Salk 2006.

Methods	Randomised controlled trial, blinded, parallel group. Follow‐up at week 2, 6, 12 and 26.
Participants	17 participants (20 originally) 18 years or older, chronic ankle pain for more than 3 months, Baseline Total AOS score of more than 30 and less than 90; 9 in Hyalgan group (mean age 57.8 (SD 14.7), 5 female, 4 male) and 8 in Saline group (mean age 60.0 (SD 13.9), 5 female, 3 male) Kellgren Lawrence score of ,II,III, or IV.AOS score of > 30 and lower than < 90 at baseline.
Interventions	Hyalgan 1 ml (1 mg/ml) intra‐articular 5 weekly injections versus saline 1 ml intra‐articular 5 weekly injections.
Outcomes	Primary outcome total AOS score. Secondary outcome: Pain (AOS, WOMAC, Pain Global Assessment (PGA), 5‐point scale), physical function: (Range of Motion, AOS), Ankle girth, Quality of life (EuroQoL‐5 Dimensions (EQ5D), SF12). Recording of outcome and adverse events at each clinic visit. Safety (number of serious adverse effects, amount of rescue medication).
Notes	Mean and standard deviation (SD) for AOS were only shown in a graph at baseline, 3 months and 6 months follow‐up. F‐values for 6 months follow‐up were provided. We contacted the author, he could not provide us with additional data. The SD at 6 months was obtained from Mean Difference (MD) data and F‐values for differences in means, according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions Chapter 7 (Section 7.7.3.3) (Higgins 2011). Adverse effects: pain at the injection site 29% adverse effects Support for portions of the study were received from Sanofi‐Synthelabo.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No description of process
Allocation concealment (selection bias)	Unclear risk	No description of process
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	Unclear risk	Three participants did not complete the study, intention‐to‐treat analysis was not described. However the author confirmed by email that a ITT was undertaken.
Selective reporting (reporting bias)	Low risk	Results show same outcomes as described in the Method section.
Other bias	Unclear risk	Inclusion criteria: Kellgren Lawrence of IV was also included, this is not common, severe arthritis is known not to respond well to hyaluronic acid treatment. There is insufficient information to permit judgement of low risk or high risk of bias.