Table 1.
Characteristics of eligible studies
| Study/institution | Design (country) |
Population (n) | Genotype(s) reported | Experimental intervention | Decision support | Control group (n) |
|---|---|---|---|---|---|---|
| 1200 Patients Project*(11, 44-49) | Intervention study (U.S.A.) | Patients aged ≥65 years receiving care from one of 17 providers at 8 primary or specialty care clinics (1,108) | ABCB1, ADD1, ADRB1, AGT, CACNA1C, CYP3A4, CYP2C9, CYP2C19, CYP2D6, GNB3, GRK4, KIF6, LDLR, LTC4S, REN, SLCO1B1, VKORC1 | • Genotyping of prospectively enrolled cohort • PGx results available to participating providers in institutional PGx CDS system. • At participants’ office visits, providers alerted verbally or by chart flagging to PGx results |
• CDS system outside EHR including green/yellow/red alerts with clinical summaries and interpretation • Providers could query CDS system for information for other drugs by name or by disease |
--- |
| AltheaDx(61, 63) | Intervention study (U.S.A.) | Patients at several long-term care facilities taking ≥5 medications (132) | COMT, CYP1A2, CYP2C9,CYP2C19, CYP2D6, CYP3A4/CYP3A5, F2, F5, HTR2A, HTR2C, MTHFR, OPRM1, SLC6A2, SLC6A4, SLCO1B1, VKORC1 | • Potential drug-drug drug-environment, and drug-gene interactions reported to physicians • Internal medication management assessment by pharmacists |
Reports listed commonly used medications categorized as “Use as directed” or “Use with caution and/or increased monitoring" | --- |
| Duke University 1 (39) | Non-randomized trial (U.S.A.) | Primary care patients with a history of statin nonadherence (58) | SLCO1B1 | PGx results available to providers through EHR and to patients through patient portal | • Genotype-specific information about patient’s myopathy risk • Recommendations for statin prescribing |
Concurrent controls: patients with prior statin prescription but without statin use in prior 3 months (59) |
| Duke University 2(40) | Intervention study (U.S.A.) | Patients receiving new or recurrent simvastatin prescriptions from pharmacists at 5 community pharmacies (19) | SLCO1B1 (+/− CYP2C19) | • PGx results accessible through lab database and faxed to pharmacist and prescriber • Pharmacists reviewed results with patients and prescribers |
Test interpretation included CPIC guidelines | --- |
| Duke University 3(37, 38) | Intervention study (U.S.A.) | Patients at 2 cardiology clinics (30) • Taking simvastatin and/or clopidogrel • No prior PGx testing or MTM in prior 3 years |
CYP2C9, CYP2C19, CYP2D6, SLCO1B1, VKORC1 | • Pre- and post-test MTM sessions with pharmacist for patients • MTM also included recommendations for lifestyle modification and OTC medications • Patients and referring cardiologists received PGx results |
Pharmacist discussed recommendations based on FDA and/or CPIC guidelines with cardiologist before sharing action plan with patients | --- |
| Duke University 4(34-36) | Non-randomized trial (U.S.A.) | Primary care patients at 2 internal medicine practices (63) | CYP2C9, CYP2C19, CYP2D6, HLA-B*1502, SLCO1B1, VKORC1 | • Site 1: Pharmacist on call: physician consulted pharmacist about PGx testing; pharmacists screened patients and notified physicians about eligibility • Site 2: Pharmacist in-house: pharmacist screened patients and alerted physicians to availability of PGx testing for relevant medications |
All participating physicians first attended a 1-hour CME session about PGx. | --- |
| Duke University 5(42, 43) | Randomized control trial (U.S.A.) | Patients not currently taking statins due to history of adverse effect, ineligible if prior rhabdomyolysis or CK >10xULN (167) | SLCO1B1 | • Genotyping at a research visit. • Patients and their physicians received PGx results by email |
Physician reports: • SLCO1B1 results • Risk of rhabdomyolysis • General expectations of LDL-C reduction from different statin types & doses Patient reports: • SLCO1B1 results • Reassurance about which statins should be tolerable and lower CVD risk |
Physician reports: • General information about LDL-C reductions from different statins Patient reports: • General information about statins and CVD risk |
| First Moscow State Medical University(41) | Intervention study (Russia) | Patients with hyperlipidemia already on statin therapy(35) | SLCO1B1 | Patients received results | Not specified | --- |
| INGENI0US**(13, 50, 51) | Randomized control trial (U.S.A.) | Safety-net hospital system of 10 clinics with common EHR (2,000 planned) • Age ≥18 years • New prescription for one of 28 index medications |
CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP4F2, DPYD, G6PD, IFNL3, ITPA, SLCO1B1, TPMT, VK0RC1 | • Enrolling prescriber receives PGx reports • PGx results uploaded to EHR and viewable by all providers |
• Reports include alternative prescribing recommendations for index medication based on CPIC guidelines • Subsequent prescription prompts an alert notifying provider a genotype report is available and gives dosing recommendations • Providers may consult PGx service that documents recommendations in EHR |
Patient does not undergo genotyping (4000 planned) |
| La Paz University Hospital(10) | Intervention study (Spain) | Patients receiving specialty care at a tertiary care teaching hospital (600) | ABCB1, ABCC2, ABCG2, APOE, COMT, CFTR, CYP2C19, CYP2C8, CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP4F2, DPYD, ERCC1, EPHX1, FCGR2A, HTR2A, IL10, IL23R, KCNJ6, MTHFR, POR, SLC15A2, SLC22A1, SLC22A2, SLC22A6, SLCO1B1, TLR2, TLR9, TNF, TP53, TPMT, UGT1A1, UGT2B7, VKORC1, XPC, XRCC1 | Providers request testing from PGx unit, which generates report according to prespecified drug-gene protocol or after PGx consultation | Recommendation from PGx unit, based on CPIC and DPWG reviews | --- |
| Marshfield Clinic***(12, 52) | Intervention study (U.S.A.) | Adults aged ≥50 years with healthcare system primary care physician and no prior use of simvastatin, warfarin, or clopidogrel (750 planned) | CYP2C9, CYP2C19, SLCO1B1, VKORC1 | • Providers receive PGx results • Patients have access to website with information about their PGx results |
Active CDS alerts with CPIC dosing recommendation triggered by prescription in EHR | --- |
| MedSeq Project(66, 67) | Randomized control trial (U.S.A.) | Generally healthy adult primary care patients (100) | Genome sequencing including monogenic disease variants, carrier status, 8 polygenic risks, and 5 PGx results: ABCB1, C11orf65, CYP2C9/VKORC1, CYP2C19, SLCO1B1 | Patients discussed interpreted genome report and family history pedigree with physician | Report included statement about simvastatin-associated myopathy risk | Patients discussed family history pedigree alone with physician |
| OSU-Coriell Personalized Medicine Collaborative*(11, 49, 58, 59, 62, 64, 65) | Intervention study (U.S.A.) | Participants with heart failure and hypertension enrolled in RCT of genomic counseling for polygenic risk estimates and CYP2C19 (208). | Polygenic risk estimates for 8 diseases plus PGx results for CYP2C9, VK0RC1, CYP4F2, CYP2C19, SLCO1B1 | • Patients received genetic reports by mail and by patient web portal • Reports also uploaded to EHR • Half of patients were randomly allocated to in-person genomic counseling; half could access a genetic counselor by phone if requested |
Reports to patients and in EHR included CPIC recommendations | --- |
| PRIMER(60) | Intervention study (U.S.A.) | Patients of 27 providers with likelihood of exposure to a relevant medication (705) | COMT, CYP2D6, CYP2C19, CYP2C9, CYP1A2, CYP3A4, CYP3A5, F2, F5, MTHFR, OPRM1, SLCO1B1, SLC6A4, VKORC1 | Providers ordered PGx panel testing and received report | Report with drug-drug and drug-gene interactions categorized as contraindicated, major, moderate, or minor, some with explanatory annotations. | --- |
| RIGHT Protocol***(8, 11, 12, 53-56) | Intervention study (U.S.A.) | Health system patients, including biobank participants, likely to initiate statin treatment within 3 years (3,788) | CYP2C9, CYP2C19, CYP2D6, HLA-B*1502, HLA-B*5701, SLCO1B1, TPMT, VKORC1 | Preemptive genotyping, with results available to provider in EHR and to patients through patient portal | Active CDS • Alerts triggered when simvastatin ordered on high-risk patients • Alerts sent to provider and added to problem list Passive CDS • Internal online medical info system, AskMayoExpert |
--- |
| Yale University(57) | Intervention study (U.S.A.) | Series of consecutive high-risk cardiovascular patients (32) | CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, F2, F5, MTHFR, SLCO1B1, VKORC1 | Results reported to clinicians | Not specified | --- |
*
Part of the Pharmacogenomics Research Network Translational Pharmacogenetics Program(11)
**
Part of the Implementing Genomics in Practice (IGNITE) Consortium(13)
***
Part of the eMERGE-PGx Consortium(12)
Abbreviations: CDS (clinical decision support), CK (creatine kinase), CME (continuing medical education), CPIC (Clinical Pharmacogenetics Implementation Consortium), CVD (cardiovascular disease), DPWG (Dutch Pharmacogenetics Working Group), EHR (electronic health record), FDA (Food & Drug Administration), LDL-C (low-density lipoprotein cholesterol), MTM (medication therapy management), OSU (The Ohio State University), OTC (over-the-counter), PGx (pharmacogenetics), ULN (upper limit of normal)