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1 Supplementary Online Content Hinman RS, McCrory, irotta M, et al. Acupuncture for chronic knee pain: a randomized clinical trial. JAMA. doi: /jama etable 1: Exclusion criteria etable 2: Acupuncture points that could be selected by acupuncturists when administering needle, laser and sham laser acupuncture etable 3: Treatment attendance, adverse events, medication use and co-interventions according to treatment group etable 4: Blinding to laser and sham laser acupuncture, recorded after the first treatment by participants and acupuncturists etable 5: d differences between arms at 12 weeks using complete case analysis etable 6: d differences between arms at 1 year using complete case analysis etable 7: d differences between arms at 12 weeks when analyzed as-treated etable 8: d differences between arms at 1 year when analyzed as-treated etable 9: d differences between each acupuncture group compared to control at 12 weeks (with multiple imputation for missing data) in the hypothetical scenario of full adherence to the randomized intervention etable 10: d differences between each acupuncture group compared to control at 1 year (with multiple imputation for missing data) in the hypothetical scenario of full adherence to the randomized intervention etable 11: Number (percentage) of participants reporting global improvement and estimated odds ratios (OR) from mixed effects regression models (complete case analysis) This supplementary material has been provided by the authors to give readers additional information about their work.

2 etable 1: Exclusion criteria Criterion History of any systemic arthritic condition History of knee arthroplasty on the most painful knee Wait-listed for any knee surgery for either knee History of any knee surgery in previous 6 months Any other condition affecting lower limb function (eg trauma, malignancy, neurological condition) History of any knee injection in past 6 months (eg cortisone, hyaluronic acid) Current use of oral or injectable anticoagulant medication Use of acupuncture in past 12 months Any bleeding disorder Allergy to light Referral to pain clinic or use of morphine or pethidine within past 6 months Any other medical condition precluding participation in the trial (eg kidney or liver disease, deep vein thrombosis) Knee pain subject to compensation claim Unable to give written informed consent

3 etable 2: Acupuncture points that could be selected by acupuncturists when administering needle, laser and sham laser acupuncture Location Acupuncture points Local points S9, 10 ST34, 35, 36 LR7, 8, 9 KI10 BL39, 40, 57 GB34, 35, 36 Local extra points in the hamstring muscles Distal points ST40 LR3 S6 GB41 BL60 Segmental points BL21, 22, 23 GB30, 31 Non-segmental and general points Ear Knee point DU20 Li11 GV14 BL11

4 etable 3: Treatment attendance, adverse events, medication use and cointerventions according to treatment group articipants accepting treatment Needle (n=57) Laser (n=59) Sham laser (n=61) Treatments attended (Median (IQR)) Attended 8 treatments, n (%) 10.0 ( ) 10.0 ( ) 54 (92%) 8.0 ( ) 46 (75%) 52 (91%) Adverse events, n (%) Increased knee pain 5 (10%) 7 (12%) 2 (3%) ain in other areas Tingling Nausea and/or dizziness 0 (0%) Tiredness Swelling Sensitive skin 0 (0%) 0 (0%) 0 (0%) 2 (3%) 0 (0%) 0 (0%) All randomized participants Control (n=71) Needle (n=70) Laser (n=71) Sham laser (n=70) Medication use at 12 weeks, a n (%) Analgesics 25 (37%) 21 (35%) 17 (27%) 21 (37%) NSAIDs 14 (21%) 10 (17%) 8 (13%) 12 (21%) COX-2 inhibitors 1 (1%) 4 (7%) 4 (6%) Opioids 1 (1%) 0 (0%) 0 (0%) 0 (0%) Glucosamine 13 (19%) 12 (20%) 8 (13%) 11 (19%) Fish oil 11 (16%) 8 (13%) 7 (11%) 11 (19%) Co-interventions at 12 weeks, b n (%) hysical therapy 2 (3%) 7 (11%) 0 (0%) Surgery 2 (3%) 2 (3%) 0 (0%) 2 (4%) Acupuncture 2 (3%) 0 (0%) 0 (0%) 0 (0%) Exercise 12 (18%) 7 (12%) 5 (8%) 7 (12%) Hydrotherapy 1 (1%) 3 (5%) 2 (4%) Medication use at 1 year, a n (%) Analgesics 20 (29%) 17 (28%) 20 (31%) 22 (29%) NSAIDs 12 (18%) 8 (13%) 14 (22%) 6 (11%) COX-2 inhibitors 1 (1%) 2 (3%) 2 (3%) 3 (5%) Opioids 1 (1%) 0 (0%) 0 (0%) Glucosamine 9 (13%) 9 (15%) 8 (13%) 6 (11%) Fish oil 10 (15%) 7 (12%) 7 (11%) 7 (12%) Co-interventions at 1 year, c n (%) hysical therapy 10 (15%) 5 (8%) 6 (9%) 5 (9%) Surgery 4 (6%) 5 (8%) 3 (5%) 5 (9%) Acupuncture 0 (0%) 0 (0%) 0 (0%) Exercise 12 (18%) 12 (20%) 7 (11%) 8 (14%) Hydrotherapy 2 (3%) 4 (6%) 4 (7%) a defined as medications purchased over previous 4 weeks for knee pain; b defined as treatments sought for knee pain over previous 12 weeks; c defined as treatments sought for knee pain over previous 9 months; NSAID= non-steroidal antiinflammatory drugs; COX-2= cyclooxygenase-2.

5 etable 4: Blinding to laser and sham laser acupuncture, recorded after the first treatment by participants and acupuncturists articipants Acupuncturists Laser acupuncture (n=59) Correctly identified 16 (30%) 8 (16%) Incorrectly identified 3 (6%) 3 (6%) Unsure 35 (65%) 39 (78%) Sham laser acupuncture (n=61) Correctly identified 5 (9%) 3 (6%) Incorrectly identified 16 (29%) 7 (14%) Unsure 34 (62%) 40 (80%) NOTE- there was some missing data from participants and acupuncturists across both groups.

6 RIMARY etable 5: d differences between arms at 12 weeks using complete case analysis Compared to control group Other planned contrasts Needles Laser Sham laser Needles vs Laser Needles vs Sham laser Laser vs Sham laser Overall pain a 1.2 ( 1.9, ( 1.6, ( 1.7, 0.2) ( 1.1, 0.3) ( 1.0, 0.4) ( 0.7, 0.8) 0.84 WOMAC function a 4.4 ( 7.7, 1.1) ( 5.2, 1.1) ( 6.1, 1.0) ( 5.5, 0.8) ( 5.4, 1.7) ( 2.9, 3.9) 0.77 SECONDARY ain on walking a 1.3 ( 2.0, 0.6) < ( 1.4, ( 1.6, ( 1.4, ( 1.3, 0.3) ( 0.7, 1.0) 0.72 ain on standing a 1.0 ( 1.7, 0.3) ( 1.2, 0.3) ( 1.8, 0.3) ( 1.3, 0.2) ( 0.6, 0.9) ( 0.2, 1.4) 0.11 Activity restriction a 1.0 ( 1.7, 0.2) ( 1.7, 0.2) ( 2.2, ( 0.8, 0.8) ( 0.5, 1.2) ( 0.4, 1.2) 0.36 WOMAC pain a 1.5 ( 2.6, 0.4) ( 2.1, ( 2.4, ( 1.6, 0.7) ( 1.4, 1.0) ( 1.0, 1.5) 0.68 AQoL 6D b 0.01 ( 0.03, 0.05) ( 0.04, 0.03) ( 0.02, 0.04) ( 0.03, 0.05) ( 0.04, 0.04) ( 0.05, 0.02) 0.48 SF 12 CS b 3.1 (0.2, 5.9) ( 1.8, 3.8) ( 1.5, 4.3) ( 0.7, 4.8) ( 1.2, 4.5) ( 3.2, 2.4) 0.77 SF 12 MCS b 1.5 ( 4.5, 1.5) ( 3.7, 1.6) ( 3.4, 2.7) ( 3.3, 2.3) ( 4.3, 2.0) ( 3.5, 2.1) 0.64 anegative values indicate better (adjusted) mean in that (first named) group compared with comparison group; b ositive values indicate better (adjusted) mean in that (first named) group compared with comparison group; WOMAC= Western Ontario and McMaster Universities Osteoarthritis Index; AQoL 6D= Assessment of Quality of Life instrument version 2; SF 12=12 item Short Form Health Survey; CS= physical component summary; MCS= mental component summary.

7 RIMARY etable 6: d differences between arms at 1 year using complete case analysis Compared to control group Other planned contrasts Needles Laser Sham laser Needles vs Laser Needles vs Sham laser Laser vs Sham laser Overall pain a 0.8 ( 1.7, ( 1.4, 0.3) ( 1.6, 0.2) ( 1.1, 0.6) ( 1.0, 0.8) ( 0.7, 1.0) 0.77 WOMAC function a 5.1 ( 9.3, 0.9) ( 6.2, 1.8) ( 7.4, 0.7) ( 7.2, 1.4) ( 6.0, 2.6) ( 3.0, 5.3) 0.57 SECONDARY ain on walking a 0.7 ( 1.7, 0.2) ( 1.2, ( 1.4, 0.4) ( 1.3, 0.6) ( 1.2, 0.7) ( 0.8, 1.0) 0.81 ain on standing a 0.6 ( 1.5, 0.3) ( 0.9, 0.7) ( 1.6, 0.2) ( 1.5, 0.4) ( 0.9, 1.0) ( 0.4, 1.5) 0.22 Activity restriction a 1.1 ( 2.1, 0.2) ( 1.4, 0.4) ( 1.4, 0.3) ( 1.6, 0.3) ( 1.5, 0.3) ( 0.9, 0.9) 0.94 WOMAC pain a 1.6 ( 2.9, 0.2) ( 2.0, 0.6) ( 2.5, 0.0) ( 2.2, ( 1.6, 1.0) ( 0.8, 1.8) 0.41 AQoL 6D b 0.01 ( 0.03, 0.05) ( 0.04, 0.04) ( 0.03, 0.04) ( 0.03, 0.05) ( 0.03, 0.05) ( 0.04, 0.04) 0.92 SF 12 CS b 4.8 (1.4, 8.3) ( 1.9, 4.7) ( 3.0, 3.6) (0.3, 6.6) (1.4, 7.7) ( 1.9, 4.1) 0.48 SF 12 MCS b 0.9 ( 4.6, 2.7) ( 4.7, 2.3) ( 3.1, 4.2) ( 2.9, 3.4) ( 4.7, 1.8) ( 4.9, 1.4) 0.28 anegative values indicate better (adjusted) mean in that (first named) group compared with comparison group; b ositive values indicate better (adjusted) mean in that (first named) group compared with comparison group; WOMAC= Western Ontario and McMaster Universities Osteoarthritis Index; AQoL 6D= Assessment of Quality of Life instrument version 2; SF 12=12 item Short Form Health Survey; CS= physical component summary; MCS= mental component summary.

8 etable 7: d differences between arms at 12 weeks when analyzed as-treated RIMARY Overall pain a -1.5 (-2.1, - 0.8) WOMAC function a -4.4 (-7.6, - 1.2) Compared to control group Other planned contrasts Needles Laser Sham laser Needles vs Laser Needles vs Sham laser < (-1.7, - 0.3) (-6.1, (-1.9, (-6.9, - 0.3) (-1.2, 0.2) (-4.9, 2.1) (-1.0, (-4.5, 2.9) (-0.5, 1.0) (-3.1, 4.2) Laser vs Sham laser SECONDARY ain on walking a -1.4 (-2.1, - < (-1.6, (-1.9, (-1.3, (-1.1, (-0.6, ) 0.4) 0.2) 1.1) ain on standing a -1.2 (-1.8, (-1.4, (-2.1, - < (-1.3, (-0.5, (-0.1, ) 0.3) 1.0) 1.6) Activity restriction a -1.3 (-2.0, (-1.9, (-2.4, - < (-0.8, (-0.5, (-0.5, ) 0.8) 1.2) 1.2) WOMAC pain a -1.6 (-2.6, (-2.3, (-2.7, (-1.7, (-1.2, (-0.9, ) 0.9) 1.3) 1.7) AQoL-6D b 0.01 (-0.03, (-0.03, (-0.02, (-0.04, (-0.05, (-0.05, ) 0.04) 0.04) 0.06) 0.05) 0.03) SF-12- CS b 2.5 (-0.2, (-1.9, (-0.9, (-1.3, (-2.2, (-3.8, ) 3.7) 4.5) 4.6) 3.6) 2.1) SF-12- MCS b 1.2 (-1.8, 4.1) (-1.8, 3.5) (-2.1, 3.7) (-2.5, 3.2) (-2.8, 3.5) (-2.9, 2.9) 0.99 a Negative values indicate better (adjusted) mean in that (first named) group compared with comparison group; b ositive values indicate better (adjusted) mean in that (first named) group compared with comparison group; WOMAC= Western Ontario and McMaster Universities Osteoarthritis Index; AQoL-6D= Assessment of Quality of Life instrument version 2; SF-12=12-item Short Form Health Survey; CS= physical component summary; MCS= mental component summary

9 etable 8: d differences between arms at 1 year when analyzed as-treated Compared to control group Other planned contrasts Needles Laser Sham laser Needles vs Laser Needles vs Sham laser Laser vs Sham laser RIMARY Overall pain a -0.7 (-1.5, 0.2) WOMAC function a -3.2 (-7.4, 1.1) (-1.5, (-6.4, 1.7) (-1.6, (-7.1, 0.9) (-1.0, 1.0) (-0.9, 1.0) (-0.9, 1.0) (-5.5, 3.9) (-4.7, 4.6) (-3.8, 5.3) 0.74 SECONDARY ain on walking a -0.4 (-1.4, (-1.1, (-1.3, (-1.2, (-1.0, 1.1) (-0.8, 1.2) ) 0.6) 0.4) 0.9) ain on standing a -0.5 (-1.4, (-1.0, (-1.5, (-1.4, (-0.9, 1.2) (-0.4, 1.5) ) 0.7) 0.2) 0.6) Activity restriction a -0.8 (-1.7, (-1.7, (-1.9, (-0.9, 1.1) (-0.8, 1.3) (-0.8, 1.1) ) WOMAC pain a -1.2 (-2.6, (-2.0, (-2.4, (-2.0, (-1.5, 1.4) (-0.9, 1.9) ) 0.0) 1.0) AQoL-6D b 0.01 (-0.04, (-0.04, (-0.02, (-0.04, (-0.05, (-0.06, ) 0.04) 0.05) 0.06) 0.04) 0.03) SF-12- CS b 4.8 (1.0, 8.5) (-1.7, 5.2) (-1.7, 5.3) (-0.4, 6.5) (-0.6, 6.6) (-3.4, ) SF-12- MCS b -0.5 (-4.1, 3.1) (-4.8, 2.1) (-2.4, 4.5) (-2.7, 4.3) (-5.1, 2.0) (-5.9, 1.1) 0.18 a Negative values indicate better (adjusted) mean in that (first named) group compared with comparison group; b ositive values indicate better (adjusted) mean in that (first named) group compared with comparison group; WOMAC= Western Ontario and McMaster Universities Osteoarthritis Index; AQoL-6D= Assessment of Quality of Life instrument version 2; SF-12=12-item Short Form Health Survey; CS= physical component summary; MCS= mental component summary.

10 etable 9: d differences between each acupuncture group compared to control at 12 weeks (with multiple imputation for missing data) in the hypothetical scenario of full adherence to the randomized intervention Needles Laser Sham laser RIMARY Overall pain a -1.5 (-2.4, -0.6) (-1.9, (-2.1, 0.07 WOMAC function a -5.4 (-10.2, -0.7) (-6.3, 2.1) (-8.4, 2.5) 0.29 SECONDARY ain on walking a -1.7 (-2.6, -0.7) (-1.7, 0.2) (-2.2, 0.2) 0.09 ain on standing a -1.1 (-2.0, (-1.5, 0.4) (-2.3, 0.0) 0.05 Activity restriction a -1.2 (-2.2, -0.2) (-2.1, (-2.7, -0.2) 0.03 WOMAC pain a -1.6 (-3.1, (-2.7, 0.2) (-3.2, 0.4) 0.13 AQoL-6D b (-0.07, 0.06) (-0.05, 0.06) (-0.06, 0.07) 0.92 SF-12- CS b 3.8 (-0.3, 7.9) (-2.7, 4.8) (-3.8, 6.7) 0.58 SF-12- MCS b -2.7 (-7.1, 1.6) (-5.2, 2.1) (-6.6, 3.6) 0.56 anegative values indicate better mean in that (first named) group compared with comparison group; bositive values indicate better mean in that (first named) group compared with comparison group; WOMAC= Western Ontario and McMaster Universities Osteoarthritis Index; AQoL 6D= Assessment of Quality of Life instrument version 2; SF 12=12 item Short Form Health Survey; CS= physical component summary; MCS= mental component summary.

11 etable 10: d differences between each acupuncture group compared to control at 1 year (with multiple imputation for missing data) in the hypothetical scenario of full adherence to the randomized intervention Needles Laser Sham laser RIMARY Overall pain a -0.9 (-2.1, 0.3) (-1.9, 0.4) (-2.3, 0.22 WOMAC function a -4.9 (-10.5, 0.7) (-6.1, 4.7) (-10.4, 5.5) 0.54 SECONDARY ain on walking a -0.7 (-2.0, 0.6) (-1.5, 0.8) (-1.9, 1.0) 0.52 ain on standing a -0.6 (-1.8, 0.6) (-1.4, 1.0) (-2.4, 0.7) 0.27 Activity restriction a -1.4 (-2.6, -0.2) (-1.7, 0.6) (-2.0, 0.9) 0.44 WOMAC pain a -1.7 (-3.5, 0.0) (-2.2, 1.3) (-3.3, 2.2) 0.69 AQoL-6D b (-0.09, 0.06) (-0.05, 0.07) (-0.11, 0.09) 0.86 SF-12- CS b 3.4 (-1.7, 8.4) (-5.2, 4.3) (-6.6, 4.8) 0.76 SF-12- MCS b -0.9 (-6.3, 4.4) (-6.3, 4.4) (-8.2, 7.0) 0.87 anegative values indicate better mean in that (first named) group compared with comparison group; bositive values indicate better mean in that (first named) group compared with comparison group; WOMAC= Western Ontario and McMaster Universities Osteoarthritis Index; AQoL 6D= Assessment of Quality of Life instrument version 2; SF 12=12 item Short Form Health Survey; CS= physical component summary; MCS= mental component summary.

12 etable 11: Number (percentage) of participants reporting global improvement and estimated odds ratios (OR) from mixed effects regression models (complete case analysis) Number (%) improved Compared to control group Other planned contrasts Needles Laser Sham laser Needles vs Needles vs Laser Sham laser Control Needles Laser Sham laser Laser vs Sham laser Improvement a in OR OR OR OR OR OR (95% CI) 12 weeks n=68 n=63 n=65 n=57 ain 22 (32%) 48 (76%) 42 (65%) 41 (72%) 6.7 (3.1, 14.5)*** Function 21 (31%) 42 (67%) 38 (58%) 38 (67%) 4.5 (2.2, 9.3)*** Overall 22 (32%) 48 (76%) 40 (62%) 37 (65%) 6.7 (3.1, 14.5)*** 3.8 (1.9, 7.8)*** 3.2 (1.5, 6.4)** 3.4 (1.6, 6.8)** 5.4 (2.5, 11.6)*** 4.5 (2.1, 9.5)*** 3.9 (1.8, 8.1)*** 1.8 (0.8, 3.8) 1.3 (0.6, 2.8) 0.7 (0.3, 1.5) 1.4 (0.7, 2.9) 1.0 (0.5, 2.1) 0.7 (0.3, 1.5) 2.0 (0.9, 4.3) 1.7 (0.8, 3.8) 0.9 (0.4, 1.8) 1 year n=60 n=57 n=57 n=51 ain 12 (20%) 28 (49%) 30 (53%) 24 (47%) 3.9 (1.7, 8.8)** 4.4 (2.0, 1*** 3.6 (1.5, 8.2)** 0.9 (0.4, 1.8) 1.1 (0.5, 2.3) 1.3 (0.6, 2.7) Function 10 (17%) 28 (49%) 26 (46%) 21 (41%) 4.8 (2.1, 11.4)*** 4.2 (1.8, 9.9)** 3.5 (1.5, 8.4)** 1.2 (0.6, 2.4) 1.4 (0.6, 3.0) 1.2 (0.6, 2.6) Overall 12 (20%) 28 (49%) 29 (51%) 25 (49%) 3.9 (1.7, 8.8)** 4.1 (1.8, 9.4)** 3.9 (1.7, 8.9)** 0.9 (0.5, 1.9) 1.0 (0.5, 2.1) 1.1 (0.5, 2.3) a participants who rated themselves as much better or slightly better on a 5-point ordinal scale (ranging from much worse to much better); **<0.01;***<0.001.