Conflicts of Interest and Fraud in Medical Research | Chris Kresser
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Behind the Veil: Conflicts of Interest and Fraud in Medical Research

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Recent reports have revealed that conflicts of interest and research fraud are rarely reported in the scientific literature or announced to the general public, which raises questions about the integrity of clinical trials and the reliability of public agencies like the FDA and CDC.

Medical conflict of interest
Medical conflicts of interest are more prevalent than we think. zest_marina/iStock/Thinkstock

In this article, I’m going to discuss two other reasons that the public mistrusts scientific research: fraud, and conflicts of interest.

Why conflicts of interest and fraud harm the public’s trust of medical research.

Fraud in Medical Research: “Out of Sight, out of Mind, and out of the Peer-Reviewed Literature”

A large part of the subtitle above comes directly from a paper published in JAMA Internal Medicine, authored by Charles Seife. (1) In short, Seife discovered that clinical trial data determined to be fraudulent or mishandled by the FDA is rarely excluded from research studies published in scientific journals.

One of the FDA’s roles in the drug approval process is to inspect clinical trial sites to determine whether these sites are complying with FDA regulations. A typical inspection might involve auditing the records of the site, verifying that investigators adhered to the trial protocol, and comparing an investigator’s notes in hospital records with data reported to the study sponsor to ensure that there aren’t any discrepancies.

If there is a violation, the FDA classifies it in one of two ways: Voluntary action indicated (VAI) means the inspectors have found violations, but the problems aren’t serious enough to require sanction. Official action indicated (OAI) means that the inspectors have found violations significant enough to warrant official action.

Siefe and his assistants used the Freedom of Information Act to request information from the FDA, and supplemented that data with Google searches of the FDA database. They found 57 clinical trials that were directly linked to an OAI inspection.

The misconduct identified by the FDA in these cases included:

  • Falsification or submission of false information
  • Underreporting of adverse events
  • Failure to follow the investigational plan or other violations of protocol
  • Inadequate record keeping
  • Failure to protect the rights, safety, and welfare of patients
  • Use of experimental compounds in patients not enrolled in trials
  • Failure to supervise clinical investigations properly

The 57 trials Seife identified were in turn linked to 78 research articles published in the peer-reviewed scientific literature. 96 percent of these articles failed to mention the violations identified by the FDA inspection—despite the fact that in the majority of cases the inspection was completed at least 6 months before the article was published.

Doctors, researchers, and other health professionals rely on scientific studies to establish treatment protocols and public health policies. If the data in some of these studies are fraudulent, but the doctors and researchers have no way of knowing that, the decisions they make may be unsound and even put people at unnecessary risk.

I’d like to make the significance of these omissions even more clear by sharing a couple of examples mentioned in Seife’s paper.

One case involved a researcher who falsified lab test results to hide a patient’s impaired kidney and liver function in a trial comparing two chemotherapy regimens. The first dose of the regimen proved to be fatal to this patient, and the researcher was sentenced to 71 months in prison. Despite this episode being described in both FDA and court documents, not one of the studies in the peer-reviewed literature associated with the chemotherapy trial have any mention of the falsification, fraud, or homicide.

Another case involved a clinical site in China participating in a large trial of apixaban, an anticoagulant (i.e. anti-clotting) drug. The FDA determined that this trial site had altered patient records and falsified data. If the data from this site had been excluded, the mortality benefit for the drug would have disappeared. In other words, the “proof” that this drug saved lives was dependent on this fraudulent data. Yet none of this discussion appears in the scientific literature. In fact, studies since 2011 have consistently relied on the full data set (including the fraudulent data from the China trial site), and this was even true for an article published nearly 18 months after the fraud was discovered.

How can such egregious cases of fraud and misconduct go unreported in the scientific literature and in the media? The answer is almost hard to believe. The FDA does not notify journals when a site participating in a clinical trial receives an OAI inspection, nor does it typically make any announcement which would alert the media and general public to the issues it identified.

What’s more, the documents the FDA produces about these OAI inspections are heavily redacted, which makes it extremely difficult even for researchers like Seife who’ve invoked the Freedom of Information Act to determine which published clinical trials are tainted by misconduct. The FDA redacts these documents because it considers the identity of the drug company involved in the trial to be “confidential commercial information” that it is bound to protect.

In other words, the FDA appears to believe that it’s more important to protect private, commercial interests than it is to protect public health.

Seife’s says as much in the conclusion of his paper:

However, failing to notify the medical or scientific communities about allegations of serious research misconduct in clinical trials is incompatible with the FDA’s mission to protect the public health. Such allegations are relevant to include in the peer-reviewed literature on which physicians and other medical researchers rely to help them choose treatments that they offer to patients and other research participants.

The issues highlighted here raise serious concerns not only about the trustworthiness of the data in clinical trials and published research, but the reliability and motives of the agencies tasked with protecting public health.

Which takes us to the second reason that public mistrust of scientific research is sometimes well-founded: conflicts of interest.

Conflicts of Interest in Research Are Common—and Often Unreported

In my article about the disconnect between scientists and the public, I mentioned that two-thirds of medical research is sponsored by drug companies, and industry-sponsored trials are more likely to report favorable results for drugs because of biased reporting, biased interpretation, or both. (2) This is a well-established phenomenon, and it has been explored in both the media and the scientific literature:

Is it really a big surprise that the source of funding influences study results? After all, as Upton Sinclair famously said, “It’s difficult to get a man to understand something, when his salary is dependent upon him not understanding it.” The time-honored saying “don’t bite the hand that feeds you” also applies here.

Unfortunately, just as research misconduct and fraud is often not reported, conflicts of interest in academic research are rarely disclosed. According to a 2009 report issued by the Department of Health and Human Services, very few universities make required reports to the government about the financial conflicts of interest of their researchers—and even when they are reported, the universities rarely require those researchers to eliminate or reduce these conflicts.

In fact, 90 percent of universities relied solely on the researchers themselves to decide whether to report their potential conflicts of interest, and half of universities don’t even ask their faculty to disclose the amount of money or stock they make from drug or device makers.

This isn’t likely to change anytime soon, according to Eric G. Campbell, an associate professor at Harvard Medical School that was quoted in this New York Times article covering the report. He said that “universities had no interest in putting real limits on the incomes of their star researchers for fear that those researchers would leave for institutions with fewer restrictions.”

But conflicts of interest aren’t just a problem in academia; they’re also a problem on expert advisory panels that influence public health policy. For example, back in 2008 Dr. John Briffa linked to a web page disclosing the conflicts of interest in members of the National Cholesterol Education Program, a government organization that creates the official blood cholesterol target values for the U.S..

Are you ready for this? 8 out of the 9 doctors on the panel had direct ties to statin drug manufacturers. Here’s the complete list, excerpted from a post written by Dr. Stephan Guyenet in 2008 (the companies in bold are statin manufacturers):

Dr. Grundy has received honoraria from Merck, Pfizer, Sankyo, Bayer, Merck/Schering-Plough, Kos, Abbott, Bristol-Myers Squibb, and AstraZeneca; he has received research grants from Merck, Abbott, and Glaxo Smith Kline.

Dr. Cleeman has no financial relationships to disclose.

Dr. Bairey Merz has received lecture honoraria from Pfizer, Merck, and Kos; she has served as a consultant for Pfizer, Bayer, and EHC (Merck); she has received unrestricted institutional grants for Continuing Medical Education from Pfizer, Procter & Gamble, Novartis, Wyeth, AstraZeneca, and Bristol-Myers Squibb Medical Imaging; she has received a research grant from Merck; she has stock in Boston Scientific, IVAX, Eli Lilly, Medtronic, Johnson & Johnson, SCIPIE Insurance, ATS Medical, and Biosite.

Dr. Brewer has received honoraria from AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Esperion, and Novartis; he has served as a consultant for AstraZeneca, Pfizer, Lipid Sciences, Merck, Merck/Schering-Plough, Fournier, Tularik, Sankyo, and Novartis.

Dr. Clark has received honoraria for educational presentations from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer; he has received grant/research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Merck, and Pfizer.

Dr. Hunninghake has received honoraria for consulting and speakers bureau from AstraZeneca, Merck, Merck/Schering-Plough, and Pfizer, and for consulting from Kos; he has received research grants from AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, and Pfizer.

Dr. Pasternak has served as a speaker for Pfizer, Merck, Merck/Schering-Plough, Takeda, Kos, BMS-Sanofi, and Novartis; he has served as a consultant for Merck, Merck/Schering-Plough, Sanofi, Pfizer Health Solutions, Johnson & Johnson-Merck, and AstraZeneca.

Dr. Smith has received institutional research support from Merck; he has stock in Medtronic and Johnson & Johnson.

Dr. Stone has received honoraria for educational lectures from Abbott, AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Merck/Schering-Plough, Novartis, Pfizer, Reliant, and Sankyo; he has served as a consultant for Abbott, Merck, Merck/Schering-Plough, Pfizer, and Reliant.

Another 2009 report, also from the Department of Health and Human Services, revealed similar issues with expert panels that advise the Centers for Disease Control (CDC) on vaccine safety. The report found that 64 percent of experts who served on advisory panels in 2007 to evaluate vaccines for flu and cervical cancer had potential conflicts of interest that were never identified or resolvedThe report also revealed that the CDC failed nearly every time to ensure that experts adequately disclosed that they were being paid by vaccine manufacturers.

Can you see how these conflicts of interest might be a problem, when the advisory committees mentioned above strongly influence the sales of both statin drugs ($30 billion a year) and vaccines ($20 billion a year)? 

Sadly, these financial relationships between experts who influence or formulate guidelines and drug companies whose drugs are being considered are not the exception, they’re the rule. A study published in JAMA shows that 59 percent of the experts participating in guideline creation have such financial ties. (3)

Another related problem is the “revolving door” between public agencies like the CDC and FDA or institutions like the U.S. Congress, and pharmaceutical companies. A year after leaving her position as the director of the CDC in 2009, Dr. Julie Gerberding took a position as president of Merck Vaccines. Another former CDC employee, Dr. Thomas Verstraeten, took a position with GlaxoSmithKline (a vaccine manufacturer) while he was still involved in completing a major study on the possible negative side effects of thimerosal (a mercury-containing compound used in some vaccines) at the CDC. Finally, over half of the lobbyists employed by the pharmaceutical industry in 2008 had worked in Congress or another branch of the federal government, and 35 had been former members of Congress. (4)

These conflicts of interest do not necessarily lead to fraud or misconduct. There are surely many honest and unbiased researchers and physicians investigating controversial topics like cholesterol targets and statin drugs, vaccines, and genetically-modified foods. However, studies have confirmed what common sense and an understanding of human nature would also suggest: conflicts of interest can and do influence both individuals and institutions. For example, the financial interests of researchers are positively associated with outcomes favorable to the sponsor in medical studies, and research institutions can be influenced by industry sponsorships such as grants, endowed chairs, and other gifts. (5, 6, 7, 8)

Concluding Thoughts

My purpose here is not to attack the credibility of scientific research as a whole, or scientists as a group. But science is a human endeavor, and like all human endeavors, it is subject to the vagaries of human ethics and behavior. There is good science, and bad science; there is honest science, and dishonest science.

If you’ve been following my work for several years, you’ll know that my blog used to be called “The Healthy Skeptic.” I called it that because I believe that skepticism is healthy when it comes to science. Yet all too often I see this skepticism being applied in a biased or inconsistent manner.

For example, I’ve noticed that some people who are indignant about conflicts of interest in government agencies responsible for bank bailouts or among experts responsible for establishing blood cholesterol targets are completely unwilling to consider how similar conflicts might affect research on, say, genetically-modified foods.

I’ve also encountered people who are skeptical of any challenge to the status quo, but don’t apply their skepticism with the same rigor to the the status quo itself. On the other side of the coin are those that accept unconventional or alternative ideas (regardless of whether there is evidence to support them), and tend to reject anything that could be remotely construed as conventional or mainstream. 

Someday, perhaps we’ll be able to extricate the financial interests of Big Pharma from the behavior of medical scientists and regulatory agencies. Until then, our responsibility—whether we are clinicians, patients, researchers, or members of the media—is to acknowledge the influence these relationships may have on scientific research, and take that influence into account when considering controversial issues—especially when large amounts of money are at stake.

Now I’d like to hear from you. Were you aware that research misconduct rarely gets reported on in the media or scientific literature? Are you surprised by the extent to which conflicts of interest are present on advisory panels responsible for creating guidelines? How do you feel about this subject after reading this article? Let us know in the comments section.

126 Comments

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  1. I have personally been put in this position. Not with drugs but with physical therapy.

    As the product Manager of a Vibration Training Plate company ( PP ). I recalled an entire line of products because of multiple faults , that essentially meant that even 20kg body weight caused a dampening effect on the vibration as to make it almost completely ineffective.

    The company refused to recall the product. And it was sold to people with disabilities. Plus sent to researchers already promised machines.

    Most of the researchers knew immediately there was an engineering issue. But carried on regardless. Publish or die right ?

    Hundreds of papers are invalid. They should be retracted.

    It has taken 10 years for this to start to gain some recognition.

  2. Certainly lots of interesting discussion here. Science, greed, lies etc. We all need to find some common ground that is beneficial to health and wellbeing. Lets for example sake take 100 average healthy individuals who are not taking any medications or nutritional supplements, herbs, tinctures etc. Lets randomly pull 10 naturopathic tablets out of a hat and 10 pills from the local pharmacist. Lets prescribe 5 of the pharmacy meds to 50 people to take daily for 30 days straight. Now lets do the same with the naturopathic tablets.

    Lets do this experiment with the same people using another randomly picked selection of pills and repeat the process over a period of one year.

    Which group do you think will suffer damages? I think you can easily answer that.

    Now lets take a trip to the grocery store. Why is the pharmacy section larger than the whole foods section? You got it! The food promoted and sold in the store is meant for profit not necessarily health. How many people do you see that are shopping in the store look healthy and vibrant? Not many. We need to change our diet to improve our health. Shopping wisely and preparing our own food from whole organic, unadulterated ingredients is the best way to start.

    If the sales go down on the boxed processed foods the stores will eventually quit selling it. If the sales go up in the whole foods then they will make sure to increase the supply.

    Lets take responsibility for our own health and then pill popping becomes a mute point.

  3. I find it amusing that so many anti-progressives feel that us scientists are all just out for a buck and that we would do and say anything to further our agenda and yet at the same time, they say nothing about the nutraceutical industry. There are a handful of cases of fraud or drugs/vaccines that later have to be pulled from the market, whereas hundreds of herb and other nutraceuticals have been pulled from shelves for various reasons and it has been shown that the majority of supplements out there either don’t have what they say they do or in the concentrations claimed, and/or a large amount actually have toxic substances in them. This just goes to prove your point (that business looks out for itself) but, unlike the drug companies, medical and scientific community, there really is no oversight of the nutraceutical or natural health system and thus much more fraud. I think the answer here is not to demonize one particular industry (especially when much of what is being said is incorrect), but rather to put more money into public research (that isn’t influenced by corporations) and to assure better oversight of all of these industries.

    • I agree 100% that there is fraud in the nutraceutical industry and a disturbing lack of regulation, and I’ve acknowledged that elsewhere and in the comments section below.

      That said, the nutraceutical industry does not have nearly the influence on research, public health policy, or standard of care that Big Pharma does. That is why conflicts of interest and fraud in conventional medicine are arguably more significant in their impact.

    • I am afraid more money put into the research would only echo and exacerbate the problems more. Money and greed appears to have created the problem in the first place. Private corporate interest continues to exert pressure on the scientific community and hence the solution must consist of serious attempts to isolate private intetest from the entire deal. Govermental or public funds must be available to conduct the research without fear of bias and politicization.

    • The good old…… “Look over there, they are doing it to ” trick.

      Yes we all know there are marketers out there willing to pray on desperate people to make a buck. We know they get caught often and so they should.

      What is news to lots of people is how high a % of scientists and researchers are corrupt or incompetent. And how far you guys will go to cover each others asses.

      Science put itself on a pedal-stool, telling us to trust them. And the evidence suggests out of every 100 of you, only 1 is honest and ethical.

  4. Here’s yet another recent example of what I discussed in this article:

    Deeper Ties to Corporate Cash for Doubtful Climate Researcher
    http://www.nytimes.com/2015/02/22/us/ties-to-corporate-cash-for-climate-change-researcher-Wei-Hock-Soon.html

    The story reveals that a researcher (Wei-Hock Soon) who is often cited by those who claim that human activity has played little role in climate change has accepted $1.2 million from the fossil fuel industry over the past decade while failing to disclose that conflict of interest in most of his papers.

    In correspondence with his funders, he referred to his scientific studies as “deliverables” that he completed in exchange for their money.

    Conflicts of interest can affect research that supports the consensus, and research that attacks it.

    • This was really well written and presented clearly. I do not say this lightly. I have been plowing through articles, blogs and rants that make my brain hurt, for several months now.

      Your article is clean, clear and well organized. My tired wee brain thanks you. Great information, good food for thought.

    • Chris – Your article was very good and you do great work. However, linking the NY Times article re Dr Soon was a mistake. You must know that you need to do more research before you recommend an article from NY Times, especially on a hot button issue which has only one politically coorect opinion. All of the $1.2 million went to the Smithsonian, Dr Soon’s employer and Dr Soon received $40,000 for his work. And under the rules Dr Soon was not required to report this. Plus Dr Soon was correct and truthful. I would like to add more but am writing this from memory.

  5. None of this surprises me. “Conflict of Interest” is the name of the game in Washington. In a recent petition to President Obama, Move On .org stated, “President Obama has appointed former Monsanto VP and lobbyist Michael Taylor to become senior advisor to the FDA’s commissioner. This unthinkable linkage between food safety and corporate interests that have little regard for the public health must be stopped. This example of a “fox watching the henhouse” is inexcusable. President Obama must reverse this unimaginably dangerous policy and isolate the FDA from corporate influence.” I personally remember clearly President Obama appointed Michael Taylor to the FDA in 2009, shortly after he took office, Shortly after he promised all of us who got him elected, one of the first things he was going to do when he became president would be to get GMO’s labeled, then he put the FOX in charge of the HENHOUSE….Unconscionable!

  6. Thanks Chris. I am a Health Coach and very aware of the problem of unreliable information from government agencies like the FDA and CDC. This article underscores the need to educate ourselves about what we should eat or not eat. What’s tragic is that many people don’t have the education or the time to do this for themselves. I am grateful for your articles and also hope to be a part of the effort to get the truth out!

  7. Great article. Doctors use hand held devices to prescribe. I’ve had wrong lowest doses, been told a popular med had to work when it doesn’t because I don’t fit the norm, and accused of trying to cheat the drug companies for asking to halve larger doses. The comments are great, too. Thanks for your help!