Anchor-based approaches
muscle weakness, NIS muscles weakness, ambulatory disability, Polyneuropathy, neuropathic impairment
PND, POLYNEUROPATHY, MUSCLE WEAKNESS, SENSORY DISTURBANCES
Anchor-based approaches estimate RD thresholds based on the correspondence between changes in the target measure and in an anchor measure. An anchor measure is an independent criterion measure for which there are clearly defined indicators for interpreting change in a patient’s clinical health. Appropriate anchor measures assess similar constructs as those captured by the target measure, and changes in the anchor should have at least a moderate statistical association with the target; a correlation ≥|0.30| between changes in the target measure and any anchor measure is recommended [One measure was identified as an appropriate anchor for NIS total score and sensation subscales for both the NIS and NIS-LL: the Polyneuropathy Disability score (PND). The PND is a clinician-rated classification of patients into one of five stages of ambulatory disability: Stage I, indicating sensory disturbances in limbs without motor impairment; Stage II, indicating difficulty walking without the need of a walking aid; Stage IIIa, for which one stick or one crutch is required for walking; Stage IIIb, for which two sticks or two crutches are required for walking; and Stage IV, for patients who are confined to a wheelchair or bedridden [A second measure was identified as an appropriate anchor for the NIS-LL total score and muscle weakness subscale: the lower limb function test (LLF). The LLF is a 3-item clinician assessment of a patient’s ability to walk on their toes, walk on their heels, and stand from a kneeling position [No appropriate anchor measure from the NEURO-TTR trial was identified for the NIS muscles weakness subscale or for NIS or NIS-LL reflex subscales, as no other clinician-rated assessment of neuropathic impairment that was conceptually related to these outcomes had straightforward interpretation of what would indicate clinically meaningful improvement.Three anchor-based methods were used to estimate RD thresholds for the NIS/NIS-LL measures from corresponding anchors. First, the mean change in NIS/NIS-LL scores for patients who did not exhibit meaningful worsening on the anchor (i.e., < 2-point increase on the LLF, or < 1-point increase on the PND) was subtracted from mean change in these scores for patients with a ≥ 2-point increase on the LLF/≥1-point increase on the PND [