OBJECTIVES: To determine whether adherence interventions should be administered to all medication takers or targeted to nonadherers.

DATA SOURCES AND STUDY SELECTION: Systematic search (Medline and Embase, 1966-2009) of randomized controlled trials of interventions to improve adherence to medications for preventing or treating cardiovascular disease or diabetes.

DATA EXTRACTION: Articles were classified as (1) broad interventions (targeted all medication takers), (2) focused interventions (targeted nonadherers), or (3) dynamic interventions (administered to all medication takers; real-time adherence information targets nonadherers as intervention proceeds). Cohen's d effect sizes were calculated.

DATA SYNTHESIS: We identified 7,190 articles; 59 met inclusion criteria. Broad interventions were less likely (18%) to show medium or large effects compared with focused (25%) or dynamic (32%) interventions. Of the 33 dynamic interventions, 6 used externally generated adherence data to target nonadherers. Those with externally generated data were less likely to have a medium or large effect (20% vs. 34.8% self-generated data).

CONCLUSION: Adherence interventions targeting nonadherers are heterogeneous but may have advantages over broad interventions. Dynamic interventions show promise and require further study.