Yamamoto 1994.

Methods	Randomised Controlled Trial Double‐blind Blinded assessor. Parallel‐group Multicentre (n=31) Safety analysis: ITT, n=199 Efficacy analysis: per protocol, n= 182‐184
Participants	Country: Japan Mean age: 66 % Female: 78 Mean disease duration: Not reported Duration: 5 wk Number randomised:203 (NRD 102, Artz 101) Inclusion: knee OA with definite pain or inflammatory symptom & demonstrating on xray 1 of: osteophyte formation, joint space narrowing, osteosclerosis age >=20 < 80 y if bilateral lesions, only one of lesions which satisfied criteria was selected Exclusion: definite 2o knee OA operation indicated oral or IV steroid or ia steroid or other drug within 2 wk of start of study NSAID or new PT within 2 wk lesion in hip or ankle of affected side RA pregnant, breast feeding or possibly pregnant judged by physician to be in‐ appropriate as study subject Baseline values: % pt moderate spontaneous pain NRD:31, Artz:31 % pt moderate walking disorder NRD:40, Artz:41
Interventions	NRD101 (25 mg/2.5 ml) 5 weekly injections Artz (25 mg/2.5 ml) 5 weekly injections No local anesthetics. Concurrent therapy: Analgesics, NSAIDs & physical therapy continued but no "new" therapy per‐ mitted
Outcomes	clinical findings:4 grades of none, mild, moderate, severe for pain:spontaneous, pressure,night, on passive movement, inflammation: swelling of soft part of jt, floating patella, local feverish feeling, synovial fluid retention, activities of daily living disorder: sitting upright, up/down stairs, standing up, squatting, walking passive movement: flexion/extension, drainage: volume efficacy assessed by MD: overall im‐ provement: 7 grades: marked improvement, moderate im‐ provement, slight improve‐ ment, un‐ changed,slight aggravation,moderate aggrava‐ tion, marked aggravation) pt. impression ‐ how they felt about changes in symptoms (very good, good,fair, cannot say good or not, bad) comprehensive assessment based on 3: final overall improvement ratings (8 grades: same as above+ unassessable), global safety (5 grades: no adverse reaction,mild AR, moderate AR, severe AR, unassessable), usefulness (8 grades:very use‐ ful,useful,slightly useful,cannot say useful or not, slightly undesir‐ able, undesirable, very undesirable, un‐ assessable)
Notes	Jadad's: 5/5 R‐2,B‐2,W‐1 MD who did inj different from MD who did assess‐ ment In case of bilateral OA, only one knee was evaluated. Bilateral: NRD 53, Artz 44; Unilateral: NRD 42, Artz 43 Puncture and drainage done as required. Artz provided by Seikagaku Corporation. M. Nakajima performed statistical analysis.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Low risk	A ‐ Adequate