Not that much I can say to what you are laying out, except that you pretty much got it:
- Ingredients are separate, for the mentioned biological reason. We could implement the multi-ingredient combinations (MIN in RxNorm speak), but that would be a big surgery at this point (all RxNorm Extensions would have to be changed). And there is not that big of a use case I can spot, here, other than “I want to capture as precise as possible what the doctor scribbled”. But that is not an analytical use case.
- Clinical Drug Components (ingredient+strength) only exist separately, and not as combinations. Branded Drug Components and Clinical Drug Forms do, though. It remains RxNorm’s secret why they created this idiosyncrasy. I wish it were different, and theoretically we could fix it, but again, no strong use case for that big surgery.
- Brand names are not standard concepts, because they are not clean. There is no one-to-one relationship to ingredients. It’s all over the place.
From the use case perspective, 90% of all exposure cohorts are based on ingredient definitions. 9% of them want some limitation on topical, inhalant or systemic, and Drug Forms do that for you. And there may be 1% of weird stuff. I haven’t seen a study that is going explicitly after combination drugs.
Bottom line: It is idiosyncratic, but it works for the use cases.
ATC: It is similar, except now we are on the receiving end of the same attitude. All the idiosyncrasies we are pointing out they respond to with shrugging their shoulders, claiming that the manufacturers of the drugs are the ones who request the codes, and it works for them. And there are a ton of idiosyncrasies:
- There are drugs which have no ATC code
- There are ATC codes for which there is no drug
- There are multiple ATC codes for the same drug (steroids topping the list)
- The combinations are ambiguously defined
- The combinations overlap
- The naming convention of lower ATC codes are missing most the A, T and C attributes of the higher, leaving you guessing what this thing really is (a topical or systemic steroid)
Which means, ATC cannot correctly serve as classification for an RxNorm-type hierarchy, because of the above. Particularly the combinations are a mess. We still stitched it together, but it isn’t perfect.