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Clinical Review Report: AbobotulinumtoxinA (Dysport Therapeutic): (Ipsen Biopharmaceuticals Canada, Inc.): Indication: To reduce the subjective symptoms and objective signs of cervical dystonia (spasmodic torticollis) in adults [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Aug.

Cover of Clinical Review Report: AbobotulinumtoxinA (Dysport Therapeutic)

Clinical Review Report: AbobotulinumtoxinA (Dysport Therapeutic): (Ipsen Biopharmaceuticals Canada, Inc.): Indication: To reduce the subjective symptoms and objective signs of cervical dystonia (spasmodic torticollis) in adults [Internet].

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Appendix 5Validity of Outcome Measures

Aim

To summarize the validity of the following outcome measures:

  • Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)
  • Tsui score
  • Visual Analogue Scale (VAS) pain scale and VAS symptom scale
  • Short Form (36) Health Survey (SF-36)
  • Global Efficacy Assessment and Global Safety Assessment for cervical dystonia (CD)

Findings

We conducted a focused literature search for the psychometric properties and minimum clinically important difference (MCID) of each of the stated outcome measures. We retrieved 221 results, only four of which were directly informative. Table 26 summarizes the findings.

Table 26Validity and Minimal Clinically Important Difference of Outcome Measures

InstrumentTypeEvidence of validationMCIDReferences
TWSTRSThree subscales to measure pain, disability, and severityYesUnknownConsky 1994,21
Albanese 2013,42
Consky 1990,
Tarsy 1997 43
Tsui scoreA scale measure of rotation, tilt, sagittal movement, head tremor, and shoulder tdelevationYesUnknownJost 2013,44
Tarsy 1997 43
VAS pain scale and VAS symptom scaleA psychometric response scale used as a measuring instrument for symptom intensityUnknown in cervical dystociaUnknown in cervical dystonia
SF-36A 36-item survey to measure multi-dimensional health concepts and capture a full range of health statesUnknown in cervical dystoniaUnknown in cervical dystonia
Global Efficacy Assessment and Global Safety Assessment for cervical dystoniaInvestigator subjective assessment of change in efficacy on a three-point scale or presence of safety issues on a two-point scaleUnknownUnknown

SF-36 = Short Form (36) Health Survey; MCID = minimal clinically important difference; TWSTRS = Toronto Western Spasmodic Torticollis Rating Scale; VAS = visual analogue scale.

Toronto Western Spasmodic Torticollis Rating Scale

Developed in the early 1990s, TWSTRS is a composite scale used to measure three aspects of CD: severity, disability, and pain. TWSTRS total score falls within the range of 0 to 85, where a higher score indicates a more severe condition.44

Torticollis Severity Scale (maximum subtotal score 35)

The severity subscore is a maximum of 35 and consists of 11 items scored on scales ranging from either 0 to 1, 0 to 3, 0 to 4, or 0 to 5, also emphasizing the duration of the symptoms by weighting them with a factor of 2.

  1. Maximal Excursion
    1. Rotation, score range 0 to 4
    2. Laterocollis, score range 0 to 3
    3. Anterocollis, score range 0 to 3
    4. Retrocollis, score range 0 to 3
    5. Lateral shift, score range 0 to 1
    6. Sagittal shift, 0 to 1
  2. Duration Factor (weighted by a factor of 2), score range 0 to 5
  3. Effect of Sensory Tricks score range 0 to 2
  4. Shoulder Elevation/ Anterior Displacement, score range 0 to 3
  5. Range of Motion, score range 0 to 4
  6. Time, score range 0 to 4

Disability Scale (maximum subtotal score 30)

The disability subscore has a maximum of 30 and consists of six items scored on scales from 0 to 5.

  1. Work, score range 0 to 5
  2. Activities of Daily Living, score range 0 to 5
  3. Driving, score range 0 to 5
  4. Reading, score range 0 to 5
  5. Television, score range 0 to 5
  6. Activities Outside the Home, score range 0 to 5

Pain Scale (maximum subtotal score 20)

The pain subscore has a maximum of 20 and consists of three patient-rated items, two of which are scored on a range from 0 to 5, while the third depends on patients’ score of their usual pain (factored by 2), worst pain, and best pain, on a range of 0 to 10, all divided by 4 to reach a total ranging from 0 to 10.

  1. Severity of Pain (best + worst + ((2 x usual)%4)), score range 0 to 10
    1. Best, score range 0 to 10
    2. Worst, score range 0 to 10
    3. Usual, score range 0 to 10
  2. Duration of Pain, score range 0 to 5
  3. Disability Due to Pain, score range 0 to 5

Using the TWSTRS videotape protocol, researchers filmed 200 CD patients and asked three independent movement disorders specialists to watch the videos and provide TWSTRS scores for them.45 The researchers found a substantial degree of concordance among the raters’ scores for all of the TWSTRS components of the tool (Kendall’s coefficient of concordance W range: 0.76 to 0.98). Also, the concordance between total TWSTRS score for raters was high (Kendall’s coefficient of concordance W = 0.85).45 In addition to the assessment of inter-rater agreement, construct validity was assessed in two studies where TWSTRS scores were measured for patients with CD; the researchers also recorded patient and clinician perceptions before and after treatment.21,46 Both studies have shown high correlation between the change in TWSTRS score and overall patient and clinician perception of improvement, with a reported Pearson correlation coefficient between the change in total severity score and patient perception of 0.68, and a reported Pearson correlation between the changes in the severity score and changes in disability and pain scores of 0.65 in TWSTRS and patient perception.47 Also, as a measure of score responsiveness, the TWSTRS and the Tsui scores were measured for 76 patients with CD before and after treatment with botulium neurotoxin A (BoNTA) along with a recorded global assessment scale, where assessments were conducted by the treating physician.43 This study showed a large Pearson correlation coefficient of 0.71 in the reduction of the TWSTRS total score and global assessment scale, and a large Pearson correlation coefficient of 0.57 between the TWSTRS total score and Tsui score.43

We were not able to find any study to inform us about a potential MCID for the TWSTRS score.

Tsui score

Developed in the 1980s for assessing efficacy in CD clinical trials, the Tsui score is an impairment scale that assesses the extent and duration of neck, head, and shoulder movement in patients with CD. In essence, the tool consists of four categories: amplitude of sustained movement, duration of sustained movement, shoulder elevation, and tremors. The combination of these four categories gives rise to the total Tsui score, which can be in the range of 1 to 25. The higher the score, the more aggressive the condition.48 The exact scoring algorithm is as follows:

  1. Amplitude of sustained movements: combined score ranges from 0 to 9 by adding the following:
    1. Rotation: score of 0, 1, 2, or 3 based on a degree of rotation of absent, less than 15 degrees, 15 degrees to 30 degrees, and more than 30 degrees, respectively
    2. Tilt: score of 0, 1, 2, or 3 based on a degree of rotation of absent, less than 15 degrees, 15 degrees to 30 degrees, and more than 30 degrees, respectively
    3. Sagittal movements: score of 0, 1, 2, or 3 based on a severity of absent, mild, moderate, or severe, respectively
  2. Duration of sustained movement: score of either 1 or 2 based on intermittent or constant duration, respectively
  3. Shoulder elevation: score of 0, 1, 2, or 3 based on the duration and severity of shoulder elevation where 0 = absent, 1 = mild and intermittent, 2 = mild and constant or severe and intermittent, and 3 = severe and constant.
  4. Tremor: combined score ranges from 1 to 4 by multiplying the following:
    1. Severity: score of 1 or 2 based on either mild or severe tremor
    2. Duration: score of 1 or 2 based on either occasional or continuous tremor

Total Tsui score = (amplitude of sustained movements x duration of sustained movement) + shoulder elevation + tremor

Inter-observer variability in the Tsui score was assessed in a randomized, double-blind (DB) trial of CD patients who underwent an injection of BoNTA or placebo.48 The clinical encounter with enrolled patients was filmed, and an assessment of the CD severity was carried out by two independent and blinded movement specialists using Tsui scoring.48 The agreement between raters was expressed as a large correlation coefficient of 0.86.48 Additionally, the Tsui score was measured in 76 patients with CD before and after treatment with botulinum toxin A; a recorded global assessment scale was also recorded and TWSTRS assessments were conducted by the treating physician.21 The results of the study showed a strong correlation between the Tsui and TWSTRS total scores (Pearson correlation coefficient of 0.57), a strong correlation between the Tsui score and the TWSTRS severity subscore (Pearson correlation coefficient of 0.69), and a weak correlation between the Tsui score and the TWSTRS pain subscore (Pearson correlation coefficient = 0.27). Correlation between the Tsui and the global impression of change was not reported.

Also, one study has demonstrated differences between the Tsui score and the patient’s reported subjective perception.49 The study enrolled 60 patients with CD to a randomized trial to receive BoNTA or placebo. The clinical encounter was filmed four weeks before and after the injection, and a blinded assessor provided a Tsui score of the patient. In addition, patients were asked to provide an assessment of symptoms change (nil, mild, moderate, marked) and a pain score on a scale from 0 to 10 where 10 was most severe.49 The correlation between the patients’ reported scores and Tsui scores was strong (0.64).49

We were not able to find any study to inform us about a potential MCID for the Tsui scores.

Visual analogue scale pain and symptom scale

This tool was used in Study 45 and 51. In both, for pain and symptom assessment, the patient was asked to draw a line on a 100 mm scale that represented the severity of the patient’s pain or symptom; the longer the line, the higher the severity. Thus, at 0 mm there would be an absence of pain or symptoms.9,10 We found no published evidence to support the validity, reliability, responsiveness, or MCID of these particular VASs for pain or symptoms in patients with CD.

Short Form (36) Health Survey

The SF-36 is a generic health assessment questionnaire that has been used in clinical trials to study the impact of chronic disease on health-related quality of life (HRQoL). The SF-36 consists of eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. SF-36 also provides two component summaries: the physical component summary (PCS) and the mental component summary (MCS), which are created by aggregating the eight domains according to a scoring algorithm. The SF-36 PCS, SF-36 MCS, and eight domains are each measured on a scale of 0 to 100, which are T-scores (mean of 50 and standard deviation of 10) that have been standardized to the US general population. Thus, a score of 50 on any scale would be at the average or norm of the general US population, while a score 10 points less (i.e., 40) would be one standard deviation below the norm. An increase in score indicates an improvement in health status on any scale. In general, when using the SF-36, a change of 2 points on the SF-36 PCS and 3 points on the SF-36 MCS indicates a clinically meaningful improvement as determined by the patient.50

We found no published evidence to support the validity or the MCID of the SF-36 in patients with CD.

Global Efficacy Assessment and Global Safety Assessment for cervical dystonia

As reported by the manufacturer, this measure is an investigator-reported global impression of change related to either CD symptoms or safety. For efficacy, this was carried out on a five-point ordinal scale on the change in CD symptoms (i.e., much better, better, no change from baseline, worse, or much worse), where the investigator chose one category based on their assessment during the assessment visit. With safety, the investigator assessed the safety profile (any AE or complication) on a five-point ordinal scale (i.e., none, mild, moderate, severe, or extreme). We were not able to find any literature that provides evidence on the validity, reliability, and MCID of such a measure.

Conclusion

The TWSTRS is a validated and reliable instrument to report on the outcome of patients with CD. The Tsui score has shown good inter-rater agreement, but had a less-than-ideal correlation with patients’ perceptions. We did not find evidence supporting the validity and reliability in the population of CD patients with the use of SF-36, VAS pain and symptom scale, and Global Efficacy Assessment and Global Safety Assessment. Also, we were not able to identify evidence regarding the MCID that was specific to CD on any of the reviewed measures.

Copyright © 2017 Canadian Agency for Drugs and Technologies in Health.

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Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence (CC BY-NC-ND), a copy of which is available at http://creativecommons.org/licenses/by-nc-nd/4.0/

Bookshelf ID: NBK535053

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