To our knowledge, this study is the first to directly compare multiple adherence measures in terms of indicated levels of adherence, consistency with medical markers, researcher perspectives, and caregiver and patient perspectives. With respect to adherence outcomes, child and caregiver interviews offered the highest estimates while pill counts and MEMS yielded rates of adherence that were notably lower. Moreover, adjusting the MEMS time window (e.g., from 1 hour to 2 hours) changed adherence percentages dramatically for many patients. Consistent with our hypothesis, only MEMS data using 2-hour and 3-hour windows produced significant correlations with medical markers, both with CD4+ percentages (at 3 months) and viral load (at 3 and 6 months), suggesting that this method of assessment may be most reliable to the extent that adherence is linked to clinical outcomes. We chose to use MEMS 2-hour adherence rates in most analyses rather than 3-hour rates to be slightly more conservative. The above differences between adherence measures highlight the fact that medication-taking behavior can appear very different depending on the method of analysis and interpretation utilized.
Based on the researchers' collective experience conducting this study, numerous limitations involving each of the three adherence measures were encountered. With respect to electronic monitoring, some families declined the use of a MEMS cap because they used pill trays, thus limiting the data for our study. This problem is cited in other studies as well15,16,41
despite some research suggesting that the temporary use of MEMS caps among individuals previously using pill trays does not decrease their adherence.42
As noted previously in this paper and numerous others,16,40,43–45
MEMS data reflect only the number of times the cap is removed from the bottle rather than how many pills are ingested by the patient. In addition, target time calculations were very time-consuming, particularly for patients whose data incorporated a schedule transition.
Barriers to obtaining accurate pill counts included families forgetting to bring all medication bottles to clinic and siblings who were prescribed the same drug sharing pills. However, pill counts remain an inexpensive and relatively easy method of obtaining adherence estimates. The reliability of pill counts may be improved by providing more explicit instructions to families about the importance of bringing all pill bottles to each visit, including those not kept with the primary pill bottle (e.g., relative's house, pill trays), and calling families to remind them to bring their pills before each visit. More frequent reminders to the medical team regarding the procedures for obtaining pill count data may be useful as well, especially if pill counts have not been a routine part of medical visits prior to study initiation.
Consistent with our findings, several past studies have proposed that self-reports overestimate adherence,13,30,46
while others have found comparatively worse adherence through interviews.11,31,47
One reason that our sample may have produced inflated self-reports is that families who obtain their care at the NIH are required to be enrolled on a research protocol. These families receive all study evaluations and medications at no cost. Thus, they may have been motivated to appear adherent to avoid being removed from their primary medical protocol. Another difficulty in obtaining interview data was reaching participants by telephone; asking families to provide their email addresses to help schedule specific interview times may be helpful for future studies.
With respect to caregiver and patient perspectives, most reported that study participation was helpful, with MEMS and telephone interviews being cited as particularly helpful by both caregivers and patients. Patients also reported that phone interviews were beneficial, presumably due to the regular contact with the medical team. Specific benefits of study involvement included increased accountability and a greater support system due to more frequent monitoring, as well as normalization of adherence challenges. Many participants indicated present and anticipated future improvements in the child's medication adherence, but neither patient nor caregiver PASP ratings were significantly related to adherence percentages during the study and no follow-up measures of adherence were collected. Studies with longer-term follow-up assessments may determine whether adherence research participation leads to beneficial adherence outcomes that are maintained over time.