APPENDIX ONE
Measurement Techniques in ALS Clinical Trials

1.1 Purpose of measurement techniques

Measurement techniques should be sensitive, easily and unambiguously quantifiable, non-redundant, standardized and validated, with quantified and minimal intra- and inter-rater variability.

 

1.2 Properties of measurement techniques.

1. Measurement techniques should assess change that may represent improvement, arrest (stabilization) or retardation (slowing) of the disease in pre-symptomatic and symptomatic patients. Prevention of the onset of the disease or prevention of the spread of the disease process to unaffected areas from affected areas should also be assessed.
2. Measurement techniques should produce data that provide comparable information at different times in the course of the disease.

 

2.0 Recommended measurement techniques in ALS Clinical Trials

 

2.1 Many measurement techniques are available for ALS Clinical Trials. Particular measurement techniques may be clinically or statistically robust at different times during the course of ALS, in different subgroups of ALS patients and in different anatomical regions in the same ALS patient.

 

2.2 The measurement techniques may be bounded by the clinical questions being tested and resources available. Multiple measurement techniques are encouraged to maximize the detection of potential clinical benefits of any intervention.

 

2.3 The following minimum dataset of measurements is suggested:

1. Survival and time to failure analysis.
   a.1 ALS Clinical Trials should record the time to death, or permanent continuous ventilator dependence, until the time of study termination of all patients who were randomized during the course of the trial.
   a.2 Time to failure analysis of possible surrogate end points for death or permanent continuous ventilator dependence include various indices of change in respiratory function (e.g., FVC in earlier stages, or arterial CO2 or serum chloride in later stages, need for respiratory support, tracheostomy). These end points require further study for validation to determine whether practice patterns and geography will influence these outcomes.
   Intermittent noninvasive mechanical ventilation or enteral feeding may improve survival. These factors must be considered in future clinical trials and require further study for validation.
   a.3 Time to failure for specific clearly defined epochal events may be employed in ALS Clinical Trials. These events include loss of intelligible speech, swallowing, self–feeding, use of hands, self–turning in bed and unassisted walking.
2. Reasons for dropouts should be recorded.

 

2.4 Upper and lower limb strength measurement

1. Preferred: quantitative myometry (see Appendix 3)
2. Acceptable: manual muscle testing
   b.1 The number of muscles tested by manual muscle testing should be increased to permit proper statistical analysis

 

2.5 Respiratory function measurement (see Appendix 6)

1. Preferred: forced vital capacity
2. Acceptable: FEVI; chest expansion ratio

 

2.6 Function tests

1. Disease-specific functional rating scale
   Preferred: ALS Functional Rating Scale, Ashworth Spasticity Scale
   Acceptable: Baylor ALS Rating Scale
2. Non-disease specific functional rating scale
   Acceptable: Universal functional rating scale, Barthel or Rankin Scale
3. Timed functional tests
   Acceptable: Timed walking, Timed standing from sitting, Peg–Board

 

2.7 Bulbar Tests

Further analysis of bulbar function measurement is required to determine the most efficient and reproducible means of assessing speech and swallowing functions. This area was identified as one domain where easily performed, reproducible, valid clinical tests are still lacking (see Appendix 7).

1. Preferred: Precise measurement of bulbar function to be developed or identified, Bulbar functional rating scales, Frenchay, Hillel
2. Acceptable: Timed functional tests, Alternate Motion Rates, PaTa,PaTaKa

Back to Airlie '98 Contents