A systematic review of the inclusion of mechanisms of action in NIH-funded intervention trials to improve medication adherence.

Medication nonadherence contributes to morbidity/mortality, but adherence interventions yield small and inconsistent effects. Understanding the mechanisms underlying initiation and maintenance of adherence could improve interventions. The National Institutes of Health (NIH) support adherence research, but it is unclear whether existing NIH-funded research incorporates mechanisms. We conducted a systematic review to determine the proportion of NIH-funded adherence trials that have tested hypothesized mechanisms of intervention effects. We included randomized and quasi-randomized NIH-funded trials with medication adherence in adults as the primary outcome. Studies were identified by searching electronic databases from inception to 6/2016, references, and clinicaltrials.gov. Two of 18 (11%) NIH-funded trials tested a hypothesized mechanism of an intervention's effect on medication adherence. Another 44 studies with medication adherence as a secondary outcome were described in protocol form, and are either ongoing or never published results, but none mentioned mechanism tests. Overall, 3% of NIH-funded trials with adherence as an outcome conducted, or plan to conduct, tests of behavior change mechanisms. These results mirror previous findings that very few studies of behavior change interventions actually test the mechanism by which the intervention is hypothesized to improve health behaviors. We must understand mechanisms if we are to improve the effectiveness of interventions.