Getting diagnosed with a disease can be scary. Health providers work to find the right treatment plan based on the current standard of care guidelines. But what if in addition to the current evidence, doctors could also factor in each patient’s unique genetic makeup to help them diagnose more quickly and accurately, create a tailored treatment plan, or better yet, learn which patients are at a higher risk for developing specific diseases and employ methods for prevention or earlier detection? That’s the hope of genomic medicine, but researchers and clinicians are still gathering more evidence of its effectiveness before it can be widely implemented.
The IGNITE Network is looking to provide some of that evidence. The Network is comprised of a coordinating center and five multi-site clinical groups from Duke, Mt. Sinai, Vanderbilt, University of Indiana and University of Florida.
In order to provide the evidence that this type of practice will improve patient outcomes, IGNITE is conducting two large, network-wide genomic medicine pragmatic clinical trials (PCTs). These PCTs are focused around genetic risks for common chronic diseases and pharmacogenomics. PCTs are different than randomized controlled trials, or RCTs, which are great for studying the effectiveness of a treatment, but PCTs allow for bigger, more efficient clinical trials and help researchers and clinicians understand what to expect in real-world clinical settings.
Genetic testing to Understand Renal Disease Disparities across the U.S. (GUARDD-US) is a PCT that aims to determine the effect of returning apolipoprotein L1 (APOL1) genetic risk information to hypertensive African ancestry patients and their primary care providers on systolic blood pressure (SBP). The primary outcome is SBP at three months comparing patients with high-risk APOL1 variants (positives) versus no high-risk variants (negatives). The co-primary outcome is three-month SBP in positives versus those receiving delayed testing. Secondary outcomes include renal disease testing, and psycho-behavioral factors. The team will re-randomize APOL1 negative patients to a genotype-guided approach to anti-hypertensive therapy versus usual care and compare three-month SBP.
A Depression and Opioid Pragmatic Trial in Pharmacogenomics (ADOPT-PGx) is a pragmatic clinical trial that enrolls patients into three pharmacogenomics (PGx)-guided therapy scenarios: acute post-surgical pain, chronic pain, and depression. For each scenario, participants will be randomized to genotype-guided drug therapy versus usual approaches to drug therapy selection (“usual care”). Changes in patient-reported outcomes representing pain and depression control using standard patient-reported outcomes measurement information system (PROMIS) scales define the primary endpoints. Secondary analyses include safety endpoints, changes in overall well-being, and economic impact represented by differences in healthcare utilization.
Both GUARD-US and ADOPT-PGx teams will begin recruiting people for the PCTs in mid to late 2020.
The IGNITE Network has the potential to drastically change the face of healthcare. As results from the PCTS come in, clinicians all over the world may be able to see the clinical utility of genomic medicine for both risk assessment and disease treatment.