon a switch to weekly LA-OART. Data from future LA-OART clinical trials will help define a scoring guide and evaluate the structure and measurement properties of the PROMs.

P227 Patient experiences in ulcerative colitis: conceptual model and review of patient-reported outcome measures

Abstract Background Symptoms of ulcerative colitis (UC) negatively affect patients’ health-related quality of life (HRQoL). The aim of this study was to identify symptoms and impacts experienced by patients with UC, develop a conceptual model (CM) and evaluate available patient-reported outcome (PRO) measures for appropriateness for inclusion in UC clinical studies. Methods We conducted a landscape assessment that included: targeted literature reviews (TLRs) to identify concepts of interest and frequently used PRO measures among patients with UC; label claims searches for US and European regulatory and health technology assessment (HTA) submissions; and US and European clinical trial database searches to identify PRO measures used as primary and secondary endpoints in ongoing clinical trials. Results from the TLR informed a CM of UC. Concepts from the CM were mapped to selected PRO measures. Appropriateness of selected PRO measures for UC populations was evaluated via a gap analysis. Results Fifty-two symptoms and 72 impacts of UC were identified from the TLR. The most frequently reported symptoms were diarrhoea, incontinence/leaking/lack of bowel control, urgency, rectal bleeding, frequent bowel movements and fatigue. The most frequently reported impacts were anxiety, depression, inability to conduct daily activities, embarrassment and affected relationships with others. The CM grouped the 52 symptom concepts into eight dimensions, the 29 impacts proximal to UC into two dimensions and the 43 impacts distal to UC into five dimensions (Figure 1). Of the 69 PRO measures identified, eight were selected for conceptual analysis based on being disease-specific and having evidence of use in regulatory label claims, HTA submissions, as UC clinical trial endpoints and/or having US Food and Drug Administration (FDA) qualification status. The five PRO measures that covered the most concepts when mapped against the CM and included in the gap analysis were: the Inflammatory Bowel Disease Questionnaire (IBDQ); Symptoms and Impacts Questionnaire for UC (SIQ-UC); UC-PRO symptoms modules (UC-PRO-Signs and Symptoms [UC-PRO/SS] and UC-PRO-Systemic Symptoms); UC-PRO impact modules (UC-PRO-Daily Coping [UC-PRO-DC], UC-PRO-Daily Life Impact [UC-PRO-DLI] and UC-PRO-Emotional Impact [UC-PRO-EI]); and Crohn’s and Ulcerative Colitis Questionnaire (CUCQ) (Table 1). All five PRO measures had good or excellent support for content validity; the UC-PRO/SS fully met FDA PRO guidance for content validity and most psychometric properties. Conclusion Based on the CM and PRO measures review, the IBDQ plus UC-PRO/SS are recommended to capture UC symptoms and IBDQ plus UC-PRO impact modules to capture proximal impacts. All PRO measures reviewed require further psychometric evaluation.

Patient-reported outcomes labeling for oncology drugs: Multidisciplinary perspectives on current status and future directions.

Introduction: Regulatory agencies encourage the incorporation of the patient voices throughout clinical drug development. Patient-Reported Outcomes (PROs) offer one way of doing this and their use has markedly increased in many therapeutic areas, particularly oncology, in recent years. However, few oncology drug labels include PRO data and those which do, offer little consistency. Objective: To provide multidisciplinary perspectives (patient, pharmaceutical industry, PRO researcher, regulatory expert) on PRO data in oncology drug labels. Methods: PRO data in the labels of drugs approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for oncology indications between 2010 and 2020 were critically reviewed by authors who provided their insights on the advantages and disadvantages/gaps. Results: Forty-six oncology drugs included PRO data in their labels. Differences were observed between FDA and EMA PRO labeling (e.g., PRO concept, use of tables and graphs to display PROs or reference to clinical meaningfulness). In providing their perspectives on the number and nature of PROs in labels, authors noted limitations including: the low proportion of oncology drugs with PRO labeling, limited PRO information in labels, lack of patient-friendly language, and potential bias towards positive outcomes. Lack of consistency within- and between-agencies was noted. Conclusion: Despite regulatory agencies' commitment to incorporate patient voices in regulatory decisions, availability of PRO information is limited in oncology drug labels. While several PRO guidance documents are available from regulatory and Health Technology Assessment agencies, harmonization of PRO guidance for labeling inclusion around the world is needed to better inform prescribers and consequently their patients in the process of shared medical decisions.

Impact of adalimumab on disease burden in moderate-to-severe ulcerative colitis patients: The one-year, real-world UCanADA study.

BACKGROUNDA gap remains in documenting the impact of anti-tumor necrosis factor therapy on disease burden in ulcerative colitis (UC) patients treated in a real-world setting. The use of patient-reported outcomes (PROs) has been discussed as a primary endpoint in the context of the FDA PRO Guidance, for labelling purposes. Specifically, the efficacy and safety of adalimumab have been demonstrated in pivotal trials; however, data are needed to understand how clinical results translate into improvements in key aspects of the daily lives of UC patients, such as symptoms, health-related quality of life (HRQoL), and disability.AIMTo assess real-world effectiveness of adalimumab on PRO measures in patients with moderate-to-severe UC.METHODSUCanADA was a single arm, prospective, 1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed—with psychologic distress/depression symptoms as the primary endpoint—by patients with moderate-to-severe UC. Assessments were performed during patients’ routine care visit schedule, which was at the initiation of adalimumab (baseline), after induction (approximately 8 wk), and 52 wk after baseline. Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period. Serious safety events and per-protocol adverse events were collected.RESULTSFrom 23 Canadian centres, 100 patients were enrolled and 48 completed the study. Measured with the Patient Health Questionnaire–9 items at week 52, 61.5% (40/65) [95% confidence interval (CI): 49.7%-73.4%] of the patients improved in psychologic distress/depression symptoms, which was slightly higher in completers [65.9% (29/44); 95%CI: 51.9%-79.9%)]. At week 52, clinical response and clinical remission were achieved respectively by 65.7% (44/73) and 47.8% (32/73) of the patients. The odds of improving depressive symptoms for those achieving a clinical remission at week 52 was 7.94 higher compared with those not achieving a clinical remission (CI: 1.42, 44.41; P = 0.018). Significant changes from baseline to weeks 8 and 52 were observed in disability, HRQoL, and fatigue. Meaningful improvement was reported in work impairment.CONCLUSIONAt week 52, over 60% of the UCanADA patients had depressive symptoms significantly reduced, as well as HRQoL, fatigue symptoms, and work impairment improved. No new safety signals were detected.

Capturing the patient experience in systemic lupus erythematosus: Are widely used measures fit-for-purpose and adherent to FDA PRO guidance recommendations?

BackgroundThe 2009 Food and Drug Administration (FDA) patient-reported outcome (PRO) guidance outlines characteristics of rigorous PRO-measure development. There are a number of widely used PRO measures for Systemic Lupus Erythematosus (SLE), but it is unknown how well the development processes of SLE PRO measures align with FDA guidance; including updated versions. The objective of this study was to assess how well the LupusQoL and LupusPRO, and corresponding updated versions, LupusQoL-US and LupusPROv1.8, align with Food and Drug Administration (FDA) 2009 patient-reported outcome (PRO) guidance.MethodsLupusQoL and LupusPRO were selected as the most widely studied and used Lupus PROs in the UK and US. Original (LupusQoL (2007) and LupusQoL-US (2010)) and revised (LupusPROVv1.7 (2012) and LupusPROv1.8 (2018)) versions were reviewed. We used FDA PRO guidance to create evaluation criteria for key components: target population, concepts measured, measurement properties, documentation across the phases of content validity (item-generation and cognitive interviewing, separately) and other psychometric-property testing. Two reviewers abstracted data independently, compared results, and resolved discrepancies.ResultsFor all measures, the target population was unclear as population characteristics (e.g., ethnicity, education, disease severity) varied, and/or were not consistently reported or not considered across the three phases (e.g., LupusQoL item-generation lacked male involvement, LupusPRO cognitive-interviewing population characteristics were not reported). The item-generation phase for both original measures was conducted with concepts elicited via patient-engagement interviews and item derivation from experts. Cognitive interviewing was conducted via patient feedback with limited item-tracking for original measures. In contrast, the revised measures assumed content validity. Other psychometric testing recommendations (reliability, construct validity, ability to detect change) were reported for both original and revised measures, except for ability to detect change for revised measures.ConclusionsThe SLE PRO measures adhere to some but not all FDA PRO guidance recommendations. Limitations in processes and documentation of the study population, make it unclear for which target population(s) the current Lupus measures are fit-for-purpose.

Evaluation of the content validity of patient-reported outcome (PRO) instruments developed for use with individuals with phakic presbyopia, including the Near Activity Visual Questionnaire-presbyopia (NAVQ-P) and the near vision correction independence (NVCI) instrument

BackgroundPresbyopia is the age-related deterioration in the ability to focus on close objects. In order to develop a patient-reported outcome (PRO) instrument to assess near vision functioning, the Near Activity Visual Questionnaire (NAVQ) was adapted to incorporate modern technology (e.g. smartphones) and to be appropriate for use in phakic presbyopia, leading to the development of the NAVQ-Presbyopia (NAVQ-P). Additional single-item instruments of near vision correction independence (NVCI), correction preference (NVCP), and vision satisfaction (NVS) were also developed. The study aimed to evaluate the content validity of the NAVQ-P and additional instruments in individuals with phakic presbyopia.MethodsParticipants in the US (n = 15), Germany (n = 10) and France (n = 10) took part in face-to-face, qualitative, cognitive debriefing interviews. Seven healthcare professionals (HCPs) were also interviewed to assess the clinical relevance of the PRO instruments. Interviews started with open-ended qualitative concept elicitation questioning; participants then completed the PRO instruments on an electronic tablet using a “think-aloud” process and were asked about their understanding and relevance of each item, instruction, response scale and recall period. Interviews were conducted in two rounds allowing for modifications between rounds.ResultsThe participants interpreted the majority of the PRO instruments and recall period correctly and consistently. They were able to select an appropriate response option without difficulty. Minor modifications were made to the PRO instruments based on interview findings. Instruction/item wording was modified to include reference to use of a magnifying glass, in addition to glasses and contact lenses. Two items were added to assess difficulty with precision tasks (e.g. sewing) and taking longer to adjust from distance to near vision. HCPs confirmed the relevance of the concepts being measured for presbyopia and recommended the addition of an item assessing contrast sensitivity.ConclusionsDeveloped in accordance with the FDA PRO Guidance, the findings support content validity of the NAVQ-P as a suitable, well-understood instrument of relevant near vision functioning concepts in individuals with phakic presbyopia. The NVCI and additional PRO instruments are appropriate to assess near vision correction independence, correction preference, and vision satisfaction. Future work will assess the psychometric properties of the NAVQ-P and additional PRO instruments.

International perspectives on suboptimal patient‐reported outcome trial design and reporting in cancer clinical trials: A qualitative study

PurposeEvidence suggests that the patient‐reported outcome (PRO) content of cancer trial protocols is frequently inadequate and non‐reporting of PRO findings is widespread. This qualitative study examined the factors influencing suboptimal PRO protocol content, implementation, and reporting, and use of PRO data during clinical interactions.MethodsSemi‐structured interviews were conducted with four stakeholder groups: (1) trialists and chief investigators; (2) people with lived experience of cancer; (3) international experts in PRO cancer trial design; (4) journal editors, funding panelists, and regulatory agencies. Data were analyzed using directed thematic analysis with an iterative coding frame.ResultsForty‐four interviews were undertaken. Several factors were identified that could influenced effective integration of PROs into trials and subsequent findings. Participants described (1) late inclusion of PROs in trial design; (2) PROs being considered a lower priority outcome compared to survival; (3) trialists’ reluctance to collect or report PROs due to participant burden, missing data, and perceived reticence of journals to publish; (4) lack of staff training. Strategies to address these included training research personnel and improved communication with site staff and patients regarding the value of PROs. Examples of good practice were identified.ConclusionMisconceptions relating to PRO methodology and its use may undermine their planning, collection, and reporting. There is a role for funding, regulatory, methodological, and journalistic institutions to address perceptions around the value of PROs, their position within the trial outcomes hierarchy, that PRO training and guidance is available, signposted, and readily accessible, with accompanying measures to ensure compliance with international best practice guidelines.

Addressing Bias in Responder Analysis of Patient-Reported Outcomes

IntroductionQuantitative patient-reported outcome (PRO) measures ideally are analyzed on their original scales and responder analyses are used to aid the interpretation of those primary analyses. As stated in the FDA PRO Guidance for Medical Product Development (2009), one way to lend meaning and interpretation to such a PRO measure is to dichotomize between values where within-patient changes are considered clinically important and those that are not. But even a PRO scale with a cutoff score that discriminates well between responder and non-responders is fraught with some misclassification.MethodsUsing estimates of sensitivity and specificity on classification of responder status from a PRO instrument, formulas are provided to correct for such responder misclassification under the assumption of no treatment misclassification. Two case studies from sexual medicine illustrate the methodology.ResultsAdjustment formulas on cell counts for responder misclassification are a direct extension of correction formulas for misclassification on disease from a two-way cross-classification table of disease (yes, no) and exposure (yes, no). Unadjusted and adjusted estimates of treatment effect are compared in terms of odds ratio, response ratio, and response difference. In the two case studies, there was considerable underestimation of treatment effect.Discussion and conclusionsThe methodology can be applied to different therapeutic areas. Limitations of the methodology, such as when adjusted cell estimates become negative, are highlighted. The role of anchor-based methodology is discussed for obtaining estimates of sensitivity and specificity on responder classification. Correction for treatment effect bias from misclassification of responder status on PRO measures can lead to more trustworthy interpretation and effective decision-making.Clinicaltrials.gov: NCT00343200

Development of the Alopecia Areata Patient Priority Outcomes Instrument: A Qualitative Study.

IntroductionAlthough alopecia areata (AA) profoundly impacts patients’ physical appearance, emotional state, and daily activities, no treatment approved for AA currently exists. Patient-reported outcome (PRO) instruments currently used to capture patients’ AA experiences do not meet the requirements to support claims of treatment benefit as described in the US Food and Drug Administration’s 2009 PRO guidance. Our objective was to explore the consequences and priority treatment outcomes among individuals with AA and develop a PRO measure consistent with regulatory requirements that assesses these priorities and represents clinical benefit from the AA patient perspective.MethodsTargeted literature and instrument reviews informed an initial concept set. Concept elicitation interviews with 20 adults with AA confirmed the relevance and importance of the initial concepts, identified additional relevant concepts, and informed an AA consequence model. Thematic analysis yielded a draft item pool, which was evaluated through two iterative rounds of cognitive debriefing interviews with 16 patients with AA (9 adults; 7 adolescents).ResultsHair loss was the primary consequence of importance to patients with AA. Patients emphasized the need to differentiate hair loss by location: scalp, eyebrows, eyelashes, and body. Consequences of AA include difficulty conducting daily activities, particularly outdoor activities and exercise, and emotional impacts such as sadness, frustration, and negative self-image. Following cognitive debriefing interviews, 11 items were included to form the Alopecia Areata Patient Priority Outcome (AAPPO), assessing AA-related symptoms and impacts over the past week.ConclusionsThe AAPPO is a novel, content-valid PRO that captures the consequences of AA of the highest priority to patients.

Qualitative evaluation of the Autism Behavior Inventory: use of cognitive interviewing to establish validity of a caregiver report scale for autism spectrum disorder

PurposeThe Autism Behavior Inventory (ABI) is an observer-reported outcome scale measuring core and associated features of autism spectrum disorder (ASD). Extensive scale development (reported elsewhere) took place, in alignment with the Food and Drug Administration’s patient-reported outcome guidance, to address the need for instruments to measure change and severity of ASD symptoms.MethodsCognitive interviewing was used to confirm understanding and content validity of the scale prior to its use in clinical trials. Respondents were caregivers of individuals with ASD (N = 50). Interviews used a hybrid of the “think-aloud” and verbal probing approach to assess ABI’s content validity and participant understanding of the instrument, including: item clarity and relevance; item interpretation; appropriateness of response scales; and clarity of instructions. Audio-recordings of the interviews were transcribed for qualitative data analysis. The scale was revised based on participant feedback and tested in a second round of interviews (round 1 N = 38, round 2 N = 12).ResultsIn total, 67/70 items reached ≥ 90% understandability across participants. Caregivers were able to select an appropriate response from the options available and reported finding the examples helpful. Based on participant feedback, instructions were simplified, 8 items were removed, and 10 items were reworded. The final revised 62-item scale was presented in round 2, where caregivers reported readily understanding the instructions, response options, and 61/62 items reached ≥ 90% understandability.ConclusionsCognitive interviews with caregivers of a diverse sample of individuals with ASD confirm the content validity and relevance of the ABI to assess core and associated symptoms of ASD.

PIH36 Content Validity and Scoring of Intrauterine System Daily Bleeding Diary (IUS-DBD) for Women Using Ius for Contraception

The IUS Daily Bleeding Diary (IUS-DBD) is a single-item patient-reported outcome (PRO) measure with a 5-point Likert response scale and a 24-hour recall period, designed to evaluate the intensity and frequency of uterine bleeding. In accordance with United States (US) Food and Drug Administration (FDA) PRO Guidance for Industry 2009 requirements, this study evaluated the content validity (relevance, appropriateness, and understandability) and scoring of the IUS-DBD in a sample of women using IUS for contraception. This was a non-interventional, qualitative interview study. Participants were identified by clinicians in the US; women were eligible if they had used IUS contraception for 2–6 months and had experienced bleeding during this time or had the IUS removed due to bleeding. Interviews utilized a semi-structured interview guide with concept elicitation and cognitive debriefing methodology to evaluate the content validity of the IUS-DBD. Hypothetical bleeding profiles were assessed to explore clinically meaningful differences. Transcripts were analysed using framework analysis techniques in ATLAS.ti v7. Twenty women were interviewed. Participants (n=16/20, 80%) reported experiencing initial bothersome bleeding/spotting following IUS insertion and stated that fewer days of bleeding/spotting during the initial 3 months would be an important and meaningful improvement (n=18/18, 100%). Participants (n=20/20, 100%) interpreted the meaning of the IUS-DBD correctly (n=20/20, 100%) and found it easy to understand (n=18/19, 95%). Most correctly interpreted the recall period (n=17/20, 85%) and found the response options to be appropriate, distinct and usable (n=17/20, 85%). Based on hypothetical bleeding profiles, participants perceived a 10% reduction in days of bleeding/spotting per 30 days to be minimally improved (20%-42% participants), a 30% reduction to be minimally/much improved (>85% participants), and a 50% reduction to be much/very much improved (>75% participants). The IUS-DBD is a content valid PRO to evaluate uterine bleeding in clinical studies with women using IUS for contraception.

The Role of Patients in Alopecia Areata Endpoint Development: Understanding Physical Signs and Symptoms.

Meaningful patient input to understand disease experience and patient expectations for improvement with treatment is essential for the selection and development of outcome measures for alopecia areata (AA) clinical trials. This study explored the physical signs and symptoms of AA through 30 semistructured interviews with adult (n= 25) and adolescent (n= 5) patients experienced with severe or very severe AA. Scalp hair loss was overwhelmingly the most important sign and symptom of AA. Nearly all patients (90%) considered scalp hair loss in their top three most bothersome physical signs and symptoms of AA, with 77% (n= 23) naming scalp hair loss as the most bothersome symptom. Other identified signs and symptoms in the top three most bothersome included eyebrow, eyelash, nose, body, and facial hair loss, as well as eye irritation and nail damage and/or appearance. Eyebrow (16%, n= 4), eyelash (4%, n= 1), nasal (4%, n= 1), and body (4%, n= 1) hair loss were identified by seven adult patients as the most bothersome signs and symptoms of AA. Conceptual saturation confirmed that a comprehensive understanding of this patient population's physical AA-related signs and symptoms was obtained. These findings indicate that the primary objective for new AA treatments for this patient population should be meaningful improvement in scalp hair growth to address the most troubling unmet need.

The Vulvodynia Experience Questionnaire: Qualitative Development of a New Patient-Reported Outcome Measure for Vulvodynia

IntroductionVulvodynia is defined as vulvar pain of at least 3 months duration without a clear identifiable cause. There are currently no validated questionnaires that assess the experience of women with localized vulvodynia of the vestibule (vestibulodynia, previously known as vulvar vestibulitis) that meet the requirements of the Food and Drug Administration's Patient Reported Outcome (PRO) Guidance. AimTo develop a new content-valid PRO assessment in accordance with the Food and Drug Administration's PRO guidance to assess the symptoms and impacts of localized vulvodynia. Material and MethodsParticipants were recruited for concept elicitation interviews (ie, interviews with open-ended questions with the goal of eliciting volunteered data about the symptoms and impacts of vulvodynia). Participants were identified as having localized vulvodynia by clinicians who were experts in treating vulvar disorders. Eligibility was confirmed by the recruiting clinician, and informed consent was obtained; participants were then scheduled for in-person interviews. 25 participants were interviewed from United States (US). After concept elicitation interviews, the draft Vulvodynia Experience Questionnaire (VEQ) was developed based on the results. Cognitive interviews were conducted with 20 participants from US sites to assess the content validity of the VEQ (eg, interpretation and clarity of the items, relevance of concepts). The VEQ was further revised after cognitive interviews. All interviews were conducted face-to-face, audio-recorded, transcribed verbatim, anonymized, and analyzed using a qualitative data analysis software program. Results17 unique symptoms and 32 unique impacts were reported during concept elicitation interviews. Pain (n = 25, 100%) and burning (n = 24, 96%) were the most frequently reported symptoms of localized vulvodynia, and negative impact on emotional well-being (n = 25, 100%) was the most frequently reported impact. After analysis, item generation, and cognitive interviews, the resulting VEQ v2.0 contains 3 parts (part 1, pain; part 2, associated symptoms; part 3, impacts) with a total of 25 items that measure the most frequently reported symptoms and impacts of localized vulvodynia. Strength and LimitationsThe VEQ is a multidimensional assessment of the core symptoms and impacts of localized vulvodynia that, after additional psychometric testing including the ability to detect change, may be used in clinical trials to characterize the benefits of novel treatments. The VEQ requires additional testing to establish its cultural relevance and linguistic validity in other countries. ConclusionThe VEQ is a novel method of collecting information on localized vulvodynia symptoms and impacts that may be suitable for use in clinical trials after psychometric testing.Goldstein AT, Diez PMQ, Kapanadze S, et al. The Vulvodynia Experience Questionnaire: Qualitative Development of a New Patient-Reported Outcome Measure for Vulvodynia. J Sex Med 2020;17:2055–2066.

186: A Pan-Canadian Approach to Patient-Centered Quality Improvement Initiatives: Development and Promotion of Patient Education, Engagement and Patient Reported Outcome Guidance Documents

186: A Pan-Canadian Approach to Patient-Centered Quality Improvement Initiatives: Development and Promotion of Patient Education, Engagement and Patient Reported Outcome Guidance Documents

A Pan-Canadian Approach to Patient-Centered Quality Improvement Initiatives: The Canadian Partnership for Quality in Radiotherapy (CPQR)’s Development of Patient Education, Engagement and Patient Reported Outcome Guidance Document

In 2011 the Canadian Partnership for Quality in Radiotherapy (CPQR) released its seminal document Quality Assurance Guidelines for Canadian Radiation Treatment Programs outlining the overarching elements of quality that are important in all radiation treatment (RT) programs. Since that time, there has been an interest expressed by the radiotherapy community to expand upon these guidelines with an increased emphasis on the patient focus which would promote alignment with accreditation standards and patient-centred practice. To this end, the CPQR initiated the development of a new suite of complementary documents to provide guidance for RT programs in the development and implementation of patient-centred quality improvement initatives.

Development of a conceptual model and patient-reported outcome measures for assessing symptoms and functioning in patients with heart failure

PurposeHeart failure (HF) is a common condition that places considerable burden on patients. We aimed to develop a patient-reported outcome (PRO) measure to assess the symptoms and impacts of HF.MethodsPhase 1: a targeted literature review, expert interviews, and concept elicitation (CE) interviews with patients with HF (n = 26) were used to develop a conceptual model of the core symptoms and impacts of HF. To capture these concepts, three new fit-for-purpose PRO questionnaires were constructed in accordance with US Food and Drug Administration PRO guidance. Phase 2: three ‘waves’ of cognitive interviews were conducted with patients with HF (n = 28) to validate and refine the questionnaires.ResultsThree key symptoms—shortness of breath, oedema, and fatigue—were identified across the literature review, expert interviews and CE interviews. Several additional symptoms, cognitive changes and impacts of HF were reported in the CE interviews and included in the conceptual model. A 10-item symptom questionnaire (Heart Failure-Daily Symptom Diary) was constructed; cognitive testing showed that the final PRO measure was easy to understand/complete and relevant to patients with HF, confirming content validity. Two HF impact questionnaires were developed (Assessing Dyspnoea’s Impact on Mobility and Sleep and Heart Failure-Functional Status Assessment), but required refinement to ensure patient understanding.ConclusionsPatient input contributed to the development of a PRO instrument for assessing physical and cognitive symptoms important to patients with HF using novel measurement strategies. Inclusion of daily metrics offers differentiation from other qualified instruments and may provide clinical insight for improving lifestyles. Additionally, two draft PRO measures may, after further validation, be useful to assess the impacts of HF.

Development and content validation of two new patient-reported outcome measures for endometriosis: the Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS)

BackgroundEndometriosis is a common, chronic, impactful condition in women of reproductive age. In the absence of established sensitive and specific biomarkers, disease severity is determined by patient-reported symptoms and impacts. This article details the development of two new patient-reported outcome (PRO) measures designed to assess efficacy endpoints in clinical studies: The Endometriosis Symptom Diary (ESD) and the Endometriosis Impact Scale (EIS).MethodsThe ESD and EIS were developed according to best practice and scientific standards (including the Food and Drug Administration (FDA) PRO Guidance) and with extensive input from women with surgically-confirmed endometriosis. Research included: a review of published qualitative literature; concept elicitation interviews in the US, Germany and France (n = 45) to explore the experiences of women with endometriosis and to inform ESD and EIS development; and cognitive interviews in the US and Germany (n = 31) to assess relevance and understanding of the ESD and EIS and usability of administration using an electronic handheld device. The FDA and the European Medicines Agency (EMA) as well as PRO and clinical experts were consulted throughout the process.ResultsPelvic pain was identified as the most frequent, severe and bothersome symptom for women with endometriosis. Pain was reported to be greatest during menstruation (dysmenorrhea) and during or after sexual intercourse (dyspareunia). Pain resulted in significant impairments in physical activities, work/study, social/leisure activities, household activities and sexual functioning. All women highlighted the emotional impact of endometriosis. Descriptions of pain and associated impacts were largely consistent across participants from the US and Europe, with the most notable differences being the words used to describe the location of pain (e.g., ‘pelvis’ vs. ‘abdomen’). Testing during cognitive interviews indicated that the ESD and EIS were well understood and consistently interpreted. Furthermore, all participants found the ePRO devices easy to use and no issues regarding visual presentation, selection of responses or navigation were identified.ConclusionsEvidence from extensive qualitative research supports the content validity of the ESD and EIS as patient-reported measures of the disease-defining symptoms of endometriosis and the associated impact on women’s lives. Future research will seek to establish the measurement properties of the measures.

The atopic dermatitis itch scale: development of a new measure to assess pruritus in patients with atopic dermatitis

Introduction: Pruritus is the primary symptom of atopic dermatitis (AD). The objective of this study was to develop a patient-reported outcome (PRO) instrument for daily administration in clinical trials to measure AD-related itch in adolescents and adults that would meet the standards described in the US Food and Drug Administration’s (FDA’s) PRO Guidance.Materials and methods: Six focus groups were conducted with 49 patients with AD (32 adults; 17 adolescents). Three iterative rounds of cognitive debriefing interviews were conducted in 26 patients with AD (17 adults; 9 adolescents) to pretest and refine the instrument.Results: AD-related itching was considered the most bothersome AD symptom by nearly two-thirds of the focus group participants. The items in the initial version of the instrument, named the Atopic Dermatitis Itch Scale (ADIS), were developed to reflect concepts most relevant to the assessment of itching as described during the focus groups. Based on results of the cognitive debriefing interviews, an 8-item final version of the ADIS was created.Conclusion: The ADIS is a content valid PRO instrument addressing the concepts critical to the measurement of AD-related itching. To our knowledge, it is the first instrument developed to assess AD-related itch in patients as young as 12 years following the recommendations of the PRO Guidance.