To the best of our knowledge this is one of the first studies using standardised implicit methods to examine types of inappropriate prescribing and their association with Type A ADRs as determined by a structured causality algorithm. Our findings provide some evidence of an association of the occurrence of Type A ADRs with both drug–drug and drug–disease interactions. Chrischilles et al
] reported that the use of drugs to avoid, and the occurrence of drug–disease interactions both independently and significantly increased the risk of the occurrence of one or more self-reported ADE. They also reported a trend towards increased risk of ADEs with drug–drug interactions and therapeutic duplication. When these four explicit measures of inappropriate prescribing were combined, a statistically significant relationship with ADEs was demonstrated [5
]. Lund et al
], found that a modified summated MAI score, with the highest weights applied to drug–drug and drug–disease interactions, increased the risk of self-reported ADEs.
We did not find a significant relationship between dosage and direction problems and Type A ADRs. One possible explanation is that these two items measured by the MAI only assess whether they are incorrect. Therefore some of these incorrect ratings were due to dosage being too low or directions for use too infrequent which in both cases could lead to decreased drug concentrations and be more likely to be associated with therapeutic failure than with ADRs. This is consistent with the results from the Lund et al
], who assigned these two items a weight of zero and found they were not associated with ADRs.
This study has a number of limitations. First, the association did not achieve statistical significance. Second, the study relied primarily on chart review of information to assess prescribing and ADR causality. We may have underestimated problems if the information was not recorded or was erroneously recorded in the medical chart.
Third, we utilised a modification of the MAI incorporating only four of the original 10 items. This modification has not been independently validated. Moreover, our rate of ADRs discovered only by self-reported potential ADEs may be an underestimate especially in those with cognitive impairment and those who died (nearly 8% of subjects) before the 12 month follow-up period. It is reassuring that a previous study by our group found that nearly 60% of self-reported ADEs were also found during chart screening [11
]. It is also possible that we overestimated the use of high-risk drugs as only prescribing and not adherence was assessed. Also the generalisability of our findings is unknown as it involved mostly male frail older veteran outpatients recently discharged from hospital and thus may differ from other ADR studies of older outpatients who were not hospitalised.
Despite these limitations, our results confirm that Type A ADRs are common in frail older outpatients, and provide evidence of an association with drug interactions. Further studies, possibly with larger cohorts, are required to test the reproducibility of these findings. In the meantime, quality improvement activities to reduce ADRs by improving prescribing appropriateness should continue to include a focus on the identification of potential drug–drug and drug–disease interactions.
- Type A ADRs are common in frail older outpatients.
- This study provides evidence of an association between drug interactions and Type A ADRs in frail older outpatients.
- Future quality improvement activities should include a focus on clinically important drug interactions.