PREemptive Pharmacogenomic testing for Preventing Adverse drug REactions

INTERVENTION: Trade Name: Codeine Pharmaceutical Form: Syrup INN or Proposed INN: CODEINE CAS Number: 76‐57‐3 Current Sponsor code: 668353 Other descriptive name: codeine Concentration unit: mg milligram(s) Concentration type: not less then Concentration number: 0‐ Trade Name: Acenocoumarol Pharmaceutical Form: Tablet INN or Proposed INN: ACENOCOUMAROL CAS Number: 152‐72‐7 Current Sponsor code: 668353 Other descriptive name: acenocoumarol Concentration unit: mg milligram(s) Concentration type: not less then Concentration number: 0‐ Trade Name: Amitriptyline Pharmaceutical Form: Tablet INN or Proposed INN: amitriptyline CAS Number: 50‐48‐6 Current Sponsor code: 668353 Other descriptive name: AMITRIPTYLINE Concentration unit: mg milligram(s) Concentration type: not less then Concentration number: 0‐ Trade Name: Aripiprazole Pharmaceutical Form: Tablet INN or Proposed INN: ARIPIPRAZOLE CAS Number: 129722‐12‐9 Current Sponsor code: 668353 Other descriptive name: aripiprazole Concentration unit: mg milligram(s) Concentration type: not less then Concentration number: 0‐ Trade Name: Atomoxetine Pharmaceutical Form: Capsule, hard INN or Proposed INN: atomoxetine CAS Number: 82248‐59‐7 Current Sponsor code: 668353 Other descriptive name: ATOMOXETINE Concentration unit: mg milligram(s) Concentration type: not less then Concentration number: 0‐ Trade Name: Atorvastatine Pharmaceutical Form: Tablet INN or Proposed INN: ATORVASTATIN CAS Number: 134523‐00‐5 Current Sponsor code: 668353 Other descriptive name: atorvastatin Concentration unit: mg milligram(s) Concentration type: not less then Concentration number: 0‐ Trade Name: Azathioprine Pharmaceutical Form: Tablet INN or Proposed INN: azathioprine CAS Number: 446‐86‐6 Current Sponsor code: 668353 Other descriptive name: AZATHIOPRINE Concentration unit: mg milligram(s) Concentration type: not less then Concentration number: 0‐ Trade Name: Capecitabine Pharmaceutical Form: Tablet INN or Proposed INN: Capecitabine CAS Number: 154361‐50 CONDITION: Adverse drug reactions Therapeutic area: Not possible to specify SECONDARY OUTCOME: Secondary end point(s): Secondary outcomes include:; • Total number of ADEs (related to index and subsequent drugs); • Dose adjustments to index drug; • Drug cessation (and reason for discontinuation); • Additional drugs that are prescribed during follow‐up; • Routine drug levels (only those that are collected routinely) as a proxy for exposure; • Patient‐reported drug adherence ; • Quality of life; • Measurement of effectiveness (QALY); • Total cost estimation (healthcare consumption, cost of drugs, cost of hospitalization, cost of ADEs, cost of genetic testing etc.) Timepoint(s) of evaluation of this end point: 12 weeks after initiation of the index drug INCLUSION CRITERIA: • Subject must be = 18 years old • Subject must receive a 1st prescription (meaning no known prescription for this drug in the preceding 12 months) for a drug included in Table 5, which is prescribed to them in routine care. • Subject is able and willing to take part and be followed‐up for at least 12 weeks • Subject is able to donate blood or saliva • Subject has signed informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50 PRIMARY OUTCOME: Main Objective: To determine whether implementing pre‐emptive PGx testing of an entire panel of clinically relevant PGx markers, to guide the dose and drug selection for over 40 commonly prescribed drugs, will result in an overall reduction in the number of clinically relevant drug‐genotype associated adverse drug reactions (ADRs). We hypothesize that the implementation of PGx‐guided drug prescribing will reduce both the occurrence and severity of drug‐genotype associated ADRs in comparison to patients receiving standard of care treatment. Primary end point(s): The primary endpoint is the frequency of causal (definite, probable or possible), clinically relevant (classified as NCI‐CTCAE grade 2, 3, 4, or 5), drug‐genotype specific ADRs, for the index drug, for each patient. Secondary Objective: Secondary outcomes include other clinical outcome measures (e.g. total number of ADEs, dose changes, drug cessations etc.), a cost‐effectiveness evaluation, and process metrics for implementation; the latter includes physician and pharmacist adherence to the DPWG guidelines, and the acceptance of PGx‐informed prescribing to health care professionals and patients. Timepoint(s) of evaluation of this end point: 12 weeks after initiation of the index drug;