'BoSS Clinical Drug' Concept in Drug Model

I believe we addressed this during our meeting in Oslo, Shane Byrnes, and I agree that we need broader, more general Clinical Drug (CD) concepts.

In AMT, the equivalent CD-level concepts include the active ingredient (to enable subsumption of modified forms) and is based on the base form of the substance unless the salt form is considered clinically significant. This can be a bit tricky, but perhaps if we gather data from all the NRCs on which salt forms are considered clinically significant and which are not, we could create more general CD concepts in the international edition where at least one NRC considers the salt not clinically significant.

These views may evolve over time, but the idea is that the CD layer would be broad enough to accommodate the various extensions where it is currently too narrow for most of them.

This raises two key questions:

1. What should be done with the existing, more specific CD concepts?

2. Is everyone comfortable with the new, more general CD concepts subsuming the existing specific ones?

For the first point, I think it makes sense to leave the existing concepts in place. NRCs can choose to use them based on their own assessment of clinical significance. If, in the future, there’s consensus that certain salt forms are not clinically significant, those specific CDs could potentially be retired after sufficient consultation. But for now, removing them would be difficult and would require extensive discussion.

On the second point, I actually think subsumption of the more specific concepts by general ones is the right outcome. I raise it only because there’s been considerable effort in the past to prevent CDs from subsuming one another, which seemed to be a concern for some. Personally, I don’t see it as an issue - in fact, I think it’s a natural and correct result.

What do we need to do to move this ahead?

I agree with Dion that creating some more general CD-level concepts (using |Has active ingredient| instead of |Has precise active ingredient|) with just the base (unless everyone agrees that the salt form is clinically significant or always the BoSS) and potentially a more general dose form (could this even use a |Has dose form| attribute, rather than a |Has manufactured dose form| attribute?) is a good way forward. Also agree that these should subsume the more specific CDs. it would be great if this approach allows the existing CDs to use the hydrated form of their ingredient as their precise active ingredient, to solve the hydration subsumption issue. For example:

   New general CD - |Amoxicillin 500 mg oral capsule| : |Has active ingredient| = |Amoxicillin|, |Has dose form| = |Oral capsule|)

   Specific CD - |Amoxicillin (as amoxicillin trihydrate) 500 mg oral capsule| : |Has precise active ingredient| = |Amoxicillin trihydrate|, |Has manufactured dose form| = |Oral capsule|