Cohen 2008.

Methods	Randomised controlled trial (RCT), blinded, parallel group. Five weekly injections compared to placebo.
Participants	28 participants; aged 50 years of older (30 originally at randomisation); intention to treat consisted of 15 in Hyalgan group (mean age 56.2 (SD 15.1), 1 female, 14 male) and 13 in placebo group (mean age 43.4 (SD 14.9), 2 female, 11 male) diagnosed with ankle OA based on pain and osteoarthritis on X‐ray. Kellgren Lawrence stage 2, 3 and 4 were included.
Interventions	Hyalgan 2 ml intra‐articular 5 weekly injections versus Saline 2 ml intra‐articular 5 weekly injections.
Outcomes	Primary outcome: Ankle Osteoarthritis Scale (AOS) (pain on movement and weightbearing) for ITT population at 3 months. Secondary outcome: Western Ontario and McMasters Universities (WOMAC) osteoarthritis (OA) index of pain, Physical function, Short‐Form 12(SF12). Follow‐up at 2 weeks, 6 weeks, 3 months and 6 months.
Notes	After randomisation 2 participants declined an injection in either group. Results show same outcome as method section. Independent investigator‐sponsored trial funded by Sanofi‐Aventis.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	There is no description how the randomisation was performed.
Allocation concealment (selection bias)	Unclear risk	No description of allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Saline injections were used as comparators to blind participants. While there may be differences in the injection (e.g. difficulty injecting the more viscous hyaluronic acid), we feel it is unlikely that participants would be aware of the difference and that the blinding was adequate.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The treating investigator giving the injections did not conduct the evaluations.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data.
Selective reporting (reporting bias)	Low risk	Adverse effects were not clearly described. However the number was low and there was no preference for either group; so it is considered a low risk.
Other bias	Unclear risk	Mean age is statistically different between treatment groups. Stage 4 of Kellgren Lawrence is a severe grade of osteoarthritis (OA) and not likely to respond to treatment with hyaluronic acid, it is unclear if there was any baseline imbalance based on the grade of ankle OA. There is insufficient information to permit judgement of low risk or high risk of bias.