New advances in medicine also tend to come with a hefty dose of hype. Yes, some new cancer drugs in the hot field of precision medicine, which takes into account variables for individual patients, have worked remarkably well for some patients. But while many patients clamor for them, they aren't currently effective for the vast majority of cancers.
This stubborn fact has become a sticking point for an equally stubborn cancer doctor. At just 35 years old, Dr. Vinay Prasad has made a name for himself by calling out the hype surrounding precision medicine and confronting other examples of hype in his field.
Prasad is a hematologist-oncologist and an assistant professor of medicine at Oregon Health and Science University in Portland. Some have called him a professional troublemaker, a gadfly or a provocateur as he tweets to his 20,000-plus followers. He has sent nearly 30,000 tweets out to the Twitterverse, putting him within hailing distance of President Trump, at least in terms of output.
He is also a prolific author of scientific papers, as well as a book, that call out uncomfortable facts about the science of cancer and the business and regulation of medical treatments.
Giant cancer conventions are ripe targets for Prasad's sometimes prickly observations. We caught up with him in early June at the American Society of Clinical Oncology meeting, which drew about 40,000 attendees to Chicago's sprawling McCormick Place convention center.
Prasad's main event at the conference was to be a debate/discussion about whether precision cancer treatment is "ready for prime time." But that debate really started as soon as Prasad stepped into the convention center.
Another young cancer researcher — who feared having a public spat with Prasad and asked not to be identified — ran into Prasad while he was walking over to view the scientific posters. After thanking Prasad for raising some important issues, she chided him for his tone.
"I think both sides are too emotional," she told him, "and I think the truth is something in the middle."
He aggressively defended his position, often not letting her finish her sentences. Genetic tests now commonly given to cancer patients only identify clear treatments about 8 percent of the time, he argued, citing one of his research papers — and only 5 percent show even a temporary response to the treatment.
Cancer drugs that modify the immune system, such as checkpoint inhibitors, aren't, strictly speaking, precision medicine, since they don't depend on the results of the genome tests. But they also only work well in a minority of patients.
So, Prasad points out, most successful cancer treatment still involves much less expensive conventional chemotherapy, radiation and surgery.
He is not arguing that precision medications are all useless, as his critics sometimes seem to imply.
"I use those drugs," he says. "There are some good drugs. No one said there are no good drugs."
The problem, in his eyes, is that the field has gotten so enthusiastic about these drugs that doctors aren't waiting for actual science to distinguish between the conditions for which they are useful and for which they are, instead, a very expensive, wasted effort.
"A lot of people want to push it to the treatment side," he says. "They want to get Medicare to pay for it," even before the drug is approved for that specific purpose.
Prasad says drug companies are happy not to shoulder the costs of research when doctors will prescribe their medicine anyway. "And that's the root of what bothers me about this."
Indeed, the high costs of these unproven — and often failed — treatments fall to people who buy health insurance and who pay taxes. It is, in essence, a massive uncontrolled experiment, and nobody is collecting the data most of the time to find out what might be useful.
Often, doctors run genetic tests on tumors to see if they carry a mutation that will respond to a targeted drug. More than 90 percent of the time, there is no match.
But doctors are increasingly giving these targeted drugs anyway to patients who have the mutation in a type of tumor that has not been shown to respond to the drug. While that sounds rational, it often doesn't work in patients.
One study to explore these nonapproved uses is the National Cancer Institute's Molecular Analysis for Therapy Choice trial. At the ASCO meeting, scientists reported on early results from about 150 patients who were matched to drugs based on their tumor's genetic fingerprint, rather than the type of tumor. The results were disappointing. The tumors responded poorly or not at all to the targeted drugs.
Prasad says that when he was in medical school, he assumed he would just learn how to treat cancer and spend his career doing that. But then he discovered how much of medical practice was based on traditions rather than on actual science.
Those traditions, sometimes called "eminence-based medicine," have slowly been giving way to "evidence-based medicine."
"Even the most respected, charismatic and thoughtful experts often are incorrect," he says. That realization drew Prasad to consider a career beyond just treating patients.
"I found it harder just to observe things that troubled me and not study them," he says. "And at some point, I made the conscious decision that if it troubles me enough, I want to look at it and study it. Maybe somebody else will carry the torch and actually fix that problem someday."
Prasad got on this path after he graduated from the University of Chicago Pritzker School of Medicine. (He also has a master's degree in public health from the Johns Hopkins University.) He really launched his research career while a fellow at the National Institutes of Health.
His prolific research output is supported in part by funding from Texas billionaires Laura and John Arnold. Their foundation has a soft spot for supporting scientists who are calling out shortcomings in scientific research and suggesting ways to improve it.
Prasad's skeptical approach was on display at the ASCO meeting. As the crowd was gathering, he fired off a tweet encouraging the attendees to play "ASCO Bingo." He had filled a five-by-five grid with words such as "unprecedented," "breakthrough," "game changer" and "transformative" and invited his colleagues to listen for these words during the scientific presentations.
As thousands of doctors filed into a massive meeting room to hear the plenary talk, random tweets about the meeting flashed up on the screens, including Prasad's ASCO Bingo card. "I guess it has almost 100 retweets now," he said as the tweet flashed by.
He actually published a scientific paper in 2016 about the overuse of superlatives in presentations and news coverage.
"What really got me," he says, "was [that for] 14 percent of the drugs, the superlative was used based only on mouse or laboratory results, and they'd never given it to a human being!"
Finally, it was time for Prasad's presentation at the meeting — an informal debate of the value of precision medicine in cancer treatment. His opponent, Jeremy Warner, had suggested the discussion, which was limited to an audience of 55 to allow a more intimate conversation than is typical at the vast conference.
"So the first thing I have to say is, I'm the underdog," said Warner, a cancer doctor and researcher at Vanderbilt University. For starters, he admitted that Prasad has 40 times more Twitter followers, many of them avid supporters.
The back-and-forth turned out to be surprisingly friendly, with many points of agreement. Warner agreed that in an ideal world there would be a lot more scientific studies to figure out which drugs work in which circumstances. "But
"just saying that somebody should be on a clinical trial — I mean it sounds easy, but it's actually not easy at all."
Dr. Richard Schilsky, ASCO's chief medical officer, moderated the conversation and came away in considerable agreement with Prasad.
"I enjoy his remarks very much," he says afterward. "I mean, he's a bit of a gadfly. He's a bit of a provocateur. But frankly, he's taking a very hard and objective look at a very complex area and ... he's saying what's behind the curtain. 'Let's celebrate what really works, let's look hard at what doesn't, and let's try to develop the evidence that we need to make important decisions for patients.' "
"I think it's unfortunate that I'm thought of as a professional troublemaker," Prasad says. "We really try to find those instances where the evidence and the narrative are divergent and try to ask what we can do to bring those two closer together."
Prasad says he can't tell at this point whether he is building a strong reputation for himself or potentially damaging his career.
"I don't want to be the person to be doing all this work," he says. "I wish there were senior people doing this work."
But by and large, they aren't.
It bothers him, he says, when his colleagues think he is simply being cynical or contrary. The ultimate point is to call out the problems in this critical field so everyone does science better, he says. And, in the end, the rewards of that will flow to the patients.
You can contact Richard Harris at firstname.lastname@example.org.
SUSAN DAVIS, HOST:
And we finish the hour with this weekend's Long Listen. Precision treatments for cancer are hot right now. But one young cancer doctor is pushing back against some of the hype through scientific articles and on social media. NPR science correspondent Richard Harris met up with him recently at a big cancer conference in Chicago, where the doctors squared off in a debate about precision medicine.
RICHARD HARRIS, BYLINE: Soon after I meet Vinay Prasad, we stroll past one of the many glitzy displays that the pharmaceutical companies erect to generate buzz about their products.
VINAY PRASAD: The carpet is so plush in many of these exhibits, you could twist your ankle in it. But this is actually a really gorgeous display. You would win any science fair with a booth like this. You would just crush it. It's bathed in purple light - incredible. Oh, hey. How are you? Good to see you. Good to see you.
HARRIS: A colleague comes up and, after asking me not to quote her on this touchy subject, both thanks Prasad for raising important issues in the field but also implores him not to get so overheated. It's not as bad as you seem to make it, she argues. And she reels off a list of precision-targeted drugs that help people with melanoma, lung cancer and other diseases.
PRASAD: I use those drugs. There are some good drugs. No one said there's no good drugs. The question is, let's be honest. The truth is 8 percent of people benefit from these drugs. Of the 8 percent that get these drugs, 50 percent have tumor shrinkage. 50 percent don't.
HARRIS: And tumor shrinkage doesn't mean cure. The problem, in his eyes, is that the field has gotten so enthusiastic about these drugs that they aren't waiting for actual science to distinguish between the times when they are useful and where they are a very expensive, wasted effort.
PRASAD: A lot of people want to push it to the treatment side. They want to get Medicare to pay for it. They want to get the drugs paid for off label because they don't want to shoulder the cost on the industry side. And that's the root of what bothers me about this.
HARRIS: People who buy health insurance and taxpayers are funding a massive, uncontrolled experiment with these drugs. Nobody's even collecting the data most of the time to find out what might be useful. Prasad, a 35-year-old oncologist who treats patients at the Oregon Health and Science University, says when he was in medical school, he assumed he would spend his career as a community doctor, treating people with cancer. But then he discovered how much of medical practice was based on traditions, rather than actual science.
PRASAD: Even the most respected, charismatic and thoughtful experts often are incorrect.
HARRIS: The more he learned about what's called evidence-based medicine, the more captivated he became.
PRASAD: I found it harder to just observe things that troubled me and not study them. And at some point, I made the decision - the conscious decision - that if it troubles me enough, I want to look at it kind of and study it and try to say something about it. And maybe somebody else will carry the torch and actually fix that problem someday.
HARRIS: He started out publishing analyses in the scientific literature about bad assumptions and bad practices he encountered. His notoriety really took off when he started opining on Twitter. Today, he has more than 20,000 followers. And he has punched out nearly 30,000 tweets. His pointed commentary sometimes gets him tagged as a troublemaker.
UNIDENTIFIED PERSON: Good afternoon. I'd like to welcome you to the 2018 session.
HARRIS: And the sessions and meetings like this are ripe targets. We settle back into seats in the cavernous meeting room where thousands of doctors have gathered to hear the big talks at the American Society of Clinical Oncology conference. The screen during the warm-up presentation flashes random tweets about the meeting, including one of Prasad's. It's a bingo card that features buzzwords surrounding advances in cancer treatment.
PRASAD: The words that are displayed are unprecedented, personalized, microbiome, precision, inflection point, breakthrough, silo, big data...
HARRIS: ...Among others.
PRASAD: I guess it has almost 100 retweets now.
HARRIS: He actually wrote a scientific paper about the overuse of superlatives in scientific presentations and news coverage. He found plenty of uses of the terms game-changer, breakthrough, miracle, cure or home run.
PRASAD: But what really got me was 14 percent of the drugs - the superlative was used based only on mouse or laboratory results. And they'd never given it to a human being.
HARRIS: We lower our voices when the talks begin. Prasad joins the Twitter conversation about the session while keeping an ear tuned to the presentation.
UNIDENTIFIED PERSON: ...Was to develop a paradigm of biomarker-directed chemotherapy.
PRASAD: They're winning my bingo. Did you hear all those words?
HARRIS: Prasad retweeted some sharp critiques of the talks but also tweeted praise for one panelist who added some important caveats to a study that had just been presented. The next day, we meet again at Prasad's main event, the debate over the value of precision medicine.
RICHARD SCHILSKY: OK. Good morning, everyone.
HARRIS: Dr. Richard Schilsky, the oncology society's chief medical officer, steps up to referee the face-off between Prasad and Vanderbilt University oncologist Jeremy Warner.
JEREMY WARNER: So the first thing I have to say is that I'm the underdog.
HARRIS: Warner flashes a cartoon with two dogs, his face plastered onto one on the ground and Prasad's face spliced onto the animal looming above. A cloud of Twitter birds represents Prasad's army of followers. The so-called debate about this multibillion dollar enterprise was civil. Afterwards, Warner reflects on their considerable points of agreement. Warner disagreed, though, about how to accommodate patients' desires for these new medicines before the careful studies show whether they will actually work for their particular type of disease.
WARNER: Yeah. Saying that someone should just be on a clinical trial - I mean, it sounds easy. But it's actually not easy at all.
HARRIS: And Schilsky, the moderator, found he was in considerable agreement with Prasad as well.
SCHILSKY: I enjoyed his remarks very much. I mean, you know, he's a bit of a gadfly. He's a bit of a provocateur. But, frankly, he's taking a very hard and objective look at a very complex area. And, you know, he's calling it out. He's saying, you know, it's, you know - it's what's behind the curtain. And, you know, let's celebrate what really works. And let's look hard at what doesn't. And let's try to develop the evidence that we need to make important decisions for patients.
HARRIS: Plenty of people aren't so accommodating, particularly on Twitter, Prasad notes.
PRASAD: I think it's unfortunate that I'm thought of as a professional troublemaker because the work we do - we really try to find those instances where the evidence and the narrative are divergent and try to ask ourselves, what can we do to bring those two closer together?
HARRIS: Is this good for your career, or is this bad for your career?
PRASAD: (Laughter) To be honest with you, I don't know the answer. I guess I would say I wish I didn't - as a young person, I don't want to have to be the person to be doing all this work. I wish there were senior people who would do this work. Senior people are not doing this work.
HARRIS: The point in the end is not to be cynical about science, he says, but to help this critical field do science better. Richard Harris, NPR News.
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