Thursday, April 12, 2018

NIH Director Grilled at Appropriations Hearing About NIAAA Collusion with Alcohol Industry

At the House Appropriations Committee hearing on the NIH Budget, NIH director Dr. Francis Collins was grilled about the collusion between the NIAAA and the alcohol industry in planning a clinical trial to study the health benefits of alcohol use. Congresswomen Lucille Roybal-Allard (D-CA) expressed concern about the fact that NIAAA violated NIH policy by soliciting funding from the alcohol companies and asked Dr. Collins who authorized the solicitation of funding. While Dr. Collins did not answer the question, he did say that his office is conducting an investigation and will provide the Inspector General with any uncovered materials that are of concern.

The questioning begins at 51:30 of the video.

Sunday, April 08, 2018

Principal Investigator of Alcohol Clinical Trial is Hiding its Industry Funding from the Public and Potential Research Subjects

I have already explained why I think the Moderate Alcohol and Cardiovascular Health (MACH15) clinical trial should be immediately halted because of both scientific and ethical breaches in the way the research was planned. Today, I reveal what I believe is misconduct in the actual conduct of the trial: namely, in the communication of the research sponsors to the public.

I believe that the public -- and especially research subjects -- have the right to know who is funding a clinical trial that is seeking their participation. In fact, there are rules requiring the sponsors of such studies to be revealed to the public. However, I believe the MACH15 study is violating these principles by hiding its true sponsors from the public.

The Rest of the Story

On the study web site, the study sponsor is reported as being the "National Institute on Alcohol Abuse and Alcoholism (NIAAA)." However, nowhere on the site does it disclose that the real sponsor behind the research are alcohol companies, which have ponied up to cover two-thirds of the cost of the entire research project. The alcohol money is being funneled through a "middle man" (the NIH Foundation) on its way to NIAAA, but the source of the money is clear: this is an alcohol industry-funded study. In violation of ethical principles for the conduct of research, this critical information is not being disclosed to the public on the project web site.

Therefore, I am calling both the Department of Health and Human Services (through the Inspector General) and Congressional oversight committees to require the study researchers to disclose to the public and potential participants that this study is being funded by the alcohol industry.

This is too reminiscent of the unethical behavior of tobacco-funded researchers in the past who failed to disclose the industry funding of their research. In fact, it was this behavior that contributed heavily to the implementation of conflict of interest disclosure rules.

The rest of the story is that the principal investigator of the MACH15 trial is hiding from the public the fact that this is an industry-funded study. I believe the trial should be halted, but if it is allowed to continue, the researchers should be forced to disclose the industry funding to the public and to any potential research participants.

Sunday, April 01, 2018

Alcohol Clinical Trial Should be Halted Because It Was Designed to Promote Drinking, Not to Answer a Research Question

Digging Deeper into the Harvard/NIAAA Solicitation of Alcohol Company Funding

In a previous post, I noted that I had reviewed materials obtained by the New York Times and shared with me for the article revealing that the NIAAA solicited funding from alcohol companies for the clinical trial of potential benefits of alcohol. A deeper examination of those materials allows me to now reveal that the real purpose of the clinical trial is not to conduct research to answer a question, but to help the alcohol industry sell beer, wine, and liquor by producing newspaper headlines to get doctors to start recommending moderate drinking to their patients.

The document I reviewed is a slide presentation and accompanying summary information apparently intended for a sales pitch to alcohol companies to fund this clinical trial. According to the New York Times: "two prominent scientists and a senior federal health official pitched the project during a presentation at the luxurious Breakers Hotel in Palm Beach, Fla., in 2014." The lead scientist on the "presentation team" was Dr. Kenneth Mukamal, who is now the Principal Investigator of the clinical trial. The senior federal health official on the "presentation team" was Dr. Lorraine Gunzerath, the Senior Advisor to the Director of the NIAAA.

Importantly, according to the New York Times, Dr. Gunzerath stated that this research would not have been conducted without the support of the alcohol companies because "We were supposed to be preventing alcoholism, so to spend that kind of money on research for a possible good use of alcohol was something that would never fly."

Also, according to a previous New York Times article: "Dr. Mukamal, who has published dozens of papers on the health benefits of alcohol consumption, said he was not aware that alcohol companies were supporting the trial financially. “This isn’t anything other than a good old-fashioned N.I.H. trial,” he said. “We have had literally no contact with anyone in the alcohol industry in the planning of this.”"
Based on this information, it appears that we already have three areas of misconduct in this research study before the trial itself has even been initiated:

1. The NIAAA violated NIH policy by soliciting funding from the alcohol industry. The NIH policy does not allow institutes to solicit funding. (NIH Policy Manual 1135 [Gifts Administration] - "NIH policy prohibits employees, either directly or through another party, from requesting or suggesting donations to the NIH or to any of its components, of funds or other resources intended to support activities.")

2. The NIAAA also violated NIH policy by accepting funding for a study that would not have been conducted were it not for the alcohol company money. Institutes of the NIH may accept a contribution, but only to conduct research that is either already underway or that would have been conducted even in the absence of that contribution. (NIH Policy Manual 1135 [Gifts Administration] - "the NIH may accept a gift to support a mission-related priority if it is already conducting the activity or is prepared to conduct the activity even without the gift. However, the NIH is precluded from accepting a gift to support an activity that would not be conducted but for the gift and thereby reorders the programmatic priorities of the agency and diverts the use of appropriated dollars from activities with higher priorities.")

3. The trial's principal investigator appears to have lied about not knowing that alcohol companies were supporting the trial and "literally" not having had any contact with alcohol companies.

The Rest of the Story

These facts alone are sufficient to warrant an immediate halt to the clinical trial. But today, I am revealing that the story gets even worse.

The stated purpose of the clinical trial, according to the presentation materials, was not to conduct an impartial investigation into the health effects of moderate drinking, but to produce newspaper headlines that would get doctors to recommend that their patients start drinking. Here is how the primary aim of the research was described:

"The proposed clinical trial is designed to provide doctors with the scientific/medical justification to incorporate a moderate drinking recommendation into their advice to patients."

To execute the sales pitch, the presentation includes a slide entitled "The Ultimate Goal." What is the ultimate goal? The slide shows three newspaper headlines touting the health benefits of an olive oil diet and a Mediterranean diet. Apparently, the ultimate goal is to generate news headlines reporting that moderate drinking is part of a health diet.

In another slide, entitled "The Bottom Line," the presentation again explains that the primary purpose for the study is to "convince clinicians, patients, and policymakers that alcohol consumption in moderation is safe and a healthy part of diet..."

Yet another slide emphasizes that "What's missing" is "the type of convincing evidence that will show that moderate drinking is: 1) Safe 2) Part of a healthy diet to lower risk of common, important health problems. How do we do that?"

The rest of the story is that beyond even the violation of NIH policies and the ethical breaches committed in the planning of the study, the trial is scientifically compromised from the start because the researchers have essentially promised positive results to the alcohol industry, have demonstrated a substantial bias that undermines the objectivity of the study, and have stated that its purpose is not to answer a research question objectively but to provide the opportunity for newspaper headlines in order to convince doctors to start recommending moderate drinking to their patients.

That's a great sales pitch, and it's no surprise that it worked. If I were running an alcohol company, I would have been in on this marketing investment all the way. That the federal government -- and the nation's leading alcohol research agency to boot -- is offering this marketing opportunity is disillusioning.

Sunday, March 25, 2018

Congressional Investigation Needed into Scientific and Ethical Corruption at NIAAA

I used to think of the National Institutes of Alcohol Abuse and Alcoholism (NIAAA) as a highly-reputed, objective, science-based agency whose primary goal was to reduce alcohol consumption to improve the public’s health. The scientific integrity of the NIAAA is critical, as it describes itself as “the largest funder of alcohol research in the world.” The agency is funded by taxpayers to the tune of $480 million a year.

But then one day, all of that changed. On January 16, 2015, I was called into the office of the Director of NIAAA and was essentially reprimanded for conducting NIAAA-funded research that was detrimental to the alcohol industry. My NIAAA grant was focused on studying alcohol marketing and its possible link to underage youth drinking behavior. We identified the brands of alcohol that underage youth are consuming and found that their brand choices were related to their brand-specific advertising exposure. At the meeting, I was told that I would never again be funded to conduct research on alcohol marketing, regardless of how highly my research proposal was scored by the scientific review panel.

I later found out that the NIAAA director had extensive contact with the alcohol industry and that he promised the Distilled Spirits Council that this type of research would never be funded again: “For the record. This will NOT happen again. … I will NOT be funding this type of work under my tenure.”

Not only had the NIAAA director privately told an alcohol lobbying group that his agency would never fund research on alcohol marketing, but he then went on to participate in the industry’s marketing activities himself by appearing in a promotional video (at 3:17) for Anheuser-Busch InBev, creating the impression that the NIAAA is endorsing the alcohol company and its programs, which is a violation of NIH policy. The true purpose of the video is revealed at 3:42, when an Anheuser-Busch Global Advisory Council reveals the company's aspiration: "We're no longer a neighborhood's beer or a country's beer. We're in fact a corporation representing the world."

Finally, the truth about the relationship between the NIAAA and the alcohol industry has come out. In a New York Times article published last Saturday, Roni Caryn Rabin revealed that the NIAAA actually solicited funding from alcohol companies to conduct a study to demonstrate the “benefits” of alcohol consumption and industry officials were essentially promised positive results.

The Times reported having obtained slides from a presentation by a Harvard researcher to alcohol executives in which he makes a pitch for funding to study the health benefits of alcohol. The NIAAA apparently facilitated the meeting, at which a senior agency official was present. In the slides, the researcher suggests that the study could result in newspaper headlines reporting that alcohol is now part of a healthy diet. Promising positive results before even initiating a study and pitching the study based on its potential economic benefits to the industry violate standards of scientific integrity.

The NIAAA’s solicitation of donations for this research from the alcohol industry was a clear violation of NIH policy, not only because NIH officials are not allowed to solicit donations, but also because they are not allowed to accept funding for a study unless the agency would conduct the research even without the donation. However, a former NIAAA official apparently admitted to telling alcohol industry executives that “the research could not be done without their support.”

The story gets worse. The principal investigator of the study apparently lied about having met with the alcohol industry. In a July 2017 New York Times article, he was quoted as stating: “We have had literally no contact with anyone in the alcohol industry in the planning of this.” However, his name is on a presentation delivered directly to alcohol companies to convince them that they had “a unique opportunity to show that moderate alcohol consumption is safe and lowers risk of common diseases.”

Apparently, the director of NIAAA was also dishonest, as he appears to have told the New York Times that the NIAAA did not solicit alcohol industry funds. This conflicts with the testimony of at least two high-level NIAAA officials—one of whom was the former director—who admitted that the meetings between NIAAA and the alcohol companies were “to determine if they had interest in taking part” as funders.

In fact, the advisor to the former NIAAA director apparently recognized that studying the benefits of alcohol was not even within the scope of legitimate NIAAA research: “We were supposed to be preventing alcoholism, so to spend that kind of money on research for a possible good use of alcohol was something that would never fly.” This is why it was so essential for the agency to convince the alcohol industry to fund the clinical trial.

The solicitation was successful. The NIAAA is now funding a $100 million clinical trial—largely funded by alcohol companies— designed to demonstrate the health benefits of alcohol, and the principal investigator is the researcher who gave the presentation.

Even if the study were a legitimate use of agency funds, it would still be inappropriate because many of its primary investigators have substantial financial conflicts of interest with the alcohol industry. At my institution, such researchers would not even be allowed to be involved in a clinical trial in which they have a significant conflict of interest. Our general policy is that an investigator with a significant conflict of interest cannot conduct a clinical trial on a product made by the relevant company. We do allow conflicted investigators to conduct pre-clinical studies, such as laboratory research; however, the line is drawn definitively at the level of a clinical trial. Thus, the NIAAA also appears to be violating the NIH conflict of interest policy.

Finally, the study itself is misguided and a waste of money. Even if it were to find that moderate drinking can reduce heart disease risk, it would still not be clear that recommending that people who don’t drink start to drink is warranted. Alcohol is a known carcinogen that causes breast cancer even when consumed in extreme moderation. Recommending that people consume a known carcinogen is not something that we do in public health.

In short, the NIAAA is assisting the alcohol industry in a marketing ploy to increase the sales of its products. The research has no scientific integrity and is tainted from the start. Its principal investigator solicited money from the industry and boasted of a positive outcome before the research was even started. Multiple NIH policies have been violated in the planning of the research alone.

That the NIAAA was involved in this corruption is inexcusable. This behavior risks damaging not only the reputation of the alcohol institute, but of the entire NIH. Congress should initiate an investigation immediately to protect the scientific integrity of federal health research. Further, it is imperative that this clinical trial be immediately halted on both scientific and ethical grounds.

Disclosure: I was a recipient of a grant from the NIAAA for a project to study the effects of brand-specific alcohol advertising on youth alcohol brand consumption (R01 020309 – September 20, 2011 through June 30, 2015).

Monday, February 26, 2018

New Study Concludes that Vaping Causes Heart Attacks

A new study presented Saturday at the annual meeting of the Society for Research on Nicotine and Tobacco (SRNT) concludes that vaping causes heart attacks, increasing the heart attack risk for dual users beyond that of smoking alone. The research has not yet been published but was presented as a poster at the conference.

The study was a cross-sectional analysis of nearly 70,000 respondents to the combined 2014 and 2016 National Health Interview Surveys (NHIS), a nationally representative survey of health risk factors and outcomes in U.S. adults. Respondents were asked to report their current vaping and smoking statuses and to report whether they had ever had a heart attack. The researchers found that there was a significant association (odds ratio = 1.8) between daily e-cigarette use and having experienced a heart attack. The analysis controlled for level of current cigarette use.

Based on this observation, the study concludes that daily e-cigarette use doubles the risk of heart attacks.

The Rest of the Story

Hold your horses.

Before accepting the conclusion that vaping causes heart attacks in unsuspecting smokers, remember the old adage: correlation does not equal causation. This study is a perfect demonstration of that phenomenon.

Because this is a cross-sectional study, and because respondents were asked whether they had ever had a heart attack, one cannot determine whether the heart attacks followed e-cigarette use or preceded it. In other words, we do not know that vaping preceded the heart attack for any of the subjects. It is entirely possible that in most of these cases, the smokers suffered a heart attack and then started vaping in an attempt to quit smoking. In fact, I believe that is the most likely explanation for the observed study findings.

It is not even biologically plausible that vaping could increase the risk of cardiovascular disease beyond that of smoking. Why? Because the cardiovascular effects of tobacco smoke saturate at a very low level, meaning that it takes only a little exposure to increase your risk. But beyond that, there is little additional risk.

On the other hand, it is quite plausible that smokers make quit attempts after experiencing a heart attack and that in recent years, these quit attempts have often involved the use of e-cigarettes.

It is true that many of the adverse effects of smoking were first observed in cross-sectional studies. However, these were followed up with longitudinal studies that confirmed the findings. Before we reach a conclusion on whether vaping poses a heart attack risk, we need longitudinal studies. This single cross-sectional study is not enough because there is no way to tell the direction of the observed association between current use of e-cigarettes and having experienced a heart attack in the past.

Although I question the validity of the study's conclusions, it is still important to emphasize that smokers who use e-cigarettes should aim to quit smoking completely. The full health benefits of vaping will not accrue to smokers unless they quit smoking completely. Dual use - if the cigarette consumption drops substantially - will reduce respiratory disease risks, but it will not reduce cardiovascular disease risk because of the saturation phenomenon noted above.

Wednesday, January 24, 2018

WBUR Interview Regarding National Academy of Sciences E-Cigarette Report

Here is the link to an article on WBUR that includes edited excerpts from an interview I did regarding the new National Academy of Sciences report on electronic cigarettes.

National Academy of Sciences Report on Electronic Cigarettes Confirms that Vaping is Much Safer than Smoking and Has No Known Long-Term Health Effects

My commentary on the conclusions and implications of the National Academy of Sciences report on electronic cigarettes was just accepted as an op-ed piece in U.S. News & World Report. I expect it to be published tomorrow. For this reason, I have had to take down the original commentary. However, below I have posted the parts of the original blog post that had to be cut from the op-ed because of length concerns. Also, I will post a link to the op-ed as soon as it appears.

The key findings of the report are:

1. "There is substantial evidence that except for nicotine, under typical conditions of use, exposure to potentially toxic substances from e-cigarettes is significantly lower compared with combustible tobacco cigarettes."

2. "There is conclusive evidence that completely substituting e-cigarettes for combustible tobacco cigarettes reduces users’ exposure to numerous toxicants and carcinogens present in combustible tobacco cigarettes."

3. "There is moderate evidence that risk and severity of dependence are lower for e-cigarettes than combustible tobacco cigarettes."

4. "There is moderate evidence that second-hand exposure to nicotine and particulates is lower from e-cigarettes compared with combustible tobacco cigarettes."

5. "There is no available evidence whether or not e-cigarette use is associated with clinical cardiovascular outcomes (coronary heart disease, stroke, and peripheral artery disease) and subclinical atherosclerosis (carotid intima media-thickness and coronary artery calcification)."

6. "There is insufficient evidence that e-cigarette use is associated with long-term changes in heart rate, blood pressure, and cardiac geometry and function."

7. "There is no available evidence whether or not e-cigarette use is associated with intermediate cancer endpoints in humans. This holds true for comparisons of e-cigarette use compared with combustible tobacco cigarettes and e-cigarette use compared with no use of tobacco products."

8. "There is no available evidence whether or not e-cigarettes cause respiratory diseases in humans."

9. "There is limited evidence for improvement in lung function and respiratory symptoms among adult smokers with asthma who switch to e-cigarettes completely or in part (dual use)."

10. "There is limited evidence for reduction of chronic obstructive pulmonary disease (COPD) exacerbations among adult smokers with COPD who switch to e-cigarettes completely or in part (dual use)."

11. "While the overall evidence from observational trials is mixed, there is moderate evidence from observational studies that more frequent use of e-cigarettes is associated with increased likelihood of cessation."

12. "There is substantial evidence that e-cigarette use increases risk of ever using combustible tobacco cigarettes among youth and young adults."

13. "There is conclusive evidence that, other than nicotine, the number, quantity, and characteristics of potentially toxic substances emitted from e-cigarettes is highly variable and depends on product characteristics (including device and e-liquid characteristics) and how the device is operated."

The Rest of the Story

I agree with all of the above conclusions, other than #12, which is not wrong on its face but needs careful interpretation.

Therefore, let me say a few words about conclusion #12 above ("There is substantial evidence that e-cigarette use increases risk of ever using combustible tobacco cigarettes among youth and young adults"). It is true that youth who experiment with e-cigarettes are more likely to also experiment with tobacco cigarettes and therefore, to become smokers. It would be shocking if this were not the case because we know that youth who experiment with one risky behavior are more likely to experiment with other risky behaviors. But this doesn't necessarily mean that the experimentation with e-cigarettes is causing the youth to start smoking.

For example, there probably are not many kids who use heroin who have never taken a sip of alcohol. If you did a study, you would find that alcohol use is associated with later use of heroin. But this doesn't support the conclusion that experimenting with alcohol causes kids to become heroin junkies. It simply reflects the fact that kids who take huge health risks are more likely to already have taken smaller health risks. A youth is not going to decide to rebel one day by injecting a drug into their veins. The rebellion process would likely start with a less hazardous behavior, such as taking a toke on a cigarette and then for a very small number of kids, they would end up progressing to hard drug use.

So the important question is not whether youth who experiment with e-cigarettes are more likely to end up smoking (of course they are!), but instead, whether youth who experiment with e-cigarettes are more likely to become addicted to vaping and then be led to smoking addiction, such that without having become addicted to vaping, they unlikely would have become smokers. So far, the evidence suggests that this is not the case: very few youth have been identified who started as nonsmokers, became regular vapers, and then progressed to smoking.

Sunday, January 07, 2018

International Scientific Forum on Alcohol Research (ISFAR) is Still Hiding Conflicts of Interest of Its Members

The International Scientific Forum on Alcohol Research (ISFAR) claims to be "an independent organization of scientists that prepares critiques of emerging research reports on alcohol and health." The Forum describes itself as "an international group of invited physicians and scientists who are specialists in their fields and committed to balanced and well researched analysis regarding alcohol and health." It is "a joint undertaking of Boston University School of Medicine in the United States and Alcohol in Moderation (AIM) of the United Kingdom. Its Co-Directors are R. Curtis Ellison, MD, Professor of Medicine & Public Health, Boston University School of Medicine, and Helena Conibear, Executive Director, Alcohol-in-Moderation (AIM), UK."

The Rest of the Story

About a year and a half ago, I reported that ISFAR was hiding its conflicts of interest with Big Alcohol. At that time, ISFAR published a scathing review of a meta-analysis which concluded that moderate alcohol consumption does not reduce mortality as previously thought. The review contained statements from 14 members of ISFAR, and every one of the 14 blasted the study, with the review concluding that the study "markedly distorts the accumulated scientific evidence on alcohol and CVD [cardiovascular disease]."

It turns out that five of the Forum members who reviewed the article had conflicts of interest by virtue of either their having received research funding from the alcohol industry or serving on advisory boards of alcohol industry-funded organizations, yet none of these conflicts were disclosed.

Not only did ISFAR hide its conflicts of interest with alcohol companies on its web site, but it also hid these conflicts in a public interview.

More recently, one of the Forum members and reviewers was forced to publish a correction to a journal article because he failed to disclose that he is a beer industry consultant.

Has ISFAR reformed itself, and is it now disclosing the conflicts of interests of the reviewers who write its critiques?

The answer, unfortunately, is no.

Nowhere on its website does it list the specific conflicts of interest of its members/reviewers. Nowhere in its critiques does it disclose these conflicts of interest. And to top it all off, the biographies provided for its members do not disclose their conflicts of interest.

For example, Dr. de Gaetano's bibliography fails to disclose that he consults for the beer industry -- the precise conflict of interest for which he was forced to publish a correction in the Journal of the American College of Cardiology.

Dr. Estruth's biography states that he is a member of the Advisory Board for "ERAB." The reader is not told what ERAB stands for, hiding from the public the fact that ERAB is "supported by The Brewers of Europe, the voice of the brewing industry in Europe, whose members are the national brewing trade associations, representing more than 90% of European beer production."

Ms. Stockley's biography states that she works for the Australian Wine Research Institute, which it states is "an independent, not-for–profit research institution." But it hides the fact that this Institute is funded by the alcohol industry. Far from being independent, the Australian Wine Research Institute is actually the "wine industry’s own research organisation."

Dr. Teissedre's biography fails to disclose that his research group received alcohol industry funding.

Dr. Waterhouse's biography hides the fact that he has received alcohol industry research funding.

Dr. Skovenborg's biography fails to disclose that he was on the Board of ERAB, which is funded by the alcohol industry.

Dr. Mattivi's biography fails to disclose that he has received alcohol industry research funding.

Dr. Klatsky's biography fails to disclose that in the past, he received alcohol industry funding.

Dr. Lanzmann-Petithory's biography fails to disclose that in the past, she has received alcohol funding.

Dr. Gretkowsky's biography fails to disclose that in the past, she has received alcohol funding.

So of the supposedly "independent" and "balanced" reviewers, at least 10 of them have conflicts of interest with the alcohol industry that are not disclosed on the web site, even in their own biographies.

Unfortunately, ISFAR continues to be essentially an industry front group that is providing highly biased reviews without readily disclosing the intricate details of the financial connections of many of its reviewers to the alcohol industry.

They should not fool anybody any longer. The time to end this scam operation is now. Especially in a period in which the federal government has basically tossed scientific objectivity out the window.

Sadly, what ISFAR is doing bears a strong resemblance to the fraudulent public relations activities of the tobacco industry many years ago. 

On a personal note, I feel somewhat ashamed that the Boston University School of Medicine has been playing a role in this scam, as ISFAR has been hosted, in part, by our medical center.

On a larger note, this story illustrates why the alcohol industry-funded NIAAA study of the potential cardiovascular benefits of moderate drinking is so problematic. The background research that informs the study is tainted by serious conflicts of interest. But the worst is yet to come -- as I will reveal shortly, the research is not an objective attempt to get at the answer to this research question.