Like a St. Patrick’s Day hangover, news of federal researchers courting liquor company executives for funding leaves a bad taste in the mouth of many who care about the quality and independence of the National Institutes of Health.
The New York Times reported yesterday that the lead researchers on a $100 million study of the effects of moderate alcohol consumption had extensive discussions with the alcohol industry prior to securing their sponsorship. Those discussions–during which researchers told industry representatives they had “a strong reason to suspect” that moderate alcohol consumption is beneficial–included specifics about how the trial would be planned and conducted, according to the Times, which reviewed e-mails and travel vouchers obtained via a Freedom of Information Act request. The researchers had previously denied discussing the planning of the study with anyone in the alcohol industry.
Wired Magazine also raised questions about the role of beverage companies in the planning of the study in October, 2017.
The new revelations are pertinent to journalists who may be or will be covering the study and its eventual findings — as well as news consumers who will be reading about the study. The alcohol industry is not just interested in funding research that will help promote its products; it’s also funding journalism organizations whose members will be reporting on this research.
‘Not public health research — it’s marketing’
Here are the key excerpts from the Times describing the NIH’s discussions with industry executives:
The presentations gave the alcohol industry an opportunity to preview the trial design and vet the investigators. Indeed, the scientist leading the meetings was eventually chosen to head the huge clinical trial.
They also made the industry privy to pertinent details, including a list of clinical sites and investigators who were “already on board,” the size and length of the trial, approximate number of participants, and the fact that they could choose any beverage. By design, no form of alcohol — wine, liquor or beer — would be called out as better than another in the trial.
Dr. Michael Siegel, a professor of community health sciences at Boston University School of Public Health who was shown slides from the scientists’ presentation at The Breakers by The Times, said the study “is not public health research — it’s marketing.”
The deeply reported story includes input from Lorraine Gunzerath, PhD, a retired NIH official who helped arrange the industry sponsorship. She acknowledges that alcohol industry representatives “would have said no” if they didn’t like the research team being proposed to run the trial. Moreover, the NIH took steps to ensure that investigators acceptable to industry — including Kenneth Mukamal, MD, who had published extensively on the potential benefits of moderate alcohol consumption — were selected to receive the grant money.
While N.I.H. grants are supposed to be awarded on a competitive basis, the institute’s request for outside funding said the award would be restricted to applicants with “unique” resources and backgrounds — and specifically mentioned Dr. Mukamal, who had helped persuade the alcohol industry to fund the research.
A ‘troubling’ and ‘disturbing’ approach
Arthur Caplan, PhD, a professor of bioethics at New York University, described the Times report to me as “very disturbing.”
“The message has been going out that the Foundation for the NIH [a private entity that raises money for the agency] puts a firewall between sponsors and who to fund and what to fund,” he said. “But the suggestion here is that funders were lured in by the promise of favorable results, and the routing of the funding to particular investigators. That can’t be. The NIH’s reputation depends on independence — that’s where its trustworthiness comes from.”
Caplan said that in his view, it isn’t necessarily a problem to include industry in the mix of funders for important public health research. However, he said that such funding partnerships have to include “an ironclad policy” and “can’t deviate from gold standard practices to minimize conflict of interest.” Pointing to the NIH’s recent termination of an agreement with the National Football League to conduct concussion research, Caplan said it appeared that the federal agency was having problems maintaining those gold standard policies in its industry relationships.
“It looks like the funders have been trying either to get hoped-for results or to handpick the people to carry out the work, and that’s just not consistent with what’s necessary for independent peer-reviewed science,” Caplan said. “It’s very troubling.”
Big Booze also funding journalism
We’ve been following this story since last summer, when we learned that the alcohol industry wasn’t just funding research on moderate drinking — it was also funding journalism in a possible attempt to sway public opinion.
Our publisher, Gary Schwitzer, wrote that the Foundation for Advancing Alcohol Responsibility, founded by distillers, funded two all-expenses-paid training sessions for journalists hosted by the Poynter Institute. The Foundation CEO, Ralph Blackman, spoke to journalists at one of the meetings, another instance where a necessary firewall — this time between funders and the journalists attending the workshop — wasn’t strong enough to withstand industry pressure.
But Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, said the Poynter Institute’s policies still don’t go far enough. He said their emphasis on disclosure of relevant industry conflicts isn’t sufficient to prevent those conflicts from introducing bias.
“The answer is to say no,” he said. “Journalists shouldn’t take money and gifts from organizations they will be covering. This is not a hard ethical dilemma. Does any journalist really think that they’re getting free meals and travel money and conference expenses because the booze industry has a deep interest in their education? For that matter, why would the Beer Institute have any interest in funding a study that doesn’t promote the interests of companies that make beer?”
Daniel Goldberg, JD, PhD, an ethicist at the University of Colorado, Denver, agreed that emphasis on disclosure in these situations may ultimately distract from more important issues.
“It is not good enough to argue that disclosure of these relationships is sufficient, and we proceed at our peril when we spend all of our time and energy debating whether the disclosure was appropriate,” Goldberg said.
“Relationships with regulated industries have the significant probability of altering the professional behavior of scientists, research teams, and health professionals. We have excellent evidence for this, both experimental and natural. Moreover, industrial efforts to purchase credibility by partnering with respected scientists is part of an older historical script, one intimately connected to the manufacture of doubt.”
Connecting the dots: Industry, research, journalism
It’s not too difficult to connect the dots between the alcohol industry’s funding of medical research and its funding of journalists who might report on that research.
After all, if you’re going to invest $100 million in a study, wouldn’t it make sense to cultivate sympathetic journalists to help put a nice shine on the results?
“That’s a real danger,” said Caplan, who noted that industry is always on the lookout for opportunities to broadcast good news about its products. He said that sometimes industry really does contribute to advances that merit the positive coverage they receive. But industry also has a tendency to spin negative results to its advantage.
“You have to aware that the goal of industry is the make money and the way you make money is put out messages that are favorable,” he said.
What does this mean for journalists? Caplan emphasized three points for any reporter who may cover this story, either while the study is ongoing or when the results are eventually reported.
“Pay attention to who wrote the news release.” This is a prime opportunity for a sponsor to introduce spin, and these public relations documents should be written solely by the NIH without input from the alcohol industry. “I would be nervous about any press release that was written jointly with industry,” he said.
“Wait until the results are published in a peer-reviewed journal; don’t report from a press conference.” The peer-reviewed study will include details that investigators and sponsors will likely gloss over in any press conference about the research.
“Start lining up the critics right now.” Many public health researchers believe that the design of the current study doesn’t adequately account for the harms of alcohol, such as the potential to slide into alcoholism or the long-term risk of cancer that may be increased by regular alcohol consumption.
Says Caplan: “A lot of people would be thrilled to hear that moderate drinking is good for you because they want an excuse to justify their habit. You need to hear those balancing voices who say this may not be as good as it sounds.”
An extremely brief New York Times “Well” post published last week — “A ‘Sweet Spot’ for Heart Health” — suggests that people must be within a very narrow weight range–a body-mass index (BMI) of 21 to 23–if they want to reduce their risk of heart disease as much as possible.
The Times’ article reports on a prospective study of nearly 300,000 middle-aged British men and women, followed for about five years, who had their relative body fat measured by five methods: body-mass index (BMI), waist circumference, waist-to-hip ratio, waist-to-height ratio, and body fat percentage.
The British study adds to a growing body of research that shows that the so-called “obesity paradox” — the notion that a slightly higher than “normal” BMI may reduce mortality — may not really exist. Such was the case with this study: Increasing BMI was associated with an increased risk for heart disease, as well as with the other measurements for measuring body fat.
And there was no BMI “sweet spot,” so to speak. Overall–after researchers controlled for things like smoking and coexisting health conditions–the less people weighed, the less likely they were to develop heart disease.
But the Times’ article doesn’t provide this context and instead implies that people must be within a narrow BMI range–not too low, and not too high. It also doesn’t explain that the BMI is an imperfect tool and shouldn’t be used in isolation: Very fit athletes, for example, can have a high BMI that places them in the “overweight” category.
Nor is it mentioned that this kind of research, known as a prospective cohort study, is not designed to prove that obesity — or even fat itself — causes cardiovascular disease. All the variables that likely contribute to heart disease cannot be fully accounted for in this kind of study design.
Of course, there is extensive evidence that obesity is associated with numerous health risks including cardiovascular disease. But whether there’s really such a thing as a narrow “sweet spot” cannot be conclusively determined by this type of study, and the article should have said as much.
As one reader noted: “Once again we are treated to a correlations=causation conclusion that is not actually made by the study. It may be that meeting a target BMI will reduce your chances of having cardiovascular disease or it may be an irrelevant marker of the real causes.”
Doctors may provide that unnecessary care because they perceive that patients are expecting or requesting it.
If health care professionals don’t provide the aggressive care that patients believe they require, the thinking goes, patients won’t be satisfied and the doctor-patient relationship will suffer. Plus, the patient will just go to another provider who’ll perform the requested services anyway.
But does that explanation hold water?
Patients understand: More care is not better care
Preeti Malani, MD
The latest report from the University of Michigan’s National Poll on Healthy Aging, which recently surveyed some 2,000 US adults between the ages of 50 and 80, casts doubt.
Preeti Malani, MD, who is a professor at the University of Michigan and director of the polling effort, summarized some key findings from the report together with co-author Jeff Kullgren, MD, on the Health Affairs blog. (Malani is also an expert story reviewer for HealthNewsReview.org.) They wrote:
Only 14 percent of poll respondents agreed that more medical treatment is usually better. In contrast, more than half (54 percent) felt health care providers often order medications, tests, or procedures that patients don’t really need. One in six (17 percent) reported that in the last year a health care provider had recommended a medication, test, or procedure that they felt they did not need.
Not only do many older Americans report that they receive care perceived as unnecessary, the results show, but those patients would likely go along with clinician efforts to avoid prescribing unnecessary tests and treatments. Malani and Kullgren write:
When clinicians explained to older adults that they did not need a service they had requested, nine in 10 of these patients reported that they understood the clinician’s explanation. In contrast, when an older patient’s health care provider recommended a test or medication that the patient felt was not needed, nearly half proceeded with the recommendation regardless.
So nearly all respondents understood the explanation as to why they didn’t need a test or treatment, and more than half went along with tests or treatments they thought they didn’t need simply because the doctor ordered it. This suggests that the medical community has more influence over patient behavior than is widely acknowledged.
‘Not really a good excuse’
“It could be a little bit of a generational thing,” Malani said in an interview, noting the older cohort they surveyed may see physicians as more of an authority figure than younger patients.
Regardless of the reason, she said the results suggest the conventional wisdom about patient expectations often doesn’t apply. “When people say, ‘I have to order that test because otherwise Mrs. Jones won’t like it,’ that’s not really a good excuse for doing it,” she said.
It’s a conclusion backed up by some other research on physician-patient interactions. For example, pediatricians may perceive an expectation that antibiotics will be prescribed even when drug treatment is not directly requested. Clinicians who perceive such an expectation are more likely to prescribe antibiotics unnecessarily.
Obstacles to shared decision-making
Ade Adamson, MD, an assistant professor of dermatology at the University of North Carolina Chapel Hill who studies both over- and under-use of medical care, seconded the need for more thoughtful communication in the health care system. “I think more of these conversations should be had between patient and provider,” he said in an email. “More patients should speak up. Joint decision making, grounded in evidence, should be the ideal we strive for.”
But he cautioned that “what the patient versus the physician interpret as low value are not always the same. As result, when entering these conversations, it is sometimes easier to order the service than to have a debate/conversation as to why a certain procedure/test/medicine is of low-value.”
Adamson gave the example of certain medical interventions that are not recommended for older adults simply because patients above a certain age are not expected to live long enough to benefit from the test or treatment.
“If the reason for withholding a certain service or medication that a patient comes to expect is purely because of their age, some providers may not want to have those types of uncomfortable discussions,” Adamson said.
The need for ‘Choosing Wisely’
Malani agreed that there are many obstacles to better clinician-patient communication. She said that programs like Choosing Wisely, which aim to educate patients and consumers about wasteful medical care, are critical to facilitating these discussions. (We’ve written extensively about the Choosing Wisely campaign.)
“Time really becomes a problem when you talk about addressing this issue. It takes time for a doctor to explain to somebody why the test they want isn’t necessary, and in a clinical setting today you’re almost always running behind.”
“This is where Choosing Wisely is helpful because it can do the education component that’s hard to do in the clinic,” she said. “It’s easy to say, ‘You just need to take the time to answer the patient’s questions,’ but that’s not the reality that we live in.”
Older adults who reported excessive daytime sleepiness were also more likely to have increasing levels of a protein called beta-amyloid in their brains over time, according to a study in JAMA Neurology.
Beta amyloid deposits are one of several pathologic signs of Alzheimer’s disease.
It’s an intriguing finding, and one that adds to a body of literature suggesting that sleep may be one of the many factors that could play a role in the development of the disease — or its prevention.
But it does not justify the misleading headlines that some news organizations slapped on their stories about the study, such as this one from CNN:
Why this is wrong: The study involved healthy older adults and did not try to assess whether the participants developed Alzheimer’s disease. So any claim that sleep disturbances increased the risk of this condition goes far beyond what the evidence can support.
What the researchers did assess was participant’s self-reported levels of excessive daytime sleepiness. They also performed scans that showed levels of beta-amyloid in participants’ brains over the course of the six-year study.
Results showed that excessively sleepy individuals were more likely to have a buildup of beta-amyloid than their counterparts who didn’t report excessive sleepiness.
Daytime sleepiness and Alzheimer’s risk
However, this does not mean that sleepiness caused the beta-amyloid to accumulate, says Harold DeMonaco, MS, a visiting scientist at the MIT Sloan School of Management and one of our expert story reviewers.
“There is a difference between association and causation. Daytime sleepiness may indeed be a cause of beta-amyloid accumulation or it may be the result of other factors that support accumulation. The chicken or the egg analogy is apt here. Suggesting that intervening in daytime sleepiness will lower the risk of the development of dementia is a bit of a stretch not supported by the study.”
We see this problem all the time with stories about Alzheimer’s disease, which often don’t acknowledge that beta amyloid isn’t proven to cause the condition, and that removing it won’t necessarily prevent or treat it.
When the roughly 52,000-member American College of Cardiology (ACC) meets — as it did this past weekend in Orlando for its 67th Annual Scientific Session — it’s a big deal.
Not only does it generate significant media buzz, but some of the studies presented can lead to major changes in how heart disease is diagnosed and treated.
One area generating buzz is “mobile health” approaches; this includes smartphones, watches, and even wearable patches that can now measure much more than simply your pulse or blood pressure. This year’s meeting featured two devices — the Kardia Band for the Apple Watch, and the iRhythm Zio Patch — that provide electrocardiogram (ECG) readings. Both technologies aim to help doctors screen for atrial fibrillation — an irregular beating of the heart’s two upper chambers — that is considered a risk factor for stroke. They seek to find atrial fibrillation in individuals who show no symptoms of the problem (i.e. are asymptomatic) and might not otherwise receive medical care for this condition.
Is screening for atrial fibrillation a good thing?
Will finding more atrial fibrillation, and treating it, lead to better outcomes?
John Mandrola, MD
News coverage of these devices generally suggests that the answer is a resounding “yes.” But John Mandrola, MD, a cardiologist practicing in Kentucky who specializes in the heart’s electrical system, isn’t so sure. Although he has nothing against the “mobile health” approach, he’s not convinced detecting more atrial fibrillation — our most common abnormal heart rhythm (or, “arrhythmia”) — will necessarily improve health outcomes like preventing stroke.
The scariest part of enhanced AF detection is overdiagnosis and overtreatment
Because Afib can make blood pool in the heart and lead to clots, a mainstay of treatment is anticoagulant drugs. These “blood thinner” drugs carry significant risks, costs, and a wide range of worrisome drug interactions. People diagnosed with Afib are usually prescribed other drugs as well and put through a variety of tests, some of which can be quite invasive. All those downsides must be factored into the risk-benefit calculation of finding more cases of Afib.
Mandrola’s concern is backed up by a December 2017 report by the US Preventive Services Task Force (USPSTF) which found insufficient evidence to assess the balance of benefits and harms to support screening asymptomatic adults over age 65 for atrial fibrillation by ECG. They cited one randomized control trial (RCT) documenting harms, and no RCTs supporting benefits.
But not everyone agrees. This viewpoint published in JAMA in November, 2015 argued that screening may reduce strokes in asymptomatic, elderly adults.
However, the USPSTF recommendations alone might justify approaching wearable devices for Afib detection with some degree of skepticism. For example, let’s take a look at the data presented this past weekend from a study involving the Zio Patch — a wearable, wristwatch-sized heart monitor. Although the study findings did not capture much mainstream media attention, the news releases from the ACC are instructive, and may help readers critically evaluate the coverage that will inevitably come as these devices gain more widespread acceptance.
Is a wearable patch better for diagnosing atrial fibrillation?
Here are the broad outlines of the study:
1,732 people over age 55, with no known heart rhythm issues, but at moderate risk of Afib, were compared with a matched control group of 3,646 to see if the patch could detect Afib better than standard outpatient testing.
Primary endpoint was newly diagnosed Afib at one year: the patch group had a nearly 3 times increased likelihood of Afib diagnosis than the control group (6.3 vs 2.3 %)
The patch group had a higher rate of starting anticoagulant drugs (5.4 vs. 3.4 %), receiving anti-arrhythmic therapy (0.8 vs. 0.3%), and pacemaker placement (0.7 vs. 0 %)
And yet, despite a three-fold higher likelihood of being diagnosed with Afib, and a higher rate of treatment with anticoagulant and anti-arrhythmic drugs, the patch group showed no reduction in the risk of outcomes that actually matter, such stroke, heart attack, or thromboembolism (blood clots traveling from the heart to other parts of body) during 1-year follow-up. The researchers will keep following these patients for two more years to see if benefits begin to accrue with longer duration of treatment.
Some unanswered questions
The study — part of a larger study called mHealth Screening To Prevent Strokes (mSToPS) trial — was presented as an abstract at the meeting. It has not been published yet in a peer-reviewed journal. As is so often the case with major medical meetings, journalists either learned about the preliminary results by attending the conference, or via a news release.
Zio Patch (from irhythmtech.com)
In this case there were two news releases from the ACC – a longer one and a shorter one:
The shorter news release predominantly highlighted the study design and results, but little else. Both news releases framed the findings as an unqualified success, and buried the lack of difference on clinical outcomes in a brief acknowledgment at the bottom of the release. Neither explained what the current (“routine” or “usual”) approach to diagnosing Afib is, and how the patch compares in terms of accuracy, costs, risks, benefits, or availability.
The potential harms of using the patch — such as a false-positive result, or the risk of a major bleeding event due to subsequent anticoagulant therapy — were not mentioned.
Let’s not forget: a key finding of the report is that those who wore the patch — although they clearly used more healthcare resources — had no difference in the rate of stroke or other important health outcomes as those who did not. It’s possible those benefits will materialize with further study, but the uncertainty surrounding this result is certainly cause for tempered enthusiasm.
The issue of mass screening
Christopher Labos, MD
Christopher Labos MD, a cardiologist and regular contributor at HealthNewsReview.org, says these outcomes are important when taken in the context of screening.
“The data for screening asymptomatic patients is weak and there’s a fair amount of uncertainty about whether it’s cost effective,” said Labos.
“Right now screening asymptomatic patients beyond checking their pulse at clinic visits is not recommended. It’s unclear if the excess costs from mass screening would be offset by disease prevention, especially in lower risk populations. This study showed that their device seems to work. But a different kind of study is needed to show the benefit of mass screening the population.”
This relevant background information was not brought up in either of the two news releases from the ACC, or in any of the interviews of the lead author I came across. Which makes me wonder: who IS the target audience of news releases from medical meetings?
Another concern for me that was not highlighted in the shorter press release is that this study was at least partially funded by Janssen, a company that sells an anticoagulant (Rivaroxaban; brand name = Xarelto). Janssen would potentially stand to benefit financially from an increase in the diagnosis of atrial fibrillation among asymptomatic individuals.
A nod to novel study methods
It’s worth noting that the authors believe this study may be the first completely digital, nationwide, direct-to-participant clinical research program that didn’t require the participants to physically show up at a medical facility. The subjects were recruited by email and the wearable devices were returned by mail for analysis. The authors argue this approach, when appropriate, could lead to larger study enrollment, more diversity of subjects, and reach previously inaccessible subjects who may not be located near major medical research facilities.
Wearable technology that provides participant-generated data is a burgeoning area of research. And a booming business. As more studies of this kind generate news coverage, I’d recommend paying special attention to two things at the very least.
First, because tech companies are inevitably involved, follow the money closely. Who is funding the studies and do the authors have financial conflicts of interest? Inevitably many will, which should focus your attention on the data and tune your radar for biased spin.
Second, just because a new test or intervention features new technology, doesn’t necessarily mean it’s automatically better than existing methods. We still need to know how it measures up in terms of risks, benefits, costs … and improving outcomes that actually matter.
Here’s some of our other coverage of the American College of Cardiology’s 67th Annual Scientific Session:
A highly anticipated clinical trial result for an expensive cholesterol-lowering drug drew plenty of news coverage over the weekend, with some stories declaring the drug, Praluent, reduced the risk of death.
Praluent’s effect on mortality is a landmark in the field of cardiology, doctors said, marking the first time since the statin era that a cholesterol-lowering drug has demonstrated a significant effect on whether patients live or die.
While the coverage we saw was fairly even-handed–including the nuance that the drug showed modest benefits for patients–some stories missed a key detail: The ballyhooed mortality benefit was not the “primary endpoint” that researchers had set out to measure.
Rather, the stated aim of the randomized controlled trial was to determine how many serious complications the drug prevents.
Why should that matter?
Positive changes more likely due to chance
A trial’s primary endpoint determines how it’s designed and how many patients are enrolled.
This pricey cholesterol-lowering drug was “associated with” reduced mortality.
Secondary endpoints — which in this trial included overall mortality — are less reliable and need to be viewed cautiously.
According to a physicians’ guide called the General Practice Notebook, “secondary endpoints do not have the same statistical authority as the primary endpoint, and it is more likely that positive changes in secondary endpoints are due to chance. It has been stated that secondary endpoint results should only be used to help interpret the primary result of the trial or to provide information, or prompts, for future research.”
Those caveats didn’t make it into most of the coverage we saw.
And despite its weaker status, that mortality data captured the headlines of both the AP and STAT:
The Reuters headline reflected the fact that the drug reduced a composite endpoint of four complications — heart attack, stroke, heart-related death, or serious chest pain — by 15%.
After about three years, 9.5% of patients taking Praluent versus 11.1% of those taking a placebo experienced one of those events. That outcome was the focus of the trial.
Regeneron, which markets the drug along with Sanofi, trumpeted in its news release that the drug “was associated with reduced death from any cause.” Overall mortality was 3.5% in the group that took the drug versus 4.1% in the placebo group, it said.
But as Larry Husten of CardioBrief wrote, that mortality finding “has an asterisk attached to it.”
Mortality benefit ‘isn’t statistically valid’
Husten pointed out that Praluent did not significantly lower the risk of heart-related death — one of the four components of the primary outcome. And without hard proof that the drug reduces deaths related to heart disease, the researchers cannot confidently claim that the drug reduces overall mortality, Husten said.
The reduction in overall mortality “was considered an observational finding,” Husten wrote. Observational data are a weaker form of evidence that cannot demonstrate proof of cause-and-effect. “As a result,” he wrote “this means the company will not be able to make a mortality reduction claim without qualification.”
Cedars-Sinai Heart Institute cardiologist Sanjay Kaul, MD, “commented that the mortality finding should not be considered robust,” Husten wrote.
Writing in Forbes, Matthew Herper also picked up this point, and also quoted Kaul that the mortality benefit “isn’t statistically valid.”
To their credit, all of the stories we saw contained caveats about the modest scope of the drug’s benefits and all but STAT and the Wall Street Journal gave some absolute numbers to help readers interpret their impact.
For example, the AP wrote that “the benefit was small — 167 people would need to use Praluent for nearly three years to prevent a single death.”
The AP also included cautionary takes from two doctors:
“We need to reset our expectations” and realize that benefits for any new drug are going to be fairly small when added to already good treatments such as statins, said Dr. Jeffrey Kuvin, conference leader and cardiology chief at Dartmouth-Hitchcock Medical Center. The new drugs clearly help people at high risk and are not aimed at people at low risk, such as those who have high cholesterol but have never had a heart attack, he said.
“I’ve been unconvinced” of the drugs’ benefits but now may prescribe them for certain very high risk patients, said Duke University cardiologist Dr. Christopher Granger. But preventing fewer than one heart problem a year at the drug’s current price is not cost-effective, he said.
Business coverage zeroes in on modest impact
Some news outlets including STAT and the Wall Street Journal focused on what this trial will mean for business — namely that the findings didn’t seem to be strong enough to convince payers to cover Praluent, a type of drug known as PCSK9 inhibitor. After the trial results were announced, Praluent’s makers announced they’d cut its $14,000-a-year price for a subset of high-risk patients who appeared to respond the most.
Praluent and another PCSK9 inhibitor, Repatha, haven’t been commercially successful as payers have pushed back on their high prices and uncertain benefits.
Regeneron’s news release declared that the drug “met its primary endpoint” by showing that high-risk patients who injected Praluent along with taking statins had “significantly fewer major adverse cardiovascular events” compared to those who took statins alone.
While some of the news coverage reflected that optimistic take, Bloomberg wrote that the 15% reduction in complications was “less than the 20 percent benefit analysts say would be needed to force insurers to loosen their stranglehold.”
The cautious tone of this reporting contrasts with portrayals of Praluent as a “breakthrough” when it was approved in 2015.
In a remarkable example of PR spin, both the American College of Cardiology and Zoll, a medical devicemaker, issued misleading news releases this weekend trumpeting the results of a study examining the LifeVest, a wearable cardiac defibrillator.
The LifeVest, which has been in use for nearly two decades, is sometimes prescribed to recent heart attack patients who have “low ejection fraction,” or a reduced ability to pump blood. These patients are thought to be at high risk of sudden cardiac arrest, and the LifeVest is designed to deliver powerful shocks that resuscitate a person when it detects a deadly heart rhythm.
For years, a lack of rigorous LifeVest study results made it hard to know what the right thing was to do for patients. It’s a problem common to many medical devices: Compared to drugs, the FDA requires less evidence that devices are safe to use and work as intended, and many unsafe devices remain on the market, even when known safety problems exist.
That’s why we and many others were curious to see the results of a randomized controlled trial, known as VEST, that was presented this weekend at the American College of Cardiology’s 67th Annual Scientific Session. Would the LifeVest study results provide proof that the vest was worth the hassle? How would it be summarized and pitched to the news media?
PR machines turn on the spin cycle
The findings: The study results for the primary endpoint were negative, meaning there wasn’t sufficient evidence to show the device reduced sudden cardiac arrest in post-heart attack patients. In the group that wore the vest, 1.6% died from sudden cardiac arrest, and in the group that didn’t wear the vest, 2.4% died. That was not a statistically significant difference.
Yet two news releases issued by the devicemaker, Zoll, and the ACC, glossed over this finding, and focused on a secondary endpoint of the trial, which was the rate of overall mortality in the two groups. By playing up this finding, they made it seem like the vest was proven to work–and worth the cost and risks of wearing the device.
Not only do they hype a secondary finding, they do so by using relative risk percentages to fluff up the benefit and make it look more impactful than it really was (which, as we explain here, is a common tactic used by researchers or PR teams trying to make results look better than they really are).
In this case, the news releases say the vest reduces total mortality by 36%. That sounds like a big difference. However, in absolute terms, 3.1% of the vest group died from any cause in the three-month period, and 4.9% died in the non-vest group, a difference of 1.8% percentage points.
Based on the reporting from this Medscape news coverage of the meeting, researchers involved with the study speculated that it might be because some of the deaths in the vest group were attributed to other causes, when they actually died from sudden cardiac arrest.
“This would reduce power for sudden death, but not for total mortality,” Jeff Olgin, MD, from the University of California, San Francisco said during his formal presentation of the trial, according to Medscape.
Several cardiologists quoted in the coverage voiced skepticism around this theory, noting that until further research is conducted, we simply have no idea why there was a slightly higher overall death rate in the control group than the vest group. It could be due to chance, especially since the event rates were low overall, and because the difference in death rates was just barely statistically significant.
Harms are downplayed
As we’ve written about, there are extensive reports that the device causes problems for wearers–including serious skin rashes and inappropriate shocks. The same problems were seen in the trial.
But the risks of wearing the device–which include death–were not mentioned in either news release. Despite the negative results–and the known risks–the ACC news release even included this quote:
“What’s nice about the wearable defibrillator is that it’s non-invasive and it’s not permanent,” Olgin said. “Based on our results, I think we’ll see more widespread use of this device in these patients.”
‘Expensive and burdensome’
This spin was alarming to John Mandrola, MD, a Kentucky cardiac electrophysiologist who has long been openly critical of the vest, also referred to as a WCD, or wearable cardiac defibrillator.
As he states in his column, “If this negative trial leads to more use of the WCD, I am afraid hype, marketing, and fear will have won out over critical appraisal. And that would be a sad day for medical science.”
He later shared a photo of an advertisement for the LifeVest that’s displayed over the escalators at the ACC meeting:
“This is ugly,” he tweeted. “Cardiologists ought to be offended and then stand against this nonsense. Shame on Zoll for not advertising the primary endpoint.”
Wouldn’t it be great if a safe and readily available plant could help curb opioid addiction?
There hasn’t been a lot of research on mitragyna speciosa, also known as kratom.
That’s the idea being promoted by a group called the American Kratom Association (AKA), which has been campaigning to block a federal ban of the Southeast Asian herb due to safety concerns.
The association — which won’t disclose its funding sources and has attempted to discredit government scientists as members of a “dark state” that’s out to protect prescription opioid makers — has been widely quoted in news stories.
It aggressively promotes the message that kratom is harmless and no more addictive than coffee, and could even be a solution to the opioid epidemic.
And it’s pushing an alarmist narrative that if access to kratom is restricted, users will be driven to a black market or to prescription opioids or heroin.
“If you ban kratom, people are going to die,” AKA Chairman Dave Herman recently told alternative medicine podcaster Robert Scott Bell. “You’re going to create a prohibition-style black market with adulterated product, people being forced back to opioids, people with guns out there running that industry.”
Wide coverage of unproven “potential”
There’s no reliable evidence that kratom can help addicts safely wean themselves off of heroin or prescription opioids, or that it offers any other therapeutic benefit, according to the FDA, which has issued a public health warning about its potential for addiction.
Nevertheless some new stories have echoed the AKA’s framing of the issue, that restricting kratom could be bad. Some examples:
One person who’s bothered by this unquestioning news coverage is Adriane Fugh-Berman MD, a professor of pharmacology and physiology at Georgetown University and director of Pharmed Out, a project that raises awareness of pharmaceutical company marketing practices.
She said journalists should be pushing back on the AKA’s unsubstantiated claims.
“It’s casting it as if these are two equal sides, when one is the PR side and one is the science side,” she said.
Addiction specialist and HealthNewsReview.org contributor Michael Bierer, MD, MPH, said promoting kratom as a first-line treatment for opioid addition strikes him as irresponsible. He noted that well-tested and robust therapies are available, another point that has been missing in some news stories.
“I always worry that unregulated, un-standardized products are risky,” he said via email.
With Fugh-Berman’s help, we came up with five ways coverage about kratom could be better.
Don’t rely on positive anecdotes from kratom users. Many stories highlighted people who claim the herb helped them kick their addictions to heroin or prescription opioids, but that’s not evidence of a benefit.
Positive patient testimonials abound in kratom coverage.said it
Kratom “probably is effective for helping opioid cravings because it’s an opioid,” Fugh-Berman said. Users are “deluding themselves into thinking they are getting off opioids.”
While the AKA claims on its web site that “kratom is not an opiate,” the FDA said it studied the herb’s chemical structure and determined that kratom is in fact an opioid because compounds in the plant bind to a person’s opioid receptors.
Dig into the available evidence. Human clinical trials on kratom are lacking. But one of Fugh-Berman’s graduate students, PharmedOut intern Jane Kim, found studies and clinical reports that challenge the the AKA’s safey claims.
For example, a 2014 study of 293 kratom users, funded by the Malaysian government and the World Academy of Sciences, reported that all claimed to be dependent on kratom, and a majority reported “severe Kratom dependence problems.”
It said many habitual Kratom users were unable to quit due to withdrawal symptoms such as sleeping problems and pain.
Put death reports in perspective. The AKA says “zero deaths” have occurred from kratom, while the FDA said 44 deaths involving kratom that have been brought to its attention.
Why the discrepancy? The AKA’s Herman told Rolling Stone: “The FDA is saying people died and they found kratom in their system. It’s like if I drank a Coke and got hit by a truck.”
But it’s quite possible that kratom was a contributing factor in some deaths because people may have taken kratom with other substances not realizing its effects, Fugh-Berman said. Kratom’s effects and how it interacts with other substances haven’t been well-studied.
Also, some news stories also haven’t explained that reporting deaths and other adverse events isn’t mandated, so only a tiny fraction reach the FDA’s attention. An uptick in the number of reports is considered a signal that there might be a wider problem.
Ask who’s paying. We haven’t seen any news stories mention the AKA’s lack of transparency about its funding. That’s a problem because while the AKA claims it’s advocating for average kratom users, it’s unclear whose interests it’s representing.
We’ve reported on the importance of journalists scrutinizing the funding sources of advocacy groups, since many are supported by industry. Recently there’s been a push to mandate disclosure of pharmaceutical company payments to nonprofits.
The AKA raised $1.04 million in 2016, the last year for which IRS records are available.
In response to our emails, a spokeswoman for the AKA declined to identify its major donors or say what percentage of its revenue comes from industry. She said more than 80% of donors are “average American kratom users” and the remainder are related to the kratom industry.
The AKA has used social media to discredit FDA scientists.
Cast a wide net for sources. Some of the strongest coverage has incorporated the views of experts outside the orbit of federal regulators or kratom advocates, who haven’t been widely heard.
The Chicago Sun-Times sought out Dan Bigg, head of the Chicago Recovery Alliance, which does outreach work with drug users. Bigg noted effective drugs such as methadone and buprenorphone are available to treat opioid dependence.
Washington, D.C.’s WUSA9 tapped psychiatrist George Kolodner, MD, who said he was treating two people for kratom addiction and noted its legality in most states “makes it attractive to some people.”
The Washington Post quoted Bertha K. Madras, PhD, a professor of psychobiology at Harvard Medical School, who said benefit claims are not scientifically substantiated. “I support the FDA on this,” Madras said. “I really believe they have taken a cautionary stance, which is to protect the American public.”
A recent op-ed published Monday in STAT insists that proposed FDA guidance for Alzheimer’s drug development is “good news” that “removes unnecessary barriers” to bring new medications to market.
FDA guidance for Alzheimer’s drugs: What’s not being said in the STAT op-ed?
If the guidance is finalized, pharmaceutical companies would no longer have to prove that their drugs impact the endpoints of “cognition and function” when tested on very early-stage patients. Instead, they’d only be required to show that their products positively affect “biomarkers” (which includes things like protein levels in the brain that are linked to the disease).
This change is vital, argues author Howard M. Fillit, MD, founding executive president of the Alzheimer’s Drug Discovery Foundation. In the op-ed, he states that requiring drugmakers to prove that their products improve cognition and function is “likely a contributing factor in the high rate of failure in Alzheimer’s trials.”
At first glance, the op-ed seems like an impassioned plea to modernize outmoded FDA guidance in the name of patient advocacy–what could be more important than helping Alzheimer’s patients get better drugs faster?
But digging deeper, we found the bigger picture is more muddled.
Author has industry connections
First, Fillit has industry connections that are more complex than the bio on his op-ed suggests. These connections should have been disclosed as part of STAT’s author agreement policy–but weren’t when the piece was published. Only after HealthNewsReview.org contacted the author on Thursday was the piece updated with an additional “editor’s note” disclosing that he’s accepted payments from at least nine drug companies.
Specifically, he has received thousands in fees directly from drugmakers over the years, and his foundation lists in its annual report several pharmaceutical donors with Alzheimer’s drugs under development. Yet his bio described him merely as the “founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation.”
The lack of disclosure of conflicts of interest is an ongoing issue with STAT opinion pieces, as we highlighted last summer.
Second, and not unrelated, the FDA’s proposed changes would likely be a financial boon to drugmakers. In effect, they’d no longer have to show their drugs actually work, pointed out Vinay Prasad, MD, an oncologist at Oregon Health and Sciences University who also researches general health policy, evidence-based medicine and medical reversals.
The change could be “a catastrophically foolish decision,” he said. “It means that you could theoretically be treating healthy people for years without any evidence that it’s actually improving anything.”
Geriatric psychiatrist Susan Molchan, MD, was less critical of the FDA guidance, stating that it appeared carefully worded, and included caveats, such as requiring drugmakers to continue to follow patients after approval to show that their drug works beyond simply affecting biomarkers.
Susan Molchan, MD
What was worrisome to her, though, was the agency’s growing reluctance to make sure that kind of follow-up happens.
“Companies are notorious for not completing the followup studies needed to show effectiveness post-approval,” said Molchan, a former clinical researcher with the National Institutes of Health. “And our increasingly worthless FDA [is] more and more lax on insisting they complete them, leaving worthless and dangerous drugs on the market.”
She also was troubled by Fillit’s insistence that the FDA’s standards were to blame for the failure of so many Alzheimer’s drugs.
“Fillit’s blaming of the FDA criteria for approval as ‘a contributing factor in the high rate of failure in Alzheimer’s trials’ is spoken like a true pharma company hack, to put it nicely,” she said in an email.
What about more advanced disease?
The FDA’s focus on biomarkers mostly applies to drug development for people with “stage 1 Alzheimer’s,” which is when the disease is nearly undetectable to the patient and healthcare providers, but, in theory at least, detectable with biomarkers. (As even the FDA admits, in the final paragraph of the guidance, “currently, there is no consensus as to particular biomarkers that would be appropriate to support clinical findings in trials in early AD.”)
For patients with stage 2 Alzheimer’s, which is detectable on cognition tests but often imperceptible to loved ones, the FDA guidance shifts somewhat, too. Less emphasis would be placed on making sure drugs improve functional impairment, such as completing everyday tasks. Instead, drugmakers would only have to show improvements in cognition, which is generally measured via a standardized test.
That’s not necessarily a win for patients, Prasad said.
“Improving your ability to solve a complex puzzle that may not have anything to do with real life is not making people better off,” he said.
As with early-stage research, the FDA seems to indicate that drugmakers would need to track the progress of stage 2 patients to see if, eventually, the focus on cognition does anything to halt the disease over time.
“That is measurable, and I would agree, reasonable,” Molchan said. “It would also take, optimistically, 5 years, but trials do go on for 5 years. The bigger the effect size of the drug, the more obvious it would be sooner.”
Roy Poses, MD, clinical professor of medicine at Brown University, agreed.
“To do a prevention trial right, it should be run long enough to detect whether treated patients have less progression of disease in terms of cognition or function than untreated patients,” he said via email. “Of course, doing such a trial would be more difficult and more expensive than simply doing a trial that used surrogate outcomes.”
Molchan also pointed out a reality the STAT op-ed did not: A single-minded focus on finding a blockbuster drug may backfire, and therefore addressing “non-drug interventions are important,” too, as discussed in this New England Journal of Medicine Perspective piece:
“In fact, population-based studies have convincingly demonstrated that the vast majority of dementia cases, especially those occurring very late in life, tend to involve a mixture of Alzheimer’s disease, vascular disease, and other degenerative factors. Research on preventing late-life dementias should explore ways of reducing risk factors at both the societal and the personal levels.”
‘It should have been disclosed to the reader’
It’s perhaps not surprising that the drawbacks around weakened drug standards weren’t brought up in the STAT op-ed. After all, the author works for a drug-research foundation that lists several pharmaceutical companies as donors, and he himself has received direct payments from a number of companies developing Alzheimer’s drugs.
Fillit told HealthNewsReview.org he didn’t disclose these relationships to STAT because the publication asks for “disclosures on organizations that are ‘referenced in the article or stand to benefit from this article’s publication.'”
“The First Opinion piece included no references to pharmaceutical companies or specific drug programs,” he said. “It was an opinion on a new FDA guideline, particularly as it impacts the development of new drugs for early stages of Alzheimer’s disease and the role of biomarkers.”
“Obviously, shifting standards for drug approval will have an impact on any drug getting approved. Seems simple and obvious,” Thacker, now an investigative reporter, said.
That’s why it’s so important that STAT carefully vet their authors and disclose conflicts of interest. Adding in Fillit’s industry connections — retrieved within seconds via the Open Payments database — helps readers see the forest for the trees.
“Given his undisclosed conflicts of interest, and the undisclosed institutional conflicts of interest of the foundation he runs, there is a concern that he may be excessively sympathetic to the financial interests of industry, and that may have somehow influenced him to be so enthusiastic about surrogate variables [such as biomarkers],” Poses said.
STAT’s first-rate news operation offers a model for how journalists can proactively identify conflicts of interest and provide this critical context to readers. Earlier this week, in fact, STAT contributors reported on a study detailing millions of dollars in undisclosed payments to the authors of a popular medical textbook.
And yet, the First Opinion commentary section repeatedly fails to apply such scrutiny to articles running under the STAT banner. Thacker, who has written for First Opinion, said that the author agreement was one of the best he’s ever seen and he commends the publication for trying to improve.
“But while they are trying, they keep messing up,” he said.
“I don’t think this case is as egregious as some of the others, but it’s still problematic,” said Charles Seife, a journalism professor at New York University, in an email. “The whole issue essentially boils down to hidden financial influences over a person’s writing. …In this case, STAT got part of the way there. Disclosing that Fillet was a major force behind an Alzheimer’s research advocacy organization gives some sense of the potential issues.
“But the fact that Fillet was taking money from a number of drug companies whose Alzheimer’s pipelines were supposedly damaged by these FDA regulations, well, that’s a much more direct potential avenue of influence. It should have been disclosed to the reader.”
Until STAT updated the piece four days after it was first published, there was no such disclosure. This means readers could have come away thinking that these proposed FDA changes must happen–that they represent progress, at least from the mindset of a concerned doctor who knows a lot about these things.
But, is it progress for patients, or progress for shareholders? As we’ve seen time and again, it’s often the latter.