39. Vinay Prasad Wants to Flip Your Vote (about medicine)
Updated: Feb 9
Vinay Prasad pulls no punches in this wide ranging conversation about the realities (and delusions) about chemotherapy research, principle centered social media engagement, flipping votes, The FDA drug approval process, the importance of early palliative care, the dangers of embellishing benefit, medical reversals, effective vs‘efficacious, and trade offs in decision making.
Guest Bio: Dr Vinay Prasad is a practicing hematologist-oncologist and Associate Professor in the Department of Epidemiology and Biostatistics at the University of California San Francisco. He studies cancer drugs, health policy, clinical trials and better decision making. He is author of over 250 academic articles, and the books Ending Medical Reversal (2015), and Malignant (2020). He hosts the oncology podcast Plenary Session. Follow Vinay on Twitter.
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This episode is also brought to you by Panacea Financial, a financial services company created for doctors, by doctors -- aiming to improve the lives of physicians and physicians in training with products and services tailored to the medical community. Spotlighted in this episode is the Panacea Financial Foundation which provides grants to underrepresented minorities in medicine. Panacea Financial is a Division of Sonabank, Member FDIC.
The realities of the dissemination of scientific information on Twitter [05:12];
Journal articles have very low readership, so increasingly Twitter has become a platform for discussing science.
“As much as we wish for Twitter to be a great democratizing place for dialogue, the reality is it's a very stilted, unidimensional portrayal of ideas.”
People naturally preach to the choir on Twitter, seeking retweets and likes. You also upset people who see it in the most unfavorable light.
When Vinay posts a tweet, he hopes it reflects the way he thinks about and interprets problems. While he dislikes some things about Twitter, he finds it to be a nice way to disseminate ideas.
Vinay’s intent when he posts a controversial tweet [09:00];
He is not trying to build a brand or gain followers.
Vinay by nature is opinionated. When he tweets about a scientific issue, he usually enters the conversation with some emotional feelings. He hopes that people’s responses will show him things he wouldn't see otherwise and maybe push back in an interesting way.
Once he decides what he wants to say, Vinay spends time calculating how to phrase it so that it is persuasive.
“I do think it's important not just on Twitter, but in life, that if you have an opinion, you want to flip votes.”
Why he’s an outlier in the cancer drug policy circle [16:15];
Vinay’s minority view is that while there are a few cancer drugs that work well and are worth whatever those companies charge for them, there are many that don’t. And the only reason companies get away with selling these drugs and running flawed trials is because the companies have created a financial conflict of interest by paying expert physicians.
Oncologists who benefit financially by accepting money from drug companies often don’t view Vinay favorably.
A recent JAMA article which raises the question: Do we have a collective delusion about the potential benefits of chemotherapy? [18:20];
The paper concludes: “data available at the time of FDA drug approval indicated that novel cancer therapies were associated with substantial tumor responses but with prolonging median overall survival by only 2.40 months. Approval data from 17 years of clinical trials suggested that patients and clinicians typically had limited information available regarding the benefits of novel cancer treatments at market entry.”
These results seem contrary to how chemotherapy is viewed by society and medicine. The media has created the myth that new cancer drugs are miraculous game-changers. While there are a few that really are tremendous steps forward, the reality is that many of them are not and only yield a modest benefit.
The FDA drug approval process [20:25];
When the FDA approves drugs, for ⅓ of the drugs they don’t know if the drug makes you live longer or better. They only know that the tumors shrink ≥30% in a fraction of the patients. This seems like a low level of evidence.
For another ⅓ of drugs, they don’t know if you live longer or better, but they know that progression free survival (PFS) was delayed. PFS is a composite surrogate endpoint for the length of time until the patient passes away or the tumors get 20% bigger. When new approved cancer drugs are approved based on PFS improvements, the benefit is typically about 3 months.
For the final ⅓, drugs are approved because patients live longer. This is the evidence used in the JAMA article.
The discrepancy between what's measured in cancer clinical trials and what actually would matter to cancer patients [22:38];
For most illnesses, the 2 things that patients care about are how long they will live and how good they will feel while they’re alive. If those two were actually directly pitted against each other, often people prioritize how they feel over how long they live.
The truth about cancer drugs is the ones that make you live longer tend also to make you live a little bit better for those months.
Only ⅓ of drugs that come to the US market do so because they have been shown to make patients live longer. For ⅔, we don’t know if they make you live longer or better, we only know how it affects the size of the tumor.
“Just because you improve the surrogate marker doesn't mean you actually improve what people care about. That’s a deep theme in my work and my book, Malignant.”
The important questions to ask when being offered treatment options for cancer [24:30];
It’s important that the person being given options has a loved one in the room who can help you ask questions, take notes, and remember what the doctor said.
Patients should gravitate toward practical questions about: the average benefit the drug provides, the better and worst case scenarios, the side effects, how the doctor knows the drug works.
Most of the time, clinical decisions are made based on well done randomized trials which show survival benefit over alternative options. But when patients have failed first-line options, further treatment choices may only show tumor shrinkage without evidence that patients live longer or better. Then it’s tricky to counsel patients, since you don’t know if the treatment is worth the cost or side effects.
“My philosophy is that the right decision for the patient is not necessarily what I would do if I were in their roles. It's what they would do knowing everything that I know.”
The importance of having rich discussion with patients about treatment side effects and potential toxicities [28:30];
“People will look at things differently. Different people may be willing to tolerate certain side effects or toxicities to different degrees based on the potential to live a little bit longer.”
“I worry that in many clinical scenarios, these rich discussions are not taking place. Instead, there can be an inertia of just treating, treating, treating and not having those longer, tougher conversations to get a sense of what the patient really wants.”
The importance of early palliative care and a common cognitive pitfall in oncology [31:25];
A cognitive pitfall in oncology is to become wedded to your hope that a treatment plan will have a positive outcome. Even when the patient is deteriorating, and the hope that you can achieve a positive outcome dwindles, you can't see that reality because you are too wedded to your initial impression.
“When you are too wedded to your initial treatment plan, you can't see where you are in the moment. You're blind to it, and you're blind to it out of a good desire.”
The dangers of empathy and the better alternative: compassion [35:00];
You can be empathetic to the point of paralysis or bad decision-making. But you must always retain some compassion.
“You want the doctor who grieves for you, but you need the doctor to have a bit of space so they can see things objectively.”
Why embellishing the benefit of a treatment is the wrong thing to do [39:20];
There are many drugs in oncology that are beneficial, but they’re not wonder drugs. While they may slow the growth of a tumor, they also have side effects. Whether the side effects are worth the benefit the drugs may be providing is a personal decision.
Doctors who upsell or distort reality, making drugs seem better than they are, take away the patient’s autonomy. They take away their ability to decide if the upside is worth it to them.
Prasad’s book Ending Medical Reversal and the potential harms of sudden flip-flopping of standards of care in medicine [44:00];
While there are many things we do in medicine that we know without a doubt will benefit our patients on average, sometimes we continue a practice simply because it’s what our forebears trained us to do.
When you test established medical practice and it does not improve outcomes, this is thought to represent a misstep. Responding by changing your practice is a medical reversal.
Although changing medical practice based on evidence is part of the scientific process, the rate with which we’re ‘misstepping’ is very high right now, in part because the incentives to adopt a technology based on circumstantial evidence is very high.
“The rate with which medical reversals occur right now is only because our system is so incredibly for profit and so incredibly in pursuit of novelty that we forget to ask if it actually helps people.”
The difference between ‘effective’ and ‘efficacious’ as it relates to public health and policy [47:46];
Efficacy is how something works under ideal circumstances. Typically, efficacy has historically been assessed in randomized control trials, where we can show that there is benefit in the pristine conditions of the trial.
Effectiveness is concerned with how well products perform under real settings, outside the strict inclusion criterion of a trial. Effectiveness is what public health really cares about.
The Danish mask study is a RCT whose objective was to assess whether recommending surgical mask use outside the home reduced wearers' risk for COVID by more than 50% in a community where masks were uncommon. Results: they did not find a >50% reduction in COVID infection.
Prasad’s opinion is that the Danish mask study is more of an efficacy study than an effectiveness study. Furthermore, the theoretical perfect efficacy study is not the public health study. The public health study is the policy study which takes into account the fact that many don’t comply with policy recommendations
“Good policy has effectiveness. Good policy works with people who are flawed. Good policy still mitigates epidemics when people are people. There's always going to be some people who don't comply 100%, and so you have to account for that.”
Prasad’s thoughts on the language surrounding masks vs. the data surrounding masks [54:40];
We missed an opportunity to better understand the non-pharmacologic interventions that could be effective for future pandemics by not doing cluster randomized trials to tease out the effects of masks and face shields.
While there’s currently no level A evidence that masks make a huge difference, it’s entirely reasonable to advise people to wear them, especially in indoor settings or crowds.
There are dangers in ostracizing people for not wearing masks, and we should never blame a COVID death on their mask behaviors.
“Public health is about empowering people to make the right choices and understanding that sometimes you're not going to get everyone to make the right choices. All you can do is think about better ways to empower them.”
How not wearing a mask might be the product of a lot of long-standing failures in American economic policy and upward mobility [01:02:00];
As much as we might disagree with the decision against wearing a mask and wish they would do the right thing, blaming them is not targeting the root cause of what drives their decision.
A deficiency of the pandemic which is to not thoroughly consider the trade-offs of the decisions we make [01:06:24];
Trade-offs are a concept that is not fundamental to the field of epidemiology. It is more of a concept using the field of economics and public health.
Scientists don't have the answers to trade-offs. Scientists can tell you what you might expect with option A or option B. Only people through political representation can tell you which of those paths we ought to do; only the public can tell you what the trade-offs are.
The closure/opening of schools is an excellent example of a trade-off (and where we might have made an error). While there is a very small risk of propagating viral spread by opening schools, the trade-off is that you might avoid the disproportionate damage to kids who are poorer.
“Science can say what the outcomes are and it's people who decide (what to do about it).”
What the data tells us about the risk of COVID transmission in schools [01:08:34];
A NEJM article reported on the spread of COVID in Sweden, concluding that despite having kept schools open (and lack of mask-wearing), the incidence of severe COVID among children was very low. Of the 1.95 million students, only 15 were hospitalized for severe illness and zero died. They also stated that the risk of COVID for school teachers was equivalent to that of other occupations.
The data from North Carolina looked at 11 school districts whilst COVID was running rampant and schools were open. They found there were only 32 cases acquired in schools through contact tracing, concluding that it is feasible and safe to keep kids in school.
“This risk is actually quite low and is certainly low enough that it's offset by what school does. We only have one ladder of opportunity in this country, and it is schools. If we close schools to take a risk from very, very, very low to zero, we will do far more damage in the long run. And unlike other choices around COVID, this one will haunt us for the longest period of time.”
Shownotes by Melissa Orman, MD
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