Fixing Healthcare's $528 Billion Mistake | with Chris Grilli

This video provides an in-depth exploration of how personalized, DNA-guided medicine, specifically through genomics, can address the staggering $528 billion annual cost of medication errors and inefficiencies in healthcare. Chris Grilli, a pharmacist and genomics expert from RxMapper, discusses the critical need to move beyond "trial-and-error" prescribing by leveraging a patient's unique genetic makeup. The core premise is that by accurately identifying the most effective medication for an individual from the outset, significant financial waste can be eliminated, patient outcomes dramatically improved, and the overall burden on the healthcare system reduced.

Grilli details RxMapper's methodology, which involves analyzing an extensive 36 million data points from a patient's genome. This comprehensive genomic analysis allows for medication recommendations with nearly 90% accuracy, a substantial improvement over traditional pharmacogenomics approaches that might only identify meaningful recommendations 3-4% of the time. He clarifies the distinction between genetics (inheritable traits) and genomics (the study of an individual's entire DNA variation), emphasizing that RxMapper focuses on the latter to understand how unique variations impact drug response, food allergies, and disease susceptibility. The conversation traces the historical advancements that made this technology possible, from the Human Genome Project providing the first reference genome to the exponential progress in next-generation sequencing, which has driven down costs and enabled widespread application.

The discussion also delves into the practical application and impact of RxMapper's services. Grilli shares a deeply personal anecdote about his grandmother's preventable death due to an adverse drug event, which served as the impetus for building RxMapper. This personal mission underscores the human cost of medication errors and the drive to provide better, data-driven care. The company targets individuals struggling with medication side effects or ineffectiveness, using claims data (PBM or TPA) to proactively identify patients who could benefit most. RxMapper partners with brokers, consultants, and PBMs, positioning itself as a complementary solution that enhances existing healthcare frameworks by ensuring efficacy first, then cost-effectiveness. The long-term vision includes influencing future drug development and expanding accessibility to broader populations, including Medicare beneficiaries, to ultimately drive the $528 billion in medication mistakes closer to zero.

Key Takeaways:

• Massive Cost of Medication Errors: Healthcare spends an estimated $528 billion annually fixing mistakes related to medicines, significantly more than the cost of the drugs themselves ($460-$480 billion). This highlights a profound inefficiency in the current "guess and check" prescribing model.
• Precision Medicine through Genomics: RxMapper utilizes a patient's unique DNA signature to identify the best medicine, moving beyond population-level data. This personalized approach aims to get the right drug to the right person the first time, preventing adverse events and improving therapeutic outcomes.
• Genomics vs. Genetics: Genomics, as practiced by RxMapper, involves collecting vast amounts of data (e.g., 36 million data points per patient) to study all the variations in an individual's DNA, rather than just inheritable traits. This comprehensive view significantly increases the predictive power of medication recommendations.
• High Accuracy and Predictive Power: RxMapper's data shows that following their process leads to a meaningful recommendation almost 90% of the time, compared to 3-4% for narrower pharmacogenomics panels. This high accuracy is attributed to collecting more data and using powerful computational algorithms.
• Significant Cost Savings Per Patient: Implementing genomic-guided medicine can save over $8,600 per patient in drug costs alone, and potentially up to $12,000 in overall medical costs by avoiding ineffective treatments and their associated complications.
• Impact on Employer Health Plans: For self-insured employers, RxMapper can substantially reduce overall drug spend by preventing patients from escalating to expensive specialty drugs. Data shows a 15% reversal in specialty drug growth in a short period after implementation.
• Focus on Generics: A surprising 80% of RxMapper's recommendations are for small molecule generics. By identifying effective generic alternatives that might otherwise be overlooked, the program slows the progression to high-cost agents like GLP-1s, even if the initial generic was ineffective.
• Complementary to PBMs: RxMapper works in partnership with PBMs, enhancing their ability to guide patients to the most cost-effective drugs after efficacy has been established through genomic insights. This creates a synergistic relationship that benefits both patient outcomes and cost containment.
• Evidence-Based and Peer-Reviewed: All recommendations are evidence-based and peer-reviewed, specific to the drug in question, avoiding extrapolation. This rigorous clinical validation ensures trust and reliability in a regulated environment.
• Patient-Centric Approach: The service is voluntary, and patients receive their results directly. RxMapper also engages the patient's care team, providing them with evidence-based reasoning and support to manage the patient's therapeutic journey.
• Proactive and Targeted Outreach: RxMapper uses claims data (PBM, TPA) to identify individuals who are struggling with their current medications or have conditions where genomics has proven helpful, allowing for targeted interventions.
• Beyond Drug Selection: The service includes comprehensive pharmacist-led screening, assessing drug-drug interactions, dietary considerations (e.g., statins and grapefruit), and even vitamin deficiencies, ensuring holistic patient care.
• Reducing "Lasering" Risk: By managing significant conditions with low-cost, effective generics, RxMapper can reduce the incidence of "misadventures" in care that lead to large, expensive claims, potentially mitigating the need for "lasering" in stop-loss insurance.
• Long-Term Partnership: The service is designed for the long haul; once sequenced, the information is digitized and stored, allowing for ongoing guidance as therapies change over a patient's lifetime. The data is portable, allowing individuals to maintain membership even if they change employers.

Key Concepts:

• Genomics: The study of an organism's entire genome, including all of its genes and their interactions, to understand how unique variations impact various biological processes, including drug response.
• Pharmacogenomics: A subset of genomics that studies how genes affect a person's response to drugs. RxMapper's approach is a more comprehensive form of this, looking at a much broader set of genetic variations.
• Next-Generation Sequencing (NGS): Advanced DNA sequencing technologies that have dramatically reduced the cost and time required to sequence an entire genome, making personalized genomic analysis economically viable.
• Polygenic Risk Score: A score that estimates an individual's risk for a particular disease or trait based on the combined effect of many genetic variants. Chris Grilli's work at Mayo Clinic includes focus on these scores.
• Adverse Drug Event (ADE): Harm experienced by a patient as a result of medication, which can be preventable or non-preventable. The video highlights the significant human and financial cost of preventable ADEs.
• Step Therapy: A common practice in prescription drug plans where patients must try a lower-cost drug first before progressing to more expensive alternatives if the initial treatment is ineffective. RxMapper aims to optimize this process.

Examples/Case Studies:

• Rheumatoid Arthritis Patient: A patient on methotrexate (standard first-line therapy) was found through genomic analysis to have a poor genetic fit for the drug. They were then escalated to adalimumab (Humira, an $80,000+ specialty drug), which also showed poor response and increased side effect likelihood based on genomic data. RxMapper identified leaflunamide, a typically skipped generic, as a strong therapeutic suggestion. Switching to leaflunamide resulted in a positive response, saving significant costs and improving patient outcomes.
• GLP-1s and Weight Gain: While GLP-1 effectiveness in diabetic patients is well-studied, RxMapper is intensively studying the genetic variations that impact GLP-1 effectiveness for weight gain, a newer indication. They emphasize a disciplined, evidence-based approach to avoid misleading recommendations in this high-demand area.
• Grandmother's Preventable Death: Chris Grilli's personal story of his grandmother's death from a preventable adverse drug event during a routine procedure due to an undisclosed genetic mutation for bleeding. This incident was the catalyst for developing RxMapper to ensure such information is available to care teams.