Table 1.

Criteria for identifying clinically important drug-drug interactions for clinical decision support in electronic health records

Criteria	Description of the criteria and key sub-criteria that emerged from the literature review and expert panel discussion
1. Severity of interaction [13-15]	■ Clinical Importance: Hansten, Horn and Hazlet in their ORCA classification identify clinical importance as a function of both the inherent danger of the drug combination and the extent to which the presence of risk factors predisposes the patient to the interaction. Also consideration of potential severity of the adverse outcome (ORCA classification, Hansten, et al. [14])
	■ Likelihood of Mortality
	■ Likelihood of Morbidity
	■ Likelihood of Intervention: The probability of the suggested intervention being able to prevent harm caused by the interaction.
2. Probability of interaction [13,14]	■ Likelihood of the Adverse Reaction
	■ Timing of Administration
	■ Consideration of the pharmacokinetic properties of the interaction: Some studies such as Siedling, et al. have evaluated pharmacokinetic characteristics of DDIs between statins and various drugs. The study revealed that more than half of the concentration-dependent ADEs related to statins were considered inappropriate if the upper dose limits were taken into account.
	■ Dose and Duration of Therapy
	■ Route of Administration
	■ Sequence of Administration
	■ Monitoring planned for the patient
	■ Therapeutic window of the object drug
	■ Combination of drugs commonly used for therapeutic reasons
3. Clinical implications [14,16-18]	■ Management burden: defined as the course of action a clinician may have to take for each potential drug interaction
	■ Monitoring planned for the interaction
	■ Awareness of the intervention: Likelihood that providers may be aware of the ability to intervene in order to prevent harm caused by an interaction.
4. Patient characteristics [13,14,18]	■ Taking into account alcohol, diet, smoking and drug use which might alter the characteristics of the drug in consideration resulting in possible DDIs.
	■ Importance of age
	■ Importance of gender
	■ Concurrent diseases
	■ Other active medications on the patient's profile
5. Evidence supporting interaction [13-15,19-21]	■ Quantity of evidence: Adequacy of documentation in the literature
	■ Quality of evidence: Association of the evidence with the study design and source of evidence. For example, randomized trials can be rated as providing high quality evidence and observational studies or case reports as low quality evidence.
	■ Biological plausibility: Causal association as supported by medical evidence

Provides a descriptive representation of the criteria used to identify clinically important drug-drug interactions. This list focused on five categories, which include Severity of interaction, Probability of interaction, Clinical implications, Patient characteristics, and Evidence supporting interaction.