Article Figures & Data
Figures
- Figure 1.
Participant flow through the study. Abbreviations: LTOT, long-term opioid therapy.
- Figure 2.
Primary outcomes over time. Abbreviations: LTOT, long-term opioid therapy.
- Appendix Figure 1.
Web landing page advertised on social media to recruit participants for the pain registry for epidemiological, clinical, and interventional studies and innovation. Respondents completed the screening questionnaire by clicking on the “Participate” link (photo credit, Aleksandra Suz/Shutterstock.com).
Tables
No. (%) Control LTOT Characteristic (n = 201) (n = 201) P SDiffb Age (years) 21 to 49 59 (29.4) 57 (28.4) 50 to 64 101 (50.2) 90 (44.8) 0.29 0.05 65 to 79 41 (20.4) 54 (26.9) Gender Man 54 (26.9) 51 (25.4) 0.73 0.03 Woman 147 (73.1) 150 (74.6) Race White 152 (75.6) 159 (79.1) Black 39 (19.4) 38 (18.9) 0.25 0.05 Other 10 (5.0) 4 (2.0) Duration of low back pain (years) ≤5 51 (25.4) 48 (23.9) 0.73 0.03 >5 150 (74.6) 153 (76.1) Pain catastrophizing 0 to 17 94 (46.8) 94 (46.8) 18 to 34 68 (33.8) 68 (33.8) >0.99 0.00 35 to 52 39 (19.4) 39 (19.4) Pain self-efficacy 0 to 20 46 (22.9) 59 (29.4) 21 to 40 89 (44.3) 91 (45.3) 0.17 0.07 41 to 60 66 (32.8) 51 (25.4) Chronic widespread pain No 137 (68.2) 141 (70.1) 0.67 0.04 Yes 64 (31.8) 60 (29.9) Ever had work loss ≥1 month due to low back pain No 103 (51.2) 105 (52.2) 0.84 0.02 Yes 98 (48.8) 96 (47.8) Ever received disability or workers' compensation benefits due to low back pain No 146 (72.6) 144 (71.6) 0.82 0.02 Yes 55 (27.4) 57 (28.4) Ever filed a law suit or legal claim due to low back pain No 182 (90.5) 183 (91.0) 0.86 0.02 Yes 19 (9.5) 18 (9.0) Prior low back surgery No 159 (79.1) 156 (77.6) 0.72 0.04 Yes 42 (20.9) 45 (22.4) Health-related quality of life, mean (SD) 58.01 (7.16) 58.71 (6.36) 0.30 0.10 Low back pain intensity, mean (SD) 6.39 (1.67) 6.39 (1.92) 0.98 0.00 Back-related disability, mean (SD) 15.32 (5.49) 15.41 (5.23) 0.87 0.02 Pain impact, mean (SD) 32.57 (8.75) 32.88 (8.24) 0.72 0.04 Abbreviation: LTOT, long-term opioid therapy.
Notes: aTreatment groups were matched on propensity score using a logistic regression model that included all variables in the table, with a caliper width of .001. Health-related quality of life involved a composite measure of anxiety, depression, fatigue, sleep disturbance, and pain interference. Higher values represented worse quality of life.
bMagnitude of the standardized difference.
Outcome Treatment Group Low Back Pain Intensity Back-Related Disability Pain Impact n Mean 95% CI P Mean 95% CI P Mean 95% CI P Overall Analysis Control 201 5.92 5.68-6.17 0.46 14.81 13.99-15.62 0.36 31.22 30.00-32.43 0.13 LTOT 201 6.06 5.80-6.32 15.32 14.55-16.09 32.51 31.33-33.70 Analysis for Continuous Duration of LTOT Control 201 5.92 5.68-6.17 0.56 14.81 14.00-15.62 0.88 31.22 30.00-32.43 0.43 LTOT (months) 3 43 5.82 5.18-6.45 15.68 14.00-17.37 31.38 28.49-34.28 6 23 6.40 5.53-7.28 15.69 13.32-18.06 33.55 30.12-36.99 9 16 5.60 4.75-6.45 15.17 11.98-18.36 31.48 26.74-36.22 12 119 6.13 5.82-6.45 15.16 14.19-16.12 32.83 31.39-34.26 Analysis for Opioid Dose Response Based on Number of Quarters Used Control 201 5.92 5.68-6.17 0.73 14.81 14.00-15.62 0.81 31.22 30.00-32.43 0.50 LTOT (quarters) 1 25 5.64 4.75-6.53 15.60 13.72-17.49 30.97 27.83-34.11 2 23 6.27 5.32-7.21 14.94 12.26-17.62 32.95 28.59-37.31 3 34 5.91 5.31-6.50 15.99 14.00-17.99 32.09 29.04-35.15 4 119 6.13 5.81-6.45 15.16 14.19-16.12 32.83 31.39-34.26 Analysis for Opioid Dose Response Based on Baseline MME Dosage Control 201 5.92 5.68-6.17 0.83 14.81 13.99-15.62 0.40 31.22 30.00-32.43 0.47 LTOT (MMEs) ≤30 100 6.09 5.70-6.48 14.82 13.69-15.96 32.27 30.59-33.96 >30 to <50 66 6.10 5.66-6.53 15.98 14.77-17.19 32.93 30.95-34.90 ≥50 35 5.90 5.33-6.47 15.51 13.59-17.43 32.42 29.42-35.42 Analysis for Continuous Opioid Use or Abstinence for 12 Months Control 132 5.58 5.27-5.89 0.02 13.76 12.75-14.78 0.05 29.56 28.08-31.03 0.002 LTOT (MMEs) 119 6.13 5.81-6.45 15.16 14.19-16.12 32.83 31.39-34.26 Abbreviations: LTOT, long-term opioid therapy; CI, confidence interval; MME, morphine milligram equivalent.
aPain intensity was measured with a numerical rating scale (0-10). Back-related disability was measured with the Roland-Morris Disability Questionnaire (0-24). Pain impact was measured using low back pain intensity and the physical function and pain interference scales of the Patient-Reported Outcomes Measurement Information System (8-50). Higher scores represent worse outcomes on each measure. Results were computed using generalized estimating equations. Table entries represent mean results and P values for the observations reported from 3 months through 12 months, following determination of treatment group membership and participant matching.
Treatment Group n Outcome MIC in Low Back Pain Intensity MIC in Back-Related Disability MIC in Pain Impact HR 95% CI P HR 95% CI P HR 95% CI P Overall Analysis Control 201 Reference Reference Reference LTOT 201 0.95 0.75-1.21 0.69 0.97 0.74-1.27 0.84 0.70 0.46-1.05 0.08 Analysis for Continuous Duration of LTOT Control 201 Reference Reference Reference LTOT (months) 3 43 1.10 0.73-1.66 0.66 1.09 0.68-1.73 0.73 0.70 0.32-1.53 0.37 6 23 0.61 0.32-1.16 0.13 0.98 0.54-1.78 0.96 0.85 0.34-2.12 0.73 9 16 1.23 0.70-2.17 0.48 0.82 0.40-1.68 0.59 0.67 0.21-2.14 0.50 12 119 0.94 0.72-1.24 0.67 0.96 0.71-1.30 0.79 0.68 0.42-1.08 0.10 Analysis for Opioid Dose Response Based on Number of Quarters Used Control 201 Reference Reference Reference LTOT (quarters) 1 25 1.37 0.81 −2.31 0.24 1.16 0.62-2.17 0.63 0.97 0.35-2.68 0.95 2 23 0.81 0.45-1.46 0.48 1.02 0.56-1.85 0.95 1.19 0.54-2.61 0.67 3 34 0.88 0.56-1.38 0.58 0.90 0.55-1.48 0.67 0.39 0.14-1.06 0.07 4 119 0.94 0.72-1.24 0.67 0.96 0.71-1.30 0.79 0.68 0.42-1.08 0.10 Analysis for Opioid Dose Response Based on Baseline MME Dosage Control 201 Reference Reference Reference LTOT (MMEs) ≤30 100 1.17 0.89-1.55 0.27 1.02 0.74-1.42 0.88 0.70 0.42-1.17 0.18 >30 to <50 66 0.71 0.50-1.03 0.07 0.95 0.65-1.39 0.80 0.67 0.36-1.22 0.19 ≥50 35 0.86 0.54-1.37 0.52 0.86 0.51-1.45 0.57 0.74 0.34-1.63 0.46 Analysis for Continuous Opioid Use or Abstinence for 12 Months Control 132 Reference Reference Reference LTOT 119 0.82 0.61-1.09 0.18 0.92 0.66-1.27 0.61 0.60 0.37-0.98 0.04 Abbreviations: LTOT, long-term opioid therapy; MME, morphine milligram equivalent; HR, hazard ratio; CI, confidence interval.
aMinimally important changes were defined as a 1-point decrease on the numerical rating scale for low back pain intensity, a 2-point decrease on the Roland-Morris Disability Questionnaire for back-related disability, and a 7.5-point decrease on pain impact based on the numerical rating scale for low back pain intensity and the physical function and pain interference scales of the Patient-Reported Outcomes Measurement Information System. In all analyses, 271 (67.4%), 217 (54.0%), and 96 (23.9%) participants achieved a MIC in each of these outcome measures, respectively, except for the analysis for continuous opioid use or abstinence for 12 months. Therein, 187 (74.5%), 144 (57.4%), and 69 (27.5%) participants achieved a MIC in each of these outcome measures, respectively. Hazard ratios and P values were computed using the Cox proportional hazards model for time to achievement of a minimally important change.
- Appendix Table 1.
Overview of Analyses, Statistical Methods, and Scale and Timing of Measuresa
Analysis Propensity Score Matching Primary Outcomes Assessment Secondary Outcomes Assessment Sensitivity Analyses Logistic Regression Generalized Estimating Equations Cox Proportional Hazards Regression Generalized Estimating Equations Measure Scale Timing (months) Variable type Variable type Variable type Variable type Age Categorical 0 Independent NIA NIA NIA Gender Dichotomous 0 Independent NIA NIA NIA Race Categorical 0 Independent NIA NIA NIA Duration of LBP Categorical 0 Independent NIA NIA NIA Pain catastrophizing Categorical 0 Independent NIA NIA NIA Pain self-efficacy Categorical 0 Independent NIA NIA NIA Chronic widespread pain Dichotomous 0 Independent NIA NIA NIA Ever had work loss ≥1 month due to LBP Dichotomous 0 Independent NIA NIA NIA Ever received disability or workers' compensation benefits due to LBP Dichotomous 0 Independent NIA NIA NIA Ever filed a law suit or legal claim due to LBP Dichotomous 0 Independent NIA NIA NIA Prior low back surgery Dichotomous 0 Independent NIA NIA NIA Health-related quality of life Continuous 0 Independent NIA NIA NIA LBP intensity (NRS) Continuous 0, 3, 6, 9, 12 Independent Dependent NIA Dependent Back-related disability (RMDQ) Continuous 0, 3, 6, 9, 12 Independent Dependent NIA Dependent Pain impact (PI) Continuous 0, 3, 6, 9, 12 Independent Dependent NIA Dependent MIC - NRS Dichotomous 0, 3, 6, 9, 12 NIA NIA Dependent NIA MIC - RMDQ Dichotomous 0, 3, 6, 9, 12 NIA NIA Dependent NIA MIC - PI Dichotomous 0, 3, 6, 9, 12 NIA NIA Dependent NIA LTOT (initial assignment to LTOT or control group) Dichotomous 0, 3 Dependent Independent Independent Independent LTOT (continuous opioid use, defined as 0, 3, 6, 9, or 12 months) Categorical 0, 3, 6, 9, 12 NIA Independent Independent Independent LTOT (dose response, defined as 0, 1, 2, 3, or 4 quarters of opioid use) Categorical 0, 3, 6, 9, 12 NIA Independent Independent Independent LTOT (dose response, defined as number of MMEs used at baseline) Continuous 0 NIA Independent Independent Independent LTOT (continuous opioid use or abstention for 12 months) Dichotomous 0, 3, 6, 9, 12 NIA Independent Independent Independent ↵Abbreviations: LBP, low back pain; LTOT, long-term opioid therapy; MIC, minimally important change; MME, morphine milligram equivalent; NIA, not included in analysis; NRS, numerical rating scale; PI, pain impact; RMDQ, Roland-Morris Disability Questionnaire.
Note: aParticipants in the control group were classified as having no opioid exposure or dose in all analyses.
Outcome Low Back Pain Intensity Back-Related Disability Pain Impact Treatment Group n Mean 95% CI P Mean 95% CI P Mean 95% CI P Overall Analysis Control 201 5.99 5.74-6.24 0.48 14.88 14.09-15.67 0.38 31.38 30.19-32.57 0.14 LTOT 201 6.11 5.86-6.36 15.38 14.59-16.17 32.64 31.45-33.83 Analysis for Continuous Duration of LTOT Control 201 5.99 5.74-6.24 0.57 14.88 14.09-15.67 0.85 31.38 30.18-32.57 0.55 LTOT (months) 3 43 5.89 5.32-6.46 15.78 14.05-17.51 31.73 29.12-34.34 6 23 6.52 5.78-7.25 15.83 13.50-18.17 33.50 29.97-37.03 9 16 5.76 4.88-6.65 15.55 12.75-18.35 32.01 27.79-36.23 12 119 6.15 5.83-6.48 15.13 14.11-16.16 32.88 31.33-34.43 Analysis for Opioid Dose Response Based on Number of Quarters Used Control 201 5.99 5.74-6.24 0.68 14.88 14.09-15.67 0.78 31.38 30.18-32.57 0.60 LTOT (quarters) 1 25 5.67 4.89-6.44 15.84 13.55-18.13 31.48 28.02-34.94 2 23 6.36 5.62-7.10 15.12 12.79-17.46 33.02 29.49-36.56 3 34 6.08 5.47-6.69 16.11 14.19-18.02 32.35 29.46-35.25 4 119 6.16 5.83-6.48 15.13 14.11-16.16 32.88 31.33-34.43 Analysis for Opioid Dose Response Based on Baseline MME Dosage Control 201 5.99 5.74-6.24 0.89 14.88 14.09-15.67 0.44 31.38 30.19-32.57 0.45 LTOT (MMEs) ≤30 100 6.14 5.78-6.49 14.85 13.74-15.97 32.26 30.57-33.95 >30 to <50 66 6.13 5.70-6.57 16.10 14.72-17.47 33.18 31.10-35.27 ≥50 35 6.01 5.41-6.62 15.54 13.65-17.43 32.72 29.85-35.58 Analysis for Continuous Opioid Use or Abstinence for 12 Months Control 132 5.65 5.35-5.95 0.03 13.86 12.90-14.83 0.08 29.68 28.25-31.10 0.003 LTOT 119 6.14 5.82-6.46 15.12 14.11-16.14 32.87 31.37-34.37 Abbreviations: LTOT, long-term opioid therapy; MME, morphine milligram equivalent; CI, confidence interval.
↵Notes: aPain intensity was measured with a numerical rating scale (0-10). Back-related disability was measured with the Roland-Morris Disability Questionnaire (0-24). Pain impact was measured using low back pain intensity and the physical function and pain interference scales of the Patient-Reported Outcomes Measurement Information System (8-50). Higher values represent worse outcomes on each measure. Results were computed using linear mixed methods. Table entries represent mean results and P values for the observations reported from 3 months through 12 months, following determination of treatment group membership and participant matching.
