Development, validation and interpretation of the PROMIS Itch Questionnaire

Jonathan I. Silverberg, M.D., Ph.D., M.P.H.1, Jin-Shei Lai, Ph.D., David Cella, Ph.D.

1. Director, Eczema Center and Contact Dermatitis Clinic, Northwestern MedicineAssociate Professor, Departments of Dermatology, Preventive Medicine and Medical Social

SciencesNorthwestern University Feinberg School of Medicine

Chicago, IL USA

Jonathan Silverberg Consultant or advisory board for Abbvie, AnaptysBio, Asana, Arena, Boehringer-

Ingelheim, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa, Leo, Menlo, Novartis, Pfizer, Regeneron-Sanofi, Realm

Speaker for Regeneron-Sanofi

Jin-Shei Lai Nothing to disclose

David Cella Consultant for Galderma, Grant funding from Foamix

Itch is associated with significant impairment of health related quality of life (HRQoL), including: inability to carry out every day physical activities difficulties with social activities and relationships higher rates of sleep disturbances, depressed mood and anhedonia

There are no well-accepted biomarkers or objective tests for itch.

Patient-reported outcome measures (PROMs) are more practical and widely used to quantify itch severity and are essential for characterizing patient burden.

Current PROMs: may not capture the full extent of the patient-burden from itch suffer from limited or undocumented content validity,

structural validity or cross-cultural validity

Developing comprehensive, efficient and valid tools to assess the burden of itch in clinical care and research is a high priority.

Develop a valid patient-centered itch measurement suite using

mixed-method approaches

A systematic literature review Qualitative semi-structured interviews Binning and winnowing Initial item writing Cognitive debriefing Development of a conceptual model Item bank calibration by using IRT analyses

There were 366 distinct items extracted from original studies and previous itch assessments.

There were 1,669 distinct items extracted from review articles.

There was significant discord between the sequela of itch reported in clinical reviews compared with original research articles.

Kantor R/Dalal P, Cella D, Silverberg JI. Impact of pruritus on quality of life: A systematic review. Journal of the American Academy of Dermatology. 2016 Nov;75(5):885-886.

Silverberg JI, Kantor RW, Dalal P, Hickey C, Shaunfield S, Kaiser K, Lai JS, Cella D. A comprehensive conceptual model of the experience of chronic itch in adults. American Journal of Clinical Dermatology. 2018. 19(5):759-769.

Open-ended interviews (n=33) FreqAtopic dermatitis / Atopic eczema 4Prurigo nodularis – atopic variant 1Lichen simplex chronicus 1Contact dermatitis 3Mycosis fungoides / cutaneous T cell lymphoma 10Sezary syndrome 1Chronic urticaria 1Systemic sclerosis 4CREST syndrome 1Morphea 1Lamellar ichthyosis 3Generalized idiopathic pruritus 1Chronic renal failure 3

Silverberg JI, Kantor RW, Dalal P, Hickey C, Shaunfield S, Kaiser K, Lai JS, Cella D. A comprehensive conceptual model of the experience of chronic itch in adults. American Journal of Clinical Dermatology. 2018. 19(5):759-769.

Silverberg JI, Kantor RW, Dalal P, Hickey C, Shaunfield S, Kaiser K, Lai JS, Cella D. A comprehensive conceptual model of the experience of chronic itch in adults. American Journal of Clinical Dermatology. 2018. 19(5):759-769.

Probing cognitive interviews (n=12)

Freq

Angioedemia / Chronic urticaria

1

Nummular eczema 1Atopic dermatitis / Atopic eczema

7

Contact dermatitis 1Mycosis fungoides / CTCL

1

Generalized idiopathic pruritus

1

Lamellar ichthyosis 2

600 US adults (≥18 years old) with chronic itch. Nationwide internet panel (Op4G) Quotas were set for different itch severities

75 items were tested Numeric rating scales (NRS) for worst and

average itch over the past 7 days (0 [no itch] to10 [worst imaginable itch]).

All participants completed all items.

Characteristic %Female sex 62%Race/ethnicity

Caucasian/white 79%African American/black 9%Hispanic/Latino 7%Asian 2%Multiracial/other 3%

Age18-24 9%25-34 19%35-44 31%45-54 24%55-64 15%65+ 2%

In the past 7 days…Never Rarely Sometimes Often Always

Q64 Because of itch, I was absent from work 1

2

3

4

5

Q65 Because of itch, it was hard to work 1

2

3

4

5

Q56 Because of itch, it was hard to do even simple tasks 1

2

3

4

5

Q54 Because of itch, I made more mistakes than normal 1

2

3

4

5

Q49 Because of itch, it was hard to watch television 1

2

3

4

5

Q48 Because of itch, it was hard to shower or take a bath 1

2

3

4

5

Q67 Because of itch, I avoided being around people 1

2

3

4

5

Item bank

Pearson rItem bank NRS-itch

1 2 3 4Worst

itchAverage

itch1 1.00 0.56 0.602 0.86 1.00 0.65 0.663 0.87 0.84 1.00 0.63 0.654 0.78 0.80 0.73 1.00 0.60 0.62

• There was good convergent validity with moderate tostrong correlations of item bank T-scores with average andpeak numerical rating scale of itch (Pearson correlation,p<0.0001).

Itch severityAUC

Item bank-1 Item bank-2 Item bank-3 Item bank-4Worst itch

Moderate vs. mild 0.66*** 0.76*** 0.72*** 0.72***Severe vs. mild 0.82** 0.92*** 0.87*** 0.85***Severe vs. moderate 0.68*** 0.75*** 0.71*** 0.69***Very severe vs. mild 0.89*** 0.95*** 0.92*** 0.93***Very severe vs. moderate 0.80*** 0.85*** 0.83*** 0.82***Very severe vs. severe 0.66*** 0.70*** 0.70*** 0.69***

Average itchModerate vs. mild 0.67*** 0.74*** 0.72*** 0.73***Severe vs. mild 0.86*** 0.93*** 0.89*** 0.88***Severe vs. moderate 0.74*** 0.77*** 0.78*** 0.73***Very severe vs. mild 0.89*** 0.94*** 0.91*** 0.91***Very severe vs. moderate 0.81*** 0.85*** 0.85*** 0.80***Very severe vs. severe 0.66** 0.69** 0.68** 0.64**

• There was good discriminant validity with itch intensity as judged by analysis of variance and receiveroperator curve (ROC) characteristics

* P < 0.05** P < 0.01*** P < 0.0001

There was very good internal consistency for item-banks 1, 2, 3 and 4(Cronbach’s alpha was 0.98, 0.97, 0.97 and 0.91)

The proportions of respondents with lowest and highest values for itembanks-1 (5.7% or 1.5%), 2 (2.0% or 2.2%), 3 (6.5% or 2.3%) and 4 (5.0% or4.8%) were below 15%, indicating there were no floor or ceiling effects.

Average itchItem bank-1 Item bank-2 Item bank-3 Item bank-4

Thresh Sens Spec Thresh Sens Spec Thresh Sens Spec Thresh Sens SpecMild vs. no itch 46.4 52.2% 100% 44.8 56.1% 75.0% 48.5 58.0% 100% 42.2 36.3% 100%Moderate vs. mild 50.5 58.5% 67.5% 49.7 70.7% 73.2% 49.8 72.8% 65.6% 49.7 67.1% 71.3%Severe vs. moderate 56.5 66.2% 69.9% 56.9 69.1% 72.0% 57.9 63.2% 80.5% 58.1 61.8% 77.6%Very severe vs. severe 62.7 61.4% 70.6% 65.0 59.6% 75.7% 65.3 56.1% 80.9% 63.0 54.4% 71.3%

Scores are reported on a T-score metric, with a T-score of 50 being theaverage score for people with chronic itch drawn from the USpopulation.

Severity thresholds were selected based on maximizing the concordanceprobability in ROC analysis

The PROMIS® Itch Questionnaire (PIQ) consists of 4 item-banks (Itch-interference, mood and sleep, clothing and physical activity andscratching behavior). The PIQ are now available and can be administeredusing

Computerized Adaptive Testing

4-item and 8-item Short-forms

Translations for short-forms available in: French, German, Polish andSpanish

Translations for short-forms soon to be available in: Italian, Japanese,Korean and traditional Chinese

Multiple clinical validation studies are underway or completedwith readouts pending.

One or more item banks have been incorporated into multipleclinical trials of pruritic disorders.

Examine utility of PIQ in clinical practice.

Additional opportunities for collaboration.

Thank youJonathanISilverberg@gmail.com

Confirmatory factor analysis summary.Factor No. of

itemsCFI

(>0.9)TLI

(>0.9)RMSEA (<0.1)

R-square (>0.3)

Residual corr (<0.15)

1. General 28 0.976 0.974 0.09 all >0.3 all <0.1525 0.981 0.98 0.089 all >0.3 all <0.15

2. Mood and sleep 21 0.949 0.944 0.144 all >0.3 all <0.1518 0.953 0.947 0.149 all >0.3 all <0.15

3. Clothing and physical activity

20 0.966 0.962 0.137 all >0.3 Q16 vs. Q17=0.155,Q16 vs. Q18=0.161otherwise, all <0.15

15 0.989 0.987 0.104 all >0.3 all <0.154. Scratching behavior 5 1.000 1.000 0.014 all >0.3 all <0.15