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Comments on First Amendment Issues

Re: Docket No. [02N-0209] Food and Drug Administration’s Request for Comment on First Amendment Issues

Attachment 1(pdf)

Public Citizen Health Research Group submits these comments in response to the vital public health concerns raised by the Food and Drug Administration (FDA) Notice dated May 16, 2002.

Public Citizen is a national public interest organization, with over 125,000 members nationwide. Since its founding in 1971, Public Citizen has been active before Congress, regulatory agencies, and the courts in matters relating to public health in general and drug and medical device safety in particular. Through its Health Research Group, Public Citizen has submitted comments on FDA proposed rules relating to regulation of drugs, devices, and dietary supplements, and has petitioned the FDA to take action to remove unsafe products from the market.

The organization has also been in the vanguard in pressing for extending constitutional protection for truthful commercial speech. For example, Public Citizen’s attorneys represented the consumer plaintiffs in Virginia State Board of Pharmacy v. Virginia Citizens Consumer Council, Inc., the first case recognizing that commercial speech is entitled to significant protection under the first amendment.[1] Recently, we have also handled two other commercial speech cases.[2],[3] We have also filed amicus briefs in a number of other commercial speech cases.[4],[5],[6],[7]

Public Citizen Health Research Group submits these comments to highlight the interests of the people who have the most at stake in this matter ­ ordinary consumers.


As the Supreme Court has repeatedly stated, misleading commercial speech may be regulated without running afoul of the First Amendment.[8],[9]

In the area of food and drug law, health claims unsupported by significant and reputable scientific evidence are unreliable and misleading. Where the public health is threatened by such claims, they can be suppressed in their entirety. As the Supreme Court has emphasized:

Obviously, much commercial speech is not probably false, or even wholly false, but only deceptive or misleading. We foresee no obstacle to a State’s dealing effectively with this problem. The First Amendment, as we construe it today, does not prohibit the State from insuring that the stream of commercial information flows cleanly as well as freely.[10]

As the Congress recognized in enacting the Food, Drug and Cosmetic Act, there are few if any absolutes in terms of safety of drugs and medical devices. Therapies well tolerated by many ­ even aspirin ­ pose a risk to some. Accordingly, the Act is premised on the idea that the FDA, in each instance, ought to weigh the potential benefits of drugs and devices against the risks that they carry. For that reason, the safety and effectiveness of drugs and medical devices is a relative thing and not a matter of absolute truths. Accordingly, the FDA is empowered to determine whether a new drug application is supported by “substantial evidence” or an application for premarket approval of a medical device offers “reasonable assurance” of safety and effectiveness of the product for specified indications.[11],[12] Of course, even FDA approval is no guarantee of safety and effectiveness. Eight new drugs approved since the mid-1990s have subsequently been withdrawn from the market for safety reasons. Nonetheless, the FDA’s review ensures an objective scientific evaluation of the relative safety of proposed products and the health claims that manufacturers want to employ to sell their products.

The FDA does not approve drugs and devices generally; it approves them for specific indications. For example, in November 2001, the FDA approved a new drug application for the drug valdecoxib (Bextra) for the treatment of the signs and symptoms of osteo – and rheumatoid arthritis and painful menses, but denied the New Drug Application insofar as it sought approval to market the product to treat acute pain. In other words, the FDA found insufficient assurance that the drug was safe and effective for the latter use. The marketers of this drug, Pfizer and Pharmacia, later issued a press release announcing the publication of a study ­ sponsored by the companies ­ that concluded that valdecoxib was effective in treating acute pain. The issue addressed in these comments is whether publication of a study in those circumstances constitutes misleading commercial speech, or whether, despite the FDA’s rejection of approval for this indication, the companies were entitled to make this claim under the First Amendment.


The concept of “truth” in the realm of science is an elusive one. According to the dictionary, the word truth means “the state of being the case: fact.” But in science facts are hard to come by and then open to question. Galileo’s conception of the universe might have been accepted as “fact” until Copernicus demonstrated the error in Galileo’s theory. And in trying to ascertain the facts about the relative risks and benefits of drugs and medical devices, the “truth” is often uncertain, even when the best scientific methods are used for evaluation. Sellers can take advantage of uncertainty by making claims that are not certain to be true, but are not yet demonstrably or certainly false.

Government can serve no more important role than to level the information playing field about drugs and medical devices for patients. This is a function that has not been effectively filled by the FDA, and the FDA’s ability to do so has now been called into question by this request for comment.

Government must play an active role in proctoring the information drug and medical device manufacturers provide to physicians and patients because the incentives for the manufacturers to distort the “truth” by providing the public a misleading, one-sided presentation of the scientific evidence, are enormous. These manufacturers operate in highly competitive environments and owe a fiduciary duty to their stockholders to maximize the profits and growth of the company as best as possible within the bounds of the law. So it is no surprise that their promotional material accentuates the positives of their products and minimizes the risks.

While the Health Research Group is interested in all forms of communication between drug and device manufacturers and physicians and patients, these comments will focus on what we see as the breeding ground for the most egregious and worrisome abuses: “peer reviewed” literature circulated to physicians by drug companies.

We recognize that published research sponsored and controlled by a manufacturer about one of its drug products can be either pure scientific communication or a commercial message intended to influence the drug selection process. If companies were operating solely under the axiom that the research they sponsor and control will be published to further scientific knowledge, in the interest of public welfare, then all research sponsored and controlled by a company would be freely published, both that which reflects positively and negatively on a particular drug.

But that is not how drug and device companies work. Most publish favorable results, but are wary of, and often decline to, publish negative results. But plainly a decision to publish negative results when, for example, positive results have already appeared in the literature, when it is clear that the publication of the positive results, untempered by subsequent negative findings, is plainly a promotional communication, and little else.

Compounding the negative effects on the public health of published research that appears to be a scientific communication that may, in fact, be a misleading promotion is that such a misleading promotional publication is almost always undetectable by the commercial audience.

One of the keys to the definition of what constitutes truthful speech regarding a pharmaceutical is an appreciation of the meaning of truth, by necessity, in the scientific sense. As we said above, scientific truth is a “moving target” and there is always a level of uncertainty that is implicit in the definition of scientific truth.

The legal standard for marketing a new drug in the United States is not proof that the drug is effective, as an indisputable fact, but rather that there is substantial evidence of the drug’s efficacy. Substantial evidence is defined as:

evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.[13]

The standard is a procedure, not a definition, established by Congress to create a standard of evidence that provides the public a level of certainty, not absolute certainty, that a ” drug will have the effect it purports or is represented to have .” Congress delegated the responsibility for determining substantial evidence to the FDA.

The quality of evidence used by the FDA in making a determination to approve a new drug, or to approve an old drug for a new use, is significantly greater than that found in a peer reviewed medical journal study. A single peer reviewed medical journal article may be the sole foundation for prescribing a drug for an off-label use. The agency bases its determination of efficacy on its own examination of the data, including statistical analyses done by highly skilled, Ph.D.- level statisticians. In addition, the FDA has the authority and the responsibility to audit clinical research sites to ensure that the data the agency uses in making its decisions are valid.

The FDA’s method contrasts sharply with the process that medical journal editors use in deciding whether or not to publish a study. Medical journal editors accept the veracity of a manuscript submitted for publication. The journal editor has neither the authority nor the resources to audit clinical research sites. The journal editor may reject the manuscript outright as poor science or send the manuscript for peer review, a process that may take as little as a few hours of the reviewer’s time. If the author of a manuscript persists, no matter the quality of the work, the manuscript will almost invariably be published in a peer reviewed journal.

One example of the substantial disparity between the FDA’s approval process and the published medical literature are surveys demonstrating statistical errors in a large percentage of studies appearing in medical journals over the past 25 years.[14],[15],[16],[17],[18],[19],[20] If an incorrect statistical test is chosen by the author(s) of a peer reviewed medical journal article in arriving at a conclusion, the conclusion is invalid.

The arguments proposed by those who contend that the First Amendment forbids restrictions on the distribution of peer reviewed medical journals for promotional purpose are premised on the idea ­ wholly inaccurate in our view ­ that practicing physicians because of their medical expertise can distinguish between peer review journals of sound quality and those that employ faulty statistical methodology. But the evidence suggests that the statistical mistakes that are far too common in peer review journals escape the attention not just of the journal’s editors, but of all but the most sophisticated readers. Put simply, physicians are at risk of accepting uncritically the published results in a peer review journal as are the editors of such journals.

This concern is strengthened by the fact that a number of studies have documented the lack of understanding by many physicians of basic statistical concepts. The available evidence suggests that most physicians depend on the journals, through the editorial and peer review processes, to ensure that the statistical methods in published research are being used and interpreted properly. Except in the largest circulation medical journals, the probability of statistical methodologic review of original research is low.[21]

In the 1962 Kefauver-Harris amendments to the Food, Drug and Cosmetic Act that established an efficacy requirement for the marketing of new drugs, Congress made the judgment that physicians are not qualified to choose drugs for their patients without the help of experts (the FDA) in weeding out ineffective drugs and leaving only drugs whose efficacy has been proven on the market. Congress also recognized that the market could not weed out worthless or dangerous drugs, misleadingly promoted for unsubstantiated uses. Markets do fail, particularly those that are characterized by imperfect information, such as the pharmaceutical marketplace.

The FDA’s approval process does not eliminate uncertainty about the safety and efficacy of a new drug. However, to suggest that the conclusion of a peer reviewed medical journal article is comparable to the FDA’s drug approval process is untenable. On what logical basis can it possibly be argued that the initial FDA approved claim for a drug, say the relief of pain, should be supported by the standard of substantial evidence, but that successive claims, for instance the cure of acne reported in a medical journal, need not be so supported?

The remainder of these comments consist of four examples that illustrate that patients have been and are now being harmed both physically and economically from the promotion of drugs for off-label uses.

The first example is the antibiotic chloramphenicol (Chloromycetin), a drug that is now over 50 years old. Promotion for unsubstantiated uses led to its indiscriminate use and patients needlessly died from a blood disorder.

Valdecoxib (Bextra), a redundant nonsteroidal anti-inflammatory drug (NSAID), is the second example. This drug was promoted off-label for acute pain using the peer reviewed medical literature. The FDA was complicit in this promotion by not releasing to the public information about the failure of valdecoxib to gain approval for the treatment of acute pain. This also may be viewed as promotion of valdecoxib for a disapproved use.

The last two examples involve the tremendously popular drugs, celecoxib (Celebrex) and gabapentin (Neurontin). Together, more than 27 million prescriptions were written for these drugs with total sales exceeding $3.7 billion in 2001. In both cases, misleading promotional peer reviewed medical literature articles were used to stimulate sales, to the detriment of the public.

Little has changed since Congress prohibited the promotion of prescription drugs for uses other than those approved by the FDA, with the possible exception of the sophistication of promotional strategies now being used by the pharmaceutical industry.


One of the earliest and most carefully documented cases of the negative effect of drug promotion on the public health and safety concerns the antibiotic chloramphenicol (Chloromycetin), a drug first marketed in 1949 by Parke Davis. Chloramphenicol had a legitimate role in the treatment of serious and potentially fatal infections and today is reserved only for severe infections when less hazardous drugs are ineffective.

The first warning linking chloramphenicol to a serious blood disorder appeared in 1949 at the time of its initial marketing. By 1952 it had become clear that chloramphenicol could cause aplastic anemia, a potentially fatal adverse reaction, and other blood disorders. A strong warning of possible blood damage was published in 1953. At this time, the FDA, in conjunction with the National Research Council, documented the link between chloramphenicol and blood damage. The FDA ordered warnings added to the drug’s professional product information and made a recommendation that chloramphenicol not be used indiscriminately or for trivial infections. The warnings caused a precipitous fall in chloramphenicol sales, but only temporarily. Parke-Davis intensified its promotion of the drug and sales again soared.

In 1960, the Journal of the American Medical Association wrote:

Although the warning statement specifically cautions against the indiscriminate use of the drug or against its use for minor infection, an examination of the reports received by the registry reveals that the drug has been used in such conditions as upper respiratory infections, including the common cold, bronchial infections, asthma, sore throat, and tonsilitis, miscellaneous urinary tract and ear infections, undiagnosed low-grade fever, and even disseminated lupus erythematosis, gout, eczema, malaise, and iron deficiency anemia.

Sales of chloramphenicol were off markedly in 1961, but the downturn was short-lived, and by 1962 a reversal in production of the drug and number of prescriptions had begun. Surveys indicated that perhaps 90 percent of the patients treated with chloramphenicol received it for inappropriate reasons that raises serious questions about the “expertise” of physicians.

In November 1967, Senator Gaylord Nelson (D-WI) held hearings about antibiotics in general and chloramphenicol in particular. The publicity engendered by these hearings finally led the public and the medical profession to appreciate the dangers of chloramphenicol. By 1968 chloramphenicol prescribing was plunging precipitously.

Senator Nelson caustically remarked to a spokesperson for the American Medical Association defending the prescribing practices of American physicians during the hearings ” many doctors have been blind, dumb, and deaf. It has been a horrible tragedy in this country and it is an indictment of the medical profession.” 

Free market proponents are fond of insisting that companies will not engage in the misleading promotion of their products and will act in enlightened self interest not to sully their reputations that could negatively affect sales. A dip in sales is easily corrected by only increasing advertising. Parke-Davis and chloramphenicol is only a first example of this type of behavior. Any suggestion that the health and safety of the American public should be left to the whims of the marketplace is irresponsible. 


A more recent example of a peer reviewed journal article that is inherently misleading involves the drug valdecoxib (Bextra), a nonsteroidal anti-inflammatory drug (NSAID) marketed by Pfizer and Pharmacia that was approved on November 16, 2001. Approval of valdecoxib brought to over 20 the number of drugs in this class. A press release six months earlier indicated that approval for the treatment of acute pain was being sought for valdecoxib.[23] But valdecoxib did not receive FDA approval for acute pain.[24] The Health Research Group examined the FDA reviews for valdecoxib posted on the agency’s Web site and found that all information concerning the efficacy of the drug for the treatment of acute pain had been removed from the reviews. We were told that it is FDA policy to remove information about a use for a new drug that failed to be approved. The agency’s explanation was that this information is exempt from Freedom of Information Act (FOIA) disclosure because it is confidential commercial information. 

Yet, at the same time the Health Research Group was attempting to access information about the use of valdecoxib and acute pain, a press release[25] was issued announcing the publication of studies in the Journal of the American Dental Association (JADA)[26] that claimed effectiveness for valdecoxib in the treatment of acute pain associated with dental surgery. 

This publication was co-sponsored by Pfizer and Pharmacia. Three of the five authors were employees of Pharmacia, the corporation’s director of Biostatistics, director of Medical Development, and the clinical vice-president of Medical Development. These three individuals certainly must have known that valdecoxib failed to gain FDA approval for acute pain. 

Again, only those studies showing valdecoxib in the brightest light appeared in the medical literature at the time ­ preceded by a press release. Pfizer and Pharmacia cannot claim that they followed the scientific standard of communication with their JADA publication and at the same time claim that negative studies are confidential commercial information when they announced that they were seeking approval for the treatment of acute pain for valdecoxib from the FDA. The JADA publication can only be considered to be misleading promotion on the part of these companies. 

Valdecoxib is also an example where agency FOIA policy has kept physicians in the dark that has contributed to the misleading promotion of the drug. Present FDA policy tips the information playing field totally in favor of the sellers (the pharmaceutical industry) allowing them to selectively communicate only the positive aspects of their products, while using FOIA to claim that negative evidence is confidential commercial information. This can cause patients to purchase drugs that may be less safe and less effective, or both, at exorbitant prices. 


Celecoxib, a drug marketed by Pfizer and Pharmacia, exploded onto the market in early 1999 with a successfully managed media campaign calling it “super-aspirin”­ a “breakthrough” drug that is as effective as the older NSAIDs and supposedly without the same risk of gastrointestinal (GI) toxicity, the adverse effect that is the most serious concern with the use of NSAIDs. 

Overlooked by uncritical journalists, too many physicians and a duped public was the fact that celecoxib was approved by the FDA with exactly the same warnings about risk of GI bleeding and death as the other 19 NSAIDs that were on the market at that time. Celecoxib’s manufacturer could not, and has not, proved to the FDA that their drug was any safer as far as GI toxicity is concerned, than the legion of other NSAIDs already available at much lower cost. 

Celecoxib is remarkable in one respect. Despite the fact that it is an unremarkable treatment for arthritis and pain, it racked up $1 billion in sales before a single clinical trial was published comparing it to an existing drug for the treatment of arthritis.[27] In recent years, the core business of the pharmaceutical industry has been marketing, not research, and celecoxib is the icon of how successful marketing can be, even for a drug that is no better or safer (just more expensive) than drugs already on the market. 

Pfizer and Pharmacia scored an apparent advertising coup with the publication of the CLASS study (Celecoxib Long-term Arthritis Safety Study) in the September 13, 2000 issue of the Journal of the American Medical Association (JAMA).[28] The results of this six-month-long study were “spun” to conclude that celecoxib was safer on the GI tract than other NSAIDs. A cautiously optimistic editorial about the therapeutic benefits of celecoxib accompanied the publication of the CLASS study.[29]

The FDA’s Arthritis Advisory Committee met on February 7, 2001, to review a request to change celecoxib’s labeling to indicate that it is a GI-safe NSAID, based on the results of the CLASS study. At this meeting it was revealed that the company actually had data on the safety of celecoxib for as long as 16 months rather than just the six months of results published in the JAMA

The FDA medical officer who reviewed the CLASS study for the February advisory committee meeting concluded that the company had failed to show a statistically significant lower rate of serious GI adverse reactions compared to usual doses of the NSAIDs ibuprofen (Motrin) and diclofenac (Voltaren).[30]

The misleading findings published in the original JAMA article appear to be widely distributed and believed. Approximately 30,000 reprints of the CLASS study were bought from the publisher and a recent search of the Science Citation Index yielded 169 other articles citing CLASS within months of its publication. This wide distribution and citation has coincided with the sales of celecoxib increasing from $2.62 billion in 2000 to $3.1 billion in 2001.[31]

The FDA has indicated that it is investigating whether the company knowingly disseminated the misleading CLASS reprints.[32]


This drug was originally produced by Parke-Davis, which was acquired by Pfizer, Inc, of New York in 2000. The only FDA approved use for gabapentin at that time was as an add-on treatment for epilepsy. This is a very limited market with little upward sales potential. Court documents in a civil case recently unsealed from the United States District Court in Massachusetts allege that Parke-Davis knew that pain management, psychiatric disorders, anxiety and depression, all off-label uses, were immense markets which, if tapped, could yield enormous profits from sales of gabapentin. The company made a measured economic decision to make an “end-run” around the FDA’s drug approval process and promote gabapentin for unsubstantiated uses. 

According to the court documents, after an extensive economic analysis, senior officials at Parke-Davis determined that it was not sufficiently profitable for Parke-Davis to obtain FDA approval for gabapentin’s alternative uses by doing the types of studies necessary for approval. Instead, company officials developed a strategy that would allow Parke-Davis to avoid the costs of proving gabapentin’s safety and effectiveness for these other uses, while allowing the company to enter the lucrative off-label markets. 

Taking advantage of a loophole in the FDA’s off-label marketing rules, Parke-Davis decided to employ a “publication strategy” that would allow it to promote gabapentin by the massive distribution of publications supposedly written by independent researchers who purportedly described the scientific evaluation of gabapentin. Another advantage of this strategy, from the company’s perspective, was that it could be done immediately. There was no need to wait for the results of scientifically conducted clinical trials to determine if gabapentin was actually effective in the treatment of these conditions and submit them to the FDA for approval. 

The company’s “publication strategy” required physicians to perform the work normally performed by the company’s sales force. This necessitated that Parke-Davis make tens of thousands of payments to the physicians who would act as a surrogate sales force as well as to the practicing physicians who would receive the message. In other words, adoption of the “publication strategy” required the company to pay physicians to either recommend the prescription of gabapentin or to order gabapentin, in violation of the federal anti-kickback regulations, according to allegations made in court documents. 

A common tactic used by Parke-Davis to funnel payments to physicians to encourage them to prescribe gabapentin off-label was through “consultants'” meetings. Under this front, Parke-Davis invited doctors to dinners or conferences and paid them to hear presentations about off-label uses of the drug. Under the guise that these physicians were acting as consultants, Parke-Davis sometimes, but not always, had the physicians sign bogus consulting agreements. At these meetings, the company would give these physicians lengthy presentations relating to gabapentin, particularly regarding off-label usage. Presentations would be made by Parke-Davis employees or physician speakers hired by the company for the purpose of promoting gabapentin, and questions relating to the use of gabapentin would be solicited and answered. At some conferences, the sponsoring organization or Parke-Davis intentionally posed questions to the speakers about off-label use to insure that the physicians were exposed to such information. 

Parke-Davis would routinely analyze whether the consultants’ meetings were successful in getting physicians to change their prescription writing practices. At some meetings, the so-called consultants were asked directly if they would write more gabapentin prescriptions as a result of the meeting. This question would have been irrelevant if the actual purpose of the meeting was to receive the consultants’ advice. Parke-Davis also routinely tracked consultants’ gabapentin prescription writing practices after these meetings. Parke-Davis actually analyzed whether the doctors they had paid had in fact written more gabapentin prescriptions after the meeting, using market data purchased from third parties. 

The court documents revealed another platform used by the company to pay kickbacks to physicians to hear off-label promotion of gabapentin. These were programs billed as Continuing Medical Education (CME) seminars. These conferences and seminars were set up to appear to qualify for an exception to the FDA’s off-label marketing restrictions which permits doctors to learn about off-label uses of drugs at independent seminars. Such seminars, however, must be truly independent of the drug companies. The companies may make “unrestricted grants” for the purpose of a seminar, but may not be involved in formulating the content of the presentations, picking the speakers or selecting who attends the seminars. Parke-Davis retained third party companies to present seminars while in fact retaining control of virtually every aspect of these events. The seminar companies obtained Parke-Davis’ approval for all content presented at the seminars. Parke-Davis also paid all expenses, including all the seminar companies’ fees. 

The company designed and approved the seminars, hand-picked the speakers, approved the seminar presentations, previewed (in most cases) the contents of the seminars prior to a presentation, selected the attendees based on their ability and willingness to prescribe high quantities of gabapentin, evaluated the presentations to make sure Parke-Davis’ “message” was appropriately delivered, black-listed presenters whose presentations were not sufficiently pro-gabapentin, and monitored the prescribing patterns of the physicians who attended. 

Parke-Davis also made outright payments, in the form of grants, to reward demonstrated gabapentin advocates. Company sales managers identified key physicians who actively prescribed gabapentin or programs which were willing to host gabapentin speakers and encouraged such persons or programs to obtain “educational grants” from the company. Parke-Davis’ sales people informed leading gabapentin subscribers that significant advocacy for gabapentin would result in the payment of large grants.

Another method of paying physicians for backing gabapentin was to pay honoraria for the use of their names on scientific articles intended for publication in various neurology and psychiatry journals. These articles were allegedly ghost-written by technical writers hired by Parke-Davis, which retained control of all such articles. In 1996 Parke-Davis paid for at least 20 such articles, most of which dealt with off-label use of gabapentin, and were placed according to the company’s “publication strategy.”

Once Parke-Davis and the technical writers conceived the articles, the company and its outside firms attempted to find recognized gabapentin prescribers whose names could be used as the authors of these articles. In some cases, drafts of the articles were completed even before an “author” agreed to place his or her name on the article. This even occurred in connection with case histories that purported to describe the “authors” personal treatment of actual patients. The “authors” were paid an honorarium of $1,000.00 to lend their names to these articles, and also were able to claim publication credit on their professional resumes.

According to the court documents, Parke-Davis also formed a Speakers’ Bureau, another tactic to make large and numerous payments to physicians who recommended gabapentin at teleconferences, dinner meetings, consultants meetings, educational seminars, and other events. These speakers repeatedly gave short presentations relating to gabapentin for which they were paid anywhere from $250 to $3,000. Some speakers received tens of thousands of dollars annually in exchange for recommending to fellow physicians that gabapentin be prescribed, particularly for off-label uses. Speakers who most zealously advocated gabapentin were hired most frequently for speaking events, regardless of the fact that many of these events were billed as independent medical education seminars where objective information was supposed to be delivered. 

The revelations surrounding the success of gabapentin have shattered some widely held myths. 

First, and perhaps most important to the health and safety of patients, is the belief that physicians are not fooled or influenced by drug company promotional ploys such as gifts to attend medical meetings or expensive meals. The evidence presented in the court documents unambiguously shows that such schemes work and underscores why Congress created a process by which the FDA approves drugs based on validated science for specific uses ­ to protect the public. 

Second, the sacrosanct position of peer reviewed medical literature as a vehicle for scientific exchange has been seriously damaged. In defense of the many physicians who do try their best for patients by diligently keeping up with the medical literature, there is no way for a physician, scientist, or medical journal editor to know if a published study is a part of a carefully orchestrated promotional strategy by a company or science. 

Circumstantial and some direct evidence over the years suggests that the behavior of Parke-Davis in the off-label promotion of gabapentin is not isolated, but rather an integral part of the pharmaceutical industry’s marketing practices. In our experience, the gabapentin episode is the most complete and well documented case of off-label promotion to ever come into public view. Because of the detail of fabrications, pay-offs, manipulation, and their effect on gabapentin sales the Amended Complaint in this case is presented as Attachment I to these comments. 


The decision by Congress over four decades ago to limit the promotion of pharmaceuticals to their FDA approved uses was carefully considered and based on evidence that patients were being harmed, both physically and financially, from products promoted for uses for which they had not met the legal standard for safety and effectiveness. Patient protection from the off-label promotion of drugs was seriously undermined with the passage of the 1997 Food and Drug Administration Modernization Act. And because there are no adequate systems in place in the general population to determine who is harmed from drugs, let alone if anyone is helped, there is no reason to believe that patients today are at less risk of physical or financial harm than they were four decades ago from the off-label promotion of drugs.

The extent to which the pharmaceutical industry controls the flow of information about its products is chilling, including the opportunity to manipulate the peer reviewed medical literature. The notion that market forces or physician expertise can adequately protect the public from being prescribed drugs for uses for which they have not been shown to be safe and effective flies in the face of the facts. 

To the extent that the FDA has authority under the law to regulate prescription drug promotion, including off-label promotion, the agency should err on the side of public protection and not pander to the commercial interests of the pharmaceutical industry. 

Larry D. Sasich, Pharm.D., M.P.H.
Staff Research Analyst
Public Citizen Health Research Group
Washington, DC



[1] Virginia State Board of Pharmacy v. Virginia Citizens Consumer Council, Inc., 425 U.S. 748 (1976).

[2]< Zauderer v. Office of Disciplinary Counsel, 471 U.S. 626 (1985).

[3] Edenfield v. Fane, 113 S. Ct. 1792 (1993).

[4] Rubin v. Coors Brewing Co., 514 U.S. 476 (1994).

[5] Peel v. Attorney Registration and Disciplinary Comm’n of Ill., 496 U.S. 91 (1990), In re Primus, 436 U.S. 412 (1978)

[6] Ohralik v. Ohio State Bar Ass’n, 436 U.S. 447 (1978).

[7] Bates v. State Bar of Arizona, 433 U.S. 733 (1977).

[8] Thompson v. Western States Medical Center, 122 S. Ct. 1497, 1506 (2002).

[9] Central Hudson Gas & Electric Corp. v. Public Service Comm’n of New York, 447 U.S. 557, 563-64 (1980).

[10] Friedman v. Rogers, 440 U.S. 1, 9-10 (1979) (citations omitted).

[11] 21 U.S..C. 355(c),(d).

[12] 21 U.S.C. 360e(d)(1)(A)(i)(d)(2).

[13] 21 U.S.C 355(d).

[14] White SJ. Statistical errors in papers in the British Journal of Psychiatry. British Journal of Psychiatry 1979;135:336-342.

[15] Avram MJ, Shanks CA, Dykes MHM, Roanai AK, Stiers WM. Statistical methods in anesthesia articles: An evaluation of two American Journals during two six-month periods. Anesthesia and Analgesia 1985;64:607-611.

[16] Gardner MJ, Bond J. An exploratory study of statistical assessment of papers published in the British Medical Journal. Journal of the American Medical Association 1990;263:1355-1357.

[17] Gore SM, Jones G, Thompson SG. The Lancet’s statistical review process: areas for improvement by authors. Lancet 1992;340:100-102.

[18] Concato J, Feinstein AR, Holford TR. The risk of determining risk with multivariable models. Annals of Internal Medicine 1993;118:201-210.

[19] McGuigan SM. The use of statistics in the British Journal of Psychiatry. British Journal of Psychiatry 1995;167:683-688.

[20] Welch II, GE, Gabbe SG. Review of statistics usage in the American Journal of Obstetrics and Gynecology. American Journal of Obstetrics and Gynecology 1996;175:1138-1141.

[21] Goodman SN, Altman DG, George SL. Statistical reviewing policies of medical journals. Journal of General Internal Medicine 1998;13:753-56.

[22] This discussion is based on Silverman M, Lee PR. Pills Profits & Politics. Berkeley CA: University of California Press 1974, chapters 3 and 12.

[23] Press Release. PR Newswire: Pharmacia Submits New Drug Application for Valdecoxib, dated March 23, 2001.

[24] Bextra (valdecoxib) Professional Product Labeling, dated November 2001.

[25] Press Release. PR Newswire: Pharmacia’s New COX-2 Specific Inhibitor Valdecoxib Compared to Oxycodone/Acetaminophen for Pain Relief After Dental Surgery, dated May 8, 2002.

[26] Daniels SE, Desjardins PJ, Talwalker S, Recker DP, Verburg KM. The analgesic efficacy of valdecoxib vs. oxycodone/acetaminophen after oral surgery. Journal of the American Dental Association 2002;133:611-621.

[27] Lieberman T. Health matters when hype stands in for solid science. Los Angeles Times, June 18, 2001.

[28] Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. Journal of the American Medical Association 2000; 284:1247-1255.

[29] Lichtenstein DR, Wolfe MM. COX-2-selective NSAIDS. Journal of the American Medical Association 2000; 284:1297-1299.

[30] Goldkind L. Medical Officer’s Gastroenterology Advisory Committee Briefing Document, June 12, 2000, p.68.

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