Kimmel 2012.

Methods	Randomized controlled trial
Participants	The study location was an outpatient hospital of the University of Pennsylvania Anticoagulation Management Center 53 participants were randomized to the intervention group and 48 participants were randomized to the control group The inclusion criteria were age over 21 years, attending the out‐patient clinic at University of Pennsylvania Anticoagulation Management center, INR between 2 and 3.5, and had, at any time in the past, achieved stable warfarin anticoagulation, defined as 2 INRs within their target range over 2 consecutive clinic visits The exclusion criteria were no access to a telephone line (which was required to use the Med‐eMonitor (Informedix, Rockville, MD), as discussed below), unwillingness to participate or to sign a consent form, dementia or any other impairment affecting ability to provide informed consent and/or use the Med‐eMonitor, illness with anticipated life expectancy of 6 months or less, INR over the upper limit for the individual's range at the time of enrollment (to avoid possibly exacerbating this overanticoagulation if a patient's adherence improved during the study), and antiphospholipid antibody syndrome or abnormal INR before starting warfarin
Interventions	Intervention: LOTTERY‐BASED INCENTIVES Patients in the intervention group were offered financial incentives to remain adherent. All patients were provided with an Informedix Med‐eMonitor System, which has a display screen and separate medication compartments in which to place their warfarin. The monitor connects to an analog telephone line. They were enrolled in a daily lottery, administered via the Med‐eMonitor, with an expected daily value of USD 3, or no lottery intervention. Participants had a 1 in 5 chance of a USD 10 reward and 1 in 100 chance of a USD 100 reward each day if they opened the monitor's pill compartment and confirmed that they took their warfarin as prescribed that day. If patients were told to not take warfarin on a particular day, they would only be eligible for the lottery if they did not take a pill that day Control: CONTROL Patients in the control arm were set up with the Med‐eMonitor in order to measure medication adherence. Participants were also seen by their anticoagulation clinic practitioner as they normally would and by the study staff at baseline, 2 weeks, 3 months, and 6 months
Outcomes	The measures of adherence were measured with the Informedix Med‐emonitor system. If the patient opened the monitor's pill compartment and confirmed that they took their warfarin as prescribed that day they were deemed adherent. The device was programmed to communicate by telephone with a central database at 3 AM each night.The system was automated so that there were no personnel required to run the lotteries. All other reminder systems and feedback from the Med‐eMonitor were disabled for both groups The patient outcomes were anticoagulation control, bleeding events, and thromboembolism. Study staff collected the clinical outcome data at baseline, 2 weeks, 3 months, and 6 months (corresponding to times when patients were returning for regular clinic visits). Instrument or technique of data collection not explicitly mentioned in the article
Notes	―
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization was carried out using a random‐number generator (pg 269). (pg 2) "Randomization was carried out using a random‐number generator and via permuted block randomization with variable block sizes of 2, 4, and 6. Because of the a priori hypothesis that patients within therapeutic INR range at the time of randomization might benefit less from the intervention than those with an INR below the target range, randomization was stratified by INR below range and INR within range at enrollment."
Allocation concealment (selection bias)	Unclear risk	No mention of allocation concealment
Selective reporting (reporting bias)	Unclear risk	No obvious bias; appeared to have reported all outcomes. Protocol not available, hence deemed unclear
Other bias	Unclear risk	Author notes the following: (pg 271) "...degree of anticoagulation control in the cohort was better than anticipated, both limiting the study's power and the opportunity for the intervention to improve adherence" (pg 272) "Other limitations of the study include its inability to discern if patients took the correct number of pills from the Med‐eMonitor compartment, use of a single anticoagulation clinic, and the potential for gaming of the system by opening pill doors but not taking the drug (which, although unlikely that patients would not go ahead and take the pill at that point, is why our primary outcome was INR control, not adherence)."
Blinding of outcome assessment (detection bias) Adherence measure	Low risk	(PRIMARY) MED‐EMONITOR ‐ (pg 269) "Neither field staff nor study participants could be blinded to study arm because of the nature of the intervention; study investigators and analysts, however, remained blinded to intervention assignments until all follow‐ups and data cleaning were completed." Data collectors were blinded
Blinding of outcome assessment (detection bias) Patient outcome	Low risk	(PRIMARY) ANTICOAGULATION CONTROL ‐ INR analyses is an objective measure, unlikely to be biased due to lack of blinding
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) MED‐EMONITOR ‐ No mention that patients were blinded and they would be aware of the intervention. (pg 269) "Neither field staff nor study participants could be blinded to study arm because of the nature of the intervention; study investigators and analysts, however, remained blinded to intervention assignments until all follow‐ups and data cleaning were completed."
Blinding of participants (performance bias) Patient outcome	Low risk	(PRIMARY) ANTICOAGULATION CONTROL ‐ INR analyses is an objective measure, unlikely to be biased due to lack of blinding
Blinding of personnel (performance bias) Adherence measure	Low risk	(PRIMARY) MED‐EMONITOR ‐ (pg 269) "Neither field staff nor study participants could be blinded to study arm because of the nature of the intervention; study investigators and analysts, however, remained blinded to intervention assignments until all follow‐ups and data cleaning were completed." Lack of blinding unlikely to affect results
Blinding of personnel (performance bias) Patient outcome	Low risk	(PRIMARY) ANTICOAGULATION CONTROL ‐ INR analyses is an objective measure, unlikely to be biased due to lack of blinding
Incomplete outcome data (attrition bias) Adherence measure	Unclear risk	(PRIMARY) MED‐EMONITOR ‐ No statistically significant difference between groups in primary outcome. However, missing data not uniformly distributed. Reasons for missing data provided but unclear the impact incomplete data would have
Incomplete outcome data (attrition bias) Patient outcome	Low risk	(PRIMARY) ANTICOAGULATION CONTROL ‐ No statistically significant difference between groups in primary outcome. Missing data not uniformly distributed. Reasons for missing data provided, but unclear how this may have impacted the results