Objective: The aim of this study was to develop and validate a neuropathy sensory symptom scale, the Neuropathy Total Symptom Score-6 (NTSS-6), which evaluates individual neuropathy sensory symptoms in patients with diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN) in clinical trials, with the intent of distinguishing a response to therapy. Methods: The NTSS-6 questionnaire was developed to evaluate the frequency and intensity of individual neuropathy sensory symptoms identified frequently by patients with DPN lie, numbness and/or insensitivity; prickling and/or tingling sensation; burning sensation; aching pain and/or tightness; sharp, shooting, lancinating pain; and allodynia and/or hyperalgesia). The NTSS-6 was administered 8 times over a I-year period to DPN patients. The NTSS-6's reliability (determined by internal consistency and test-retest reproducibility), construct validity, convergent validity, and minimally clinically important differences (MCIDs) were determined. Results: The NTSS-6 was administered to a total of 205 patients at 10 centers in the United States, Canada, Belgium, Germany, Hungary, Croatia, Slovenia, and the United Kingdom. Internal consistency was demonstrated at all 8 visits (Cronbach's a > 0.7). Test-retest reproducibility (intraclass correlation coefficient > 0.9) was observed during the baseline period and at end point. Construct validity was demonstrated by statistically significant correlations between the NTSS-6 total score and the Neuropathy Symptoms and Change (NSC) score (r = 0.773-0.885, P < 0.001). Convergent validity was demonstrated by statistically significant correlations between the change in NTSS-6 total scores and the following: change in NSC scores (r = 0.519-0.708, P < 0.001); change in Neuropathy Impairment Score of the Lower Limbs and composite nerve function scores (r = 0.188-0.202, P < 0.007), and categories of the Clinical Global Impressions (r 0.402, P < 0.001). The within- and between-groups MCIDs for the total NTSS-6 total scores were -1.26 and 0.97 points, respectively. The mean (SD) within-group MCID for all patients who improved on the Clinical Global Impression was -2.29 (3.4) points. Conclusions: The NTSS-6 provided a valid assessment of neuropathy sensory symptoms in this sample of patients with DM and DPN, which suggests that it may be useful for symptom evaluation in clinical trials and practice. The NTSS-6 showed internal consistency, test-retest reliability, and construct validity. There was also convergent validity of the scores, indicating that the NTSS-6 may be a suitable questionnaire for clinical trials that evaluate symptoms of DPN in this well-defined patient population.
