Table 2 Barriers and considerations for including clinically important drug-drug interactions (DDIs) in electronic health records (EHRs)

1. Large disparities between drug knowledge bases and among local experts [22, 23]

The overlap between what is deemed as clinically significant by different knowledge bases is low. Besides the disparity across databases there is often disagreement among local experts (depending on clinical expertise and role) on the list of critically important DDIs.

2. Resource intensive process

The process of conducting literature reviews and vetting them with users of the EHR is a resource intensive process. Not all organizations have the ability to expend clinical resources in order to customize their knowledge bases from a commercially supplied DDI set. The knowledge management committee might need to re-evaluate the customized DDI set at the time of every update provided by the vendor.

3. Need for ongoing review

The list of clinically significant DDIs must be reviewed periodically in order to keep the knowledge base current. This involves conducting ongoing literature reviews to assess whether the evidence surrounding a DDI has changed since the time it was first assessed as critically important.

4. Lack of context of patient populations [24]

Knowledge base vendors lack the ability to contextualize DDIs based on the specific patient populations where the EMR is used. Some guidelines can be provided in order to improve specificity (e.g. for a geriatric population) however the use of these guidelines is limited and dependent on the clinical practice where the EMR is implemented.

5. Inability to alert on DDIs caused by discontinuation of drugs [25]

DDI alerts are based on drugs that are co-prescribed or administered together. Knowledge base vendors are unable to provide DDI alerts for an interaction that may be caused by the discontinuation of a drug. For example, the drug combination of clonidine and propranolol where the discontinuation of clonidine from combined therapy with propranolol may produce elevation of blood pressure.

6. Close integration with patient data in EMR

Several patient characteristics play an important role in being able to identify the set of clinically significant DDIs. While these patient characteristics, such as age, gender, or specific lab values, are known to knowledge base providers they cannot be readily implemented because these require close integration with the EHR in which the knowledge base is used. Since KB vendors do not have control over the use, expression or standardization of these data elements, their consideration in filtering the list of DDIs is limited.

7. Implementation of strategies to reduce “alert fatigue” based on physician responses

One mechanism of reducing "alert fatigue" is taking into account previous responses of the user to an alert. For example, if a physician has already seen an alert for a DDI should the same alert be shown upon renewal of the medication? Additionally, if a physician has previously determined a particular drug combination to be appropriate for a patient then should he/she be re-alerted when renewing the drug combination for the same patient? The inability to account for physician responses limits KB vendors from providing solutions that take into account provider responses in the EHR system.

8. Customizing DDI list based on clinical workflow

Consideration of the clinical workflow can also help streamline the alerts seen by clinicians. For example, certain DDI alerts can be shown only to nurses since these would occur only if the administration times of the medications were close together or where the sequence of administration of the drugs is important. In this scenario, the physician need not be alerted. It is difficult for knowledge base providers to implement such mechanisms of streamlining the sub-set of DDIs shown to specific providers.

9. Software sophistication

The sophistication of the software necessary to implement a DDI into a CDS system that also considers patient information i.e. lab results is a challenge when it comes to space and the upkeep necessary to such a system.