Is It Possible Some Doctors Still Don’t “Get” the Extent of Big Pharma’s Financial Ties to “Standard of Care” Research?

In May 18, 2000, Dr. Marcia Angell, former editor-in-chief of the New England Journal of Medicine, wrote an editorial, “Is Academic Medicine for Sale?”, which began:

In 1984 the Journal became the first of the major medical journals to require authors of original research articles to disclose any financial ties with companies that make products discussed in papers submitted to us. We were aware that such ties were becoming fairly common, and we thought it reasonable to disclose them to readers. Although we came to this issue early, no one could have foreseen at the time just how ubiquitous and manifold such financial associations would become.

(Above emphasis is mine.)

One year later, in 2001, Dr. Catherine DeAngelis, editor of JAMA, wrote a similar editorial, “Reporting Financial Conflicts of Interest and Relationships Between Investigators and Research Sponsors.” It began:

The financial aspects of biomedical research currently are under intense examination. Increasing attention and concern have been directed toward the financial ties of individual investigators as well as the complex relationships among researchers, academic medical centers, commercial clinical research entities, and industry.

(Above emphasis is mine.)

Almost echoing Dr. Angell, Dr. DeAngelis continued: “Since 1985, The Journal  has requested authors to disclose financial interests related to the subject matter of their research and since 1989 has required authors to submit signed financial disclosure statements.”

Thus, the editors of two of the most prestigious medical journals in America, acknowledged several years ago that financial ties between Big Pharma and medical researchers has been a problem since the 1980s. Both editors were firm in their conviction that researchers must, at the very least, disclose their financial connections to Big Pharma.

Yet, over time, the problem has only gotten worse, with John Abramson, MD, and Barbara Starfield, MD, writing in the September–October 2005 edition of the Journal of the American Board of Family Practice (“The Effect of Conflict of Interest on Biomedical Research and Clinical Practice Guidelines: Can We Trust the Evidence in Evidence-Based Medicine?”)

Approximately 75% of clinical trials published in The Lancet, the New England Journal of Medicine (NEJM), and the Journal of the American Medical Association (JAMA) are industry funded.

and

. . .  among even the highest quality clinical research . . . the odds are 5.3 times greater that commercially funded studies will support their sponsors’ products than noncommercially funded studies.

and

Readers should carefully evaluate whether conclusions in randomized trials are supported by data.

and

. . . approximately 70% of physicians’ continuing medical education is now paid for by the drug and other medical industries.

Drs. Starfield’s and Abramson’s obvious message here is that you can't trust what you read about clinical trials – especially when the results of the trial favor the drug being “studied.”

One would think, with all the articles (and books, too) being published, that things would have gotten better by now. However, what we have now, three years later, is a situation that has actually escalated, as Robert Steinbrook, MD, acknowledges in his August 7, 2008  NEJM “perspectives” piece, “Disclosure of Industry Payments to Physicians”:

Most physicians in the United States have financial relationships with industry, ranging from the acceptance of meals to the receipt of large sums of money for consulting, speaking, or conducting research.

Today, it is common practice that, instead of disclosing financial ties to drug companies, these ties are more cleverly hidden. In addition to funding the trials and dictating how the results will turn out, pharmaceutical companies also hire marketing company employees to write the “scholarly articles” that are published in the medical journals. Big-name researchers are then paid to affix their names to the articles. According to Adriane Fugh-Berman, MD, in her article, “The Corporate Coauthor,” this is how it works:

Drug marketing techniques include the sponsorship of articles signed by academic physicians or researchers and submitted to peer-reviewed medical journals. Some of these articles are authored or coauthored by ghostwriters who work for pharmaceutical companies or medical education companies hired by pharmaceutical companies. Conflicts of interest may be difficult to detect in the subset of articles and presentations sponsored by pharmaceutical companies that never mention the targeted drug, but focus on stimulating the perceived need for the targeted drug or highlighting problems with competing drugs. The current voluntary standards for declaring conflicts of interest to readers of medical journals and audiences at medical conferences are inadequate. A public database that contains conflicts of interest of physicians and researchers would be useful.

And Dr. Abramson writes in his excellent book, Overdosed America:

Rigging medical studies, misrepresenting research results published in even the most influential medical journals, and withholding the findings of whole studies that don't come out in a sponsor's favor have all become the accepted norm in commercially sponsored medical research. To keep the lid sealed on this corruption of medical science - and to ensure its translation into medical practice - there is a complex web of corporate influences that includes disempowered regulatory agencies, commercially sponsored medical education, brilliant advertising, expensive public relations campaigns, and manipulation of free media coverage. And last, but not least, are the financial ties between many of the most trusted medical experts and the medical industry.

Both Dr. Abramson's book, and Melody Petersen’s Our Daily Meds, describe this ghostwriter/co-author phenomenon in great detail; both books should be on every doctor’s reading list. (The subtitle of Ms. Peterson's book, by the way, is: "How the Pharmaceutical Companies Transformed Themselves into Slick Marketing Machines and Hooked the Nation on Prescription Drugs.")

Then, in April, 2008, JAMA itself published two articles and an editorial; all three pieces exposed this ghostwriting phenomenon, as it related to Merck’s so-called “clinical trials,” and the ghostwritten journal articles about Vioxx.

But, it seems that, this time, JAMA’s editors had had enough.  The journal itself sent out a video news release (VNR) -- a polished video, ready for airing on television stations nationwide -- which it distributed to media outlets throughout the country. A majority of TV stations aired it. You may view the VNR by going to JAMA's website, here, and read the video transcript here:

And yet, curiously, many practicing physicians still seem not to be aware of these exposés, even those that have been published in their own journals. Many naively hold onto the belief that, when they prescribe pharmaceutical treatments, these treatments will be safer than the four treatments I wrote about in my most recent postings,"Four Lifesaving Medical Treatments: Not So 'Anecdotal,' After All," and "Why Calling Lifesaving Treatments 'Anecdotal' Keeps Doctors From Being More Curious."

Why do doctors believe these pharmaceutical treatments are safer for their patients than are the so-called “anecdotal” treatments I described? Because, they tell us, the pharmaceutical treatments are backed up by the clinical trials -- the very same “standard of care” studies that so often have the financial connections described in the articles, editorials and videos included above.

Between 2001, when Dr. DeAngelis’ editorial was written, and the present, there have also been many books on the topic, and literally hundreds of articles have appeared in both professional and lay publications. The articles have been so numerous, so constant and so consistent in their message, that it would seem difficult for doctors to ignore them.  In addition to the NEJM and JAMA, articles on the topic of financial malfeasance have also appeared in (to name just a few) The British Medical Journal, The Guardian, the New York Times, Wall Street Journal, Los Angeles Times and Washington Post. I name these particular high-readership, high-intellect publications, to drive home the point that one would have to be an almost total non-reader to have missed the nearly omnipresent discussion of this topic.

So, just in case I am correct in my suspicion that many doctors simply have not read these books or articles, I have compiled a list of 37 articles, from 2005 to the present, complete with hyperlinks and selected passages. 

I have also created a pdf version of this list, which you are welcome to download and share with your doctor, the next time he (or she) is hesitant about, or fails to be interested in, reading information you have put together about a promising non-pharmaceutical treatment you would like to consider. These articles will be eye-opening for both you and your doctors.

I realize that many, many patients now self-medicate with holistic treatments, without telling their doctors. This is a fact. While I can certainly understand why this is true, given the fact that many doctors (including several of my husband Tim’s) react negatively to questions about non-pharmaceutical treatments, there are some cases, especially when a patient has a serious illness, when it is crucial to have your doctors’ cooperation.  For instance, if you have multiple sclerosis or lupus, and want to try Low Dose Naltrexone, you’ll need a doctor’s prescription, even though LDN was approved by the FDA in 1984 at 10 to 20 times the dose recommended for these off-label conditions.

I am hopeful that these articles (with hyperlinks) will help patients and doctors to be better informed about how Big Pharma influences our doctors’ treatment choices.

In closing, I’d like to suggest that we find another term, less pejorative than “anecdotal,” to use when we refer to credible, non-pharmaceutical treatments like those I've been writing about before. In fact, perhaps, we should come up with new terms to describe both kinds of medical treatments.

Two Possibilities:

1)    Patient Evidence-Based Medicine, suggested by my friend and colleague, Mary Shomon, to describe the non-so-anecdotal treatments Mary and I (and others) have written about.

2)    Pharmaceutical Evidence-Based Medicine, to describe treatments whose evidence has been provided to the FDA by pharmaceutical companies, which have also funded the studies.

The reason I feel that it is important that both of these new terms contain the words, “evidence-based,” is that doctors and medical journals respect this term, and use it in a positive sense to signify that the treatments they recommend have gone through a certain level of science-based study/trials. Unfortunately, as more and more people are now realizing, a startling percentage of these trials rely on “evidence” provided and funded by Big Pharma. It’s time we started analyzing the “evidence” more objectively. It’s also time we started respecting evidence provided by patients, especially if the same evidence is provided by hundreds, or even thousands, of patients.

Comments

[Gregory D. Pawelski]

Supporters of transparent clinical trials argue that conflicts of interest undermine public trust in and support for scientific research, endangers research subjects and patients, and boosts medical costs by encouraging physicians and patients to use new treatments that are no better than cheaper alternatives.

The collaborations between academia and industry has clearly brought discernible influence on clinicians, bringing with it erroneous results, suppressed data, or harmful side effects from these drugs.

Thanks to the fact few of us look forward to dying and none of us wants to suffer, there will always be a market for "snake oil" schemes. The sophistication, greed and political influence of big pharma has gotten way out of control. This is one area where the government has a role. But corporations own our elected officials, appointed officials and the media.

[Dan]

The Atrophy Of Objectivity

If I were to rate the corruptive tactics performed by big pharmaceutical companies during my intimate experience with them , the frequent and intentional strategy of implementing fabricated and unreliable results of clinical trials performed by others possibly tops the list of corruptive tactics by the pharmaceutical industry that sponsors such trials. By this atrophy of the scientific method absent of authenticity that has been known to occur, harm and damage is possibly done to the health of the public.
Most would agree that the science of research should be sound and as aseptic as possible- completely free of deliberate and reckless interference. However, it appears, money and increased profits can be a catalyst for disregard for human health with the clinical trial process that is largely unregulated.
This is particularly a factor on post-marketing studies of various pharmaceutical companies, as some pharmaceutical corporations seem to be deliberately conducting nothing less than seeding trials- with about a 50 percent tax credit for these trial sponsors. Trials that are in fact pointless and void of scientific benefit.
Decades ago, clinical trials were conducted at academic settings that focused on the acquisition of knowledge and the completely objective discoveries of drugs and devices to benefit mankind. Then, in 1980, the Bayh-Dole Act, Public Law 96-517,was created, which allowed for such places with their researchers to profit off of their discoveries that were performed for pharmaceutical companies and others in the past.
Furthermore, such academic institutions were coerced to license patented inventions to those pharmaceutical companies that will then commercialize these discoveries paid for in large part by the taxpayers who funded this research to a degree.
This resulted in the creation of for-profit research trial sites without any academic affiliation that are called Contract Research Organizations. CROS utilize primarily community patient care clinics whose staff are absent of any research training compared with the former researchers that existed decades ago. Because of this structure, the clinical trial investigators of these pharmaceutical sponsored trials are likely novice compared with academic researchers.
This, of course, happens with intent by the sponsor who can and does control all aspects of the clinical trial protocol at the site locations of a clinical trial that the pharmaceutical company structures and even gives the trial the title they want for their marketing purposes.
These quite numerous CROS are in fact for- profit, with some CROs making billions of dollars a year, and this market continues to grow.
The trials conducted at such places again are sponsored by pharmaceutical companies that control and manipulate all aspects of the trial being conducted involving their particular drug chosen to be studied. Etiology for their deception regarding this manipulation is because the pharmaceutical company that sponsors such a trial is basically creating a marketing tool for this drug of theirs to be studied in this manner. This coercion is done by various methods of deception in subtle and tacit methods. As a result, research in this protocol of the sponsor ensures favorable results of the sponsor’s medication that is involved in the clinical trial they clearly own.
These activities are again believed to be absent of true or applied regulation to any degree, and therefore have the autonomy to create whatever they want to benefit the pharmaceutical sponsor. There likely is a collusive relationship between the sites, the CRO, and the sponsor, as this whole system is planned beforehand by the pharmaceutical sponsor of their clinical trial to again be utilized to increase the market share of the drug studied that they promote.
Guest authorship has been known to be aggressively recruited by sponsors by paying a known opinion leader to sign off on the completed clinical trial. Furthermore, the pharmaceutical sponsor recruits investigators to be used for this function of what ultimately is a fabricated clinical trial protocol. The trial manuscript and protocol design is prepared by those employed by the drug company sponsor upon specific direction of this sponsor on how this should be prepared.
The medical program coordinator of a particular sponsored trial is an actual employee of the sponsoring drug company and also may act as the publisher, manuscript version reviewer, and the clinical trial director who works with the drug company’s hired CRO editors whose objectives are to benefit the sponsor. Typical and ultimate cost of the final manuscript of the trial to the sponsor created by the hired CRO and the recruited ghostwriters exceeds 1000 dollars per page, some have said.
Merck engages in this behavior, which shocked many, as they were always viewed as an ethical pharmaceutical company that always placed patients over profits. Apparently, this is no longer the case. There are other well known and large pharmaceutical corporations that consider this plan of action standard operating procedures to ensure growth of their drugs.
Further disturbing is that once the creation of the trials is completed, the research paper is often composed with specific directions by the sponsor to writers known again as ghostwriters. These people are usually not identified and acknowledged by the sponsor, and may not be trained in clinical research overall, as they are simply freelance writers.
One does not need research training or certification in order to perform this function. Rarely do clinical trial ghostwriters question their instructions about their assignment, which is clearly deceptive and undocumented by the pharmaceutical sponsor. Also, these hired mystery writers are known to make about 100 grand a year performing this deception full time.
This activity removes accountability and authenticity of the fabricated clinical trial even further. The corruptive act is finally completed by the sponsor hiring again a known thought leader as an author to have their name be placed on the trial, while this hired author likely had absolutely no involvement with the trial, or even reviewing the trial is not asked or required by the hired author, others have said.
To have the trial published, the sponsor has been known to pay an obscure journal, and the sponsor bribes the journal in a few ways, such as the sponsor purchasing from a selected journal thousands of reprints of their study from the journal, for example. Again, how often this process is performed is unknown, yet frequent enough to create hundreds of such false writers mentioned earlier and progressively growing research sites to receive the support the pharmaceutical industry. So benefits of pharmaceuticals that are studied in such a malicious way potentially can harm patients and their treatment options along with clear safety risks as a result of this process.

The purchased reprints of the fabricated clinical trial are then bought by the sponsor of the study from the medical journal they hired to publish this trial. The reprints are eventually distributed to the sponsor’s sales force to share the content with prescribers, with the sales force completely unaware about this manipulation that has happened with such a trial that benefits the drug they promote for their employer. As a bonus, the sponsor may agree to pay the chosen medical journal to advertise their products to be placed in this journal as well.
Such misconduct discussed so far impedes research and the scientific method with frightening ethical and harmful concerns, as stated previously. If so, our health care treatment options with drugs that are claimed to have benefits that are absent have now become unreliable in large part due to such corruptive situations. Not to mention the absence of objectivity that has been intentionally eliminated with trials produced in this way.
More now than ever, meds are removed from the market or are given black box warnings due to the damaging effects of drugs approved by the FDA. We as citizens need to dig deep and ask why this is happening.
Transparency and disclosure needs to happen with the pharmaceutical industry for reasons such as this as well as many others, in order to correct what we have historically relied upon for conclusive proof, which is the scientific method. More importantly, research should be conducted in a way that the sponsor cannot in any way interfere in such ways described in this article, which would require independent clinical trial sites with no involvement from the maker of the drug studied in a clinical trial.
And clearly, regulation has to be enforced not selectively, but in a complete fashion regarding such matters. Public awareness would be a catalyst for this to occur, after initially experiencing a state of total disbelief that such operations actually are conducted by such people, of course. We can no longer be dependent on others for our optimal health.
Knowledge is power, and is also possibly a lifesaver.
“Ethics and Science need to shake hands.” ……. Richard Cabot
Dan Abshear
Author’s note: What has been written was based upon information and belief.