Implementing Genomics in Practice (IGNITE) Proof of Concept Study: Genotyping in Family Medicine Clinics

Codeine and tramadol are opioid analgesics that depend on cytochrome P450 2D6 (CYP2D6) for
bioactivation to morphine and O-desmethyltramadol, respectively. Morphine and
O-desmethyltramadol have much greater affinity for the opioid receptor and thus are more
powerful analgesics.

Individuals with genotypes associated with low CYP2D6 activity (poor metabolizers) are unable
to convert sufficient amounts of codeine or tramadol to their active metabolites and may fail
to derive sufficient pain relief. At the opposite extreme, individuals with genotypes
associated with increased CYP2D6 activity (ultra-rapid metabolizers) are at risk for serious
toxicity with usual codeine or tramadol doses.

The CYP2D6 genotype also has implications for response to other drugs, such as tricyclic
antidepressants (TCAs), which are commonly used for neuropathic pain.

Patients will be recruited from family medicine clinics, serving as either implementation
sites or control sites. Patients from implementation sites will undergo CYP2D6 genotyping,
with results placed in the medical record to assist with prescribing of pain medications.
Pain medications prescribed from baseline to 3 months will be assessed through medical record
review. A pain assessment questionnaire will be administered to patients enrolled from both
sites at baseline and 3 months.

At the end of the study, a 20-item survey will be administered to physicians at the
implementation sites. We will assess whether having CYP2D6 genotype results is useful to
inform prescribing decisions for pain medication from the physician's perspective.

We will also assess medicines prescribed to patients enrolled from both sites over the
12-month period after enrollment from medical record review and determine the number of
patients who were prescribed a medication that has genetic information in its FDA-approved
label.

Inclusion Criteria:

- Treated in family medicine clinic

- History of pain for at least 3 months

- Prescribed medication for pain relief

Exclusion Criteria:

- Pain for less than 3 months

- Not currently prescribed any medication for pain