Validation of the Itch Reported Outcome (ItchRO) Diaries in Pediatric Cholestatic Liver Disease

This research will examine the psychometric performance of the electronic diaries for the
itch-reported outcome (ItchRO) measure for both patients and caregivers in a stand-alone
2-week validation study in the target patient population. The study is non-interventional in
nature; the purpose of the study is to validate the ItchRO prior to the analysis of
longitudinal treatment effect data being generated in ongoing clinical trials. Following
training and initial completion of the electronic diaries, families will return home and
complete the diaries twice daily over the course of two weeks. Additional assessments include
the numerical rating scale to assess itching, the patient impression of change (PIC), the
caregiver impression of change (CIC), PedsQL (pediatric quality of life), children's sleep
habits questionnaire (CSHQ), and clinical scratch scale.

Longitudinal data will be used to follow the natural (non-interventional) course of the
disease and the quality of the data. Test-retest reliability will be assessed using diary
data from Day 1 to Day 14 in stable subjects as measured by the PIC for the child-completed
measure and the CIC for the caregiver measure. Convergent validity (correlations between the
ItchRO and similar concepts on the other measures included in the study) will also be
explored (such as the correlation between sleep and morning ItchRO diary scores). Clinical
validity (correlation between the ItchRO and clinician reports) and preliminary
responsiveness of those who changed in their itching status over the two week period will
also be assessed if sample sizes allow.

Inclusion Criteria for subjects with ALGS or PFIC

1. The subject has voluntarily provided verbal assent or written assent in accordance
with the site's Institutional Review Board (IRB) guidelines;

2. The subject's legal guardian has voluntarily provided permission for study
participation and authorization for access to personal health information in
conjunction with HIPPA;

3. The subject has a diagnosis of ALGS or PFIC;

4. The subject is able to speak and comprehend US English (applicable only for children
age 5 and older);

5. The subject is willing and able to participate in the two-week validation study
(applicable only for children age 5 and older); and

6. The subject is able to understand the nature, scope, and possible consequences of the
study, and/or does not present evidence of an uncooperative attitude (applicable only
for children age 5 and older).

Inclusion Criteria for caregivers of subjects with ALGS or PFIC:

1. The caregiver voluntarily provided written informed consent;

2. The caregiver is 18 years of age or older;

3. The caregiver has served as a consistent caregiver for the subject with ALGS or PFIC;

4. The caregiver's child or subject with ALGS or PFIC meets all of the study inclusion
criteria for subjects with ALGS or PFIC;

5. The caregiver is able to speak, read, write, and comprehend US English;

6. The caregiver is willing and able to participate in the two-week validation study; and

7. The caregiver is able to understand the nature, scope, and possible consequences of
the study, and/or does not present evidence of an uncooperative attitude.