This study demonstrates that there is a poor agreement between compliance measured by electronic monitoring and compliance determined by filled prescription data within the same population of hypertensive patients. A remarkable finding is that many patients, who according to refill compliance data are not compliant with antihypertensive medication, are not identified as such by electronic monitoring which is considered to be the "gold standard". With electronic monitoring, less than four percent of the patients could be identified as poor complier. Using refill data, the percentage of patients with inadequate compliance was 18.5 percent. Determination of compliance based on filled prescriptions was expected to be a rather insensitive method to measure compliance. Only a part of the poor compliers can be identified using this method, because obtaining the medication is no guarantee that the patient actually takes them. Therefore refill compliance is expected to identify the minimum proportion of poor compliers within a population. Despite this fact, the use of refill data identified a higher percentage of patients with inadequate compliance than electronic monitoring. Several explanations may account for these results.
First, it may be argued that the proportion of poor compliers identified with electronic monitoring would be much higher when a more stringent measure to define compliance, such as correct dosing, was used. Correct dosing reflects the percentage of days on which the medication is taken as prescribed and is therefore much more sensitive for deviations from the prescribed regimen than taking compliance data. However, when this measure was applied to our population only six instead of five patients were identified as poor complier.
Second, it is possible that electronic monitoring in itself improves compliance because patients are aware that their medication behavior is being monitored. This awareness may have encouraged them to be more compliant than they used to be before the start of electronic monitoring. The hypothesis that electronic monitoring in itself improves compliance, is in agreement with the findings in other studies, which also point in this direction. First, most recent studies using electronic monitoring very often report relatively low proportions of patients with poor compliance [11
] in contrast with the general assumption that 40 to 50% of the patients do not take their antihypertensive medication as prescribed. Second, Burnier et al. [14
] demonstrated that a two-month period of monitoring of compliance was associated with a significant improvement of blood pressure, most likely resulting from increased compliance with antihypertensive drug therapy. Also Waeber et al. [12
] found that three-month period of monitoring was associated with a significant improved control of blood pressure.
It can be concluded that the findings in our study stress the importance of the conditions that need to be met before electronic monitoring can be used to obtain accurate compliance data. First, it seems extremely important to conceal the purpose of the monitor from the patient to obtain valid compliance data, but this is really hard to accomplish in practice. Kruse and Weber [19
] found a compliance of 91% in informed individuals compared to 78% in a group who did not understand the value of the electronic monitor. Second, studies with a monitoring period of at least 6 months demonstrate a clear-cut decrease in compliance over time suggesting that the effect of awareness of being monitored wanes over time [20
]. From these studies it can be concluded that it is important to monitor compliance for at least six months in order to obtain valid measures of compliance [23
Some methodological issues deserve further attention. First, the time periods wherein refill and taking compliance were measured, differed. The short duration of electronic monitoring (two months) and low refilling frequency during this time precluded stable estimation of refill compliance during the monitoring period itself. In this respect the present study is comparable to the study performed by Choo et al[24
] which found moderate agreement (r = 0.32) between compliance measured during a three month monitoring period and refill compliance in the twelve months before electronic monitoring. The additional value of the present study is that it gives information about the proportion of patients with inadequate compliance instead of mean values of compliance. Whereas mean values give the impression that refill compliance is higher than monitoring compliance, proportions indicate that it is the other way around: in comparison with electronic monitoring, refill compliance measurements trace more poor compliers.
Second, in the primary analysis a cut-off point for compliance of 85% was used. It is accepted that patients are considered adherent with the prescribed medication regimen when they take 80–90% of their medicines [25
]. However, historically used cut-off points are in many cases meaningless as some drugs are much more "forgiving" than others in term of missed dosing and the timing of ingestion [28
]. The answer to the question "how much compliance is enough" requires knowledge of the pharmacokinetic and pharmacodynamic properties, which vary between antihypertensive drugs and also vary between individuals. At this stage we do not really know what level of compliance is necessary for individual antihypertensive medications. To undermine this problem Cohen's kappa was determined for different cut-off points. The agreement between both methods was poor, irrespective of the used cut-off point.