Bradley 1994.

Methods	Randomised controlled trial 2‐arm parallel group design Trial duration: 4 weeks Randomisation stratified according to centre Multicentre trial with 2 centres Power calculation: reported and protocol based for 3 pain scales Funding by non‐profit organisation: no information provided
Participants	48 patients were randomised in study centre A*, 33 in study centre B 81 patients with osteoarthritis were reported at baseline Affected joints: 81 knees Number of females: 41 of 48 (85%) in centre A, 7 of 33 (21%) in centre B Average age: 58 years in centre A, 63 years in centre B Average disease duration: 10.9 years in centre A, 12.4 years in centre B Radiographic severity of OA: (% grade 2/% grade 3) in site A: 62.5%/37.5% in SAMe,  54%/46% in placebo. In site B: 59%/41% in SAMe, 69%/31% in placebo
Interventions	Experimental intervention: S‐Adenosylmethionine, on 5 consecutive days intravenous 400 mg once daily, then oral 200 mg 3 times daily Control intervention: placebo, on 5 consecutive days intravenous once daily, then oral 3 times daily Treatment duration: 4 weeks Analgesics other than study drugs allowed, intake assessed and found to be lower in SAMe group compared to placebo at site A, and higher in SAMe compared to placebo at site B.
Outcomes	Extracted pain outcome: pain on walking after 4 weeks, described as "walking pain" Extracted function outcome: walking disability after 4 weeks, described as "walking distance before having to stop because of knee pain" Primary outcome: > 2 reported; for HAQ pain, rest pain and walking pain
Notes	*In the original report the investigators presented results separately for site A and B, because the randomisation, although concealed, resulted in marked baseline differences between patients at the 2 sites with respect to demographic and disease related characteristics
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Use of random‐number table
Allocation concealment?	Low risk	Use of coded pharmacy
Blinding of patients?	Low risk	The trial was described as a double‐blind study randomising patients to indistinguishable interventions
Blinding of physicians?	Unclear risk	No information provided
Blinding of outcome assessors?	Unclear risk	No information provided
Interventions reported as indistinguishable?	Low risk	Quote: "Placebo Injectate and placebo tablets were employed that contained the same stabilizers and inert ingredients as the active agent and were packaged identically."
Double‐dummy technique used?	High risk	—
Intention‐to‐treat analysis performed? Pain	High risk	Center A: no information provided. Center B: 13 out of 17 (76%) in SAMe group, 14 out of 16 (87%) in placebo group analysed.
Intention‐to‐treat analysis performed? Function	High risk	See above
Funding by commercial organisation avoided?	High risk	Supported by a grant from Asta Medica