Okeke 2009.

Methods	Randomized controlled trial
Participants	The study location was Wilmer Eye Institute, Baltimore, Maryland; and Scheie Eye Institute, Philadelphia, Pennsylvania, USA 35 participants were randomized to the intervention group and 31 participants were randomized to the control group The inclusion criteria were one of open‐angle glaucoma, angle‐closure glaucoma, glaucoma suspect, or ocular hypertension. Patients were 18 years of age or older, using or prescribed a topical prostaglandin analog, and able to return for 3‐ and 6‐month follow‐up visits. No laser or surgical glaucoma therapy within the 3 months before enrollment. Used 75% or fewer administered doses of topical prostaglandin analog in Phase 1 The exclusion criteria were: unable to understand the study, did not instill their own drops, or were incapable of using the Dosing Aid (DA) after a brief demonstration
Interventions	Intervention: INTERVENTION The intervention consisted of 4 components. (1). a 10‐minute educational video created through Alcon, Inc. marketing branch for the DA device, which stressed the importance of regular drop‐taking, its rationale and expected effects, alternatives to eyedrops, and methods to maximize co‐operation, such as linking drops to a daily activity, keeping a drop‐taking calendar diary, and using family members to help in reminding them; (2) a structured discussion with the study co‐ordinator to develop a strategy for improving adherence that included finding the best time of day to take the medication, distributing a blank calendar diary and going over details of how to keep it, and discussing individual patient barriers to taking the medication; (3) reminder telephone calls from the co‐ordinator, including administration of a questionnaire about drop‐taking behavior, difficulty with drops, side effects, and eliciting questions about therapy (this call was made once per week for the first follow‐up month and then every other week for the next 2 months); and (4) activation of the audible and visible alarms on the DA Control: USUAL CARE Usual care group were told that it is important to take their eyedrops as prescribed but had no other intervention
Outcomes	The measures of adherence were drop use by Dosing Aid (DA) device at 6 months (3 months post‐randomization). The data from the DA were downloaded onto computer‐based software at the 3‐month and 6‐month visits The patient outcome was intraocular pressure (IOP), measured at baseline, 3, and 6 months
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomized using random numbers placed in serially marked, sealed envelopes that were opened at the time of randomization. To perform the randomization procedure, a string of random numbers was selected from a random numbers table. The numbers were placed into envelopes and then sealed and initialed across the seal. The envelopes were numbered consecutively starting with 1. When an eligible patient was identified, an envelope was opened; if the envelope contained an even number then the participant received the intervention (pg 2287)
Allocation concealment (selection bias)	Unclear risk	Does not indicate the envelopes were opaque. "Participants were randomized using random numbers placed in serially marked, sealed envelopes that were opened at the time of randomization. To perform the randomization procedure, a string of random numbers was selected from a random numbers table. The numbers were placed into envelopes and then sealed and initialed across the seal. The envelopes were numbered consecutively starting with 1. When an eligible patient was identified, an envelope was opened; if the envelope contained an even number then the participant received the intervention." (pg 2287)
Selective reporting (reporting bias)	Low risk	No protocol available but the only outcome measure is "...change in drop use adherence as determined by the DA device."
Other bias	Unclear risk	The author notes that the intervention group had more veteran eyedrop takers. This may have increased the magnitude of the intervention effect, because our univariate analysis showed lower adherence among less experienced eyedrop takers. Some patients took their drops without placing the bottle in the devices, which decreased the measured adherence rate in the intervention group, but not significantly. When excluding those who took drops without the DA, the measured adherence improved slightly in the control group, but still the difference in magnitude of improved adherence between the intervention group and the control group remained large. Also, the findings were limited to the use of 1 prostaglandin analog, because only its bottle fits in the device (pg 2291)
Blinding of outcome assessment (detection bias) Adherence measure	Unclear risk	(PRIMARY) DOSING AID ‐ The information was downloaded directly from the DA to computer software, which has a low risk for bias. However, the data were manipulated somewhat: "In phase 2, participants with 75% or fewer administered doses were randomized to either intervention or usual care. The data used for this determination included values obtained during the 8 weeks starting 2 weeks after enrollment and ending 2 weeks before the follow‐up visit. Only these data were used because we detected that there was significantly greater adherence just after a visit and just before a visit. A dose was considered taken if the lever of the DA was depressed and recorded beta4 hours from that patient's median dosing hour (as determined from the DA data). Because we recognized from our previous study that the device has the potential to make extra recordings when the lever is depressed erroneously, we did not count more than 1 dose taken per eye per day in our adherence rate calculation. When the lever was depressed outside the time window it was assumed that a dose was not taken, and when the lever was depressed multiple times in the time window only a single dose for 1 or both eyes was assumed to have been delivered." (pg 2288)
Blinding of outcome assessment (detection bias) Patient outcome	Low risk	(PRIMARY) INTRAOCULAR PRESSURE ‐ No mention of who took the IOP measurements and whether that person was blinded to the study groups; but this is an objective measure
Blinding of participants (performance bias) Adherence measure	Unclear risk	(PRIMARY) DOSING AID ‐ No mention of blinding of participants to the study group
Blinding of participants (performance bias) Patient outcome	Low risk	(PRIMARY) INTRAOCULAR PRESSURE ‐ This is an objective measure of outcome
Blinding of personnel (performance bias) Adherence measure	Unclear risk	(PRIMARY) DOSING AID ‐ No information on blinding given. There is insufficient information to permit judgment of 'Low risk' or 'High risk'
Blinding of personnel (performance bias) Patient outcome	Unclear risk	(PRIMARY) INTRAOCULAR PRESSURE ‐ This is an objective measure of outcome
Incomplete outcome data (attrition bias) Adherence measure	Low risk	(PRIMARY) DOSING AID ‐ The authors report on how many people participated in the intervention. There is no information about missing data for results. In Table 3 and Figure 1 also, they list intervention n = 35 and control n = 31, which are the original sample sizes at baseline. This suggests that data from all the participants were collected
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) INTRAOCULAR PRESSURE ‐ No mention of whether the outcome data are complete or not. Only baseline IOP reported