===== Drug Domain =====

The drug exposure domain concepts capture records about the utilization 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 or biochemical effect. The following products are **not** considered Drugs, but Devices:

  * Diagnostic radiopharmaceuticals.
  * Contrast material for imaging (barium sulfate, gadolinium, etc.).
  * Nutritional products and supplements, including infant feeding. In reality that results in the slightly arbitrary and in some cases difficult to ascertain situation that solutions of salts are Drugs (hydrating patients and maintaining ionic balance), while the addition of nutrients such as glucose or vitamins makes them devices (feeding patients).
  * Parenteral nutrition (aminoacids and/or lipid mixes).
  * Solution for dialysis, catheter maintenance etc.
  * Products directly derived from blood (erythrocytes, plasma, serum, thrombocytes), while immune globin or albumin preparations, monoclonal antibodies, coagulation factors and homeopathy derived from blood are Drugs.
  * Transplants of any kind.
  * Artificial saliva, artificial tears, and lubricants.
  * Non-medicated cosmetics (creams, ointments, soaps, deodorants, shampoos), including SPF sunscreens.
  * Glucometric strips, needles, tubes with anticoagulants, etc.
  * Surgical materials like bone cement.
  * Hemostatics materials (cellulose, flour, collagen, etc.).
  * Disinfectants for inert surfaces.

**Devices that contain drug substances (e.g. bone cement with antibiotics) are considered Devices, but should obtain additional mapping to the Drug Domain concepts.**

Drug domain Concepts should be used in the drug_concept_id of the DRUG_EXPOSURE the DRUG_ERA and the DOSE_ERA (both only at the Ingredient level) tables, or in the value_as_concept_id field of the OBSERVATION or MEASUREMENT table (e.g. for Measurements like "Plasma level").

==== Overall Structure ====
{{ :documentation:vocabulary:drugdomain.jpg?nolink |Structure of Drug Domain}}

The Drug Domain consists of Source Concepts (below the horizontal line), Drugs (Standard Concepts) and Classifications (Classification Concepts). As usual, Source Concepts are non-Standard Concepts that are used as coding schemes in various databases. As such, they are mapped to Standard Concepts. 

Standard Concepts are based on the [[documentation:vocabulary:rxnorm|RxNorm]] and [[documentation:vocabulary:rxnorm_extension|RxNorm Extension]] vocabularies. All Standard RxNorm and RxNorm Extension Concepts are used in the drug_concept_id fields.

RxNorm is the foundation for the combined Domain space. All valid RxNorm Concepts (invalid_reason is null) are used as Standard Concepts. However, RxNorm only contains Drug Concepts for products sold in the United States. All Concepts derived from international products are availabe in the RxNorm Extension vocabulary. Apart from the different vocabulary_id, both RxNorm and RxNorm Extension form a combined Concept space with identical rules for relationships and Concept Ancestry.

RxNorm and RxNorm Extension Concepts are hierarchical. Therefore the Concepts can also be used as Class Concepts: descendants of any Standard Concept in the CONCEPT_ANCESTOR table can expected to be a correct semantic match in a query. For example, a query for the descendants of an ingredient should turn up all drug products (Clinical Drug or Branded Drug) containing that ingredient.

On top of this combined RxNorm/RxNorm Extension Drug Domain are drug classification systems. These are derived from a variety of different vocabularies. **Note:** Any classification Concept may exist in different classifications, and therefore cannot be considered as unique. For example, NSAID Analgesics exist with very similar memberships as ETC, VA Class and SNOMED classes. **Also note**: Only ATC is defined for both RxNorm and RxNorm Extension drugs, and can therefore serve as a universal drug classification system for all drugs. The other classifications are defined for RxNorm, only, and future additions for subsets of RxNorm Extension.

==== Concept Classes ====
Those for the Source and Classification Concepts are specific to the source vocabulary (see there). 
The Concept Classes for the Drug Concepts are based on a subset of RxNorm [[https://www.nlm.nih.gov/research/umls/rxnorm/docs/2015/appendix5.html|Term Types]]:

^Term Type^Name^Concept Class^
|IN|Ingredient|Ingredient|
|PIN|Precise Ingredient|Ingredient (standard_concept = NULL)|
|MIN|Multiple Ingredients|Not implemented|
|BN|Brand Name|Brand Name|
|SCDC|Semantic Clinical Drug Component|Clinical Drug Component|
|SCDF|Semantic Clinical Drug Form|Clinical Drug Form|
|SCDG|Semantic Clinical Dose Form Group|Not implemented|
|SCD|Semantic Clinical Drug|Clinical Drug or Quantified Clinical Drug|
|SBDC|Semantic Branded Drug Component|Branded Drug Component|
|SBDF|Semantic Branded Drug Form|Branded Drug Form|
|SBDG|Semantic Branded Dose Form Group|Not implemented|
|SBD|Semantic Branded Drug|Branded Drug or Quantified Branded Drug|
|GPCK|Generic Pack|Clinical Pack|
|BPCK|Brand Name Pack|Branded Pack|
|DF|Dose Form|Dose Form|
|DFG|Dose Form Group|Not implemented|
|PSN|Prescribable Name|Not implemented|
|SY|Synonym|Implemented in the CONCEPT_SYNONYM table|
|TMSY|Tall Man Lettering Synonym|Not implemented|
|ET|Dose Form Entry Term|Not implemented|

Concepts of the Concept Classses "Clinical Drug" and "Branded Drug" (SCD and SBD) of liquid formulations have their drug strength provided as concentrations, with or without the total quantity provided. That means, many of them exist in pairs. RxNorm does not represent this distinction using different Term Types, however, we defined addtional Concept Classes "Quantified Clincal Drug" and "Quantified Branded Drug" for those drugs where a quantity factor is provided.

In addition to the RxNorm-derived Concept Classes, international coding schemes brake drugs down according to their package or box size. This is due to the fact that prescription drugs are generally sold as prepackaged products, while most prescription drugs in the US get packaged at the time of the prescription filling in the pharmacy. Note, that these boxes are different from the RxNorm packs. Packs represent the smallest unit of drug product combinations, while boxes define the total amount of units sold as a product. In addition to boxes, international coding scheme also distinguish products of different manufacturers or resellers (suppliers). To make those coding schemes work seamlessly with the RxNorm system, additional Concept Classes were defined in the RxNorm Extension vocabulary:

^Vocab^Name^Ingre dient^Drug strength^Dose form^Brand name^Quantity factor^Box size^Pack content ^Supplier^
^RxNorm|Ingredient|   x   | | | | | | | |
^:::|Clinical Drug Component|  x  |  x  | | | | | | |
^:::|Clinical Drug Form|  x  | |  x  | | | | | |
^:::|Clinical Drug|  x  |  x  |  x  | | | | | |
^:::|Branded Drug Component|  x  |  x  | |  x  | | | | |
^:::|Branded Drug Form|  x  | |  x  |  x  | | | | |
^:::|Branded Drug|  x  |  x  |  x  |  x  | | | | |
^:::|Clinical Pack|  x  | | | | | |  x  | |
^:::|Branded Pack|  x  | | |  x  | | |  x  | |
^Rxnorm (not explicit)|Quantified Clinical Drug|  x  |  x  |  x  | |  x  | | | |
^:::|Quantified Branded Drug|  x  |  x  |  x  |  x  |  x  | | | |
^RxNorm Extension|Clinical Drug Box|  x  |  x  |  x  | | |  x  | | |
^:::|Branded Drug Box|  x  |  x  |  x  |  x  | |  x  | | |
^:::|Quantified Clinical Box|  x  |  x  |  x  | |  x  |  x  | | |
^:::|Quantified Branded Box|  x  |  x  |  x  |  x  |  x  |  x  | | |
^:::|Clinical Pack Box|  x  |  x  |  x  | | |  x  | | |
^:::|Branded Pack Box|  x  |  x  |  x  |  x  | |  x  | | |
^:::|Marketed Product|  x  |  x  |  x  |optional|optional|optional|optional|  x  |

This system of Concept Classes is fully normalized. I.e. that for each defined, say, Branded Drug there are the equivalent Clinical Drug, Clinical Drug Component, Branded Drug Component, Clinical Drug Form and Branded Drug Form available. For combination drugs with several Ingredients equivalent combinations are defined in the same manner. **Note** that the latter is not true for Clinical Drug Components. These only exist as single-ingredient Concepts. The reason for this is not discussed in the technical documentation by RxNorm. Ingredients are only defined as single Ingredients, RxNorm's MIN (Multiple Ingredients) are not implemented.

==== Relationships ====
As usual, all Source Concepts are mapped to the RxNorm or RxNorm Extension Concepts. The mapping is either constructed from the vocabulary source and in some cases curated by the vocabulary team. Generally, mappings are between equivalent Concept Classes, and if possible to Clinical or Branded Drugs, or more detailed Concept Classes further down in the hierarchy. However, in some cases this is not possible (e.g. when mapping Procedure Drugs) or if insufficient information is known about a Source Concept, at which point a more general Concept can be used. Such non-equivalent mappings are carried out as following:

  * One-to-many mappings to Ingredients or Clinical Drug Components
  * One-to-one mappings to all other Concept Classes

The internal relationships between Drug Concepts are derived from RxNorm relatinships and extended to cover the additional Concept Classes of the RxNorm Extension vocabulary ("Drug" without any attribute means either "Clinical" or "Branded"):

^Source^Original name^relatinship_id^Connecting Concept Classes^
|RxNorm|consists_of|Consists of|Drug or Quantified Drug and Drug Component|
|:::|constitutes|Constitutes|Drug Component and Drug or Quantified Drug|
|:::|contained_in|Contained in|Drug or Quantified Drug and Pack|
|:::|contains|Contains|Pack and Drug or Quantified Drug|
|:::|dose_form_of|RxNorm dose form of|Dose Form and Drug, Drug Form|
|:::|form_of|Form of|(Precise) Ingredient and Ingredient|
|:::|has_dose_form|RxNorm has dose form|Drug, Drug Form and Dose Form|
|:::|has_form|Has form|Ingredient and (Precise) Ingredient|
|:::|has_ingredient|RxNorm has ing|Clinical Drug Form/Component and Ingredient, and Branded Drug Form/Component and Brand Name. Not implemented between Branded Drug and Brand Name|
|:::|has_precise_ingredient|Has precise ing|Brand Name/Clinical Drug Component and (Precise) Ingredient|
|:::|has_quantified_form|Has quantified form|Drug and Quantified Drug|
|:::|has_tradename|Has tradename|Clinical and Branded Concept Class equivalents|
|:::|has_tradename|Has brand name|Ingredient and Brand Name|
|:::|ingredient_of|RxNorm ing of|Ingredient and Clinical Drug Form/Component, and Brand Name and Branded Drug Form/Component. Not implemented between Branded Drug and Brand Name|
|:::|inverse_isa|RxNorm inverse is a|Drug Form and Drug|
|:::|isa|RxNorm is a|Drug and Drug Form|
|:::|precise_ingredient_of|Precise ing of|(Precise) Ingredient and Brand Name/Clinical Drug Component|
|:::|quantified_form_of|Quantified form of|Quantified Drug and Drug|
|:::|reformulated_to|Reformulated in|Brand Name and Brand Name (name changes)|
|:::|reformulation_of|Reformulation of|Brand Name and Brand Name (name changes)|
|:::|tradename_of|Tradename of|Branded and Clinical Concept Class equivalents|
|:::|tradename_of|Brand name of|Brand Name and Ingredient|
|:::|  -  |Concept replaced by|Concepts in RXNATOMARCHIVE with merged_to_rxcui information|
|:::|  -  |Concept replaces|Concepts in RXNATOMARCHIVE with merged_to_rxcui information|
|RxNorm Extension|  -  |Available as box|Drug and Drug Box|
|:::|  -  |Box of|Drug Box and Drug|
|:::|  -  |Has marketed form|Drug and Marketed Product|
|:::|  -  |Marketed form of|Marketed Product and Drug|
|:::|  -  |Has supplier|Drug and Supplier|
|:::|  -  |Supplier of|Supplier and Drug|

For a discussion of the relationships between Drugs and Classifications and within Classifications please see the individual vocabulary sections.

==== Drug Strength ====
The Drug Domain has an additional DRUG_STRENGTH table defining the strength of each ingredient. This is defined for all Drug Concept Classes except Ingredient, Clinical Drug Form and Branded Drug Form, Dose Form, Brand Name and Supplier.