Clinical decision support for drug related events: Moving towards better prevention

Table 1 Definitions of drug related events

Term	Definition
Medication error[2]	“Any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient or consumer. This may include errors in prescribing, distribution, administration and monitoring”
Adverse drug reaction[3]	“Any undesired, unexpected, or unintended outcome associated with drug use“
Drug-related hazardous condition[3,4]	“Is the antecedent to injury or the temporal gap between the identification of an adverse drug reaction and the drug induced injury”. It occurs in the presence or absence of a medication error
ADE[5]	“Injury associated with the use of a drug”
Preventable ADEs[6]	“Injury associated with a medication error”
Potential ADEs[5]	“Medication errors with the potential to cause harm, but harm does not actually occur. Potential ADEs can be further described as intercepted and non-intercepted”
Trigger[6]	“Signals or clues used to identify adverse events”

ADE: Adverse drug event.

Table 2 Examples of alerts designed to detect drug-related events

Ref.	Alert designed for detection
Stockwell et al[37]	Abnormal laboratory value exceeding recommended upper limit Examples
Harinstein et al[38]	ACE inhibitor/ARB and patient’s serum potassium is > 6 mmol/L INR > 4 and on warfarin Blood glucose < 40 mg/dL and on antidiabetic agent Platelet count < 50000/mm3 and on a drug that causes thrombocytopenia
Kane-Gill et al[39]	Unexpected discontinuation of drug
Kane-Gill et al[17,39]	Antidote evaluations such as flumazenil, naloxone, sodium polystyrene, protamine, dextrose 50%; lepirudin use; argatroban use

ACE: Angiotensin converting enzyme; ARB: Angiotensin II receptor blocker; INR: International normalized ratio.

Table 3 Examples of preventative alerts

Ref.	Drug related hazardous condition for alert detection	Adverse drug event prevention	Criteria for prevention alert
Rommers et al[43]	Before a DRHC occurs-eventually hemoglobin drop	Bleed	Elderly patient who is not taking a PPI and is started on an NSAID
Moore et al[42]	Hypoglycemia	Mental status changes	Receiving a new antidiabetic agent and 3 consecutive low glucose results that are steadily declining over a period of time
Moore et al[42]	Hypokalemia	Dysrhythmia	Drug started causing hypokalemia + potassium level under 3.8 mEq/L
Moore et al[42]	Thrombocytopenia	Bleed	Drug started causing thrombocytopenia and platelets slowly decrease over 50000/mm3 within 4 d
Moore et al[42]	Hyperkalemia	Dysrhythmia	Drug started causing hyperkalemia + potassium level over 5.5 mEq/L and increasing slowly over 72 h
Raschke et al[35]	C. difficile	Permanent gastrointestinal disorders (i.e., irritable bowel syndrome, colectomy)	Antidiarrheal and recent aggressive antibiotic therapy OR history of Clostiridum difficile
Rommers et al[43] and Silverman et al[44]	Before DRHC occurs-eventually digoxin level elevated	Dysrhythmia, confusion	Patient with 3 consecutive increasing serum creatinine levels and also on digoxin therapy (or other renally cleared drugs would apply such as metformin, enoxaparin, vancomycin)
Rommers et al[43]	Constipation	Bowel obstruction	Narcotic started recently and patient has a history of constipation or narcotic started recently and patient has not had a bowel movement in over 24 h
Van Doormaal et al[45]	Constipation	Bowel obstruction	Opioid prescribed without a co-prescription of a stimulant laxative
Van Doormaal et al[45]	KDIGO stage 1 AKI-in the future biomarkers may be the early sign of AKI before SCr rise	KDIGO stage 3 AKI	Sulfonamide urea derivate is prescribed and the patient has a creatinine clearance of less than 10 mL/min
DiPoto et al[46]	Before a DRHC occurs-eventually hemoglobin drop	Bleed	Patient has epidural and started on an anticoagulant or antiplatelet
DiPoto et al[46]	Sedation	Mental status changes	Fentanyl patch and no documented history of long-acting opioid use
Silverman et al[44] and Jha et al[47]	ALT rising	Hepatic failure	Hepatotoxic drug and ALT increase by 20%
Silverman et al[44] and Jha et al[47]	Osmolarity increasing	Mental status changes, risk of death	Lorazepam use and osmolarity increasing

DRHC: Drug related hazardous condition; KDIGO: Kidney Disease Improving Global Outcomes; AKI: Acute kidney injury; ALT: Alanine aminotransferase.

Table 4 Alerts to predict an impeding adverse drug event using percent changed in the laboratory value

Ref.	Drug related hazardous condition for alert detection	Adverse drug event preventing	Criteria for prevention alert
Harinstein et al[38]	Platelet drop	Bleed	≥ 50% decrease in platelets between most recent and second most recent platelet count
Harinstein et al[38]	Platelet drop	Bleed	2 consecutive decreases in platelets with ≥ 25% difference between the third most recent and the most recent platelet count

Table 5 Summary of proposed approaches to developing clinical decision support to prevent adverse drug events

Proposed approach	Description
Trajectory analysis	Identify laboratory values as they are on the incline or decline before they reach a critical value
Biomarkers	Use biomarkers that identify patients at risk for organ damage
Drug combinations	Generate alerts for drug combinations that place the patient at risk for drug-induced injury
Drug induced physiologic events	Add alerts for possible drug induced alterations in physiologic parameters to clinical decision support
Predictive analytics and forecasting models	Develop models that predict possible drug induced injury based on risk factors and use this information for advanced alerts using machine learning for adaptive response