Development of the Scalp Hair Assessment PRO™ measure for alopecia areata.

BACKGROUND: Valid patient-reported outcome (PRO) measures are required to evaluate alopecia areata (AA) treatments. OBJECTIVES: To develop a content-valid and clinically meaningful PRO measure to assess AA scalp hair loss with scores comparable with the five-response-level Alopecia Areata Investigator Global Assessment (AA-IGA™). METHODS: A draft PRO measure was developed based on input from 10 clinical experts in AA. The PRO measure was cognitively debriefed, modified and finalized through two rounds of qualitative semistructured interviews with patients with AA who had experienced ≥ 50% scalp hair loss. Data were thematically analysed. RESULTS: Adults (round 1: n = 25; round 2: n = 15) and adolescents aged 15-17 years (round 1: n = 5) in North America participated. All patients named scalp hair loss as a key AA sign or symptom. Patients demonstrated the ability to self-report their current amount of scalp hair using percentages. In round 1 not all patients interpreted the measurement concept consistently; therefore, the PRO was modified to clarify the measurement concept to improve usability. Following modifications, patients in round 2 responded without difficulty to the PRO measure. Patients confirmed that they could use the five-level response scale to rate their scalp hair loss: no missing hair, 0%; limited, 1-20%; moderate, 21-49%; large, 50-94%; nearly all or all, 95-100%. Almost all patients deemed hair regrowth resulting in ≤ 20% scalp hair loss a treatment success. CONCLUSIONS: The Scalp Hair Assessment PRO™ is a content-valid, clinically meaningful assessment of distinct gradations of scalp hair loss for evaluating AA treatment for patients with ≥ 50% hair loss at baseline.

The Alopecia Areata Investigator Global Assessment scale: a measure for evaluating clinically meaningful success in clinical trials.

BACKGROUND: Content-valid and clinically meaningful instruments are required to evaluate outcomes of therapeutic interventions in alopecia areata (AA). OBJECTIVES: To develop an Investigator's Global Assessment (IGA) to interpret treatment response in AA treatment studies. METHODS: Qualitative interviews were conducted in the USA with expert dermatologists and with patients with AA who had experienced ≥ 50% scalp-hair loss. Thematic data analysis identified critical outcomes and evaluated the content validity of the new IGA. RESULTS: Expert clinicians (n = 10) judged AA treatment success by the amount of scalp-hair growth (median 80% scalp hair). Adult (n = 25) and adolescent (n = 5) patients participated. Scalp-hair loss was the most bothersome AA sign/symptom for most patients. Perceived treatment success - short of 100% scalp hair - was the presence of ~ 70-90% scalp hair (median 80%). Using additional clinician and patient insights, the Alopecia Areata Investigator Global Assessment (AA-IGA™) was developed. This clinician-reported outcome assessment is an ordinal, static measure comprising five severity categories of scalp-hair loss. Nearly all clinicians and patients in this study agreed that, for patients with ≥ 50% scalp-hair loss, successful treatment would be hair regrowth resulting in ≤ 20% scalp-hair loss. CONCLUSIONS: We recommend using the Severity of Alopecia Tool to assess the extent (0-100%) of scalp-hair loss. The AA-IGA is a robust ordinal measure providing distinct and clinically meaningful gradations of scalp-hair loss that reflects patients' and expert clinicians' perspectives and treatment expectations. What is already known about this topic? The Severity of Alopecia Tool is widely used to assess the extent of scalp-hair loss in patients with alopecia areata. Guidelines define treatment success as a 50% improvement in scalp hair, and clinical trials have used dynamic thresholds of 50% and 90%. However, there is no clinical consensus on these endpoints, and patient perspectives on treatment success are unknown. What does this study add? Through qualitative interviews with 10 expert dermatologists and 30 patients with alopecia areata who had experienced ≥ 50% scalp-hair loss, we developed the Alopecia Areata Investigator Global Assessment (AA-IGA™) to measure five clinically meaningful gradations of alopecia areata scalp-hair loss that reflects patients' and clinicians' perspectives and expectations of treatment success in alopecia areata treatment studies. What are the clinical implications of this work? The AA-IGA is a robust ordinal measure that can inform clinical evaluation of alopecia areata treatment outcomes. The AA-IGA can be used to determine clinically meaningful treatment success for alopecia areata, with success defined by patients and clinicians as reaching ≤ 20% scalp-hair loss. Linked Comment: Blome. Br J Dermatol 2020; 183:609.

Patient-reported outcome measures in psoriasis: the good, the bad and the missing!

As a long-term condition, psoriasis demands significant personal and professional input for optimal self-management. Low levels of well-being and high levels of psychological distress in patients with psoriasis are associated with reduced resources for self-care. Patient-reported outcome (PRO) measures can be used to assess physical, social and psychological functioning in order to guide treatment. In this article, we systematically reviewed the development and validation of existing PRO measures. PubMed (Medline), PsycINFO and CINAHL were searched systematically using predefined search terms. The search was limited to articles in the English language relating to human subjects. Articles were selected for full review through explicit inclusion/exclusion criteria. PRO measures were critically reviewed in accordance with the published guidelines and theory on the development and validation of PROs. The search identified 967 abstracts; 71 of these articles met the criteria for full review. In these 71 articles, 45 PRO measures were found: 16 were specific to psoriasis, 21 assessed other dermatological conditions and eight were developed for generic nondermatological health conditions. The review revealed several limitations of the existing measures, including: (i) a composite structure assessing multiple, poorly-defined concepts; (ii) a lack of evidence for face and content validity; (iii) a failure to include both patient and clinician perspectives and requirements and (iv) a lack of evidence regarding the feasibility and acceptability for patients and physicians. No single PRO measure with adequate evidence of validity, reliability and sensitivity to change captures patient well-being in psoriasis. A valid, sensitive, specific and acceptable PRO that assesses the full impact of psoriasis on well-being is needed for the comprehensive clinical management of psoriasis.

Oncology patient-reported claims: maximising the chance for success.

OBJECTIVES/PURPOSE: To review Patient Reported Outcome (PRO) labelling claims achieved in oncology in Europe and in the United States and consider the benefits, and challenges faced. METHODS: PROLabels database was searched to identify oncology products with PRO labelling approved in Europe since 1995 or in the United States since 1998. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) websites and guidance documents were reviewed. PUBMED was searched for articles on PRO claims in oncology. RESULTS: Among all oncology products approved, 22 were identified with PRO claims; 10 in the United States, 7 in Europe, and 5 in both. The language used in the labelling was limited to benefit (e.g. "…resulted in symptom benefits by significantly prolonging time to deterioration in cough, dyspnoea, and pain, versus placebo") and equivalence (e.g. "no statistical differences were observed between treatment groups for global QoL"). Seven products used a validated HRQoL tool; two used symptom tools; two used both; seven used single-item symptom measures (one was unknown). The following emerged as likely reasons for success: ensuring systematic PRO data collection; clear rationale for pre-specified endpoints; adequately powered trials to detect differences and clinically significant changes; adjusting for multiplicity; developing an a priori statistical analysis plan including primary and subgroup analyses, dealing with missing data, pooling multiple-site data; establishing clinical versus statistical significance; interpreting failure to detect change. End-stage patient drop-out rates and cessation of trials due to exceptional therapeutic benefit pose significant challenges to demonstrating treatment PRO improvement. CONCLUSIONS: PRO labelling claims demonstrate treatment impact and the trade-off between efficacy and side effects ultimately facilitating product differentiation. Reliable and valid instruments specific to the desired language, claim, and target population are required. Practical considerations include rationale for study endpoints, transparency in assumptions, and attention to subtle variations in data.

Familial allergic rhinitis in cattle.

A group of Angus X Holstein cattle were determined to have allergic rhinitis. Clinical signs included nasal discharge, tearing, sneezing, and nasal pruritus. The diagnosis was made on the basis of intradermal skin testing of affected and clinically normal cattle. The affected cattle had positive test results to various tree, grass, weed, and mold allergens. The clinical signs and seasonal occurrence were similar to those features for allergic rhinitis in man. Breeding data indicated an inherited mode of transmission, although only females were affected.

Crystalline inclusions in erythrocytes parasitized with Babesia equi following treatment of ponies with imidocarb.

Four splenectomized Welsh ponies were infected with Babesia equi. Two ponies were treated with imidocarb dipropionate, and two were not treated. By light microscopic examination, 1% to 2% of the parasitized erythrocytes of treated ponies contained crystalline inclusions. The crystals were rectangular, diamond, or burr shaped. They occupied most of the erythrocytic cytoplasm, and, as a result, the remainder of the pale staining cytoplasm was inconspicuous in Wright-Giemsa-stained blood smears. The size and shape of intraerythrocytic inclusions varied when examined by electron microscopy, but in most instances they were either adhered to or were located close to the parasite. The sides of crystals were either smooth or serrated, and corners were either sharp or notched. Fractures or faults were common in large crystals. Parasitized erythrocytes of nontreated ponies and nonparasitized erythrocytes of treated ponies did not contain crystals. Four hemoglobulin types were identified in five noninfected, nontreated Welsh ponies from the same herd.

Ontogeny of equine haemoglobins.

Studies were made of the O2 affinities of fetal and maternal haemoglobins in the horse, and correlations were found with erythrocytic levels of 2,3-diphosphoglycerate.

Dermatophilosis in two polar bears.

Dermatophilosis was diagnosed in 2 of 13 captive polar bears (Thalarctos maritimus), causing generalized dermatitis of 3 years' and 6 months' duration, respectively. Progressive clinical signs included yellowing and darkening of the hair, pruritus, encrustation of skin, and reluctance to bathe. Dramatic resolution of lesions occurred during 8 weeks of twice-weekly intramuscular treatment with long-acting penicillin.