The most straightforward way to implement a local drug Vocabulary is to utilize RxNorm Extension logic to extend standard Drug concept pool and map source drug products to concepts in RxNorm extended hierarchy.
Standard concepts in Drug domain are placed in a single comprehensive hierarchy based on their attributes. To correctly implement a vocabulary in CDM and find or build an counterpart for each source drug concept, the following attributes must be extracted:
Such attributes may be given explicitly in a well-structured source vocabulary or have to be extracted from drug product names. In case of drug products or discrete attributes like Ingredients or Brand Names not having their own codes, new codes have to be constructed combining the word “OMOP” and a running number. The running number should be unique across all vocabularies. That means, each time a new vocabulary is added or refreshed, the next Concept Code should be the one of the last (without the 'OMOP' string) +1.
All source vocabulary concepts, extracted attributes, dosage and packaging information must be staged in standardized format of input tables, that can processed to be included into OHDSI Standardized Vocabularies.
To implement a tool to create and maintain the above structure, a number of issues need to be taken care of:
The new vocabulary should be prepared in the following tables:
|concept_name||Yes||string(255)||An unambiguous, meaningful and descriptive name for the Concept in English language|
|domain_id||Yes||string(20)||A foreign key to the DOMAIN table. The standard content is 'Drug', but for non-drugs it could be 'Device' or 'Observation'|
|vocabulary_id||Yes||string(20)||A foreign key to the VOCABULARY table. The value of this field should be identical for all records, indicating the new vocabulary being added.|
|concept_class_id||Yes||string(20)||One of the above listed RxNorm Concept Classes|
|concept_code||Yes||string(50)||The code in the source vocabulary. If the source vocabulary does not contain a code, e.g. for ingredients or dose forms, they will be created automatically (see below OMOP created codes)|
|source_concept_class_id||No||string(20)||Concept class that is given by the source vocabulary|
|possible_excipient||No||string(1)||A flag only relevant to ingredients, indicating whether or not they are not active ingredients and could be omitted from an ingredient list. Currently ignored.|
|valid_start_date||No||date||Date when the Concept became valid. This may or may not coincide with the date the product went to market. Default value is 01.01.1970, unless source gives explicit date.|
|valid_end_date||No||date||Date when the Concept became invalid. Market withdrawal does not mean a Concept is invalid. Deprecated concepts have VALID_END_DATE of a day before update, unless source gives explicit date. VALID_END_DATE for all valid source concepts must be 31.12.2099|
|invalid_reason||No||string(1)||Flag indicating wether the Concept is active (today's date between valid_start and valid_end_date), or upgraded ('U') or deprecated ('D').|
This table is expected to contain concepts having following Concept Classes:
It may contain Branded or Clinical Drug Forms or Components, but if not they will be derived (see below). Note that units should not necessarily have an entry in the DRUG_CONCEPT_STAGE table. Instead, they should be used as verbatim. If the precise Concept Class of a Drug Product is relevant, it can be preserved in source_concept_class_id field.
Brand Names that are simple combinations of generic international name of active substance and manufacturer name (e.g. “Aspirin Bayer”) should not appear as attributes for Drug Products. Manufacturer information should be stored as a concept with Supplier class.
Concepts that belong to the source vocabulary, but do not belong to Drug domain by OMOP CDM conventions, should be classified as 'Device'. Typically, these belong to different substance groups:
Animal drugs can be handled as Drugs or Devices, depending on what their role in patient data can be expected to be. Note that only concepts from Drug domain can have attributes.
This table should contain the mapping between source codes and Standard Concepts for Ingredients, Brand Names, Dose Forms, Suppliers and Units. All other relationships will be ignored.
|concept_code_1||Yes||string(255)||The source code|
|concept_id_2||Yes||integer||The existing target Concept|
|precedence||No||integer||For multiple concept_code_1/concept_id_2 combination the order of precedence in which they should be considered for equivalence testing. The mapping with the highest prevalence among the drugs will be used for writing a record to the CONCEPT_RELATIONSHIP table. A missing precedence will be interpreted as precedence 1. Every precedence value should be unique per concept_code_1|
|conversion_factor||No||float||The factor used to convert the source code to the target Concept. This is usually defined for units|
This table should contain all mappings from the new to existing Concepts and their precedence.
Units should be mapped to Standard Concept Units. Weight units should be converted to milligram, volume units should be mapped to milliliter, molar - to millimole with the right conversion factor. The source_code field should contain the verbatim string of the unit. It is highly desirable to only use units that are in use by Standard native RxNorm concepts. Query DRUG_STRENGTH table for a distinct list.
Ingredients are usually mapped to Standard concepts one to one. If ingredient is given as a mix (e.g. Co-dried gel of Magnesium Carbonate and Aluminium Hydroxide), it should be split in multiple entities with distinct new codes; each component of the mix must be mapped to standard ingredient.
One to many mappings with precedence should be used if:
Dose Forms are commonly mapped to multiple RxNorm dose forms with precedence. Modified release forms should be first mapped to corresponding forms in RxNorm vocabulary (like Delayed Release Oral Capsule), and then to more generic forms (Oral Capsule) with lower precedence.
|concept_code_1||Yes||string(255)||One source code of the pair|
|concept_code_2||Yes||string(255)||The other source code of the pair|
This table should contain relationships for each Drug Concept: To the Ingredients (always), the Dose Form (if appropriate),the Supplier (if appropriate) and the Brand Name (if appropriate). All other relationships will be derived and ignored if they exist in the table. The relationships don't need to be symmetrical, only the one initiating from the Drug Concept is required.
If Drug Product concept does not have an Ingredient attribute, it will be non-standard (as all source concepts) and not have any standard mapping target after processing. Supplier attribute will not be considered for concepts without DS_STAGE or PC_STAGE entry since Marketed Product concepts can't exist without dosage information.
|drug_concept_code||Yes||string(255)||The source code of the Drug or Drug Component, either Branded or Clinical|
|ingredient_concept_code||Yes||string(255)||The source code for one of the Ingredients|
|amount_value||No||float||The numeric value for absolute content (usually solid formulations)|
|amount_unit||No||string(255)||The verbatim unit of the absolute content (solids)|
|numerator_value||No||float||The numerator value for a concentration (usually liquid formulations)|
|numerator_unit||No||string(255)||The verbatim numerator unit of a concentration (usually liquid formulations)|
|denominator_value||No||float||The denominator value for a concentration (usually liquid formulations). It should contain a number for Quantified products, and null for everything else.|
|denominator_unit||No||string(255)||The verbatim denominator unit of a concentration (usually liquid formulations)|
|box_size||No||integer||The number of units per box|
This table contains the dose of each ingredient in each drug, as well as the box_size. For drugs which have no strength information or have only for some of the containing ingredients, the ds_stage record must be omitted. '0' values in ds_stage are only allowed for inert drugs. Drug ingredients should match those in internal_relationship_stage. If ingredients are mapped to the same one in relationship_to_concept their dosages should be summed up as for a single ingredient before processing. A drug should not contain ingredients in solid (amount) and liquid (numerator/denominator) form. This might be caused be either source data aberration or drug pack, which must be split into separate Drug Products and processed in PC_STAGE table. If denominator value is given, quantified drug will be created with given denominator value and unit as total volume.
|pack_concept_code||Yes||string(255)||The source code of the Pack, either Branded or Clinical|
|drug_concept_code||Yes||string(255)||The component drug product in the Pack|
|amount||No||integer||The number of units of the drug product in a pack|
|box_size||No||integer||The number of packs if the pack is boxed (several packs in a larger container|
This table contains the composition of a Clinical or Branded Pack: The Clinical or Branded Drug and, number of doses in each box and number of boxes in each pack. If it is a boxed Pack, it will also contain the box size, since Packs have no records in DS_STAGE like the other drug products. Packs are allowed to have branded drugs as components, although usually Brand Name is only attributed to packs as a whole. Supplier may only be attributed to the pack as a whole.
Box size equal to 1 can also be omitted.
This table contains alternative names for concepts. These are either alternative names provided by source or names in original languages, since DRUG_CONCEPT_STAGE will contain english names only.
|synonym_concept_id||integer||Always and empty field in this table|
|synonym_name||string(255)||Alternative name of the concept. There is no need to copy the entry from DRUG_CONCEPT_STAGE|
|synonym_concept_code||string(50)||Concept code in source vocabulary|
|synonym_vocabulary_id||string(20)||VOCABULARY_ID of source vocabulary|
|language_concept_id||integer||CONCEPT_ID for Standard concept representing language|
This table allows to manually map source concepts to existing standard concept in OMOP CDM circumventing standard vocabulary building process. This is useful to represent source concepts that should be mapped to a concept from non-drug domain, preserve relationships inside the vocabulary or to map concepts to standard Drug concepts from outside of RxNorm and RxNorm Extension logic (e.g. standard concepts in CVX vocabulary. It is also recommended to provide manual mapping for drugs that may have poor source representation yet are usually of special interest for researchers, like insulins or vaccines.
|concept_code_1||Yes||string(255)||CONCEPT_CODE of source concept in either CONCEPT or DRUG_CONCEPT_STAGE tables|
|concept_code_2||Yes||string(255)||CONCEPT_CODE of target concept in either CONCEPT or DRUG_CONCEPT_STAGE tables|
|vocabulary_id_1||Yes||string(20)||VOCABULARY_ID value of source concept|
|vocabulary_id_2||Yes||string(20)||VOCABULARY_ID value of target concept|
|relationship_id||Yes||sting(20)||Indicates the type of relation from source to target; most usually will indicate equivalence mapping ('Maps to'). Must be one of the values from RELATIONSHIP table|
|valid_start_date||No||date||Date when the relation became valid|
|valid_end_date||No||date||Date when the relation became invalid|
|invalid_reason||No||string(1)||Non-null entry allows for manual deprecation of existing relationship. Deprecated relationships that are absent from CONCEPT_RELATIONSHIP table will not be added to Standardized Vocabularies|
This table needs not to be symmetrical like CONCEPT_RELATIONSHIP; complementary relationships will be built automatically. Note that concepts with equivalence mappings in this table should not have relations to attributes in other input tables.
The input tables need to have the following quality requirements:
|Rule||If rule is violated|
|Each record should be unique in all tables.||The processing will fail.|
|Concept Codes should be unique and should not repeat for different products.||The processing will fail.|
|Combinations of product components should be unique. These are Ingredient-strength(s) combination, Dose Form, Brand Name, Quantity, Box size.||Only the highest Concept Code is retained, and the other ones are treated as non-standard Concepts and mapped to the highest.|
|Each product should have links (records in INTERNAL_RELATIONSHIP_STAGE) to all their Ingredients.||The product will be treated as if it had only the linked Ingredients. If no Ingredients are linked, the product will be processed into the CONCEPT_STAGE table, but as an orphan without any related Concept Classes.|
|Ingredients should be linked to their Standard counterparts if such concepts exist.||These Ingredients are treated as new Standard Ingredients, which may lead to creation of duplicates.|
|Dose Forms should be linked to their valid counterparts if such concepts exist.||These Dose Forms will be treated as new valid Concepts, which may lead to creation of duplicates.|
|Brand Names should be linked to their valid counterparts if such concepts exist.||These Brand Names will be treated as new valid Concepts, which may lead to creation of duplicates.|
|All % in source dosages should be converted into mg/ml (mg) unless it is a gas.||A drug would not be mapped to it's Standard Concept|
|Marketed Product (a drug that has relationship to it's supplier in INTERNAL_RELATIONSHIP_STAGE) should have both dosage and Dose Form||The product won't be processed into CONCEPT_STAGE table.|
|Boxed drug should have both dosage and Dose Form.||The product won't be processed into CONCEPT_STAGE table.|
|Product ingredients should match in INTERNAL_RELATIONSHIP_STAGE and DS_STAGE||The processing will fail.|
|When mapping Ingredients, Dose Forms or other attributes are mapped to multiple targets precedence values must be present and unique for each source concept||Processing will create orphaned meaningless branches of RxNorm Extension concepts.|
|Concepts with active 'Maps to' relations inside CONCEPT_RELATIONSHIP_MANUAL should not have any entries indicating relationships with attributes||Redundant branches of RxNorm Extension or multiple mappings may be created|
For quality assurance of input tables you can use drug_stage_tables_QA.sql script from project's github.
All propositions to add a new vocabulary into CDM may be submitted (optionally with prepared input tables) as issues on github.