Challenges integrating genetic information into clinician workflow
The vastness of the human genome and the complexity of the association between DNA sequences and disease remind us how little we know about our genes. The human genome displays tremendous variation, including over 84 million single nucleotide polymorphisms (SNPs). For physicians, the connection between genetic abnormality and clinical significance is far from clear. Given such uncertainty, physicians have questioned what genetic information is clinically actionable versus what findings are unlikely to impact patient care.
The American College of Medical Genetics and Genomics (ACMG) sought to answer this question by recommending that physicians share 59 “highly medically actionable” genes associated with 24 inherited conditions if found incidentally. These genes, which are associated with potentially life-threatening health conditions including familial hypercholesterolemia, breast or ovarian cancer and Lynch syndrome, were selected for their high penetrance and actionability. Since these genes are likely to be phenotypically expressed as disease, informed patients can adopt preventative measures, such as taking cholesterol-lowering medications, opting for preemptive surgeries or undergoing repeat colonoscopies.
While sequencing can uncover actionable mutations, it can also reveal variants of unknown significance (VUS) whose association with disease risk is less clear. ACMG guidelines suggest that VUS detection should not change physicians’ treatment plan but does allow for additional monitoring, such as increased frequency of screening tests. However, physicians can act inappropriately in response to VUS detection. For example, patients with VUS detected in early-stage breast cancers choose to undergo bilateral mastectomy at similar rates of women with pathologic variants. Both physicians and patients find detection of VUS distressing, as physicians question what to disclose and patients worry about the meaning of such findings. As more data is gathered for particular VUS, their risk may be upgraded or downgraded, requiring physicians to stay informed on the clinical importance of such findings.
An additional concern for both physicians and patients is the trustworthiness of the results of genetic tests. Many genetic tests, particularly those marketed directly to patients, identify only a few disease-associated variants. For example, the 23andMe BRCA test includes just three genetic variants for breast and ovarian cancer, those most common among Ashkenazi Jews. A recent report revealed that 94% of non-Ashkenazi patients with pathologic variants would have been mistakenly classified by the 23andMe test as having no increased cancer risk. Misleading findings like these suggest that physicians should recommend a second test to confirm disease risk before taking drastic action.
Companies addressing challenges of genetic information integration
Many emerging companies are attempting to help healthcare providers collect, process, interpret and integrate genetic information into their daily practice.
Genomics informatics platforms
Genomics analysis software companies, including Fabric Genomics and PierianDx, help clinicians decipher genetic information. Fabric helps clinicians interpret genetic information to diagnose rare diseases and direct treatment course. In time-sensitive scenarios such as diagnosing childhood rare disease, Fabric rapidly translates WGS data to help clinicians identify disease-causing variants and shorten the diagnostic process. PierianDx simplifies genetics interpretation by comparing patient data with its genomics knowledgebase of shared medical interpretations, practice guidelines and clinical trials. The company recently partnered with sequencing giant Illumina to interpret its comprehensive tumor profiling assays to guide precision oncology treatments.
Companies including OneOme and YouScript aim to help physicians personalize medication management. OneOme’s RightMed PGx test sequences 27 genes to predict adverse reactions to over 300 medications. Developed in partnership with the Mayo Clinic, RightMed has been ordered by more than 550 hospitals at a price of $349 per test. YouScript takes medication management one step further by incorporating patient PGx data to offer physicians clinical-decision support. This EHR-integrated tool provides drug and dosage recommendations based on the patient’s genotype. Published research describes YouScript’s strong value proposition of reducing hospital readmissions, ED visits, and healthcare costs in polypharmacy patients. As researchers continue to unravel the complexities of drug metabolism and companies demonstrate the value of adjusting medications based on patient’s genes, adoption of pharmacogenetic testing should accelerate.
Genomics services companies
Helping clinicians select the most appropriate genetic test and assisting health plan reimbursement decisions are genetic testing benefit management companies. These companies, such as Genome Medical, InformedDNA and Concert Genetics, intend to address these issues by streamlining the genetic test selection, ordering, and payment processes. As the first “telegenomics” technology company, Genome Medical aims to bring genetic medicine into everyday care. The company virtually connects individuals and providers to genetic experts, who help navigate the expanding field of genetics to understand disease risk, accelerate diagnosis and improve treatment decisions. InformedDNA works with providers to offer patients medically necessary genetic tests while reducing volume overbilling and pricing variation for health plans. Similarly, the Concert Genetics platform allows clinicians to compare available genetic tests and receive insurance reimbursement. For health plans, Concert Genetics helps deliver actionable insights, cost savings, and effective management of genetic testing.
A major hurdle for these genomics services companies is the current lack of Medicare reimbursement for genetic counseling. Widespread implementation has been challenging as many of these companies serve older oncology patients, and providers are reluctant to bear the costs without guaranteed reimbursement. Unless Medicare changes its coverage determination, these companies must convince healthcare systems and commercial payers of their value by preventing the ordering of unnecessary genetic tests and ensuring their clinical actionability.
The future of clinical genetic testing
As the availability of genetic information expands, emerging companies will help clinicians translate genetic data into clinical practice, offer patients more targeted therapies and educate health plans on the cost effectiveness and medical necessity of genetic tests. The widespread adoption of these tests will depend on the ability of clinicians and patients to understand the utility and value of their use in practice and avoid unproven or even fraudulent genetic testing ventures hoping to exploit them. The combined effort of genetic testing companies, alongside new technology and service vendors, will likely work to demonstrate these new diagnostic tests can deliver a return-on-investment. The ability to show that genetic testing can reduce healthcare costs will influence insurance coverage decisions, leading to a virtuous cycle in which more patients receive genetic testing and more research connects genetic variations to disease. These findings will lead to real clinical outcomes, offering actionable solutions for doctors and patients. This evolution creates an opportunity for companies to integrate genetic testing with clinical workflows to translate genetics from research labs to clinical settings.