Discontinuation vs Continuation of Long-term Opioid Therapy in Suboptimal and Optimal Responders With Chronic Pain

Baseline is defined as the mean of the available Average PI scores on the 0-10 Numerical Ratings Scale (NRS) over the 7-day Baseline Period. For the scheduled post-randomization visits, mean Average Pain Intensity is defined as the means of the respective PI scores over the 7 days preceding the visit. If there is only one daily PI score available, the mean is not calculated, and the data point is considered missing.

PI = Pain Intensity. Higher scores indicate more pain intensity; lower scores less pain intensity. Scale range 0-10.

Percent pain intensity difference (PID) relative to baseline is defined as 100* ((baseline Average PI - mean Average PI at visit)/baseline Average PI). The percentages are based on number of subjects in the Intent-to-Treat set per treatment group. PI is measured on the Numerical Ratings Scale (NRS). Higher scores indicate more pain intensity; lower scores less pain intensity. Scale range 0-10.

This outcome measure applies only to Suboptimal Responders.

Percent pain intensity difference (PID) relative to baseline is defined as 100* ((baseline Average PI - mean Average PI at visit)/baseline Average PI). The percentages are based on number of subjects in the Intent-to-Treat set per treatment group. PI is measured on the Numerical Ratings Scale (NRS). Higher scores indicate more pain intensity; lower scores less pain intensity. Scale range 0-10.

This outcome measure applies only to Optimal Responders.

The MOS Sleep Scale is a 12-item questionnaire which measures sleep quality in 7 scales over the past 4 weeks: sleep disturbance, snoring, sleep short of breath or headache, sleep adequacy, sleep somnolence, and 2 sleep problems indexes. In addition, the average hours of sleep over the past 4 weeks is recorded as a raw measure and also coded as an optimal sleep index.

The MOS is scored and the sleep scales calculated according to the MOS Sleep Scale User's Manual v1.0 (Spritzer and Hays, 2003). The scores on the dimensions and the sleep indices were converted to a 0-100 scale, with higher scores reflecting more of the attribute implied by the name (e.g. greater sleep disturbance, greater sleep adequacy of sleep).

Optimal Sleep Index is based on the average number of hours of sleep each night during the past 4 weeks. Index=1 represents 7-8 hours and Index=0 represents < 7 hours or > 8 hours.

The PHQ-8 is an 8-item questionnaire that aims at assessing the level of mood of a subject. Each item is scored from 0 = "not at all" to 3= "nearly every day"; the total score, which is the sum of the score for each item, can be from 0 to 24. A score ≥10 is considered major depression and ≥20 is severe major depression.

The PHQ-8 is an 8-item questionnaire that aims at assessing the level of depression of a subject. Each item is scored from 0 = "not at all" to 3= "nearly every day"; the total score, which is the sum of the scores for each item, can be from 0 to 24. A score >= 10 is considered major depression and >= 20 is severe major depression.

The EQ-5D-5L is a self-administered general measure of health outcome applicable to a wide range of health conditions and treatments.The EQ-5D-5L measures quality of life in 5 dimensions: Mobility, Self-care, Usual activities, Pain/discomfort, and Anxiety/depression. Each is rated in 5 levels from no problems/pain/anxiety to being unable/extreme pain/extreme anxiety. The responses for each category are summarized by treatment and visit with frequencies and percentages reporting each level.

The EQ-5D-5L is a self-administered general measure of health outcome applicable to a wide range of health conditions and treatments. The visual analog scale (VAS) rates the subject's health on a 0-100 scale from the worst imaginable health state to the best imaginable health state.

Overall neuropsychological function is assessed using the DSST, a test that is sensitive to brain damage, dementia, age, and depression, and is a widely used instrument for measuring the neuropsychological effects of opioid therapy. The digits (1-9) are paired with symbols, and the test consists of matching the symbol for a series of digits as fast as possible. Score is number of correct symbols in 90 seconds. A decrease from baseline detects deterioration in processing speed. An increase from baseline detects improvement in processing speed.

The Patient Global Impression of Change (PGIC) is a self-administered questionnaire that assesses the participant's level of improvement/worsening from the beginning to the end of treatment. Participants are asked to select the category of change that most closely describes any change experienced in the pain of their painful areas from the beginning of the Blinded Structured Opioid Discontinuation Period to Week 12 and to Week 24. The scale has levels describing change as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse.

For the International Index of Erectile Function (IIEF)(15-items) each question is scored on a scale of 0 or 1 to 5, with 0 as no sexual attempts, 1 as the highest frequency, and 5 as the lowest, except where 1=1-2, 2=3-4, 3=5-6, 4=7-10 attempts, and 5=11 or more attempts. Missing responses are scored as 0. For the Female Sexual Function Index (FSFI)(19 items) each question is scored on a scale of 0-5 or 1-5. The FSFI examines the following 6 domains with minimum and maximum scores as indicated: desire(1.2-6.0), arousal(0-6.0), lubrication(0-6.0), orgasm(0-6.0), satisfaction(0.8-6.0), and pain(0-6.0). A computational formula sums the scores within each domain and multiplies that sum by a prescribed weighting factor: desire 0.6, arousal 0.3, lubrication 0.3, orgasm 0.4, satisfaction 0.4, pain 0.4. Higher scores indicate greater functionality. The single final score range is 2.0 to 36, which is reported as an average for each group of female study participants as change from baseline.