#133 - Vinay Prasad, M.D., M.P.H: Hallmarks of successful cancer policy
Vinay Prasad, a hematologist-oncologist and meta-researcher at UCSF, discusses the disconnect between medical evidence and clinical practice, particularly in oncology. He outlines structural problems in cancer care, including high costs and slow progress, concluding with his six hallmarks for successful cancer policy.
Deep Dive Analysis
19 Topic Outline
Vinay Prasad's Background and Entry into Medicine
Observing Disconnects Between Practice and Evidence in Residency
Medical Reversal: Practices Adopted on Low Evidence
The Seductive Nature and Pitfalls of Stenting for Chronic Angina
The Broad Landscape of Medical Practice and Evidence Pitfalls
Choosing Oncology and the Steep Learning Curve
The Importance and Continuous Improvement of Bedside Manner in Oncology
Structural Problems in Oncology: Small Benefits, High Costs
The Disconnect Between Clinical Trial Patients and Real-World Patients
Societal vs. Individual Cost Decisions in Healthcare
No-Regret Moves and Fool's Gold Treatments in Oncology
Hallmark 1: Independence and Conflicts of Interest in Medicine
Hallmark 2: Evidence and Measuring What Matters in Clinical Trials
Hallmark 3: Relevance and Studying Average Patients
Hallmark 4: Affordability and Drug Pricing Policy
Hallmark 5: Possibility and Funding Basic Science Research
Hallmark 6: Agenda and Managing the Clinical Trials Landscape
The Role of Tumor Genome Sequencing and Liquid Biopsies
Balancing Skepticism and Action in Clinical Practice
5 Key Concepts
Medical Reversal
Medical reversal refers to medical practices that were widely adopted based on low levels of evidence, but later found not to work as intended, or even to be harmful, by more rigorous studies. It's not about being replaced by something better, but about finding that the previous practice was ineffective or detrimental.
Sham Intervention
A sham intervention is a control procedure in a clinical trial where a patient undergoes a mock treatment that appears similar to the actual intervention but lacks the active therapeutic component. This method helps determine if the perceived benefit of a treatment is due to the specific intervention or a placebo effect from the psychological stimulus of receiving care.
Progression-Free Survival (PFS)
PFS is a common endpoint in cancer trials, measuring the time from study enrollment until one of four events occurs: death, a new tumor lesion, a tumor growing 20% larger, or a tumor growing 20% from its smallest point. It's often an arbitrary cutoff for tumor growth and doesn't always correlate with patients living longer or feeling better.
Utilitarian Ethics in Healthcare
This ethical framework prioritizes actions that achieve the greatest good for the greatest number of people. In healthcare policy, it suggests that societal resources should be allocated to interventions that provide the most cumulative benefit across the population, even if it means making tough decisions about covering costly drugs with marginal individual benefits.
Blue Sky Science
Blue sky science, or basic inquiry, refers to research pursued purely out of curiosity to understand fundamental processes, without an immediate translational goal or promise of curing a specific disease. Many significant scientific advancements have originated from this type of inquiry, where findings and their applications were serendipitous.
6 Questions Answered
Vinay Prasad's interest in medical evidence stemmed from observing disconnects between clinical practice and strong evidence during his residency, particularly in cardiology where procedures like stenting were used for questionable indications despite trial results.
For 71 consecutively approved drugs for solid cancers, the average improvement in survival was 2.1 months, often at a cost of $100,000 to $200,000 per year of treatment.
Clinical trial patients are typically 10 years younger, healthier, and have fewer comorbidities than average cancer patients, leading to potentially inflated benefits in trials compared to real-world outcomes where drugs may offer little to no benefit.
The US system allows Medicare to pay for any FDA-approved cancer drug without price negotiation, and also for off-label uses recommended by guidelines often influenced by industry-funded experts, creating a powerful incentive for high prices and broad market share without strong evidence of value.
NGS is essential for identifying specific mutations with approved targeted therapies (e.g., lung cancer, melanoma, MSI-high status) and for matching patients to clinical trials. However, its use for off-label drug selection based on 'seductive' mutations without trial data can be problematic, as not all mutations drive tumor growth, and results can vary across tumor sites or testing companies.
Doctors can maintain balance by engaging in clinical practice, having conversations with real patients, and participating in multidisciplinary discussions like tumor boards. The understanding that perfect information is rarely available necessitates making decisions with humility and empowering patients to choose based on their values and the known risks and benefits.
22 Actionable Insights
1. Minimize Conflicts of Interest
Policymakers should create incentives and rules to minimize financial conflicts of interest for medical experts involved in guideline creation and policy. This ensures that recommendations are unbiased and prioritize patient interests over financial gains.
2. Require True Patient Benefit
Regulators should require new cancer drugs to demonstrate actual survival or quality of life benefits for approval, rather than relying solely on surrogate endpoints like tumor shrinkage. This policy shift would lead to fewer, but more effective, drugs reaching the market.
3. Study Average Patients
Researchers and regulators should design clinical trials to include patient populations that accurately represent average Americans, not just highly selected, healthier individuals. This ensures that reported drug benefits are truly applicable to real-world patients.
4. Link Drug Price to Value
Policymakers should empower major payers, such as Medicare, to negotiate drug prices and encourage state-level experimentation with pricing models. This approach aims to connect drug cost to its actual value and improve access to transformative treatments.
5. Increase Blue Sky Science Funding
Policymakers and funding bodies should increase stable, long-term funding for basic, ‘blue sky’ scientific inquiry, separating it from political cycles. This fosters fundamental discoveries that often lead to serendipitous, transformative medical advances.
6. Oversee Clinical Trial Agenda
Regulators and research consortia should oversee the overall clinical trial landscape to prevent redundant studies and ensure efficient use of scarce patient resources. This optimizes research efforts and improves the interpretability of findings across the field.
7. Empower Patient Choices
Doctors should empower patients by transparently explaining drug benefits, uncertainties, known toxicities, and risks, then guide them in deciding if those risks align with their personal values. This approach respects patient autonomy and facilitates informed, individualized treatment decisions.
8. Critically Evaluate New Drug Benefits
Patients and doctors should critically evaluate the actual survival or quality of life benefit versus the high cost of new cancer drugs. Understand that reported clinical trial benefits may not fully translate to average patients in real-world settings.
9. Continuously Improve Bedside Manner
Medical professionals should continuously strive to improve their bedside manner, recognizing it as a crucial art in medicine. This enhances patient trust and provides essential emotional support, especially during difficult times.
10. Prioritize Dying Patient Care
Medical professionals should recognize that dying patients often need their care and presence more than living patients, requiring heightened compassion and support. This ensures dignified and supportive end-of-life care.
11. Use Empathetic Language
Medical professionals should use precise and empathetic language, such as stating ’the therapy failed the patient’ instead of ’the patient failed the therapy.’ This shifts blame away from the patient and fosters a more supportive and understanding environment.
12. Balance Skepticism with Action
Medical professionals must balance healthy skepticism about treatments with the need for action in patient care, recognizing the potential cost of inaction. This involves making informed decisions with imperfect information, often in consultation with colleagues.
13. Engage in Multidisciplinary Discussions
Medical professionals should regularly participate in tumor boards or multidisciplinary meetings to gain diverse perspectives and inform complex patient care decisions. This practice enhances decision quality and broadens understanding of challenging cases.
14. Pragmatically Evaluate Alternative Therapies
When considering alternative or complementary therapies, patients and doctors should assess if they are low-cost, non-harmful, and do not interfere with established medical treatments. This allows for patient choice without compromising primary care.
15. Maintain Humility in Knowledge
Medical professionals should maintain humility about the limits of current medical knowledge and be transparent about what is known and unknown. This fosters realistic expectations and builds trust with patients.
16. Prioritize Proven Cancer Cures
For localized cancers, surgery is often a highly effective ’no-regret’ treatment. For specific cancers like Hodgkin’s lymphoma, testicular cancer, and CML, established and often curative drug combinations exist and should be prioritized.
17. Question Mechanical Interventions
For subjective symptoms like angina or pain, patients and doctors should critically evaluate mechanical interventions, as studies suggest they may be no better than sham procedures due to a strong placebo effect. Consider the true benefit beyond psychological stimulus.
18. Strategic Tumor Genome Sequencing
Routinely perform tumor genome sequencing (NGS) for specific cancers (e.g., lung, melanoma, colon for MSI-high) where FDA-approved targeted therapies exist. Also, use NGS to match patients with appropriate clinical trials, especially for rarer tumor types or younger patients.
19. Caution with Unproven Targeted Therapies
Avoid automatically gravitating towards targeted drugs based on NGS findings if there’s no strong clinical trial evidence, especially if it means foregoing established therapies with better track records. Some mutations may not be primary drivers or may vary across tumor sites.
20. Utilize Liquid Biopsies
Employ liquid biopsies for non-invasive mutational information and for serial monitoring of cancer over time, particularly where tissue biopsies are difficult or repeated sampling is needed. Be mindful of test sensitivity and the potential need for tissue confirmation if liquid biopsy is negative.
21. Dexamethasone for COVID-19
Administer dexamethasone to hospitalized COVID-19 patients requiring supplemental oxygen or mechanical ventilation, as studies show an all-cause mortality benefit. Avoid its use in hospitalized patients not requiring supplemental oxygen, as it may cause harm.
22. Explore Vinay Prasad’s Content
Listeners interested in clinical trials, critical thinking, and decision-making should check out Vinay Prasad’s ‘A Plenary Session’ podcast, his YouTube channel, and his Twitter account (@VPrasadMDMPH) for tutorials and insights.
5 Key Quotes
You place this stent and the patient comes back in your office nine times out of 10, and they're happy that you did it. They believe you have saved their life or extended their life. They may even believe they feel better. And in fact, we could talk about Orbita and whether or not that's a real effect or a placebo effect. We can come to that. But they believe they feel better. They believe you saved their life. So you pair that incredibly powerful feeling of gratitude. You pair that with one other thing, which is you get a little bit of money and you get more money, the more you do. So when you combine that powerful psychological stimulus of gratitude with a little bit of financial remuneration, I think that's the methamphetamine of being a doctor.
Vinay Prasad
I can't say that I'm good at it after doing it for 30 years, but I can say I try to be better at it each year.
Senior Oncologist (recounted by Vinay Prasad)
Six months, 11 months. And he said, Oh, he said, what are you talking about? He said, do better than that. That's not good. I mean, 11 months, not good enough, man. He just said it. And it was just his gut reaction. He didn't go to medical school.
Vinay Prasad's High School Friend (recounted by Vinay Prasad)
Patients who are dying need us more than patients who are living.
Steve Rosenberg (recounted by Peter Attia)
It's not the doctor's role to determine what treatment is right for someone. It's really the doctor's role in my mind to empower the patient with what I know about the drug, what's been shown, what hasn't been shown, what the benefit might be, what are the uncertainties, what are the known toxicities and risks, and then to walk them through how they would decide.
Vinay Prasad
2 Protocols
Six Hallmarks of Successful Cancer Policy
Vinay Prasad- Independence: Minimize conflicts of interest by separating industry funding from expert oncologists and guideline writers, and incentivize conflict-free participation in policy-making.
- Evidence: Prioritize measuring what truly matters to patients, such as overall survival and health-related quality of life, rather than relying on arbitrary tumor shrinkage cutoffs (e.g., 30% reduction) or progression-free survival as primary endpoints for drug approval.
- Relevance: Conduct more clinical studies in patient populations that accurately reflect average Americans, including older, frailer patients with more comorbidities, to better understand real-world drug efficacy.
- Affordability: Implement policies that allow entities like Medicare to negotiate drug prices and decline coverage for drugs with marginal benefits, and encourage state-level experimentation in drug pricing to find effective solutions.
- Possibility: Significantly increase stable, long-term funding for basic 'blue sky' science through institutions like the NIH, and reform grant-giving mechanisms to support a broader range of researchers and high-risk, high-reward inquiries.
- Agenda: Establish a system to oversee the overall clinical trials landscape, preventing redundant or duplicative trials, especially for drugs with low promise, and ensuring that scarce patient resources are used efficiently to address critical unanswered questions.
Vinay Prasad's Clinical Philosophy for Patient Interaction
Vinay Prasad- Empower the patient with comprehensive information about the drug, including what has been shown and not shown, potential benefits, uncertainties, and known toxicities and risks.
- Guide the patient through the decision-making process, helping them weigh whether the risks are worth it to them personally.
- Accept that different people will make different choices based on the same information, and respect those choices.
- Recognize that medicine is an art and perfect information is rarely available, requiring decisions to be made with less than ideal data.
- Keep skepticism in check by grounding it in real-world patient interactions and multidisciplinary discussions, understanding the cost of inaction.