Shichikawa 1983b.

Methods	Randomised Controlled Double‐blind Multicentre (n=16) Safety analysis: ITT, n=103 Efficacy analysis: per protocol, n=98
Participants	Country: Japan Mean age: 62 % Female: 83 Mean disease duration: NR Duration: 5 wk Number randomised:107 (HA 52, PL 55) Inclusion: apparent clinical signs with pain on movement xray at least 1 of joint space narrowing, spur formation, osteosclerosis consent Exclusion: moderate to severe JSN varus or valgus deformities synovial effusion IA corticosteroid injection in past 2 wk pregnant or lactating females hard to communicate cases thought to be inadequate for trial by doctors in charge Baseline values: % pt moderate walking pain HA:52, PL:46 ROM HA:133.4, PL:128.6 pain score HA:1.03, PL:1.12
Interventions	sodium hyaluronate 5.0 ml of 0.5% SPH solution 5 weekly injections + 2 sugar coated lactose pills tid Placebo: 5.0 ml of 0.01% SPH solution 5 weekly injections + 2 sugar coated lactose pills tid Concurrent therapy: No "new" arthritis therapy permitted
Outcomes	pain: rest, walking, up and down stairs, press, flexion and extension, sense of fever, swelling, range of motion, ballotement of patella (4 point scale: no symptom, mild, moderate, severe) disturbance of 4 activities of daily living: walk 10 min, up/down stairs, squat to pick up things from floor, sitting on floor or tatami: 5 ranks: can do as the normal people, scarcely possible by one‐ self and not so in‐ convenient, scarcely possible by oneself but inconvenience necessary for aid, totally impossible diary for activities of daily living and pain (knee pain at rest and at the beginning of motion:0=no pain,1=mild, 2= painful but mo‐ bile,3=painful & immobile,4=un‐ endurable pain & can do nothing) general improve‐ ment (1‐7: sig. improved,moder‐ately improved, lightly improved, no change,lightly worsened, mod‐ erately worsened sig. worsened) impression by pt (1‐7:sig. improved,fairly improved,slightly improved, no change,slightly worsened, fairly worsened, sig. worsened) general evalua‐ tion (1‐7: sig. improved,moder‐ately improved, slightly improved, no change, slightly worsened, moderately worsened, sig. worsened) general safety (1‐3: no side effect,side effect seen but can continue treat‐ ment, stop treat‐ ment because of side effect) usefulness judged on general improvement and general safety: 7 ranks: extremely useful, fairly useful, slightly useful, cannot judge whether useful or not useful, slightly undesir‐ able, fairly unde‐ sirable, extremely unde‐ sirable
Notes	Jadad's:4/5 R‐1,B‐2,W‐1 Pt with moderate to severe synovial effusion excluded. If bilateral, evaluation completed on knee fulfilling entry criteria. Test drug provided by Seikagaku Kogyo Co., Ltd.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Low risk	A ‐ Adequate