RxNorm Extension

RxNorm Extension is an OHDSI resource to represent international drugs in a structure adapted from RxNorm. This describes the process, rules and resulting structure of incorporating international drug vocabularies into an overall RxNorm-like system, called RxNorm Extension.

Drug vocabularies contain drug products and their components. Only about a third of these products are identical in the drug markets of individual countries or jurisdictions of a drug marketing approval agency. Even if the active ingredients are the same, they can differ in their Drug Strengths, Drug Forms, Brand Names, package sizes and manufacturers or distributors.

Therefore, these vocabularies need to be incorporated into the existing Drug Domain in such a way that all existing drugs and their components are correctly mapped, and the missing ones added as new concepts. This includes a life cycle for each Concept, allowing to generation, deprecation and update over time.

The processing script that follows these instructions can be found here.

General structure

The Drug Domain should be organized in a hierarchical structure described in Drug Domain. This structure is based on RxNorm, which also forms the core of the content. RxNorm comprehensively describes the drug market in the United States. It may not contain products sold in the markets of other countries. It also does not contain US medical food or food supplement products.

This structure contains at a minimum (from bottom to top):

Concept Class	Composed of
Branded Drug	Ingredients, their strength, form, brand name
Clinical Drug	Ingredient, their strength, form
Branded Drug Form	Ingredient, form, brand name
Clinical Drug Form	Ingredient, form
Branded Drug Component	Ingredient, strength, brand name
Clinical Drug Component	Ingredient, strength
Dose Form	Form
Brand Name	Brand name
Ingredient	Ingredient
Drug Class	Drug class

It may optionally contain

Concept Class	Composed of
Marketed Product	Ingredients, their strength, form, supplier (brand name and box size are optional)
Quantified Branded Drug Box	Ingredients, their strength, form, brand name, size and box size
Quantified Clinical Drug Box	Ingredients, their strength, form, size and box size
Branded Drug Box	Ingredients, their strength, form, brand name and box size
Clinical Drug Box	Ingredients, their strength, form and box size
Quantified Branded Drug	Ingredients, their strength, form, brand name, size
Quantified Clinical Drug	Ingredients, their strength, form, size
Branded Pack	Branded Drugs, their number (box size is optional)
Clinical Pack	Clinical Drugs, their number (box size is optional)
Supplier	Supplier

Currently not supported are the following classes:

Concept Class	Composed of	Remarks
Precise Ingredient	Ingredient	Ingredient used instead; Precise Ingredients are mapped to Ingredients inside CONCEPT_RELATIONSHIP table
Multiple Ingredient	Ingredients	Single ingredients used instead
Dose Form Group	Dose Form	Explicit Dose Forms used instead; Dose Form Groups exist as Classification concepts and bear relation to standard concepts only inside native RxNorm vocabulary

The Concepts are connected through hierarchical and lateral relationships.

Combined target structure

To incorporate a new set of drug information, a structure that contains every Concept only once and preserves the RxNorm structure, no matter which vocabulary the additional Concept is coming from should be achieved. This means that for each source drug concept a standard concept that follows RxNorm logic is created and correctly placed inside a hierarchy. In a way, it should create a mixed RxNorm/drug vocabularies union.

In order to achieve this, any two equivalent Concepts have to be matched through its components: Ingredients to Ingredients, Forms to Forms, Supplier to Supplier, etc. Concepts are defined as matching if all components match. For example, a Clinical Drug matches another Clinical Drug if it contains the same Ingredients at the same strength and the same Dose Form.

Rules for adding Concepts

To add a Concept for which there is an existing equivalent:

• It should be recorded as a non-standard (source) Concept.
• It should be mapped through a “Maps to” relationship to its standard equivalent.
• All other relationships are optional and for QA and convenience. The standard Concept will take its place as the official representation.

To add a Concept that does not have an equivalent:

• It should be recorded as a standard Concept (standard_concept = 'S'), with the exception of Brand Names, which should be recorded as a non-standard Concepts.
• It should have hierarchical and lateral relationships in the same manner as RxNorm Concepts do.
• It should form relationship to relevant drug classes. The relationship_id of these relationship do not have to follow the RxNorm standard, as it differs for every drug class. Classes are most often defined for Ingredients, but some non-Ingredients may directly designate a Concept Class and “jump over” the Ingredient or even Drug Forms or Drug Components. They will be inferred automatically.

Units used in the strength determination are not added. They must be mapped to a Standard UCUM Concept instead. If a unit is not present in the UCUM vocabulary it has to be added.

Implementation

Concepts from source vocabularies must be added following the International drugs vocabulary implementation process.

Result

Concepts belonging to source drug vocabularies have 'Maps to' relations to standard concepts in RxNorm and RxNorm Extension vocabularies.

Equivalence relationship to valid non-standard concepts (like Brand Names and Dose forms) is indicated by entry in CONCEPT_RELATIONSHIP table with RELATIONSHIP_ID = 'Source - RxNorm eq'. Such relations are built for attributes like Dose Forms and Brand Names.

Relationships between Drug Products or derivatives (Drug Forms and Components) are connected through CONCEPT_RELATIONSHIP_STAGE records with the the following relationship_id values:

Concept Class 1	Concept Class 1	Relationship
Brand Name	Branded Drug	Brand name of
Brand Name	Branded Drug Comp	Brand name of
Brand Name	Branded Drug Form	Brand name of
Brand Name	Ingredient	Brand name of
Brand Name	Quant Branded Drug	Brand name of
Brand Name	Marketed Product	Brand name of
Branded Drug	Brand Name	RxNorm has ing
Branded Drug	Branded Drug Comp	Consists of
Branded Drug	Branded Drug Form	RxNorm is a
Branded Drug	Branded Pack	Contained in
Branded Drug	Clinical Drug	Tradename of
Branded Drug	Clinical Drug Comp	Consists of
Branded Drug	Dose Form	RxNorm has dose form
Branded Drug	Quant Branded Drug	Has quantified form
Branded Drug	Quant Clinical Drug	Tradename of
Branded Drug	Marketed Product	Has marketed form
Branded Drug Comp	Brand Name	RxNorm has ing
Branded Drug Comp	Branded Drug	Constitutes
Branded Drug Comp	Clinical Drug Comp	Tradename of
Branded Drug Comp	Quant Branded Drug	Constitutes
Branded Drug Form	Brand Name	RxNorm has ing
Branded Drug Form	Branded Drug	RxNorm inverse is a
Branded Drug Form	Clinical Drug Form	Tradename of
Branded Drug Form	Dose Form	RxNorm has dose form
Branded Drug Form	Quant Branded Drug	RxNorm inverse is a
Branded Pack	Branded Drug	Contains
Branded Pack	Clinical Drug	Contains
Branded Pack	Clinical Pack	Tradename of
Branded Pack	Dose Form	RxNorm has dose form
Branded Pack	Quant Branded Drug	Contains
Branded Pack	Quant Clinical Drug	Contains
Branded Pack	Marketed Product	Has marketed form
Clinical Drug	Branded Drug	Has tradename
Clinical Drug	Branded Pack	Contained in
Clinical Drug	Clinical Drug Comp	Consists of
Clinical Drug	Clinical Drug Form	RxNorm is a
Clinical Drug	Clinical Pack	Contained in
Clinical Drug	Dose Form	RxNorm has dose form
Clinical Drug	Quant Branded Drug	Has tradename
Clinical Drug	Quant Clinical Drug	Has quantified form
Clinical Drug	Marketed Product	Has marketed form
Clinical Drug	Marketed Product	Contained in
Clinical Drug Comp	Branded Drug	Constitutes
Clinical Drug Comp	Branded Drug Comp	Has tradename
Clinical Drug Comp	Clinical Drug	Constitutes
Clinical Drug Comp	Ingredient	Has precise ing
Clinical Drug Comp	Ingredient	RxNorm has ing
Clinical Drug Comp	Quant Branded Drug	Constitutes
Clinical Drug Comp	Quant Clinical Drug	Constitutes
Clinical Drug Form	Branded Drug Form	Has tradename
Clinical Drug Form	Clinical Drug	RxNorm inverse is a
Clinical Drug Form	Dose Form	RxNorm has dose form
Clinical Drug Form	Ingredient	RxNorm has ing
Clinical Drug Form	Quant Clinical Drug	RxNorm inverse is a
Clinical Pack	Branded Pack	Has tradename
Clinical Pack	Clinical Drug	Contains
Clinical Pack	Dose Form	RxNorm has dose form
Clinical Pack	Quant Clinical Drug	Contains
Clinical Pack	Marketed Product	Has quantified form
Dose Form	Branded Drug	RxNorm dose form of
Dose Form	Branded Drug Form	RxNorm dose form of
Dose Form	Branded Pack	RxNorm dose form of
Dose Form	Clinical Drug	RxNorm dose form of
Dose Form	Clinical Drug Form	RxNorm dose form of
Dose Form	Clinical Pack	RxNorm dose form of
Dose Form	Quant Branded Drug	RxNorm dose form of
Dose Form	Quant Clinical Drug	RxNorm dose form of
Dose Form	Marketed Product	RxNorm dose form of
Ingredient	Brand Name	Has brand name
Ingredient	Clinical Drug Comp	RxNorm ing of
Ingredient	Clinical Drug Form	RxNorm ing of
Marketed Product	Brand Name	Has brand name
Marketed Product	Branded Drug	Marketed form of
Marketed Product	Branded Pack	Marketed form of
Marketed Product	Clinical Drug	Marketed form of
Marketed Product	Clinical Drug	Contains
Marketed Product	Clinical Pack	Marketed form of
Marketed Product	Dose Form	RxNorm has dose form
Marketed Product	Quant Branded Drug	Marketed form of
Marketed Product	Quant Clinical Drug	Contains
Marketed Product	Quant Clinical Drug	Marketed form of
Marketed Product	Supplier	Has supplier
Quant Branded Drug	Brand Name	RxNorm has ing
Quant Branded Drug	Branded Drug	Quantified form of
Quant Branded Drug	Branded Drug Comp	Consists of
Quant Branded Drug	Branded Drug Form	RxNorm is a
Quant Branded Drug	Branded Pack	Contained in
Quant Branded Drug	Clinical Drug	Tradename of
Quant Branded Drug	Clinical Drug Comp	Consists of
Quant Branded Drug	Dose Form	RxNorm has dose form
Quant Branded Drug	Quant Clinical Drug	Tradename of
Quant Branded Drug	Marketed Product	Has marketed form
Quant Clinical Drug	Branded Drug	Has tradename
Quant Clinical Drug	Branded Pack	Contained in
Quant Clinical Drug	Clinical Drug	Quantified form of
Quant Clinical Drug	Clinical Drug Comp	Consists of
Quant Clinical Drug	Clinical Drug Form	RxNorm is a
Quant Clinical Drug	Clinical Pack	Contained in
Quant Clinical Drug	Dose Form	RxNorm has dose form
Quant Clinical Drug	Quant Branded Drug	Has tradename
Quant Clinical Drug	Marketed Product	Has marketed form
Quant Clinical Drug	Marketed Product	Contained in
Supplier	Marketed Product	Supplier of

Name of the Branded and Clinical Pack concepts is built by combining names of the contents.

Relationships between any Drug Concept Class and a Classfication Concept Class is recorded through the “Drug has drug class” and “Drug class of drug” generic relationship pair.

Inferring of missing Concept Classes

After RxNorm Extension Standard concept with the fullest attribute set is created for each source entity, all missing preceding Concept Classes are inferred from the existing ones, from bottom upwards.

Concept Class	Defined by
Clinical Drug Component	Ingredient-strength. Note that Clinical Components are always single-Ingredient. This is in contrast to all other Concept Classes
Branded Drug Component	Ingredient-strength(s), Brand Name
Clinical Drug Form	Ingredient(s), Dose Form
Branded Drug Form	Ingredient(s), Dose Form, Brand Name
Clinical Drug	Ingredient-strength(s), Dose Form
Branded Drug	Ingredient-strength(s), Dose Form, Brand Name
Quantified Clinical Drug	Ingredient-strength(s), Dose Form, Quantity
Quantified Branded Drug	Ingredient-strength(s), Dose Form, Brand Name, Quantity
Clinical Drug Box	Ingredient-strength(s), Dose Form, Box size
Branded Drug Box	Ingredient-strength(s), Dose Form, Brand Name, Box size
Quantified Clinical Box	Ingredient-strength(s), Dose Form, Quantity, Box size
Quantified Branded Box	Ingredient-strength(s), Dose Form, Brand Name, Quantity, Box size

Even though all drug classes are inferred, only those will be created as concepts that have no mapping to an existing equivalent Standard Concept.