2.5 Retrospective documentation and validation
For the retrospective data analysis and validation as part of this
study, the clinical pharmacologist (SR), the clinical pharmacist (DN)
and a pharmacist in training (AR) reviewed all available original
medical records, referral letters, pharmacotherapy prescriptions and
laboratory results. Patient characteristics and clinical factors
including current pharmacotherapy, laboratory results and medical
history were extracted and compiled in a study database. Comedications
were also categorized according to their potential for moderate or
strong inhibition of cytochrome P450 enzymes 2C19 and 2D6 according to
the mediQ-database (www.mediq.ch).
All clinical recommendations from the reports were validated and
categorized as appropriate.
First, in patients where a specific drug-gene pair was the indication of
PGx testing, we documented if the test result of the related gene led to
a recommendation to change therapy with the drug that triggered PGx
testing.
Second, current comedication and results for all 16 genes of the PGx
panel were analysed for any additional clinically relevant drug-gene
interactions.
Third, for all subjects including those with a screening indication, we
documented if any PGx variants were detected that related to a drug-gene
pair with “actionable”, “recommended” or “required” classification
according to PHARMGKB. Such variants were presented in our PGx reports
as potentially relevant for future medication and further discussed in
the individual clinical context of tested subjects.
Drug-gene pairs, their classification of clinical relevance according to
PHARMGKB, and the assignment of genotypes to according phenotypes are
presented in supplementary Table S2 .