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The Most Powerful Personality Trait You May Never Have Heard Of

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The flashier personality traits—narcissism, neuroticism and extraversion—get a lot of attention in the popular literature. But there’s a quieter trait that may be even more powerful: Intellectual humility, which, as the name suggests, refers to our capacity to be humble about our own intellect, to question whether what we know is actually correct and even to adjust our beliefs if we’re presented with new information. And rating higher in intellectual humility may go way beyond helping in our personal relationships (although it does that, too). It may be a great benefit in realms like politics, where people are famously resistant to changing their minds. Luckily, as the authors of a new study argue, the trait is very likely malleable, meaning that it’s something that can be learned, and perhaps even adjusted over time.

The aim of the new research, published today in Personality and Social Psychology Bulletin, was to determine how the trait affects people’s reactions to various types of information. In one experiment, participants read essays that were fundamentally counter to their own views on religion. Then they rated how much they were aligned with the essay’s message, how it made them feel, and how they felt about the author of the essay. It turned out that people who ranked lower on intellectual humility also thought less of the essay’s author, rating them lower on morality, honesty, competence and warmth. People with more intellectual humility didn’t judge the character of the author in the same way. They were also less sure that their views on religion were correct and less likely to think their views “better” than others.

Follow-up experiments explored the trait in other areas—like political—where people tend to be pretty sure that they’re right about things. The team had people rate how likely they’d be to vote for a candidate who’d flip-flopped on a view based on emerging evidence. Interestingly, Republican participants were less likely to be dissuaded by flip-flopping if they were higher in intellectual humility. Democrats were on average less likely to view the politician critically for changing his mind, regardless of their intellectual humility level.

 “There are stereotypes about conservatives and religiously conservative people being less intellectually humble about their beliefs,” said lead author Mark Leary in a news release. “We didn’t find a shred of evidence to support that.” Which of course has a lot of relevance to today’s climate. “If you think about what’s been wrong in Washington for a long time, it’s a whole lot of people who are very intellectually arrogant about the positions they have, on both sides of the aisle,” added Leary, a psychology and neuroscience professor at Duke University.

A final phase looked at how people with different levels of intellectual humility evaluated different types of evidence. They presented participants with science-based evidence for flossing one’s teeth and anecdotal evidence for it. As they’d suspected, people higher in intellectual humility were better able to differentiate between the quality of evidence than people lower in the trait.

 The results suggest that people who know that their beliefs are just beliefs may fare better than others in number of realms. The value of intellectual humility, of course, reaches into other areas still, like business and personal. “If you’re sitting around a table at a meeting and the boss is very low in intellectual humility, he or she isn’t going to listen to other people’s suggestions,” Leary said. “Yet we know that good leadership requires broadness of perspective and taking as many perspectives into account as possible.” A similar thing probably makes for a good marriage.

Luckily, the trait could very likely be developed—perhaps even taught in school, and without a lot of effort. A mention or two of the importance of questioning one’s own beliefs from time to time might be enough to cultivate it in kids. And keeping that idea in mind throughout life is probably wise for the rest of us. “I think if everyone was a bit more intellectually humble,” said Leary, “we’d all get along better, we’d be less frustrated with each other.”

Source: forbes.com

Amgen Drug Prevents Heart Attacks, Not Deaths, Disappointing Experts

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Repatha, a new drug from Amgen, prevents heart attacks and strokes better than any medicine since the cholesterol-lowering statin drugs that are a daily preventative for millions of middle-aged people, according to a new study.

But the results fall below what doctors and patients had hoped for the drug, and set the stage for an intensified battle over Repatha’s $14,523-a-year list price, several times what the most expensive branded statins cost before they went generic.

“I think it’s a solid ‘B,’” says Harlan Krumholz, a cardiologist and epidemiologist at Yale Medical School, of the result. “If they’d met the expectations on what the drug was going to achieve, it would have made a big difference. On the other hand, they could have shown nothing.” Adds Steven Nissen, of the Cleveland Clinic and an Amgen investigator: “Now the debate is who should get the drugs.”

Analysts at investment banks and top cardiologists had been hoping that Repatha would reduce by as much as 30% the risk of a combined measure of heart attacks, strokes, deaths from heart disease, hospitalizations due to chest pain, and stent and heart bypass procedures. Instead, that result was just 15%, although the drug did better on reducing heart attacks and strokes, two of the measures that matter most. But Repatha also had no effect at all on whether patients died.

Repatha was not supposed to be just any drug. It is one of the first medicines developed based on the discovery of real-life mutants: people with variations in a gene called PCSK9 who have extremely low cholesterol levels and heart attack risk. Before Repatha was introduced, CVS Caremark, one of the largest managers of drug benefits for U.S. employers, warned that drugs like it could cost the U.S. healthcare system $200 billion. Yet Repatha sales last year were only $140 million globally. Praluent, a similar drug made by drug firms Sanofi and Regeneron, had sales of just $116 million. The drugs are injections, not pills.

The hope among investors and cardiologists was be that this 27,564-patient study, presented this morning at the annual meeting of the American College of Cardiology in Washington, D.C., and published in the New England Journal of Medicine, would blow the barriers that keep patients from getting PCSK9 drugs. Now doctors, patients and insurance companies still struggle with the question: is Repatha worth the money?

A Lower-Than-Expected Result

It wasn’t just genetics that got expectations for PCSK9 drugs hot. Reducing LDL as much as Repatha did should have resulted in a 31% reduction in heart attacks and strokes, says Sekar Kathiresan, a cardiologist and geneticist at Massachusetts General Hospital.

So why was the result only 15%? One reason is the measure of success Amgen chose. In order to get more statistical power in clinical trials, drug companies and cardiologists often lump “hard” measures like heart attacks, strokes and deaths together with less important but more common problems like being hospitalized for chest pain or needing a stent to open a clogged artery.

Repatha reduced the rate of heart attacks 27%, from 4.6 in 100 patients to 3.4 in 100 patients. It reduced stroke 21%, from 1.9 in 100 patients to 1.5 in 100. It reduced stents and heart bypass procedures 22%, from 7 in 100 to 5.5. But on hospitalizations for chest pain, it did nothing–1.7 of 100 people in both groups were hospitalized for chest pain.

It may be that chest pain is no longer a good measure for clinical trials, says Marc Sabatine, the Brigham & Women’s Hospital cardiologist who led the study for Amgen. Blood tests can now detect whether people with chest pain are having heart attacks or need stents. Those hospitalized for chest pain may actually have other problems, like acid reflux. “You’re not going to intervene on heartburn,” says Sean Harper, Amgen’s head of research and development.

Haste Makes Waste?

But Repatha also didn’t impact a more important measure: whether patients lived longer. On Repatha, 1.8 of 100 patients died of cardiovascular causes; for placebo, that figure was 1.7.  For the most part, these “cardiovascular causes” were not heart attacks and strokes, but sudden cardiac deaths, when a patient dies suddenly for unknown reasons. It could be that a cholesterol drug had no effect on sudden cardiac death. But only 0.4% of patients died from either a heart attack or stroke; the rates of fatal heart attacks and fatal strokes were actually better in the Repatha group, but were too small to draw conclusions. Doctors may just be better at preventing death compared to 20 years ago, when the first statin studies were run.

It could be that Amgen rushed too fast, choosing to run a gigantic-but-short study to get quicker results. Trials in which statin drugs prevented deaths lasted five years. Patients were followed, on average, for a little more than two years in this study. For both statins and the PCSK9 drugs, it appears that effectiveness takes time to appear, and is half what it would be expected to be in later years, says Rory Collins, an Oxford epidemiologist who is one of the world’s top experts on cholesterol medicines. A shorter trial means a much lower effect as a result. What’s more, it may take time to prevent deaths by preventing buildup in the arteries. “The underestimation could be a duration effect,” Collins says. “And it could be really quite substantial.”

That leads to the possibility that a longer trial might show better results. Sanofi and Regeneron are running a study of their PCSK9 drug, Praluent, in which all patients will take drug for at least two years. “My belief is whatever Amgen shows I hope we’ll have a better or higher result,” said Elias Zerhouni, the head of R&D at Sanofi, before seeing the Amgen results.

Patients Denied

A logjam in drug benefit plans has kept PCSK9 medicines from being used, even for patients who obviously need them. Take Cameron Credle, 30, a woodworker in Chapel Hill, N.C. At age three, he had a total cholesterol of 430 milligrams per deciliter, almost quadruple normal levels. (He has a genetic disease called familial hypercholesterolemia.) He’s spent his whole life trying to get his LDL down. Statins brought it down to about 250 mg/dL. It took him four months to get approval to try Praluent, the Sanofi/Regeneron drug. It gave him diarrhea. He spent another eight months getting approval for Repatha, instead taking samples of the drug his doctor obtained. He says his doctor’s office logged 15 hours of work to get him the medicine.

Craig Davis, 57, the former chief information officer of the Veterans Affairs Medical Center in Orlando, Florida, also has familial hypercholesterolemia. He went on federal disability after his second coronary bypass surgery. Three decades ago, he learned his total cholesterol was 840 mg/dL and his LDL 420 mg/dL. He’s been on statins since they were introduced, and got five stents between when he was 35 and 40. His next option would be a heart transplant, his doctors tell him. He wanted to switch to Repatha from Juxtapid, a $300,000-a-year drug that was damaging his liver. Getting approval took weeks. Then, he changed insurers–and was denied again. “It was a bureaucratic nightmare, and that’s coming from a career bureaucrat,” Davis says.

Both Credle and Davis were identified by the Global Healthy Living Foundation, a nonprofit that gets some funding from drug companies including Amgen. Both say they receive no compensation. Their stories show that there are people who would benefit from PCSK9 drugs who are clearly having trouble getting them. But the vast majority of patients are not at nearly as much risk.

The Pharmacy Middlemen

Answering the question of who should get Repatha is largely being left to the giant companies that manage drug benefit programs for insurers and employers, including CVS Caremark, Express Scripts and some units of UnitedHealthcare. Representatives of CVS and Express Scripts say they expect the results are good enough to drive increased use of the medicines. “If we sense the consensus is that this demonstrates there’s a substantial decrease in cardiac outcomes, it will increase the number of people increasing PCSK9 inhibitors,” says Troyen Brennan, the chief medical officer at CVS Caremark.

Steven Miller, the chief medical officer at Express Scripts, says that part of the reason the drugs weren’t being prescribed is that doctors weren’t pushing very hard for them, even for the sickest patients. He thinks that will change. “Getting the patients approved had been difficult, and because there was no endpoint data many practitioners didn’t push very hard,” Miller says. “Now that there is endpoint data they are going to be pushing a lot harder to write these scripts.”

Miller says Express Scripts has been working to make sure that patients who really need the PCSK9 drugs can get them. Half the denials of Repatha or Praluent at Express Scripts were because the company was asking doctors to send not just a lab value, but also an actual copy of a lab report. For a $14,000 drug, it seemed fair. But for doctors’ offices, this turned out to be difficult, because the lab report itself was not always in the medical record. Express Scripts has changed its requirements as a result, he says. Still, Miller says, companies like his are also “stewards” of their clients’ cash.

Is Avoiding A Heart Stent Worth $1 Million?

The question for many drugs is not whether Repatha prevents heart attacks–it clearly does–but whether that is worth the money. Sanjay Kaul, a cardiologist at Cedars Sinai Medical Center in Los Angeles, calculates that it costs $2 million to prevent a heart problem (cardiologist jargon: an event) at Repatha’s list price. “Even with 50% price discount, $1 million per event prevented is too steep a price to justify!” he says. David Rind, chief medical officer of the Institute for Clinical and Economic Review, says it would be “surprising” if the new results make economic analyses of Repatha look better.

“People care about more than just surviving,” counters James Stein, of the University of Wisconsin School of Medicine and Public Health. He plans to use PCSK9 drugs more.

Adds Nissen, the Cleveland Clinic cardiologist: “We give very expensive cancer drugs that extend life for six weeks. I just want to be able to offer patients the best therapies that are available. I look after many patients after [heart attack], they go out and they try to do things and their exercise tolerance is never the same. I follow patients who have had a stroke and now walk with a cane. They’re alive, but their quality of life is never the same. Do I wish these drugs cost $4,000 a year instead for $14,000? I do.”

Says Yale’s Krumholz: “The drug has been priced on speculation, in my mind. What do you get from a 60 mg/dL reduction in cholesterol? People thought you’d eliminate heart disease. But that’s not what happened here. But you’re in the range of what happens with statins. If you’re giving me a new statin, we should be paying pretty much what we paid when the statins were introduced. Why should we be paying a premium for that?”

Amgen, for its part, says that even at $14,000, Repatha is cost-effective. And it actually gets much less than that. Drugmakers pay rebates to pharmacy benefit managers; for a drug like Repatha, those rebates could be 30% or more.

Many doctors say one of their main takeaways from the trial will just be that lower levels are better, no matter how low a heart patient’s LDL is. Ethan Weiss at UCSF says he will start reaching for generic Zetia, a generic Merck drug, before he ever goes for the PCSK9 shots. What that means for sales, which Wall Street analysts hope will pass $2 billion for both Repatha and Praluent, is not clear. Another factor for investors to consider: there is ongoing patent litigation between the two companies that almost led Praluent to be removed from the market.

The debate over these amazing, potent and (still) potentially life-saving drugs is a snapshot of medicine in 2017. Science is great. But what does it cost in dollars and cents? We’re getting to the point where  we need to know.

Source : https://www.forbes.com