The Twitter crusader for solid scientific evidence in medicine

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Prasad

Vinay Prasad

Dr Vinay Prasad is a professional and inluential scold: He takes to Twitter each day to critique this cancer drug as ineffective, or blast that one as overpriced, or dismiss the clinical trial of another as completely irrelevant. So, says a Stat News report, it’s a bit of a surprise to catch him at the bedside of an elderly man with lymphoma, laughing gently with his patient as he inquires about his day – and painstakingly explains a potent drug’s unpleasant side effects.

The report says Prasad’s empathic bedside manner – and generally affable mien – is at stark odds with his digital persona as a caustic crusader for the principle that solid scientific evidence, not hope or hype, should guide how we as a society spend $700bn a year on health care.

Just 34, Prasad has become an influential voice in the medical community through his prolific, high-impact publishing, a steady stream of media cameos, and – and course – his vociferous Twitter presence. The report says among his main arguments: Drug costs have spiraled out of control. Conflicts of interest run amok in health care. We don’t have any idea how well new cancer drugs and diagnostics work, thanks to ill-designed clinical trials. And more than half of all practiced medicine is based on scant evidence – and possibly ineffectual.

The report says needless to say, such positions haven’t won him many close friends among pharma companies – or even among some fellow doctors. He doesn’t much care. Anyone is fair game for his ire: scientific journals have the “long term memory of a squirrel”; medications are “insane and unsustainable”; eminent researchers back “unproven and likely-to-be-useless” strategies; meeting with drug sales reps is a “waste of time”; and Scott Gottlieb, the new US Food and Drug Administration commissioner, won praise from Democrats only because “the alternative was a box of rotting fish.”

“He tends to be so cynical and nihilistic,” said Dr Eric Topol, a cardiologist and geneticist at Scripps Research Institute in La Jolla, California. “I try to encourage him to see some of the optimism in medicine.” The report says while he takes issue with Prasad’s style, Topol is a fan overall. That’s a common reaction. Many doctors don’t like his tone, or disagree with some of his specific conclusions – but nonetheless laud him for rigorous research. Prasad, who talks nearly as fast as he works, has co-authored nearly 150 articles since 2011, many of them published in top medical journals. (And he still, somehow, finds time to sleep at least eight hours a night – and bikes to work daily.)

“I think he’s rare in the fact that he thinks about individual patients, but also thinks about society and the population as a whole,” said Dr Daniel Goldstein, a cancer researcher at Rabin Medical College in Israel who has done research with Prasad.

The report says critics point out that although Prasad champions transparency, he has blocked some foes who challenge him on Twitter, effectively shutting off dialogue with them. He rails against conflicts of interest and has taken no money from pharma, but he has accepted a $2m grant from a foundation with an agenda that aligns with his own, including promoting efforts to rethink drug pricing and physician billing models.

The report says Prasad himself acknowledges that although he dismisses many new cancer drugs as nearly worthless – and way overpriced – he will, at times, prescribe them if his patients insist, even after he has explained his reservations. But by and large, he sticks by his credo – that the only drugs worth prescribing are those that have been rigorously validated in clinical trials.

“I get the sense that he really holds a grudge against the pharmaceutical industry,” said Yevgeniy Feyman, a fellow at the conservative Manhattan Institute. But, the report says, Gregg Gonsalves, an associate professor of law at Yale University and co-director of the Global Health Justice Partnership, takes a different angle on Prasad – he has dubbed him a “swashbuckling crusader for medicine.” “He’s the guy who says the emperor has no clothes,” Gonsalves said.

True, the report says, the topics Prasad writes about can be rather dry. He frequently bemoans the fact that when a clinical trial fails to meet its stated goals, the researchers root around to find alternative metrics that will let them declare success. Recently, he was deep in the weeds of research costs, with a paper that concluded companies might spend $650m to develop a drug that can ring up $1.6bn in sales.

But with his quick wit, conversational tone (he has been known to exclaim “omg” on Twitter) – and, yes, his habit of flinging colorful insults – the report says Prasad has a way of drawing the public eye to this most unsexy side of medicine. He has more than 9,000 followers on Twitter, which doesn’t make him a celebrity, but it’s not bad for a guy who throws around jargon like QALY (a metric of quality of life) and R-CHOP (a chemotherapy regimen) and earnestly dissects the validity of Kaplan-Meier curves (a statistical analysis used in clinical trials to project survival rates).

“You might catch more flies with honey, and sure – Vinay could be sweeter with his critiques,” Gonsalves said. “But I don’t think that’d get very much attention.”

Prasad, who studied philosophy in college, credits his entrance into the medical field to his college roommate at Michigan State: He was taking the MCAT, so Prasad decided to try out the medical entrance exam out himself. “I don’t know if I would have signed up on my own volition,” Prasad said. Had his roommate pursued law, Prasad might have as well.

The report says he hated the first two years of medical school at University of Chicago, which involve hours upon hours of basic science lectures. He even considered quitting: “I couldn’t stand the rote memorisation of things that seemed so useless,” he said. As for research, he said, “I avoided it at all costs.”

It wasn’t until Prasad’s third year of medical school, when he began rotating in hospitals and interacting with patients, that he began to take serious interest in medicine. He hails from a family full of engineers, so had few preconceptions about clinical practice. And he soon began to notice that many routine medical procedures didn’t have any solid evidence to back them up.

During his rotation through the hospital’s cardiac critical care unit, for instance, he was taken aback by the widespread use of stents, which are inserted in blocked arteries to open them up. They work well, of course, in severe cases when arteries are completely blocked. But in people who have chronic, stable angina – that is, mild heart disease with some chest tightness – there’s no evidence whatsoever that stents improve survival rates. Yet 80% of stents are placed in patients who have this mild angina. It’s become a $15bn industry.

And, the report says, it’s not without risk: During that rotation, Prasad saw a patient who’d had a severe heart attack related to the stent, and another who’d developed brain damage from complications during the surgery. “All interventions have complications, sure,” Prasad said. “But if there’s no benefit to a procedure – then what the heck are we doing?”

Such realisations led Prasad to co-write a book in 2015 with his medical school mentor, Dr Adam Cifu, a general internist studying evidence-based medicine at the University of Chicago. The book, tantalisingly titled Ending Medical Reversal, focuses on cases of treatment flip-flopping – in which medical creed is disavowed after being subjected to randomised clinical trial. “The more you see this, you can’t look away,” Prasad said. “Everywhere I look, it’s the same thing.”

The report says Prasad began to make enemies early on: Radiologists aren’t happy that he deems routine mammography pointless. Urologists don’t like him, either, because he’s been deeply critical of the PSA diagnostic test for prostate cancer. In both cases, Prasad is concerned that there are too many false positives, which can cause patients great psychological distress. Scouring the data, he also argues that too often, the tests turn up cancer that does not really need to be treated – but is taking a physical and financial toll on the patient and sometimes leaving lasting side effects, like erectile dysfunction for men who have prostate surgery.

Of course, the report says, screening also sometimes finds highly malignant cancers and saves lives – so many urologists and radiologists resent Prasad for crusading against the tests. It says Prasad takes that fury as proof that many doctors are too concerned with making money to follow the evidence where it leads (radiologists, after all, earn their living from conducting tests like mammograms, and urologists make money doing prostate surgeries).

“It feels like in medicine, if we forget the history, we’re condemned to repeat the errors,” Prasad said. “But why do we repeat them? Well, it just so happens that lots of people benefit financially from committing those errors.”

His critics, however, say Prasad is putting too much weight on statistical tables, instead of listening to the real-world experience of real-life patients and physicians. They also dismiss him as a generalist who doesn’t really understand the specialty fields he so angrily attacks – and doesn’t try to. “He never wanted to hear the other side,” said Dr Ben Davies, a urologist at University of Pittsburgh who has clashed online with Prasad. “In general, there’s an absolutism to his voice, which grates a lot of researchers the wrong way.”

The report says Dr Tomasz Beer, a prostate cancer researcher at Oregon Health and Science University (OHSU) – and the man responsible for bringing Prasad up to Portland – has been called upon to defend some of his more controversial remarks: “I’ve gotten calls from people at respected institutions saying, ‘Why the hell did you hire this guy?’” Beer said. “My answer: We support academic freedom and he’s doing good work.” “When we recruited him, we weren’t sitting around saying we need an iconoclast-in-chief,” Beer said. “He was just a really fantastic talent.” How fantastic? Beer reaches for an analogy that’s sure to raise eyebrows among Prasad’s critics, likening him to a misunderstood genius, ahead of his time: “Where does Leonardo da Vinci fit in the art scene of 15th century Venice?” he said. “But if you see Leo, you get working with him.”

The report says for his part, Prasad delights in shaking things up. Too often, he said, physicians tread cautiously so as to not anger their peers by taking strong stands, declining even to step in when other doctors “are saying things that are completely erroneous or unsupported.”

But the world is quickly changing, and the traditional channels of sharing scientific research have morphed. “In a way, medicine is being democratised,” Prasad said. Some blogs, he argued, “are way better than any journal editorial – they’re more thoughtful, and have better points.”

And then, of course, the report says, there’s Twitter. Prasad frequently uses the medium to critique clinical trial design – and press for better studies that more accurately assess whether a drug really works.

In oncology, many trials don’t assess whether a drug helps a patient lives longer – just whether it buys her additional weeks or months before her tumours start to grow again. (That metric is known as “progression-free survival.”) That bothers Prasad.

“Our results show that most cancer drug approvals have not been shown to, or do not, improve clinically relevant endpoints,” he wrote in a research letter published in 2015, citing his review of five years of cancer drug approvals. He also complains that too many trials aren’t gold-standard, random controlled studies that compare experimental drugs against the standard of care.

Dr Vincent Rajkumar, an oncology professor at Mayo Clinic who has collaborated with Prasad and supports his work, nonetheless finds such critiques a bit unrealistic. For instance, he noted, in the case of treatments for life-threatening diseases, if we waited to see whether a new drug improved overall survival, important medications wouldn’t be approved for many years. “And it’s extraordinarily hard to do a randomised controlled trial in the US,” Rajkumar said. “If we just wait for that, it’s not going to happen.”

It’s not hard to critique a clinical trial’s design after the results are out, Rajkumar is quoted in the report as saying. But between funding woes, patient recruitment challenges, and prolonged regulatory timelines, the finished trial – and the outcomes that are evaluated – often end up a far cry from the original intention. “It’s easy to look at a trial and say, ‘how on earth did anyone approve this design?’” Rajkumar said. “By the time a trial’s complete, it doesn’t look anything like the principal investigator envisioned.”

The report says one of Prasad’s favourite parts of his gig at OHSU? Training the next generation of doctors to be sceptics. He helps lead the school’s oncology fellowship programme, assigning trainees to give 15-minute talks every time a new drug is approved by the FDA. The young physicians must convince the OHSU tumour board that the drug truly deserved regulatory sanction. Most of the time, they can’t.

He has also hired a small cadre of research peons – that is, medical students and residents – to carry out his grunt work. Right now, for instance, they’re busy trawling Twitter in search of physicians who use social media to praise drugs without disclosing that they’ve been paid by pharma companies.

The report says his job is structured so that he devotes most of his time to research, working in a simply decorated office – with his many diplomas (including a master’s in public health from Johns Hopkins) taking up much of the wall space. His research grunts work on computers in a small attached vestibule.

Roughly one day a week, Prasad pulls on his white coat and walks over to the university hospital, where he treats patients with leukaemia and lymphoma. According to the report, that’s where he sees the human stories behind the black-and-white statistical tables he spends hours parsing in his research. True to his principles, Prasad makes sure to offer his patients the treatments that have the most proven survival benefits.

But he does also tell them about other options. He’ll tell them, for instance, that a new therapy is gaining popularity – but then explain why he’s reluctant to prescribe it. One example: He’s not yet sold on combining immunotherapy drugs, though that is an increasingly hot field of study.

“I’m a bit of an evidence-based purist, but a big believer in shared decision-making with my patients,” Prasad said. “There are some things I feel strongly about, but in terms of my practice, I’m not some outlier. I’m way within the spectrum of how people practice oncology.”

The report says he even enrolls some patients in clinical trials – if, of course, they meet his standards for proper research design.

Stat News report
JAMA Internal Medicine analysis


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