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Peter Attia MD#133 - Vinay Prasad, M.D., M.P.H: Hallmarks of successful cancer policy
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CHAPTERS
- 0:11 – 12:09
Vinay Prasad's Path from Philosophy to Medicine
Peter Attia introduces Vinay Prasad and the episode, then asks about his background. Prasad describes studying philosophy and science at Michigan State, his demoralizing first two years at the University of Chicago, and his residency at Northwestern.
- •Prasad began college in the sciences, added philosophy, and only later considered medical school
- •He found the first two years of memorization frustrating and only felt it was the right choice on the wards in third year
- •He saw himself as a future private-practice clinician until a disconnect between practice and evidence emerged mid-residency
- •Studying that disconnect led to his work on medical reversal and gradually became a research career
- 12:09 – 22:51
Stents, ORBITA, and the Psychology of Procedures
Attia asks about a stent patient story from Prasad's book, and Prasad explains what stents are and how they were extended from heart attacks to stable angina. They discuss how gratitude and payment make procedures hard to give up, and how the ORBITA sham-controlled trial showed little benefit on exercise time.
- •Stents transform outcomes in acute heart attacks but were extended to chronic stable angina
- •The COURAGE trial found no survival or heart attack benefit for stable angina, yet patients believed the stent served that purpose
- •Prasad says grateful patients combined with payment is the 'methamphetamine of being a doctor'
- •ORBITA found only a 16-second treadmill difference between stent and sham, which was not significant
- •Sham interventions help separate the benefit of the procedure itself from reassurance and expectation
- 22:51 – 30:04
Choosing Oncology and Learning at the NCI
Prasad explains why he chose internal medicine and then oncology, influenced by mentors who combined evidence knowledge with bedside skill. He describes the steep learning curve of his fellowship at the National Cancer Institute, and both speakers reflect on its special atmosphere.
- •Positive experiences with oncologists at Northwestern pushed him toward oncology
- •Oncology is barely taught in internal medicine training, so the fellowship learning curve is steep
- •He does not pretend to know all of cancer; he starts from the patient and works outward
- •Both speakers speak fondly of the NCI and the NIH campus
- 30:04 – 37:10
Bedside Manner and Delivering Hard News
Attia asks about bedside manner, and Prasad recounts a senior NCI oncologist who gave grace-filled bad news to a long-time patient. That oncologist said he tried to get better at it each year. Attia shares a similar lesson from his mentor Steve Rosenberg.
- •Oncology includes cures, long-term follow-up and hard end-of-life conversations
- •The senior oncologist said he was not sure he was good at it but tried to improve every year
- •Never becoming complacent was the secret of his skill
- •Attia recalls being taught that the therapy fails the patient, not the reverse, and that dying patients need clinicians more
- 37:10 – 44:41
Marginal Cancer Drugs and the Start of Medical Reversal
Prasad describes how a friend's reaction to a six-to-eleven-month survival gain crystallized his concerns about modest benefits and high prices. He then explains medical reversal with examples such as hormone therapy and CAST.
- •A friend's blunt response to the 11-month survival figure prompted deeper investigation
- •Across 71 approved solid-tumor drugs the average survival improvement was 2.1 months
- •Many drugs cost $100,000–$200,000 per year, raising the question of why there are so many 'me-too' drugs
- •Medical reversal means practices adopted on weak evidence later shown by rigorous trials to be worse than before
- •Hormone replacement therapy (WHI) and CAST reversed plausible, widely adopted practices
- 44:41 – 54:32
Cancer Progress, Trial Populations, and Industry Incentives
Attia contrasts progress against cardiovascular disease with cancer despite hundreds of billions invested. Prasad explains that trial patients are far fitter than real patients, using sorafenib as an example, and that industry incentives encourage curating trials.
- •Prasad agrees hundreds of billions have been spent and the average patient still faces a grave prognosis
- •Trial participants are younger and healthier, so benefits may shrink or vanish in real-world patients
- •Sorafenib offered about three months in the trial but about four months in both treated and untreated Medicare patients
- •Prasad says companies act rationally given the money at stake, so gaming the design is expected
- •Other thumbs on the scale include weak comparators and poor access to new drugs after progression
- 54:32 – 1:06:56
Who Pays: Cost, Rationing, and Skin in the Game
Using Avastin and UK cost thresholds, the speakers discuss societal versus individual willingness to pay, and Prasad frames his position as utilitarian. Attia's Saudi air-conditioning story raises the problem of skin in the game, and Prasad argues cancer drugs often have a net downside.
- •Prasad says spending on Avastin has opportunity costs against interventions that may add more life years
- •The U.S. rations too, but by excluding people from the system
- •Prasad describes a utilitarian view, while acknowledging deontological views that value end-of-life care regardless
- •Attia asks how to reconcile skin in the game with prohibitive costs
- •Prasad says drugs can have a net downside through no survival benefit and time spent tethered to infusion suites
- 1:06:56 – 1:16:27
No-Brainers and Fool's Gold in Oncology
Prasad lists no-regret moves such as surgery for localized cancer, radiotherapy, and curative regimens for Hodgkin's, testicular cancer and CML. He then gives the example of olaparib in BRCA-mutated pancreas cancer, with an explanation of progression-free survival.
- •Localized surgery, radiotherapy, and some curative drug regimens are no-regret moves
- •CML treated with a BCR-ABL inhibitor can approach normal life expectancy
- •CAR T, multiple myeloma, and Keytruda are discussed as promising but case-by-case
- •The POLO trial of olaparib showed progression-free survival benefit but no overall survival benefit, at about $12,000 a month
- •Progression-free survival relies on arbitrary cutoffs such as a 20% tumor growth
- 1:16:27 – 1:28:17
Hallmark One: Independence and Conflicts of Interest
Prasad introduces the six hallmarks of cancer policy, modeled on Hanahan and Weinberg's biological hallmarks, starting with independence. The conversation covers industry funding of advocacy groups, regulators, and expert oncologists who write guidelines, plus why disclosure is not enough.
- •Prasad says six policy hallmarks emerged as he finished the book
- •Large consulting payments to senior oncologists who write guidelines concern him more than pens and meals
- •Guidelines can compel Medicare to pay for off-label drug use without price negotiation
- •Prasad prefers incentives that favor conflict-free guideline members over punitive rules
- •He argues disclosure is incomplete and may even increase trust, and that reform will likely have to come from outside the profession
- 1:28:17 – 1:32:07
Hallmarks Two and Three: Evidence and Relevance
Prasad explains hallmark two as measuring what matters, noting two-thirds of approvals rest on tumor shrinkage or delay rather than survival or quality of life. He traces the 30% shrinkage cutoff to a 1976 marble-measuring study, then describes relevance as testing drugs in average patients.
- •Only one-third of approved cancer drugs show better survival or quality of life
- •The 30% response threshold derives from a 1976 inter-rater reliability experiment with marbles and foam rubber
- •Requiring survival or quality-of-life benefit would change trial design and likely mean fewer but better drugs
- •Relevance means studying people who look like average Americans
- 1:32:07 – 1:47:07
Hallmark Four: Affordability, Medicare, and Insurers
Prasad discusses affordability, including Medicare's inability to negotiate prices and pay-for-guideline rules, and global access gaps. He and Attia debate pharma incentives, CMS negotiation, why private payers do not push back, and the roles of the medical loss ratio and employers.
- •Medicare must pay for approved cancer drugs and cannot negotiate, which Prasad says rewards approval alone
- •He favors state-level experimentation and value-based pricing
- •Only one in a hundred eligible patients received trastuzumab at an Indian referral center
- •Attia argues pharma has outsourced early risk to venture-funded biotech but is wary of government pricing decisions
- •Prasad suggests the medical loss ratio and reputational risk weaken insurers' incentive to hold costs down
- 1:47:07 – 1:54:31
Hallmarks Five and Six: Possibility and Agenda
Prasad describes possibility as increased, stable and better-distributed NIH funding including blue-sky science, with Attia suggesting two funding arms. Prasad then explains agenda: duplicative Coke-and-Pepsi trials, multiple-testing concerns, and patients as a scarce resource.
- •Prasad would raise science funding slowly and steadily, insulated from political cycles
- •He proposes studying how grants are given out through randomized experiments
- •Attia suggests separate translational and basic-inquiry funding streams
- •Many redundant trials across similar drugs raise the risk of false positives by chance
- •In some tumor types there are more trials than patients available
- 1:54:31 – 2:03:29
Tumor Sequencing and Liquid Biopsies
Attia asks about tumor genome sequencing and shares his own experience, including a Lynch syndrome patient who responded to Keytruda. Prasad outlines when sequencing is clearly useful, when it can mislead, and his cautious optimism on liquid biopsies.
- •Prasad would allow low-cost, low-harm alternative approaches if they do not interfere with care
- •Sequencing is clearly indicated for known actionable mutations like EGFR, ALK, BRAF and MSI-high status
- •It is reasonable to use sequencing to match patients to clinical trials
- •Matching an unproven targeted drug to a mutation can displace a standard drug with a better track record
- •Tumor heterogeneity and differing results between companies are concerns
- •Liquid biopsies already have a role and serial tracking may be their main benefit
- 2:03:29 – 2:12:03
Balancing Skepticism and Practicing Without Perfect Information
Attia asks how Prasad avoids contrarianism for its own sake. Prasad uses his stance on the dexamethasone COVID press release as an example of too much skepticism and describes his clinical philosophy of empowering patients to decide under uncertainty.
- •Prasad is usually critical of medicine by press release but judged the dexamethasone result credible given the public protocol and analysis plan
- •He says seeing real patients keeps skepticism in balance
- •He sees the doctor's role as informing patients of benefits, uncertainties and toxicities so they can decide
- •Both agree doing nothing is also a decision and that colleagues' debate keeps skepticism in check
