Clinical outcomes: Rating scales

Clinical Outcomes: Rating Scales

HD is a multifaceted disorder affecting cognitive, behavioral and motor function, all of which play a role in functional disability, and the successful development of therapeutic interventions for HD will require novel, sensitive clinical assessments. CHDI, in collaboration with external consultants, provides recommendations on existing HD assessments after evaluation of their clinimetric and psychometric properties and, when necessary, collaborates to develop new or modified clinical assessments adhering to FDA/EMA guidance. In recent years we have developed the Huntington’s Disease – Cognitive Assessment Battery (HD-CAB) in collaboration with Julie Stout of Monash University (Stout JC et al., 2014). We are also currently developing a self-report functional rating scale, the Functional Rating Scale Taskforce 2.0 (FuRST 2.0), with our collaborators Glenn Stebbins, Sheng Luo, and Nancy LaPelle, which is designed to be more sensitive in premanifest and early manifest HD stages than current functional assessments. Further scale reviews and scale development are underway.

Frequently Asked Questions

Which rating scales are used most frequently in HD?

Please see this systematic review of outcome measures used in HD research. The Unified Huntington’s Disease Rating Scale (UHDRS) was enhanced in 1999 and again in 2005 and is one of the most widely used rating scales.

Which rating scales are used currently in Enroll-HD?

Enroll-HD launched in 2012 and collects longitudinal clinical data and biosamples to accelerate the development of new therapeutics for HD. See the Enroll-HD protocol (page 11) for a list of the rating scales used in the study.

 What information is available regarding rating scales in HD and their evaluation?

The National Institute of Neurological Disorders and Stroke (NINDS) provides a list of many of the HD rating scales. Also, the Movement Disorder Society Committee on Rating Scale Development has evaluated 27 HD rating scales to measure behavioral systems and provides recommendations, as well as a list of approved and recommended rating scales for movement disorders.

 What will be the outcome of your current rating scale evaluations?

CHDI and colleagues are currently evaluating the assessments used in Enroll-HD to determine whether there are floor and ceiling effects, whether they adequately cover all stages of HD progression, and to test the validity of these assessments in HD gene expansion carriers. Subsequently, development and/or adoption of alternative assessments may be considered.

When will the FuRST 2.0 be available to the HD research community?

We expect to be able to offer a content valid functional rating scale in 2019.

When will the FuRST 2.0 be validated?

We expect the completion of a validation study in 2020 at which time the scale will be fit for the purpose of evaluating functional outcomes in the premanifest and early manifest HD.

What is the validation process for the HD-CAB?

We are following the FDA guidance for the qualification of Clinical Outcome Assessments (COAs). We are currently at the stage of Longitudinal Evaluation of Measurement Properties/ Interpretation Methods. We evaluated 16 cognitive assessments and selected 6 of them based on sensitivity, reduced practice effects, reliability, domain coverage, feasibility, and tolerability that now comprise the HD-CAB.

Selected reading

  • Carlozzi NE & Tulsky DS. Identification of health-related quality of life (HRQOL) issues relevant to individuals with Huntington disease.  Health Psychol.(2013) 18:212
  • Craufurd D et al. Behavioral changes in Huntington disease. Cogn Behav Neurol.(2001) 14:219
  • Hocaoglu MB et al. The Huntington’s Disease health‐related Quality of Life questionnaire (HDQoL): a disease‐specific measure of health‐related quality of life. Clin Genet.(2012) 81:117
  • Kingma EM et al. Behavioural problems in Huntington’s disease using the Problem Behaviours Assessment. Gen Hosp Psychiatry.(2008) 30:155
  • Unified Huntington’s disease rating scale: reliability and consistency. Mov Disord.(1996) 11:136
  • Schneider L et al. Validity and reliability of the Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change. Alzheimer Dis Assoc Disord. (1997) 11:S22
  • Snaith RP et al. A clinical scale for the self-assessment of irritability. Br J Psychiatry.(1978) 132:164
  • Stout JC et al. HD‐CAB: A cognitive assessment battery for clinical trials in Huntington’s disease. Mov Disord.(2014) 29:1281
  • Zigmond AS & Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. (1983) 67:361