My Formal Response to the Nashville Scene December 2, 2010 journal article about Pharmaceutical Industry and Physician Ties

I am Hal Roseman, one of the physicians mentioned in the December 2, 2010 Nashville Scene article titled “Should you be worried if your doctor is on Big Pharma's payroll?-Pharm League”: http://www.nashvillescene.com/nashville/should-you-be-worried-if-your-doctor-is-on-big-pharmas-payroll/Content?oid=2052989. Having been misrepresented by the Scene’s report, I feel obligated to offer a written response. On the face of it, the Scene article, and the ProPublica article from which the Scene article is copied, seems reasonable. Pictured is a physician cheering on their Big Pharma benefactor. The message is clear- yet again, another large corporation buying influence. But when you start looking at the substance of the article, the report falls short in fully demonstrating that the relationship between industry with physicians, or for that matter, with large institutions (such as Vanderbilt Medical Center, which receives an estimated $250 million dollars in grants) causes harm. The inferences of the article were obvious, but actual damages not identified or fully clarified. The implication underlying this article is that money buys influence, but does it? Are the activities of the pharmaceutical industry causing harm? 

The article fails to demonstrate damages, other than possibly increased sales of newer drugs. It should be emphasized that these drugs have been rigorously evaluated and found to be safe and efficacious by the FDA. Given the advantages of these agents over more legacy treatments, their wider utilization may be beneficial to society. In the case of the educational programs that are part of the promotional efforts of marketing, I know of no studies that have demonstrated adverse effects from the educational programs provided by Big Pharma. In fact, I suspect, because of fair balance requirements built-in to the lecture format, the healthcare providers attending such conferences are better knowledgeable about and avoid inappropriate usage of medications. I believe that those practitioners that know new medications and their appropriate usage are better equipped to handle the nuances of clinical problems posed by individual patients.

Although the reporter asserts that the relationship of physicians lecturing for industry as being corrupting, he offers no concrete proof, just innuendos.

To begin with, today’s highly regulated environment, with presentations being limited to approved slides, makes it unlikely that the intended usage of a drug be distorted by a lecturer. Certainly, the confining and proscribed nature of these presentations, with the content being carefully monitored to maintain fair balance and consistency with the designated FDA approved package information, minimizes the likelihood that a drug would be misrepresented.

The reporter references the University of Minnesota bioethicist Dr. Carl Elliott, who carries impressive credentials (M.D. and Ph.D. in philosophy). In the article, Dr. Elliott is ascribed with asserting that pharmaceutical companies use the lecture program to drum up new business. Citing a conversation with a single unnamed “drug rep”, Dr. Elliott claims, “if a speaker didn’t write a bunch of prescriptions, he wouldn’t speak.” Based upon twelve years of being involved with the pharmaceutical industry, this certainly has not been my personal experience. The decision for the pharmaceutical company to place an individual on their speaker's bureau is not based upon their prescribing behavior! It may be that a physician’s prescribing habits brought them initially to the attention of a pharmaceutical company, because their adoption of a product suggests that their perspectives may be aligned with that of the company. However, it is still their credibility, their professional standing in their community, and their ability to teach that ultimately leads to an invitation. In my case, I do not get any benefits financially for prescribing a product. I am not rated by the industry as to my prescription contribution to their bottom line. I have never been threatened with losing my place on a lecture bureau if I didn’t prescribe more drugs. If pharmaceutical companies dependent upon my low prescribing volume, the company would go backrupt! It is probably true that individuals that speak for a pharmaceutical company favor the use of that company's drug. For me, my endorsement of a drug is the result of the familiarity and knowledge acquired with usage of the drug in my clinical practice supplemented by the lecture preparedness process. Healthcare providers prefer treatments, including medications, about which they are most knowledgeable and familiar- human nature at work! 

By the way, Dr. Elliott in a published 2001 article lamented that none other than the American Society of Bioethics and Humanity was considering accepting money from institutions with potential conflicts with their society. As he stated, “we all get our money from somewhere-universities, grants, hospitals, managed care organizations. Few of us are so unsophisticated that we would allow our money to corrupt our moral judgment.” Dr. Elliott indicates that the gifting act carries subtle messages of influences. However, later in the article he cites several prominent bioethical departments being funded by private corporations. I surmise that despite the appearance of conflict, even the bioethical community has been able to maintain objectivity despite their funding sources.

Then the reporter cites Dr. Adriane Fugh-Berman, a Georgetown University School of Medicine professor and director of PharmedOut, a research and education project examining industry-physician interactions. According to her website, interestingly she is a promoter of alternative medicine, including herbal and natural remedies, and is a “paid expert witness on behalf of plaintiffs in litigation regarding pharmaceutical marketing practices.” Her potential conflicts are obvious, none of which were reported in the article.

But, lets examine her comments, because the appearance of bias does not necessarily confirm its presence.  Dr. Fugh-Berman stated that pharmaceutical companies disguise their training of physician lecture recruits as marketing indoctrination. What is interesting about this accounting is the internal contradictions that are apparent in the article. On the one hand, the reporter clearly sees us physicians as “sophisticates”, but on other hand, we are somehow unable to recognize a marketing message implicit in pharmaceutical lecture training.

In a recently published May/June 2010 Boston Review article, Dr. Fugh-Berman, indicates that the development of a marketing campaign begins 7-10 years before the expected release of an agent, beginning with disease awareness campaign stressing the under-diagnosis of a condition, a novel understanding of a disease, or serious consequences of delayed treatment. (By the way, that is certainly not my understanding. No pharmaceutical company, given the failure rate of a drug coming to market, would engage resources so early in the drug life cycle.) “A classic way to expand the market for a drug is to invent a disease state or exaggerate the importance or prevalence of an existing condition.” This characterization of the birth of a drug misses one major fact, that the process to market is heavily orchestrated, requiring years of basic science and clinical research, and governed by a highly suspicious FDA. If a new disease is discovered, it is the FDA that defines its significance. In fact, the process that Dr. Fugh-Berman is describing is what is better known as the advancement of science. It is the process that leads to greater understanding of the human body and the identification of new and potential pharmaceutical targets for the treatment of significant conditions in the body. Given the stiff barrier to market, with an estimated $800 million - $1 billion dollars in development costs, a pharmaceutical company would be financially suicidal to attempt to bring an agent with minimal benefits to market.

If the reporter had spent more time investigating his experts, his “investigative reporting” would have been more credible!

To begin my review of the article, it should be emphasized that when the reporter first approached me, I requested evidence that the reporter was knowledgeable of the subject matter and that he would approach the subject in a fair-balanced manner. Since it was obvious that he assumed that I was bias, that I should exact some evidence of his lack of bias. What is good for the gander is good for the goose! He failed to respond to my lengthy questionnaire. When I asked for proof from the reporter of his unbiased perspective, he offered this response in writing: "It’s not that I’m avoiding your questions; I’m simply not interested in the hardships the industry faces when attempting to bring a drug to market. They made $300 billion last year. In 2004 they spent more than 24 percent of their budgets on marketing and only 13 percent on R & D. They seem to be doing fine to me. And if the way the spend money is any indication, they seem more interested in marketing than they are in developing new drugs and bringing them to market." The reporter was obviously prejudiced against the pharmaceutical industry before he even wrote the story, which may explain his single sided approach expressed in the article.

As far as my credentials, I completed my undergraduate education from the University of Pennsylvania, my medical degree from the University of Tennessee, my masters in public health specializing in epidemiology of cardiovascular diseases from Yale University. My clinical training included stints at Yale University affiliated programs for my internal medical training, at Brown University for my cardiology fellowship training, and at Harvard Medical School affiliate Massachusetts General Hospital for my post-cardiology fellowship. Since my formal training, I have been certified by written examination in the area of hypertension (Specialist of the American Society of Hypertension) and lipidology (Fellow of the National Lipid Association). It is true that I have not published significantly, but publication by itself is not a definitive measure of one’s expertise. In fact, many of the community’s finest treating physicians in this area have never published an article! Furthermore, I engage in clinical research projects; my practice is one of a limited investigative sites involved in international large trials examining the effects of newer diabetic agents on cardiovascular disease. Over the years, my speaker engagements have included many non-promotional continuous medical education programs at several regional academic medical centers.

As it relates to his reporting of my defense of Avandia (rosiglitazone), I just wish the reporter would get his facts straight. It should be emphasized that the scientific information surrounding this contentious issue is complex and confusing. A definitive consensus about the safety of Avandia has yet to be established; the recent actions of the FDA to severely limit the distribution of Avandia were taken as a prudent measure given this uncertainty. My statements, which have been taken out of context in this and the ProPublica articles, have been consistent. The scientific evidence for affirming a cardiovascular risk to Avandia is incomplete and conflicting. In fact, in the FDA statement explaining its  ruling on Avandia, Dr. Woodcock, the director of the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA) stated that “the cardiovascular safety profile of rosiglitazone is still an open question because there are conflicting data on the existence and magnitude of the risk.” If interested, please refer to Dr. Woodcock's complete statement that has been published on FDA’s website: http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM226959.pdf. Finally, my opinions comport with that of the American College of Cardiology and American Heart Association: http://circ.ahajournals.org/cgi/reprint/CIR.0b013e3181d34114. Contrary to the representation of me in this article, I believe that my viewpoint is credible and defensible, regardless of the appearance of bias related to my GSK association.

I have always made it clear that a signal suggesting cardiovascular risk associated with Avandia is present in some, but not all, of the observational studies. However, the more exacting six randomized clinical trials whose treatment protocols included Avandia, which represent a higher level of evidence, failed to show a risk!  In fact, two trials, the BARI-2D and VADT, suggested a benefit. (By the way, contrary to his report, three of the these six trials were not sponsored by industry, but by the United States government!)  Although the reporter refers to my July 14, 2010 presentation to the joint FDA advisory board: (http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM224749.pdf), he failed to acknowledge that my main point at the meeting was to demonstrate the lack of conclusive evidence to take Avandia off the market. (By the way, contrary to the insinuation of the reporter, I was not compensated by GSK in any way for going to the meeting or provided with any support to make my presentation.) Guess what, the FDA agreed with me! Admittedly, the restriction of Avandia use is prudent, until the uncertainty of its safety profile can be reassessed following re-analysis of the singly dedicated safety trial RECORD trial. As it relates to reporter’s comments that RECORD trial was “viscerated”, he should check the record. None other than Dr. Unger, FDA Deputy Chief, came to aid of the trial, reporting that his division within the FDA still had confidence in the results, especially the mortality end-point. 

Additionally, my statement about the small absolute risk of Avandia holds; the actual event rates were small! For example, in the referred Nissen study, the absolute risk difference was 0.1% rate of myocardial infarction but took on impressive numbers when translated into a percentage of relative risk.  

As mentioned in the article, GSK did present a meta-analysis in 2005 (not in 2006 as reported) that suggested, but did not prove, a cardiovascular risk associated with Avandia. The increased risk did not reach statistical significance, which meant that a relationship was not definitively found. This information was made known to the FDA who requested additional studies. [A more thorough review of the events surrounding this subject can be found in GSK’s White Paper Response to Senate Finance Committee]. The referenced 2007 Nissen meta-analysis, which has since been disputed and discredited, was not confirmed by the FDA’s own study using similar information. In fact, like the GSK study, the FDA did not determine a statistical significance. As a precaution, the FDA in 2007 issued a warning based upon this data of short-term trials (median duration of six months); however, the FDA warning also emphasized that the three longer clinical trials did not demonstrate a risk. All in all, the 2007 FDA warning indicated that the risk was far from conclusive. Although this point should have been emphasized, the reporter failed to mention this important distinction. By overlooking this difference, the reporter inferred that a risk had been confirmed. His own need for a consistent good by-line took preeminence over carefully researching and presenting the factual evidence of the issue! 

Contrary to the reporter’s claims, the FDA did not attribute 100,000 deaths to the use of Avandia; this assertion, based upon questionable statistical manipulation, was made by only one of their FDA statisticians, Dr. David Graham, whose analysis was not accepted by the FDA higher brass. As to the assumed bias of industry directed trials, which the reporter quotes, the ACCORD, BARI-2D, and VADT trials were government sponsored and did not indicate a risk from the use of Avandia.

I would also like to address several general issues. Let's begin with the assumed issue of prejudice that is ascribed to lecturers for the pharmaceutical industry. Just because someone receives compensation from a company does not necessarily indicate bias or prejudice. Were the views of the reporter colored, influenced, affected, tainted, or altered by his employer, The Scene? Certainly, there is presumption of bias when one is an agent of an institution or corporation. What dictates the nature of that agency relationship is the integrity of the individual, not the source of his income! Judge me for what I say and do; don't prejudge me simply because I am associated with a company. Using financial ties offers a beginning point to determine a person's bias but that metric is deficient in providing a conclusive and complete analysis of the individual's character. Should everyone be judged solely by one’s relationship to his employer?

The article, as the title suggests, infers that clinical physicians who work with industry are so biased in their prescribing approach that they have a disregard for  for the welfare of their patients. In my own practice, my patients are quite aware of my involvement with industry; they seem quite satisfied with my knowledge. I explain the benefits and risks of all agents and reference major studies, guidelines, and national scientific statements to justify the use of an agent, not infrequently choosing a competitive agent to the one I represent in my lectures.

As it relates to recruitment into industry’s lecture bureau, I believe that doctors are selected for such positions because of their capacity to represent professionally disease states relevant to a medication and the proper pharmaceutical usage of the drug featured in the lecture. It should be noted that there are strict guidelines of what can be said and presented at these meetings. A lecturer is required to adhere to rigid FDA guidelines, which require that information is consistent with the approved indications of the drug and not deviate from the approved package insert of the product. Discussions about off-label usage are strictly prohibited. By the way, there are many lectures that are not directed at all to marketing of a specific drug; these lectures, known as "disease state awareness", are presented to disseminate newer concepts about a disease. By the way, in such lectures, direct mentioning of products is discouraged.

In my own case, I became a lecturer because I wanted to be in a situation to influence health care practice and to channel my interests in education. I believe that I was selected because of my educational and scientific background and my capacities of distilling knowledge. Certainly, I could have entered an academic professional tract and was offered an academic position with the University of Tennessee. However, I remained in private practice to pursue my life-long love of treating individual patients, with the hope that I could make a difference in their lives. Lectureship through these pharmaceutical activities offered me yet another avenue to give back what I have learned.

By the way, my relationship with the pharmaceutical industry has had many professional benefits. I am a more fully informed physician as result of my attendance of the many conferences and symposia sponsored by industry. I have access to the latest research, which is only possible through industry’s largesse. I am exposed to latest insights of disease pathophysiology and new potential targets for pharmaceutical intervention.

I have become a better practicing physician as a result of my relationship with industry. In order to be fully prepared for my lectures on preventive cardiology, I read extensively in both the clinical and basic science literature. I have access to medical research, sometimes before its publication. I have personal relationships with many of the key academic physicians who are nationally recognized in lipidology, hypertension, coronary artery disease, and diabetes. As a result of the challenges of being a lecturer, I am knowledgeable of the latest scientific guidelines that form the basis of care in modern medicine. These experiences have translated in more discriminating administration of medications and choices of technology in treating my own patients.

As it relates to the conduct of the pharmaceutical industry, I am not here to defend it. As in any industry, there have been excesses and improper actions of marketing that have led to very well publicized charges and fines. There is not any industry, including journalistic publishing, which is free from similar charges. However, I do find it objectionable that the reporter’s view of the pharmaceutical industry was not fair-balanced. Even as a passing comment, he failed to mention the positive attributes of the industry and its contribution to the health of the nation and the world. The reporter failed to indicate that longevity in this country has increased by an average of 7 years since 1960, of which an estimated 40% of that change can be attributed to medications.  He failed to report that pharmaceutical industry spends more on research and development as a percentage of sales than many other research-intensive companies (e.g., computer software, electrical and electronics, automotive, and telecommunications). He failed to report that the “exorbitant” profits made by the pharmaceutical industry are similar to other companies in a variety of industries (e.g. Microsoft). He failed to report that it costs nearly a $1 billion dollars to get a new drug approved for the US market and the investment costs require expedient market adoption because of the short patent life of 10-15 years for the agent. Marketing is a necessary part of that process.

As it relates to the issues of profits earned by the pharmaceutical industry, the reporter failed to take into account that the pharmaceutical industry is part of our capitalistic system. Is the reporter insinuating that profits made by an industry are unjust; in the case of the pharmaceutical industry, these profits are the engine that drives innovation and scientific research for the world. Most of the pharmaceutical companies offer answers to the charges that the marketing budgets are excessive and their R&D efforts are low relative to their profits. The website of two large pharmaceutical companies, GSK and Lilly, offers responses:  http://us.gsk.com/html/healthcare/healthcare-common-questions.html and: http://www.lilly.com/research/value/. None of this was mentioned when the reporter was actively discrediting the industry. Not fair-balanced reporting, just grand-standing!

I offer these insights to make a point: there are many sides to the same coin. Journalism needs to be fair-balanced and credible. Unfortunately, although the reporter brings up several valid concerns and raises important issues, the report fails to offer any new information or insights, merely inferences, implied accusations, and in some cases misanalysis. Sensationalism, rather than even-handed reporting, appeared to have won out in the writing of this article. When I asked the reporter whether there was an editorial board governing his actions, he indicated no to the question. Given the article’s mishandling of some of the issues, maybe the Scene should institute one.