Drug Exposure

The Drug Exposure domain captures records about the utilisation of a drug when ingested or otherwise introduced into the body. A drug is a biochemical substance formulated in such a way that when administered to a person it will exert a certain physiological effect. Drugs include prescription and over-the-counter medicines, vaccines, and large-molecule biologic therapies.

Radiological devices ingested or applied locally do not count as drugs.

Drug Exposure is inferred from clinical events associated with orders, prescriptions written, pharmacy dispensing, procedural administrations, and other patient-reported information, for example:

• The “Prescription” section of an EHR captures prescriptions written by physicians or from electronic ordering systems.
• The “Medication list” section of an EHR for both non-prescription products and medications prescribed by other providers.
• Prescriptions fulfilled by pharmacies.
• Drugs administered as part of a procedure, such as chemotherapy or vaccines.

Field	Required	Type	FK Table	Description
drug_exposure_id	Yes	bigint		A system-generated unique identifier for each Drug utilisation event.
person_id	Yes	bigint	PERSON	A foreign key identifier to the Person who is subjected to the Drug. The demographic details of that Person are stored in the PERSON table.
drug_concept_id	Yes	bigint	CONCEPT	A foreign key that refers to a Standard Concept identifier in the Standardized Vocabularies for the Drug concept. Preferably at the RxNorm Ingredient level.
drug_exposure_start_date	Yes	date		The UTC start date for the current instance of Drug utilisation.
drug_exposure_start_datetime	No	datetime		The UTC start date and time for the current instance of Drug utilisation.
drug_exposure_end_date	No	date		The UTC end date for the current instance of Drug utilisation. This is populated in the event that a datetime is not available (e.g. for home administrations).
drug_exposure_end_datetime	No	datetime		The UTC end date and time for the current instance of Drug utilisation. It is NULL if the administration is not complete.
verbatim_end_date	No	date		The end date or discontinuation date as it appears from the source data or NULL if unavailable.
drug_type_concept_id	Yes	bigint	CONCEPT	A foreign key to the predefined Concept identifier of the “Type Concept” domain in the Standardized Vocabularies reflecting the type of Drug Exposure recorded. See Drug Type below.
stop_reason	No	varchar(20)		Not used.
refills	No	integer		Not used.
quantity	Yes	numeric/float		Records “dose” or “infusion rate” depending upon case use.
days_supply	No	integer		Days supply of the drug. This should be the verbatim days_supply as given on the prescription. If the drug is physician administered use duration end date if given or set to 1 as default if duration is not available.
sig	No	text		The written out instructions for the drug as it is verbatim in the source, if available.
route_concept_id	No	bigint	CONCEPT	A foreign key to a predefined concept in the Standardized Vocabularies reflecting the route of administration.
lot_number	No	varchar(50)
provider_id	No	bigint	PROVIDER	Not used.
visit_occurrence_id	No	bigint	VISIT_OCCURRENCE	A foreign key to the Visit Occurrence during which the Drug Exposure was initiated.
visit_detail_id	No	bigint	VISIT_DETAIL	A foreign key to the Visit Detail during which the Drug Exposure was initiated.
drug_source_value	No	varchar(50)		This field houses the verbatim value from the source data representing the drug exposure that occurred. For example, this could be an NDC or Gemscript code.
drug_source_concept_id	No	bigint	CONCEPT	If the drug_source_value is coded in the source data using an OMOP supported vocabulary put the concept id representing the source value here.
route_source_value	No	varchar(50)		The field is meant to contain a value indicating when and how a drug was given to a patient.
dose_unit_source_value	No	varchar(50)		Not used.

Conventions

• Valid Concepts for the drug_concept_id field belong to the “Drug” domain. Most Concepts in the Drug domain are based on RxNorm, but some may come from other sources (like dm+d). Concepts are members of the Clinical Drug or Pack, Branded Drug or Pack, Drug Component or Ingredient classes.
• All drug administrations refer to inpatient administrations where we are able to identify the formulation, and time of specific delivery.
• For mixtures, it is preferred that the product can be represented as a VMP, AMP or other high level concept available in dm+d to represent mixtures. If this is not possible, then all active ingredients should be provided as simultaneous administrations and linked through a Fact Relationship:
  • For example, co-amoxiclav (amoxicillin and clavulanic acid).
• A Drug Type is assigned to each Drug Exposure to track from what source the information was drawn or inferred from. The valid domain_id for these Concepts is “Drug Type”.
• The route_concept_id refers to a Standard Concept of the “Route” domain. Note: Route information can also be inferred from the Drug product itself by determining the Drug Form of the Concept, creating some partial overlap of the same type of information. However, the route_concept_id could resolve ambiguities of how a certain Drug Form is actually applied. For example, a “Solution” could be used orally or parenterally, and this field will make such determination.
• If possible, the Visit in which the drug was prescribed or delivered is recorded in the visit_occurrence_id field through a reference to the VISIT_OCCURRENCE table.

Variable Rate Infusions vs. Other Administrations

From an analytic perspective, there are two situations we need to account for.

1. Where the dose of the drug is salient information (e.g 5mg bisoprolol given orally)
   • quantity is used to represent the total dose of drug administered.
   • drug_exposure_start_datetime indicated when the drug administration was started.
   • drug_exposure_end_datetime indicates when the drug administration was ended.
   • drug_exposure_start_datetime and drug_exposure_end_datetime will be the same for tablets or bolus injections.
   • Short fixed rate infusions can have a difference between drug_exposure_start_datetime and drug_exposure_end_datetime , indicating that the mass of drug denoted by quantity was infused over a period of time.
2. Where the rate of administration of the drug is salient information (e.g. 0.1 mcg/Kg/min noradrenaline)
   • quantity is used to represent the rate of infusion in standardised units as described in the data specification.
   • One row is produced for every rate adjustment recorded in the EHR.
   • drug_exposure_start_datetime indicates when the current rate of drug infusion was started (including starting the infusion).
   • drug_exposure_end_datetime indicates when the current rate of drug infusion changes (including stopping the infusion).
   • A row bounded by drug_exposure_start_datetime and drug_exposure_end_datetime indicates a period of time during which the variable rate of infusion was fixed at the rate defined in quantity .

The vast majority of cases fall under point 1, and the duration of administration, even over several hours is often not particularly relevant. The following are examples that are common and will all be represented via this method:

• Bisoprolol 5mg Orally given twice daily (each administration recorded as a row).
• Amiodarone 900mg Intravenous infused over 23 hours (the single administration recorded as a row with 23 hours difference in time between start and end).
• Salbutamol 2.5mg Nebulised given 4 times daily over a period of 15 minutes, but the end time is not documented (duration of administration is irrelevant, each administration recorded as a row with start and end times aligned).

Point 2 includes many of the drugs used in critical care, where short half-lives mean that the total amount of administrated drug is not of interest. A primary example includes:

• Noradrenaline given between 0-0.1 mcg/Kg/min with changes between 5 minutely to 4 hourly over several days.
• The units mcg/Kg/min can be recorded in dose_unit_source_value and thus specify that the information in quantity refers to a rate.

Routes of Administration

There are many routes of administration. An exhaustive list is contained in the standard concepts of the “Route” domain in Athena (primarily SNOMED codes).

Below is a convenient non-exhaustive list:

• Nasgogastric/Nasojejonal (entering the gut via a device placed in the nose)
• PEG/RIG/jejunostomy or similar (entering the gut via a device placed through the skin).
• Oral enteral (entering the gut naturally).
• Oral mucosal/buccal/sublingual (placed in the mouth and not swallowed).
• Intramuscular (an injection into muscle).
• Intraarterial (an injection into the artery. This is rare beyond fluid used to keep arterial lines patent).
• Intravenous (an injection into the vein).
• Subcutaneous (an injection into the subcutaneous tissues).
• Epidural (an injection into a space near the spinal cord).
• Intrathecal (an injection into the subarachnoid space).
• Extra-corporeal circuit (an injection into a machine external to the patient. This may or may not flow back into the patient).
• Inhaled
• Intrauterine
• Rectal
• Topical
• Urethral
• Vaginal

Standard Mappings

Drug Type

Code	Name
38000180	Inpatient administration
38000177	Prescription written
44787730	Patient Self-Reported Medication
32426	NLP derived

Trial Drugs

If a patient is on a trial drug, please use drug_concept_id “44803478” (44803478|Drug trial administration ).