DeGroot 2012.

Methods	Randomised controlled trail, double blinded, parallel group trial.
Participants	64 participants; ankle OA of at least Kellgren Lawrence grade 2. Thirty‐nine participants in hyaluronic acid (HA) group (mean age 54.1 (SD 14.5,2.3), 15 female, 24 male) and 25 in saline group (mean age 61.9 (SD 14.1,2.8), 13 female, 12 male) Diagnosed with ankle OA based on an x ray, grade 2, 3 or 4 of Kellgren Lawrence system
Interventions	Single injection of Supartz®; hyaluronic acid 2.5 ml intra‐articular versus Saline injection
Outcomes	Primary outcome: change in baseline of American Orthopedic Foot and Ankle Society score (AOFAS score) at 6 weeks and 12 weeks. Secondary outcomes: change from baseline AOS score and visual analogue scale (VAS) at 6 and 12 weeks. Safety (recording adverse effects).
Notes	No dose finding, single injection with Supartz®. 87.5 % of participants completed the study (56/64) No external funding was received from any source for this study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Simple non‐block randomisation.
Allocation concealment (selection bias)	Low risk	Selection was based on selecting an opaque envelope.
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 data.
Selective reporting (reporting bias)	Unclear risk	AOFAS (not validated) is not a common instrument to report the efficacy of hyaluronic acid compared to literature. Follow‐up is limited to 3 months, it is more common to use 6 months as either primary outcome or additional endpoint. At 3 months the effect of placebo might be higher, thus creating a more positive outcome for placebo (desired outcome) when comparing hyaluronic acid to placebo.
Other bias	Unclear risk	Treatment and placebo group are of unequal size (39 vs 25). There is insufficient information to permit judgement of low risk or high risk of bias.