Assessing Itch Severity: Content Validity and Psychometric Properties of a Patient-Reported Pruritus Numeric Rating Scale in Atopic Dermatitis.

BACKGROUND: Pruritus, or itch, is a key symptom of atopic dermatitis (AD); as such, mitigating itch is an important outcome of AD treatment. This study explored the content validity and measurement properties of the Pruritus Numeric Rating Scale (Pruritus NRS), a novel single-item scale for assessing itch severity in clinical trials of AD treatments. METHODS: In this mixed-methods study, qualitative interviews were conducted with 21 people with moderate-to-severe AD (n = 15 adult, n = 6 adolescent) to develop a conceptual model of the patient experience in AD and explore the content validity of the Pruritus NRS. Data collected daily from adults with moderate-to-severe AD enrolled in a phase 2b study (NCT03443024) were used to assess the Pruritus NRS' psychometric performance, including reliability, construct validity, and responsiveness. Meaningful within-patient change (MWPC) thresholds were also determined using anchor-based methods. RESULTS: Qualitative findings highlighted the importance of itch in AD, including severity, persistence, frequency, and daily life interference. Patient debriefing of the Pruritus NRS indicated that the scale was relevant, appropriate, and interpreted as intended. Trial data supported overall good psychometric properties. MWPC was defined as a 3-point improvement in Pruritus NRS score, a finding supported by qualitative data. CONCLUSIONS: The Pruritus NRS provides a valid and reliable patient-reported measure of itching severity in patients with moderate-to-severe AD, and can detect change, indicating it is fit-for-purpose to evaluate the efficacy of AD treatments in this population. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03443024.

The Patient and Clinician Assessment of Gastrointestinal (GI) Related Adverse Events Associated with Oral Disease-Modifying Therapies in Multiple Sclerosis: A Qualitative Study.

INTRODUCTION: Current guidelines for relapsing-remitting multiple sclerosis (RRMS) call for treatment with disease-modifying therapies (DMTs) early in the disease to prevent relapses and accumulation of neurologic impairment and disability. However, patients taking certain oral DMTs may experience gastrointestinal (GI)-related adverse events (AEs), particularly at dose titration. We conducted qualitative research with healthcare professionals (HCPs) and patients in Canada to contextualize their experiences with three oral DMTs: dimethyl fumarate (Tecfidera®), fingolimod (Gilenya®), and teriflunomide (Aubagio®). The objectives of this study were to (1) gather qualitative data to better understand the patient and HCP experience of GI AEs in oral MS DMT treatment in Canada and (2) determine to what extent two patient-reported outcome (PRO) instruments used in recent oral DMT trials capture what is important to patients regarding GI AEs in oral MS DMT treatment (content validity) and to provide qualitative data to help interpret PRO scores. METHODS: This was a qualitative, non-interventional, descriptive, cross-sectional study comprising HCP and patient interviews conducted in English and French, using a 1:1 semi-structured interview approach. RESULTS: Patients reported 16 unique GI AE concepts related to oral DMTs. The most commonly reported symptoms were diarrhea, indigestion, and nausea. While patients acknowledged the negative impact associated with GI-related AEs, most characterized the treatment experience as positive, focusing on preference for oral administration, perceived efficacy of DMTs in terms of lack of MS relapses, slowed progression of their disease, and improvement in MS symptoms. Results supported the content validity (relevance, comprehension, and comprehensiveness) of the two PROs assessed. HCP feedback reinforced patient perspectives on both GI concepts and the two PRO instruments. CONCLUSION: Outcomes of these research activities include experiential data on the symptom and impact experience of oral DMTs in MS from both patients and HCPs that contribute to the process of determining therapeutic value.

The Patient Experience of Fatigue in Systemic Lupus Erythematosus: A Conceptual Model.

INTRODUCTION: Fatigue is frequently experienced in systemic lupus erythematosus (SLE) and is a key outcome in clinical research trials. However, SLE fatigue is complex and poorly understood, and challenging to measure. We aimed to characterise fatigue from the patients' perspective and develop a conceptual model of fatigue based on qualitative interviews. METHODS: We conducted semi-structured qualitative interviews exploring fatigue in patients with SLE recruited from a social network (n = 29) and a phase 2 clinical study (n = 43). Transcripts were coded thematically, and codes were inductively categorised into a conceptual model. RESULTS: Fatigue was the most commonly reported symptom in the interviews and generated a wide range of codes. From these, our concept-driven approach revealed three overarching domains of the fatigue experienced in SLE: (i) physical manifestation of physical and bodily symptoms (including physical energy, stamina and impact on movement); (ii) mental and cognitive manifestation (including mental energy, motivation, and cognitive functioning symptoms); and (iii) susceptibility to fatigue or how easily 'fatigable' patients are, meaning how easily they become fatigued and how easily their fatigue is alleviated (including the rapid, disproportionate, and/or unpredictable onset of fatigue, non-restorative sleep, and need for more sleep/rest breaks). Within each of these, participants described the severity, variation and impact of fatigue on everyday life. Participants also described how the SLE fatigue experience differed from 'everyday tiredness'. CONCLUSIONS: The findings of this research indicate that comprehensive measurement of fatigue in SLE will require consideration and quantification of the three domains described in our conceptual model. Future research will explore whether this conceptual model can form the basis of a valid and reliable measurement of fatigue in SLE.

Development and psychometric evaluation of the assessment of self-injection questionnaire: an adaptation of the self-injection assessment questionnaire.

BACKGROUND: Patient-reported outcome (PRO) instruments provide robust and effective means of evaluating patients' treatment experience; however, none adequately cover experience using self-injection devices with enhanced features, such as an electromechanical autoinjector (e-Device). The aim of this study was to develop a PRO instrument that accurately assesses patient experience of using an e-Device and to evaluate its psychometric properties. METHODS: A mixed-methods approach was taken; two parallel, targeted literature reviews were conducted to identify relevant concepts and existing self-injection PRO instruments that could be adapted. Patient feedback obtained from two focus groups was used to inform initial instrument development. The pilot instrument was then administered in a multicenter, open-label, phase 3 clinical study in which patients self-injected certolizumab pegol using an e-Device, to gather evidence of its psychometric qualities. Exit interviews were conducted with a sub-sample of patients enrolled in the study to confirm the appropriateness and clarity of the items included and cognitively debrief the instrument. Confirmatory factor analysis (CFA) was conducted on all items, and each domain's internal consistency was measured using Cronbach's ɑ. RESULTS: The literature searches identified several e-Device-specific concepts related to device features, device function, side effects/reactions/pain, confidence, and interference/convenience in daily life. Seven existing PRO instruments were identified. The Self-Injection Assessment Questionnaire (SIAQ), containing pre- and post-injection questionnaire modules, was selected as most suitable and adapted using feedback from 19 patients in the two focus groups to form the pilot Assessment of Self-Injection (ASI) questionnaire. CFA resulted in some changes to the grouping of items in the post-injection module domains following psychometric evaluation of the ASI. Internal consistency was satisfactory for all pre- and post-injection domains (ɑ > 0.8). Cognitive debriefing results from 12 patient exit interviews confirmed the ASI's appropriateness and clarity. CONCLUSIONS: The ASI was developed iteratively with patient input and was evaluated in its intended clinical context of use. Psychometric analyses indicated promising cross-sectional results; the ASI was well understood and considered relevant by patients self-injecting using the e-Device, suggesting that it could be used in real-world settings to aid with clinical decision making. TRIAL REGISTRATION: NCT03357471.

A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.

BACKGROUND: Novel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use. METHODS: Our mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30. RESULTS: Unique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context. CONCLUSION: Supplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning.

Development of a gait module to complement the 12-item Multiple Sclerosis Walking Scale: a mixed methods study.

BACKGROUND AND OBJECTIVE: The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome instrument that quantifies the progressive loss of walking ability from the patient perspective. However, previous psychometric analyses indicated floor and ceiling effects across the multiple sclerosis severity spectrum. This study aimed to address floor effects by creating a gait module that can be used in conjunction with the MSWS-12 for better measurement of treatment benefit in the higher functioning multiple sclerosis population. METHODS: We used a step-wise mixed methods study design, with relapsing-remitting multiple sclerosis patients (wave 1, n=88; wave 2, n=30), combining qualitative (concept elicitation and cognitive debriefing interviews) and quantitative (Rasch Measurement Theory) data collection and analytical techniques and consultation interviews with three neurologists specializing in multiple sclerosis. RESULTS: Thirty-seven walking ability concepts were identified, and a five-domain conceptual framework was created. Draft items were generated and refined with patient and neurologist input. Draft items covered gait-related concepts such as dragging, shuffling, limping, tripping and falling. Rasch measurement theory psychometric analysis indicated administering MSWS-12 plus gait items improved measurement precision in targeted populations with better walking ability. CONCLUSION: Study findings indicate that new gait items could improve sensitivity to detect clinical change in walking ability for higher functioning multiple sclerosis patients.

Patient Perspective on Acute Intermittent Porphyria with Frequent Attacks: A Disease with Intermittent and Chronic Manifestations.

OBJECTIVE: Acute intermittent porphyria is a rare metabolic disorder that affects heme synthesis. Patients with acute intermittent porphyria may experience acute debilitating neurovisceral attacks that require frequent hospitalizations and negatively impact quality of life. Although clinical aspects of acute intermittent porphyria attacks have been documented, the experience of patients is not well known, particularly for those more severely affected patients who experience frequent attacks. The aim of the present study was to qualitatively characterize the experience of patients with acute intermittent porphyria who have frequent attacks, as well as the impact of the disease on daily living. METHODS: Patients with acute intermittent porphyria who experience frequent attacks were recruited and took part in 2-h qualitative one-on-one interviews with a semi-structured guide. Interviews were anonymized, transcribed, and coded. The inductive coding approach targeted textual data related to acute intermittent porphyria attack symptoms, chronic symptoms, and the impact of the disease. Saturation analysis was conducted to assess whether the research elicited an adequate account of patients' experiences. RESULTS: In total, 19 patients with acute intermittent porphyria were interviewed (mean age 40 years; 79% female). Eighteen patients (95%) experienced both attack and chronic symptoms. Patients described attacks as the onset of unmanageable symptoms that generally lasted 3-5 days requiring hospitalization and/or treatment. Pain, nausea, and vomiting were considered key attack symptoms; pain, nausea, fatigue, and aspects of neuropathy (e.g., tingling and numbness) were considered key chronic symptoms. CONCLUSIONS: In this study population of acute intermittent porphyria with frequent attacks, most patients had symptoms during and between attacks. In these patients, acute intermittent porphyria appears to have acute exacerbations as well as chronic day-to-day manifestations, and is not just intermittent as its name implies. As a result, patients reported limitations in their ability to function across multiple domains of their lives on a regular basis and not just during acute attacks.

Addressing the targeting range of the ABILHAND-56 in relapsing-remitting multiple sclerosis: A mixed methods psychometric study.

BACKGROUND: ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients. OBJECTIVE: The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients. METHODS: A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis. RESULTS: Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items. CONCLUSION: The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.