The implications of nonadherence patterns for intervention and regimen design: worked example from China

DomainSuboptimal implementationDiscontinuation
Number of participants affected748/780 (95.9%) of all participants suboptimally implemented their treatment.235/780 (30.1%) of all participants discontinued early.
Number of doses missed9487/16 794 (56.4%) missed doses were due to suboptimal implementation.7307/16 794 (43.5%) missed doses were due to early discontinuation.
Patterns displayedThe median gap length per patient was one dose, with a maximum number of gaps per participant of 24. 176/780 individuals (22.6%) had gaps of seven doses (a fortnight) or more. Suboptimal implementation increased over time.5.1% of individuals had discontinued treatment by the end of month 2, 14.4% by the end of month 4, 18.2% by the end of month 5, 36.3% by the end of month 6 (including individuals missing only their last dose).
Link between suboptimal implementation and discontinuation?Missed doses in the initiation phase due to suboptimal implementation associated with increased risk of discontinuation in the continuation phase.
Implications for intervention and regimen designThe causes of large numbers of short gaps need to be ascertained and addressed by an effective intervention.Given the burden of discontinuation and when it occurs, shortened regimens may have been helpful in this setting. Early-stage suboptimal implementation could act as an indicator of patients who require an intervention to prevent discontinuation.

In a study of 780 patients from a pragmatic cluster-randomised trial in China of electronic reminders to improve treatment adherence [9, 12], data were taken from the control arm of the trial (electronic reminders set to silent, thus no intervention to promote adherence). Medication monitor boxes provided granular data as to whether each individual dose was taken (box opening used as a proxy). Treatment was dosed every other day. All patients initiated treatment within this study. Decision-making as to which type of nonadherence should be targeted by interventions will also depend upon the relative impact of each form of nonadherence on outcomes [20].