To genotype or not to genotype – that’s the question. DPWG provides recommendations for pre-emptive genotyping

In the PREPARE study participants are genotyped pre-emptively, but what to do for all other patients? Can you initiate therapy without pre-emptive testing or is genotyping necessary for specific drugs? Recently the Dutch Pharmacogenetics Working Groups (DPWG) of the Royal Dutch Pharmacists Association (KNMP) started developing recommendations for pre-emptive genotyping.

The Dutch Pharmacogenetics Working Group (DPWG) of the KNMP has been developing pharmacogenetic guidelines since 2005. These guidelines are therapeutic (dose) recommendations for patients whose genotypes are available. However these guidelines do not indicate patients eligible for genotyping. The newly developed genotyping recommendations fill this gap.

There are three different recommendations for pre-emptive genotyping:
1. Genotyping is essential for drug safety or efficacy and must be performed before initiation of therapy
2. Genotyping is beneficial and is therefore advised before (or directly after) initiation of therapy
3. Genotyping is potentially beneficial and can be considered on an individual patient basis before initiation of therapy

The determine the recommendation for pre-emptive genotyping, four criteria are reviewed. The first criterion is the clinical effect associated with the gene-drug interaction (drug induced or induced by a diminished efficacy). For example grade 5 adverse events have a greater clinical impact than grade 3 or 4 adverse events. The second criterion is the level of evidence supporting the associated clinical effect grade ≥3. It is more likely that there is a clinical effect when more studies confirm this effect. The third criterion is the number needed to genotype (NNG) in the Dutch population to prevent one clinical effect grade ≥3. A high NNG indicates the variants are rare and pre-emptive testing may not be cost-effective. Finally, the information in the summary of product characteristics is reviewed. When genotyping is recommended or when at least one genotype or phenotype is mentioned as contra-indication the impact is greater than when genotype or phenotype are not (clearly) mentioned.

The recommendations for pre-emptive genotyping are a next step into clinical implementation of pharmacogenetics. Until a complete genotyping panel is standard of care, the recommendations for pre-emptive genotyping can help healthcare professionals to select the most relevant patients for genotyping to optimize therapy and prevent side effects.

The current genotyping recommendations will be presented at the FIP World Congress of Pharmacy and Pharmacetuical Sciences in Abu Dhabi in September and at the ESPT Congress in Sevilla in October this year.