Evaluating clinical treatment effects

Patients with NPC usually undergo long series of diagnostic tests and monitoring procedures throughout the course of disease. However, with the possibility of new methods of treatment comes the requirement for a rational evaluation of outcomes, allowing full assessments of treatment efficacy and safety. Therapeutic outcomes can be either qualitative or quantitative, based on their derivation and on how directly they reflect disease progression. Table 6 lists possible key parameters for determining treatment effectiveness in past and future NPC trials.

Table 6. Key parameters for establishing treatment outcomes in NPC
Quantitative measuresDetail
Saccade eye movement velocity A specialised ophthalmic assessment based on video-recorded eye movement and subsequent computerised measurements of peak velocity, amplitude and duration of vertical and / or horizontal saccadic eye movements.1 In particular, peak velocity has been shown to be far lower in patients with NPC compared with controls2
Kinematic analysis Motoric control / impairment can be assessed using a variety of electrophysiologic parameters: accelerometry allows the measurement of tremor amplitude and frequency, and surface electromyography (sEMG) can monitor for abnormal patterns consistent with various movement disorders3
Ambulatory index Evaluations of ambulation and gait can be performed using quantitative, categorical scales. A recent study evaluated patients across a range of scores from zero (asymptomatic or fully active) through 4 (requires unilateral support such as a cane or single crutch to walk > 80% of the time and walks 25 feet in 20 seconds) to 9 (restriction to wheelchair and unable to transfer independently)
Cognitive testing Multiple cognitive deficits, often categorised collectively as dementia, occur as NPC progresses. The mini mental-status examination (MMSE) – a generic measure quantifying cognition across a wide range of domains including orientation, recall, verbal and written comments, writing and drawing – has been established as an appropriate measure for use in children and may therefore be particularly useful in NPC4,5
Qualitative measures
Quality of life (QoL) QoL is an important measure of therapeutic outcome in NPC, where there is invariably a substantial impact on quality of life for the whole family. There are no specifi c measures for QoL related to NPC, but a number of widely used and well validated generic measures are available, including the Short-Form 36-item QoL questionnaire (SF-36)6
Swallowing Radiological videofluoroscopic (VFS) analysis of liquid barium swallowing can be used effectively to monitor treatment effects on swallowing ability and progression of dysphagia. Systematic evaluations can be achieved by sequential analyses using a sensitive and specifi c scoring system to assess all phases of the swallowing motion7,8

1. Garbutt S, Harwood MR, Harris CM. Comparison of the main sequence of refl exive saccades and the quick phases of optokinetic nystagmus. Br J Ophthalmol 2001;85:1477–83.
2. Rottach KG, von Maydell RD, Das VE et al. Evidence for independent feedback control of horizontal and vertical saccades from Niemann–Pick type C disease. Vision Res 1997;37:3627–38.
3. Floyd AG, Yu QP, Piboolnurak P et al. Kinematic analysis of motor dysfunction in Niemann–Pick type C. Clin Neurophysiol 2007;118:1010–8.
4. Jain M, Passi GR. Assessment of a modifi ed Mini-Mental Scale for cognitive functions in children. Indian Pediatr 2005;42:907–12.
5. Ouvrier RA, Goldsmith RF, Ouvrier S, Williams IC. The value of the Mini-Mental State Examination in childhood: a preliminary study. J Child Neurol 1993;8:145–8.
6. Ware JE, Sherbourne CD. The MOS 36–item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473–83.
7. Chien YH, Lee NC, Tsai LK et al. Treatment of Niemann–Pick disease type C in two children with miglustat:Initial responses and maintenance of effects over 1 year. J Inherit Metab Dis 2007, June 21; [Epub ahead ofprint].
8. Han TR, Paik NJ, Park JW. Quantifying swallowing function after stroke: A functional dysphagia scale based on videofl uoroscopic studies. Arch Phys Med Rehabil 2001;82:677–82.

© 2007 Blackwell Publishing Limited. Reproduced by permission.

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