Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network

PURPOSE: While there is growing scientific evidence for and significant advances in the use of genomic technologies in medicine, there is a significant lag in the clinical adoption and sustainability of genomic medicine. Here we describe the findings from the National Human Genome Research Institute's (NHGRI) Implementing GeNomics In pracTicE (IGNITE) Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice. METHODS: Network members and affiliates were surveyed to identify key drivers associated with implementing and sustaining a genomic medicine program. Tallied results were used to develop and weigh key constructs/drivers required to support sustainability of genomic medicine programs. RESULTS: The top three driver-stakeholder dyads were (1) genomic training for providers, (2) genomic clinical decision support (CDS) tools embedded in the electronic health record (EHR), and (3) third party reimbursement for genomic testing. CONCLUSION: Priorities may differ depending on healthcare systems when comparing the current state of key drivers versus projected needs for supporting genomic medicine sustainability. Thus we provide gap-filling guidance based on IGNITE members' experiences. Although results are limited to findings from the IGNITE network, their implementation, scientific, and clinical experience may be used as a road map by others considering implementing genomic medicine programs

Correction: Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network

The original version of this Article contained an error in the spelling of the author Geoffrey S. Ginsburg, which was incorrectly given as Geoffrey Ginsburg. This has now been corrected in both the PDF and HTML versions of the Article. Erratum for Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network. [Genet Med. 2019

Abstract 12183: SLCO1B1 Genotype-Guided Statin Therapy Lowers LDL Cholesterol in Patients With Statin-Intolerance- A Randomized Controlled Trial

Introduction: Statin-intolerance is a barrier to reducing cardiovascular disease risk. A genetic variant (*5, rs4149056) in the SLCO1B1 statin hepatic transporter gene is well characterized and linked to higher statin concentrations, statin-intolerance, and statin non-adherence. SLCO1B1*5 has a high negative predictive value for severe simvastatin myopathy; Pravastatin[P]/ fluvastatin[F]/ rosuvastatin[R] are preferred statins in *5 carriers to minimize side effects. The effects of SLCO1B1 genotype-guided statin therapy or delivery of SLCO1B1 genetic risk information are unknown. Hypothesis: Genotype-guided statin therapy (GGST) is superior to usual care in patients with statin-intolerance for statin-related outcomes. Methods: We randomly assigned 159 primary care patients with statin intolerance not prescribed statins to either GGST vs. usual care. GGST patients and their providers received *5 genetic risk information about statin side effects and genotype-specific statin prescription recommendations. Patients in the usual care arm received general information regarding statin risk and prescriptions. The outcomes measured at 3 and 8 months were statin re-initiation, LDL cholesterol (LDLc), and statin adherence using the validated Morisky Medication Adherence Survey. Results: The median age was 64.0 years, 57% were female, 41% reported intolerance to \u3e 1 statin, 75% reported myalgia with statins, and 25% were *5 carriers. Follow up was complete for 144 patients (91%) at 3-months and 118 (74%) at 8-months. At 3-months, GGST was associated with a higher proportion of patients who restarted statin therapy (55.4% vs. 38.0%, p=0.037), and lower LDLc (131.9±42.0 vs. 144.4±43.0, p=0.041), but similar statin adherence scores (p=0.96). Effects at 8-months were consistent with 3-month results for statin prescriptions (54% vs. 37%, p=0.07) and LDLc (128.6±37.9 vs. 141.0±44.4, p=0.07). Use of P/F/R was higher in *5 carriers assigned to GGST versus usual care (92% vs. 67%, p=0.24). Conclusion: In primary care patients with statin-intolerance, SLCO1B1 genotype guided statin therapy is effective in lowering LDLc compared to usual care. GGST, however, did not improve statin adherence in those who re-initiated statin therapy. Footnotes Author Disclosures: D. Voora: Research Grant; Significant; NIH, AstraZeneca. E. Perry: None. K. Singh: None. G. Trujillo: None. N. Milazzo: None. D. Savard: None. S. Haga: None. M.D. Musty: None. Y. Li: None. B. Peyser: None

Effects of Delivering SLCO1B1 Pharmacogenetic Information in Randomized Trial and Observational Settings.

BACKGROUND: Outcomes of tailoring statin-type based on solute carrier organic anion transporterfamily member 1B1 ( SLCO1B1)pharmacogenetic toxicity information on patient, provider, and pharmacological outcomes are unknown. METHODS: The trial randomized 159 patients not taking statins because of prior statin myalgia 1:1 to receiving SLCO1B1 GIST (Genotype Informed Statin Therapy) versus usual care (UC) and followed for up to 8 months. The UC arm received their SLCO1B1 results post-trial. The primary outcome was statin adherence using the Morisky Medication Adherence Scale, which was assessed in those patients who reinitiated statins. Secondary outcomes assessed in all participants included statin reinitiation and LDLc (low-density lipoprotein cholesterol), within and post-trial. Using commercial laboratory data, serial LDLc were compared between 1907 patients receiving SLCO1B1 testing and propensity-matched, untested controls. RESULTS: Trial participants were 25% SLCO1B1*5 carriers. Statin adherence was similar between arms (Morisky Medication Adherence Scale in GIST versus UC, 6.8±1.5 versus 6.9±1.6, P=0.96). GIST led to more new statin prescriptions (55.4% versus 38.0%, P=0.04) and lower LDLc at 3 months (131.9±42.0 versus 144.4±43.0 mg/dL; P=0.048) with similar magnitude at 8 months (128.6±37.9 versus 141.0±44.4; P=0.12). SLCO1B1*5 carriers exhibited a greater drop in LDLc with GIST versus UC (interaction P=0.048). Post-trial, LDLc decreased in UC participants who crossed over to GIST compared with those allocated to GIST (-14.9±37.8 versus +9.0±37.3 mg/dL, P=0.03). Patients tested for SLCO1B1 though a commercial laboratory had a greater LDLc decrease ( P=0.04) compared with controls. CONCLUSIONS: Delivery of SLCO1B1 pharmacogenetic testing that addresses statin myalgia improved statin reinitiation and LDLc but did not improve self-reported statin adherence. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01894230