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Table S1. Search Strategy MEDLINE (up to February 2016) 1. randomized controlled trial/ or controlled clinical trial.pt. or comparative study.pt or clinical trial.pt. or randomized.ab. or randomised.ab or randomly.ab,ti. or trial.ab,ti. 2. placebos/ or placebo effect/ or placebo.tw or anti-inflammatory agents, non-steroidal/ or anti-inflammator*.tw or nsaid*.tw. or acetylsalicyl* or or or alclofenac or or or or or or or or or or or or or tiapro* or metamizol or or or or or or nabumeton or .tw 3. 1 and 2 4. back pain/ or low back pain/ or dorsalgia.ti,ab. or backache.ti,ab. or (lumbar adj pain).tw. or lumbago.tw or back disorder*.tw. or neck pain/ or neck pain.tw. 5. 3 and 4 6. limit 5 to humans EMBASE (up to February 2016) 1. 'randomized controlled trial (topic)' or randomized:ab or randomised:ab or randomly:ab 2. 'placebo'/exp or placebo:ti or placebo:ab 3. #1 and #2 4. 'nonsteroidal antiinflammatory agent'/exp or 'anti inflammatory':ti or 'anti inflammatory':ab or nsaid*:ti or nsaid*:ab 5. #3 and #4 6. 'low back pain'/exp or 'low back pain' or 'backache'/exp or 'backache' or 'neck pain'/exp or 'neck pain' 7. #5 and #6 8. #7 and [embase]/lim 9. #8 and [humans]/lim 10. #9 and ([article]/lim or [article in press]/lim or [review]/lim) CINAHL (up to February 2016) 1. (MH "Clinical Trials+") or (MH "Comparative Studies") or (MH "Randomized Controlled Trials") or (MH "Clinical Trials+") or ti random* or ab random* 2. (MH "Antiinflammatory Agents, Non-Steroidal+") or (MH "Antiinflammatory Agents, Topical+") or "Antiinflammatory" or "Anti-inflammatory" or ti nsaid* or ab nsaid* 3. 1 and 2 4. (MH "Low Back Pain") or (MH "Back Pain+") or "dorsalgia" or "backache" or "lumbago" or (MH "Neck Pain") 5. 3 and 4 6. 5 limited to humans CENTRAL (up to February 2016) 1. MeSH descriptor: [Back Pain] explode all trees or MeSH descriptor: [Low Back Pain] explode all trees or (lumbar next pain) or (coccyx) or (coccydynia) or (sciatica) or (spondylosis) or MeSH descriptor: [Spinal Diseases] explode all trees or (lumbago) or (discitis) or (disc near degeneration) or (disc near prolapse) or (disc near herniation) or back disorder* or back near pain or MeSH descriptor: [Neck Pain] explode all trees or neck pain or neck disorder* 2. MeSH descriptor: [Anti-Inflammatory Agents, Non-Steroidal] explode all trees or nsaid* 3. 1 and 2 4. 3 limited to trials

LILACS (up to February 2016) 1. (anti-inflammatory or antiinflamatorio or anti-inflamatorio or anti-inflammatories or antiinflamatorios or anti- inflamatorios or NSAIDs or AINEs) and (osteoarthritis or osteoartrite or back pain or dor lombar or lumbago or lombalgia or backache or neck pain or dor cervical or knee pain or hip pain)

Table S2. Characteristics of included studies Details of Interventions (dose NSAID Outcomes and Study Country participants regimens) class time points 50 sciatica patients (group Group 1: Indomethacin 25 1=25, group mg, 1 capsule, 3 times Adverse effects; Goldie 1968 Sweden 2=25); mean age daily, 75 mg total; Group 2: at 2 weeks (SD)=NR; 52% Oral placebo male 110 back pain Group 1: Indomethacin 25 with or without mg, 1 capsule, 3 times sciatica patients daily, 75 mg total for 2 United Adverse effects; Jacobs 1968 (group 1=55, days, then 1 capsule 4 Acetic acid Kingdom at 1 week group 2=55); times daily, 100 mg total for mean age 5 days; Group 2: Oral (SD)=NR placebo Group 1: Phenylbutazone 23 sciatica 100 mg, 1 tablets, 6 times patients (group daily, 600 mg total for 2 United Adverse effects; Radin 1968 1=12, group days, then 1 tablet, 3 times Enolic acid States at 1 week 2=11); mean age daily, 300 mg total for 8 (SD)=NR days; Group 2: Oral placebo 90 acute back Group 1: Indomethacin 25 pain patients mg, 2 capsules, 3 times (group 1=30, daily, 150 mg total; Group Acetic group 2=30, Adverse effects; Goldie 1970 Sweden 2: 500 mg, 2 acid; group 3=30); age at 1 week capsules, 3 times daily, Salicylates (range)=15 to 69 3000 mg total; Group 3: years; 56 % Oral placebo male Group 1: Phenylbutazone 57 sciatica 200 mg, 2 tablets, 3 times patients (group daily, 1200 mg total for 3 Use of rescue 1=28, group Weber 1980 Norway days, then 1 tablet, 3 times Enolic acid ; at 1 2=29); mean age daily, 600 mg total for 2 week (SD)=41.0 (13.3) days; Group 2: Oral years; 54% male placebo Group 1: Naproxen Sodium 37 acute back 275 mg, 2 capsules, 2 Pain (10 cm pain patients; times daily, 1100 mg total; Propionic Berry 1982 United VAS); Adverse mean age Group 2: Diflunisal 250 mg, acid; (cross-over) Kingdom effects; at 1 (SD)=55.0 (11.8) 2 tablets, 2 times daily, Salicylates week years; 35% male 1000 mg total; Group 3: Oral placebo 30 acute back pain patients Group 1: Diflunisal 500 mg, Pain (4-point (group 1=15, Jagemann 2 tablets, once daily, 1000 scale); Disability Germany group 2=15); age Salicylates 1983 mg total; Group 2: Oral (4-point scale); (range)=18 to 57 placebo at 1 week years; 47 % male 282 acute back Group 1: Piroxicam 20 mg, Pain (100 mm pain patients 2 capsules, once daily for 2 VAS); Adverse (group 1=140, days, 40 mg total, then 1 effects; Use of Amlie 1987 Norway Enolic acid group 2=142); capsule, once daily for 5 rescue mean age=37.9 days, 20 mg total; Group 2: medication; at 1 years; 60% male Oral placebo week 89 acute back pain patients Group 1: Diflunisal 500 mg, Basmajian (group 1=44, 1 tablets, twice daily, 1000 Adverse effects; Canada Salicylates 1989 group 2=45); mg total; Group 2: Oral at 1 week mean age placebo (SD)=NR 204 sciatica Group 1: 200 mg, patients (group 1 tablet, 3 times daily, 600 Pain (100 mm 1=74, group mg total; Group 2: VAS); Adverse Bontoux 1990 France 2=69, group Acetic acid Diclofenac 50 mg, 1 tablet, effects; at 1 and 3=71); mean age 3 times daily, 150 mg total; 5 days (SD)=45.7 (13.2) Group 3: Oral placebo years; 59% male 147 sciatica Group 1: Piroxicam 40 mg, patients (group Pain (100 mm intramuscular injection, Gendrault 1=75, group VAS); Adverse France once daily, 40 mg total; Enolic acid 1992 2=72); mean effects; at 5 Group 2: Placebo saline age=44.0 years; days injection 58% male Pain (100 mm Group 1: Piroxicam 20 mg, 214 sciatica VAS); Disability 2 capsules, once daily, 40 patients (group (RMDQ); mg total for 2 days, then 1 Weber 1993 Norway 1=120, group Enolic acid Adverse effects; capsule, once daily, 20 mg 2=94); mean Use of rescue total for 12 days; Group 2: age=48.0 years medication; at 1 Oral placebo and 4 weeks 172 back pain with or without Group 1: Diclofenac sciatica patients Sodium 75 mg, Pain (100 mm Babej-Dolle (group 1=86, intramuscular injection, Germany Acetic acid VAS); Adverse 1994 group 2=86); once daily, 75 mg total; effects; at 1 day mean age Group 2: Placebo saline (SD)=50.6 (16.3) injection years; 54% male 73 acute back Group 1: 20 mg, pain patients intramuscular injection on (group 1=37, day 1, then 1 tablet, once Pain (10 cm Szpalski 1994 Belgium group 2=36); daily for 14 days, 20 mg Enolic acid VAS); at 1 week mean age total; Group 2: Matching (SD)=38.2 (9.8) intramuscular injection or years; 64% male oral placebo Group 1: Etodolac 300 mg, 194 sciatica 1 tablet, single dose, 300 Pain (100 mm patients (group mg total; Group 2: VAS); Adverse 1=67, group Acetic Tenoxicam 20 mg, effects; Use of Ghozlan 1996 France 2=66, group acid; intramuscular injection, rescue 3=61); mean age Enolic acid single dose, 20 mg total; medication; at 4 (SD)=42.0 (12.4) Group 3: Placebo saline and 12 hours years; 63% male injection 532 sciatica patients (group Group 1: Meloxicam 15 mg, 1=171, group 1 tablet, once daily, 15 mg Pain (100 mm Six 2=181, group total; Group 2: Meloxicam VAS); Adverse Dreiser 2001 Enolic acid countries 3=180); mean 7.5 mg, 1 tablet, once daily, effects; at 1 age (SD)=47.0 7.5 mg total; Group 3: Oral week (14.3) years; placebo 44% male 126 acute back pain patients Group 1: Ibuprofen 200 mg, Pain (6-point (group 1=106, United 2 tablets, 3 times daily, Propionic scale); Adverse Nadler 2002 group 2=20); States 1200 mg total; Group 2: acid effects; at 2 mean age Oral placebo days (SD)=NR; 40% male Pain (100 mm 319 chronic back VAS); Disability pain patients Group 1: Etoricoxib 90 mg, (RMDQ); (group 1=107, 1 capsule, once daily, 90 Quality of life United group 2=103, mg total; Group 2: COX-2 Birbara 2003 (SF-12); States group 3=109); Etoricoxib 60 mg, 1 inhibitor Adverse effects; mean age capsule, once daily, 60 mg Use of rescue (SD)=52.0 (13.0) total; Group 3: Oral placebo medication; at 1 years; 39% male and 12 weeks 372 acute back Group 1: Diclofenac 12.5 Pain (100 mm pain patients mg, 1 or 2 tablets, 4 to 6 VAS); Disability (group 1=124, times daily, 150 mg Acetic (RMDQ); group 2=122, maximum; Group 2: acid; Dreiser 2003 France Quality of life group 3=126); Ibuprofen 200 mg, 1 or 2 Propionic (SF-12); mean age tablets, 4 to 6 times daily, acid Adverse effects; (SD)=40.9 (11.2) 1200 mg maximum; Group at 1 week years; 49% male 3: Oral placebo 690 chronic back Pain (100 mm pain patients Group 1: 50 mg, VAS); Disability (group 1=229, 1 tablet, once daily, 50 mg (RMDQ); Katz 2003 (2 United group 2=233, total; Group 2: Rofecoxib COX-2 Quality of life trials) States group 3=228); 25 mg, 1 tablet, once daily, inhibitor (SF-12); mean age 25 mg total; Group 3: Oral Adverse effects; (SD)=53.4 (13.1) placebo at 1 and 4 years; 38% male weeks 108 acute back pain patients Group 1: Ibuprofen 200 mg, Pain (6-point (group 1=12, United 2 tablets, 3 times daily, Propionic scale); Adverse Nadler 2003-a group 2=96); States 1200 mg total; Group 2: acid effects; at 5 mean age Oral placebo days (SD)=36.7 (10.8) years 38 acute back Group 1: Ibuprofen 200 mg, Pain (6-point United pain patients 2 tablets, 3 times daily, Propionic scale); Adverse Nadler 2003-b States (group 1=34, 1200 mg total; Group 2: acid effects; at 5 group 2=4); Oral placebo days mean age (SD)=NR

293 chronic back Pain (10 cm pain patients VAS); Disability United (group 1=148, Group 1: 40 mg, COX-2 (RMDQ); Coats 2004 States & group 2=145); 1 tablet, once daily, 40 mg inhibitor Adverse effects; Canada mean age total; Group 2: Oral placebo at 1 and 4 (SD)=48.6 (12.9) weeks years; 43% male Pain (100 mm 325 chronic back VAS); Disability pain patients Group 1: Etoricoxib 90 mg, (RMDQ); (group 1=106, 1 tablet, once daily, 90 mg Quality of life United group 2=109, total; Group 2: Etoricoxib 60 COX-2 Pallay 2004 (SF-12); States group 3=110); mg, 1 tablet, once daily, 60 inhibitor Adverse effects; mean age mg total; Group 3: Oral Use of rescue (SD)=52.8 (13.0) placebo medication; at 1 years; 38% male and 12 weeks 120 acute back Pain (10-point pain patients Group 1: Diclofenac 50 mg, NRS); Disability (group 1=60, 1 tablet, 2 times daily, 100 (RMDQ); Hancock 2007 Australia group 2=60); Acetic acid mg total; Group 2: Oral Adverse effects; mean age placebo at 1 and 12 (SD)=40.7 (15.6) weeks years; 56% male 180 chronic back pain patients Group 1: Piroxicam patch (group 1=60, Pain (100 mm 14 mg daily; Group 2: group 2=60, VAS); Adverse Allegrini 2009 Italy Piroxicam 1% cream, 1.4 g Enolic acid group 3=60); effects; at 9 daily; Group 3: Placebo mean age days patch (SD)=51.0 (14.8) years; 43% male Group 1: 8 mg, 2 capsules, once daily plus 1 capsule after 8 hours, 24 171 sciatica mg total for 1 day, then 2 patients (group capsules, once daily, 16 mg Pain (100 mm 1=57, group Enolic Herrmann total for 3 days; Group 2: VAS); Adverse Germany 2=57, group acid; 2009 Diclofenac 50 mg, 1 tablet, effects; at 4 3=57); mean age Acetic acid once daily, 50 mg total for 1 days (SD)=49.7 (13.4) day, then 1 tablet, 3 times years; 44% male daily, 150 mg total for 3 days; Group 3: Oral placebo 153 neck pain Group 1: Diclofenac patch Pain (10 cm patients (group 60 mg, hydrophilic VAS); Disability 1=97, group Hsieh 2010 Taiwan adhesive, 3 times daily, 180 Acetic acid (NDI); Adverse 2=56); mean age mg total; Group 2: Placebo effects; at 1 (SD)=38.4 (10.7) patches week years; 17% male 129 chronic back Pain (10 cm pain patients Group 1: Naproxen 500 mg, VAS); Disability (group 1=88, United 1 tablet, 2 times daily, 1000 Propionic (RMDQ); Katz 2011 group 2=41); States mg total; Group 2: Oral acid Adverse effects; mean age placebo at 1 and 8 (SD)=52.1 (14.8) weeks years; 50% male 525 chronic back Pain (10 cm pain patients Group 1: Naproxen 500 mg, VAS); Disability (group 1=295, United 1 tablet, 2 times daily, 1000 Propionic (RMDQ); Kivitz 2013 group 2=230); States mg total; Group 2: Oral acid Adverse effects; mean age placebo at 2 and 8 (SD)=51.8 (17.0) weeks years; 47% male 72 neck pain Pain (10 cm patients (group Group 1: Diclofenac VAS); Disability 1=36, group diethylamine 1.16% gel (2 Predel 2013 Germany Acetic acid (NDI); Adverse 2=36); mean g), applied topically, 4 times effects; at 5 age=33.8 (10.7) daily; Group 2: Placebo gel days years; 46% male 62 chronic back pain patients Group 1: Diclofenac 50 mg, Pain (100 mm (group 1=37, Von Heymann 1 tablet, 3 times daily, 150 VAS); Disability Germany group 2=25); Acetic acid 2013 mg total; Group 2: Oral (RMDQ); at 1 mean age placebo week (SD)=38.2 (10.1) years; 54% male 30 chronic back pain patients Group 1: Ibuprofen 200 mg, Pain (6-point (group 1=5, United 2 tablets, 3 times daily, COX-2 scale); Disability Stark 2014 group 2=25); States 1200 mg total; Group 2: inhibitor (RMDQ); at 8 mean age Oral placebo hours (SD)=29.8 (7.2) years; 43% male 40 chronic back pain patients on Group 1: Parecoxib 40 mg, Pain (10 cm Wetzel 2014 opioid therapy; intravenous injection, once VAS); Disability Austria Acetic acid (cross-over) mean age daily, 40 mg total; Group 2: (RMDQ); at 30 (SD)=57.2 (12.8) Intravenous placebo minutes years; 35% male VAS = Visual Analogue Scale, NRS = Numeric Rating Scale, NR = Not Reported, SD = Standard Deviation, RMDQ = Roland-Morris Disability Questionnaire, SF-12 = 12-item Short Form Health Survey, NDI = Neck Disability Index

Table S3. Calculation of Effect Sizes for Immediate and Short-term Pain Outcomes Mean (SD), Mean (SD), NSA Plac Anal Ra Extracted Converted† IDs ebo Outcome ytic Author, Year ng Gro Gro MD (95% CI) Scale NSAID Placeb NSAID Place Met e up, up, s o s bo hod n n Immediate-term 0– –76.0 –68.0 –76.0 –68.0 –8.0 (–16.4 Amlie 1987 VAS 10 134 132 CS (35.0) (35.0) (35.0) (35.0) to 0.4) 0 0– –24.2 –15.5 –24.2 –15.5 –8.7 (–17.7 Bontoux 1990-a VAS 10 62 30 CS (20.8) (20.0) (20.8) (20.0) to 0.3) 0 0– –21.8 –15.5 –21.8 –15.5 –6.3 (–15.3 Bontoux 1990-b VAS 10 59 31 CS (21.0) (20.0) (21.0) (20.0) to 2.7) 0 0– 9.7 17.3 9.7 17.3 –7.6 (–12.5 Gendrault 1992 VAS 10 (15.1** (15.1** 75 72 FV (15.1) (15.1) to –2.7) 0 ) ) 0– 40.6§ 40.6§ 40.6 40.6 0.0 (–5.6 to Weber 1993 VAS 10 (21.9** (19.4** 120 94 FV (21.9) (19.4) 5.6) 0 ) ) 0– 41.7 54.8 41.7 54.8 –13.1 (–20.8 Babej-Dolle 1994 VAS 10 86 86 FV (25.9) (25.3) (25.9) (25.3) to –5.4) 0 0– 1.9 2.8 19.4 28.1 –8.7 (–18.2 Szpalski 1994 VAS 33 35 FV 10 (2.0) (1.9) (20.3) (19.6) to 0.8) 0– 45.9§ 53.8§ 45.9 53.8 –7.9 (–16.8 Ghozlan 1996-a VAS 10 (20.8** (20.0** 67 30 FV (20.8) (20.0) to 1.0) 0 ) ) 0– 47.6§ 53.8§ 47.6 53.8 –6.2 (–12.6 Ghozlan 1996-b VAS 10 (15.1** (15.1** 66 31 FV (15.1) (15.1) to 0.2) 0 ) ) 0– –46.0 –40.0 –46.0 –40.0 –6.0 (–12.7 Dreiser 2001-a VAS 10 171 90 CS (26.2) (26.8) (26.2) (26.8) to 0.7) 0 0– –45.0 –40.0 –45.0 –40.0 –5.0 (–11.8 Dreiser 2001-b VAS 10 181 90 CS (26.9) (26.8) (26.9) (26.8) to 1.8) 0 0– –31.5 –17.7 –31.5 –17.7 –13.8 (–20.9 Birbara 2003-a VAS 10 107 54 CS (23.8)§ (16.9)§ (23.8) (16.9) to –6.7) 0 0– –33.1 –17.7 –33.1 –17.7 –15.4 (–22.4 Birbara 2003-b VAS 10 101 53 CS (23.1)§ (16.7)§ (23.1) (16.7) to –8.4) 0 0– – –37.5 –48.4 –37.5 –10.9 (–20.0 Dreiser 2003-a VAS 10 48.4(2 107 46 CS (26.9) (26.1) (26.9) to –1.8) 0 6.1) 0– –48.8 –37.5 –48.8 –37.5 –11.3 (–20.0 Dreiser 2003-b VAS 10 103 46 CS (24.0) (26.9) (24.0) (26.9) to –2.6) 0 0– –33.6 –20.4 –33.6 –20.4 –13.2 (–18.8 Katz 2003-a VAS 10 (27.4† (19.1† 229 114 CS (27.4) (19.1) to –7.6) 0 †) †) 0– –33.8 –20.4 –33.8 –20.4 –13.4 (–18.8 Katz 2003-b VAS 10 (26.5† (19.1† 233 114 CS (26.5) (19.1) to –8.0) 0 †) †) 0– 47.0§ 58.0§ 47.0 58.0 –11.0 (–17.2 Coats 2004 VAS 10 148 145 FV (27.4¶) (26.9¶) (27.4) (26.9) to –4.8) 0 0– –29.6§ –13.9§ –29.6 –13.9 –15.7 (–22.3 Pallay 2004-a VAS 10 106 55 CS (22.3¶) (16.1¶) (22.3) (16.1) to –9.0) 0 0– –30.4§ –13.9§ –30.4 –13.9 –16.5 (–23.2 Pallay 2004-b VAS 10 109 55 CS (22.7¶) (16.1¶) (22.7) (16.1) to –9.8) 0 0– –2.0 (–6.9 to ANC Hancock 2007 VAS NA|| NA|| NA|| NA|| 60 60 10 2.9)† OVA 0– 38.3 47.6 38.3 47.6 –9.3 (–21.0 Allegrini-a 2009 VAS 10 60 30 FV (26.6) (26.6) (26.6) (26.6) to 2.4) 0 0– 42.2 47.6 42.2 47.6 –5.4 (–15.7 Allegrini-b 2009 VAS 10 60 30 FV (21.7) (26.6) (21.7) (26.6) to 4.9) 0 0– –20.5 –14.9 –20.5 –14.9 –5.6 (–10.0 Herrmann 2009-a VAS 10 57 57 CS (12.3) (12.3) (12.3) (12.3) to –1.2) 0 0– –24.1 –13.7 –24.1 –13.7 –10.4 (–21.9 Herrmann 2009-b VAS 10 (25.9** (25.3** 57 29 CS (25.9) (25.3) to 1.1) 0 ) ) 0– 2.6 3.9 25.7 39.2 –13.5 (–19.3 Hsieh 2010 VAS 97 56 FV 10 (1.8) (1.8) (17.5) (18.0) to –7.7) 0– –2.1§ –1.3§ –21.0 –13.0 –8.0 (–13.9 Katz 2011 VAS 88 41 CS 10 (2.0‡) (1.4‡) (20.3) (13.9) to –2.1) 0– –1.8§ –1.3§ –18.1 –13.1 –5.0 (–8.4 to Kivitz 2013 NRS 295 230 CS 10 (2.0¶) (1.9¶) (20.1) (19.3) –1.6) 0– 1.2 19.2 1.2 19.2 –18.0 (–22.0 Predel 2013 VAS 10 36 36 FV (2.9) (11.9) (2.9) (11.9) to –14.0) 0 0– 34.0§ 33.2§ Von Heymann 34.0 33.2 0.8 (–11.7 to VAS 10 (22.3† (25.3† 36 22 FV 2013 (22.3) (25.3) 13.2) 0 †) †) 0– 4.5 5.1 45.0 51.0 –6.0 (–15.0 Wetzel 2014 VAS 40 40 FV 10 (2.0) (2.1) (20.0) (21.0) to 3.0) Short-term 0– 20.9§ 17.6§ 20.9 17.6 3.3 (–1.5 to Weber 1993 VAS 10 (18.6** (16.5** 120 94 FV (18.6) (16.5) 8.1) 0 ) ) 0– –7.5 (–13.7 ANC Birbara 2003-a VAS 10 NA|| NA|| NA|| NA|| 107 54 to –1.3) OVA 0 0– –10.5 (–16.7 ANC Birbara 2003-b VAS 10 NA|| NA|| NA|| NA|| 101 53 to –4.2) OVA 0 0– –13.8 (–18.4 ANC Katz 2003-a VAS 10 NA|| NA|| NA|| NA|| 229 114 to –9.2) OVA 0 0– –13.5 (–18.1 ANC Katz 2003-b VAS 10 NA|| NA|| NA|| NA|| 233 114 to –8.9) OVA 0 0– 34.0 44.5 34.0 44.5 –10.5 (–16.7 Coats 2004 VAS 10 148 145 FV (27.4¶) (26.9¶) (27.4) (26.9) to –4.3) 0 0– –12.7 (–18.6 ANC Pallay 2004-a VAS 10 NA|| NA|| NA|| NA|| 106 55 to –6.8) OVA 0 0– –12.1 (–18.0 ANC Pallay 2004-b VAS 10 NA|| NA|| NA|| NA|| 109 55 to –6.2) OVA 0 0– –1.0 (–5.9 to ANC Hancock 2007 VAS NA|| NA|| NA|| NA|| 60 60 10 3.9) OVA 0– –2.6§ –2.2§ –26.0 –22.0 –4.0 (–11.1 Katz 2011 VAS 88 41 CS 10 (2.0‡) (1.4‡) (20.9) (14.3) to 3.1) 0– –1.7§ –1.4§ –17.7 –14.0 –3.7 (–7.5 to Kivitz 2013 NRS 295 230 CS 10 (2.2¶) (2.2¶) (21.8) (22.1) 0.1) SD = Standard Deviation, NRS = Numerical Rating Scale, VAS = Visual Analogue Scale, FV = Final Value, CS = Change Score, ANCOVA = Analysis of Covariance, NA = Not Applicable, CI = Confidence Interval * SD from baseline † Converted to a common 0 to 100 scale when necessary, and used to calculate treatment effect ‡ SD calculated from the sample size, mean and p-value § Mean and/ or SD calculated from graphs || Mean difference and 95% CI were provided ¶ SD calculated using SE and sample size ** SD adopted from similar studies, or from all groups within the same study †† SD calculated using 95% CI

Table S4. Calculation of Effect Sizes for Immediate and Short-term Disability Outcomes Mean (SD), Mean (SD), NSA Plac Anal Ra Extracted Converted† IDs ebo Outcome ytic Author, Year ng Gro Gro MD (95% CI) Scale NSAID Placeb NSAID Place Met e up, up, s o s bo hod n n Immediate-term 0– 8.7§ 8.5§ 51.2 50.0 1.2 (–3.8 to Weber 1993 RMDQ 120 94 FV 17 (3.3**) (2.9**) (19.3) (17.1) 6.1) 0– –5.6§ –3.1§ –23.4 –12.9 –10.4 (–15.1 Birbara 2003-a RMDQ 107 54 CS 24 (3.3¶) (3.7¶) (13.8) (15.3) to –5.7) 0– –5.4§ –3.1§ –22.5 –12.9 –9.6 (–14.8 Birbara 2003-b RMDQ 101 53 CS 24 (3.8¶) (3.6¶) (15.9) (15.3) to –4.4) 0– –8.6 –5.7 –35.9 –23.8 –12.1 (–20.2 Dreiser 2003-a RMDQ 106 45 CS 24 (5.7) (5.3) (23.8) (22.1) to –4.0) 0– –8.1 –5.7 –33.8 –23.8 –10.0 (–17.7 Dreiser 2003-b RMDQ 102 45 CS 24 (5.2) (5.3) (21.7) (22.1) to –2.4) 0– 9.1§ 11.7§ 37.9 48.8 –10.8 (–16.0 Katz 2003-a RMDQ 229 114 FV 24 (6.1¶) (4.3¶) (25.2) (17.8) to –5.7) 0– 9.1§ 11.7§ 37.9 48.8 –10.8 (–16.0 Katz 2003-b RMDQ 233 114 FV 24 (6.1¶) (4.3¶) (25.5) (17.8) to –5.6) 0– 8.8§ 10.2§ 36.5 42.5 –6.0 (–11.2 Coats 2004 RMDQ 148 145 FV 24 (5.5¶) (5.4¶) (22.8) (22.4) to –0.9) 0– –4.9§ –2.7§ –20.2 –11.4 –8.8 (–13.9 Pallay 2004-a RMDQ 106 55 CS 24 (3.9¶) (3.3¶) (16.3) (13.9) to –3.8) 0– –5.0§ –2.7§ –20.9 –11.4 –9.5 (–15.3 Pallay 2004-b RMDQ 109 55 CS 24 (4.7¶) (3.3¶) (19.6) (13.9) to –3.7) 0– –2.1 (–7.5 to ANC Hancock 2007 RMDQ NA|| NA|| NA|| NA|| 60 60 24 3.3) OVA 0– 11.3 11.7 22.5 23.5 –1.0 (–2.8 to Hsieh 2010 NDI 97 56 FV 50 (2.8) (2.9) (5.5) (5.7) 0.9) 0– –3.9§ –3.3§ –16.3 –13.8 –2.5 (–7.1 to Katz 2011 RMDQ 88 41 CS 24 (3.7‡) (2.6‡) (15.6) (10.6) 2.1) 0– 2.8 14.6 5.6 29.2 –23.6 (–28.5 Predel 2013 NDI 36 36 FV 50 (3.0) (6.8) (6.0) (13.6) to –18.7) Von Heymann 0– 8.8§ 10.8§ –23.6 –17.4 –6.2 (–20.3 RMDQ 36 22 CS 2013 24 (9.5††) (6.9††) (7.4) (7.4) to 7.9) Short-term 0– 4.8§ 4.4§ 28.2 25.9 2.4 (–2.6 to Weber 1993 RMDQ 120 94 FV 17 (3.3**) (2.9**) (19.3) (17.1) 7.3) 0– –8.6 (–14.4 ANC Birbara 2003-a RMDQ NA|| NA|| NA|| NA|| 107 54 24 to –2.8) OVA 0– –10.1 (–16.1 ANC Birbara 2003-b RMDQ NA|| NA|| NA|| NA|| 101 53 24 to –4.1) OVA 0– –9.6 (–13.7 ANC Katz 2003-a RMDQ NA|| NA|| NA|| NA|| 229 114 24 to –5.4) OVA 0– –9.2 (–13.2 ANC Katz 2003-b RMDQ NA|| NA|| NA|| NA|| 233 114 24 to –5.1) OVA 0– 7.3§ 8.5§ 30.4 35.3 –4.9 (–10.1 Coats 2004 RMDQ 148 145 FV 24 (5.5¶) (5.4¶) (22.8) (22.4) to 0.3) 0– –9.9 (–15.4 ANC Pallay 2004-a RMDQ NA|| NA|| NA|| NA|| 106 55 24 to –4.4) OVA 0– –11.8 (-17.2 ANC Pallay 2004-b RMDQ NA|| NA|| NA|| NA|| 109 55 24 to –6.4) OVA 0– –0.4 (–5.4 to ANC Hancock 2007 RMDQ NA|| NA|| NA|| NA|| 60 60 24 4.5) OVA 0– –4.8§ –4.6§ –20.0 –19.2 –0.8 (–2.2 to Katz 2011 RMDQ 88 41 CS 24 (1.1‡) (0.8‡) (4.7) (3.2) 0.5) SD = Standard Deviation, RMDQ = Roland-Morris Disability Questionnaire, NDI = Neck Disability Index, FV = Final Value, CS = Change Score, ANCOVA=Analysis of Covariance, NA = Not Applicable, CI = Confidence Interval, * SD from baseline † Converted to a common 0 to 100 scale when necessary, and used to calculate treatment effect ‡ SD calculated from the sample size, mean and p-value § Mean and/or SD calculated from graphs || Mean difference and 95% CI were provided ¶ SD calculated using SE and sample size ** SD adopted from similar studies, from all groups within the same study †† SD calculated using 95% CI