Journal of Neurology (2018) 265:1443–1453
Agreement between clinician‑rated versus patient‑reported outcomes
in Huntington disease
Noelle E. Carlozzi
· Nicholas R. Boileau
· Joel S. Perlmutter
· Kelvin L. Chou
· Julie C. Stout
· Jane S. Paulsen
Michael K. McCormack
· David Cella
· Martha A. Nance
· Jin‑Shei Lai
· Praveen Dayalu
Received: 20 November 2017 / Revised: 27 March 2018 / Accepted: 29 March 2018 / Published online: 23 April 2018
© Springer-Verlag GmbH Germany, part of Springer Nature 2018
Background Clinician-rated measures of functioning are often used as primary endpoints in clinical trials and other behavio-
ral research in Huntington disease. As study costs for clinician-rated assessments are not always feasible, there is a question
of whether patient self-report of commonly used clinician-rated measures may serve as acceptable alternatives in low risk
Aim The purpose of this paper was to determine the level of agreement between self-report and clinician-ratings of com-
monly used functional assessment measures in Huntington disease.
Design 486 participants with premanifest or manifest Huntington disease were examined. Total Functional Capacity, Func-
tional Assessment, and Independence Scale assessments from the Uniﬁed Huntington Disease Rating scale were completed
by clinicians; a self-report version was also completed by individuals with Huntington disease. Cronbach’s α was used to
examine internal consistency, one-way analysis of variance was used to examine group diﬀerences, and paired t tests, kappa
agreement coeﬃcients, and intra-class correlations were calculated to determine agreement between raters.
Results Internal consistency for self-reported ratings of functional capacity and ability were good. There were signiﬁcant
diﬀerences between those with premanifest, early-, and late-stage disease; those with later-stage disease reported less abil-
ity and independence than the other clinical groups. Although self-report ratings were not a perfect match with associated
clinician-rated measures, diﬀerences were small. Cutoﬀs for achieving speciﬁed levels of agreement are provided.
Conclusions Depending on the acceptable margin of error in a study, self-reported administration of these functional assess-
ments may be appropriate when clinician-related assessments are not feasible.
Keywords Huntington disease · Functioning · Clinician-ratings · Self-report ratings
Huntington disease (HD) is an autosomal dominant inher-
ited, progressive neurodegenerative disorder that causes
profound cognitive, behavioral, and motor decline [1, 2].
The disease often manifests near age 40 and leads to death
in 15–20 years [1, 3, 4]. Patients lose function in many areas,
including occupational, social, ﬁnancial, and activities of
daily living [5–7]. Slowing functional loss is a major unmet
need, and a prime goal of HD clinical trials [8, 9]. These tri-
als require functional rating scales that, in some cases, may
act as a primary endpoint [5, 10].
The Uniﬁed Huntington’s Disease Rating Scale (UHDRS)
is the most widely used assessment in clinical HD research
. The UHDRS includes clinician-rated assessments of
functioning, motor symptoms, and cognition. With regard
to the UHDRS functional assessments it includes: the Total
Functional Capacity (TFC), the Functional Assessment (FA)
Scale, and the Independence Scale [11, 12]. The TFC in par-
ticular is a frequently used as a primary outcome measure,
e.g., [13–15]. The entire UHDRS, including these scales,
was designed and validated as a clinician-rated instrument
. The clinician completes the scales after focused inter-
views with the aﬀect individual and/or a close informant.
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s0041 5-018-8852-5) contains
supplementary material, which is available to authorized users.
* Noelle E. Carlozzi
Extended author information available on the last page of the article