Friends:
We want to draw your attention to a potential pitfall when researching Covid-19 vaccines at the Ingredient level. Here is the deal:
RxNorm, which we use as a standard for drugs, recently introduced two new concepts for mRNA-based Covid-19 vaccines:
- Moderna’s SARS-CoV-2 (COVID-19) vaccine, mRNA-1273
- Pfizer/BioNTech’s SARS-CoV-2 (COVID-19) vaccine, mRNA-BNT162b2
But both are so-called Precise Ingredients. But they are linked to one common Ingredient concept: SARS-CoV-2 (COVID-19) vaccine, mRNA spike protein.
In other words, the Moderna and Pfizer vaccines are the same thing at the ingredient level.
Usually, for our use cases, it is expected behavior if modifications of ingredients exist but the mechanism of action is the same. For example, amphotericin B lipid complex and amphotericin B colloidal dispersion are precise ingredients of amphotericin B. In case of the vaccines both are based on mRNA in liposomes. The RxNorm makers therefore made the decision they are the same, even though the mRNA sequence is totally different.
This problem does not exist in lower levels of the hierarchy. At the product level, the two drugs are SARS-CoV-2 (COVID-19) vaccine, mRNA-1273 0.2 MG/ML Injectable Suspension and SARS-CoV-2 (COVID-19) vaccine, mRNA-BNT162b2 0.1 MG/ML Injectable Suspension. Their dose of mRNA is different, and their concept names are actually misleading, because it looks like they are containing different ingredients. But make no mistake: the hierarchy will roll them both up to the same ingredient.
When will this problem materialize?
When you are researching the vaccines and you need to distinguish them:
- In characterization, when you are reporting ingredient levels,
- In PLP or PLE, if you are using features extracted at the ingredient levels,
- In any analytic, when you are using the DRUG_ERA table.
BTW: When the AZ vaccine (currently no RxNorm) is FDA approved, the same ingredient overlap issue is likely going to happen with the J&J vaccine precise ingredient.
What should you do?
- Avoid the pitfalls above
- Use the cohorts the FDA BEST team built and made available to the community in our public ATLAS:
- Persons fully vaccinated on Moderna COVID-19 vaccine (two shots and no other vaccine)
- Exposures to Moderna COVID-19 vaccine (at least one shot)
- Persons fully vaccinated on Pfizer COVID-19 vaccine
- Exposures to Pfizer COVID-19 vaccine
How is this going to be fixed in the long run?
We are talking to the National Library of Medicine about this problem right now. We are also overhauling all vaccines, the definitions of their ingredients, and their embedding into ATC and CVX in a project led by @Adam_Black. Please join if you are affected and want to help.
We will keep you posted.