The Editorial that Wasn't: Evidence for Systematic Research Manipulation Undetectable by Critical Review

Woe to those of us who have been advocates for evidence-based medicine.  A short description of the evidence-based medicine is medicine whose practice is informed by critical, rigorous review of the best available evidence from clinical research as revealed by systematic search of the published research literature, as well as by the clinician's understanding of biology and the medical and biopsychosocial context, and by the patient's own values.

Evidence-based medicine is based on some key assumptions.  One is that a systematic review will reveal all the results of research studies that are relevant to the issue at hand.  A second is that while the research studies may be flawed and imperfect, they are reported honestly.

Unfortunately, as we have repeatedly discussed, there is more and more evidence that a systematic review will not reveal all relevant results, because research studies may be suppressed, perhaps often, when their results are unfavorable to vested interests.  (Look here for further discussion.)  There is also considerable anecdotal evidence that the design, implementation, and analysis of research studies may be manipulated to make the results more likely to favor vested interests.  (Look here for further discussion.)

An article by Vedula et al just published in the renowned New England Journal of Medicine suggests that such manipulation might be systemic, and that the reporting of manipulated studies may not clearly show what manipulation was done. (1)

To summarize, the authors got access through legal proceedings to internal study protocols and research reports from clinical trials sponsored by Parke-Davis (later merged into Pfizer Inc) of gabapentin (Neurontin) for a variety of clinical problems other than seizures.  Gabapentin was originally marketed as an anti-seizure drug, but Pfizer later "admitted guilt for off-label marketing."  (We discussed the stealth marketing campaign for Neurontin here.)  Vedula et al compared the primary outcome variables specified in the original research protocols, internal research reports, and any publications of the trials' results.  They identified 21 trials, 13 of which were published.  For 12 of the 13, the authors had access to the internal protocol, report, or both.  The main results were:

For 8 of the 12 published trials, there was a disagreement between the definition of the primary outcome in the protocol and that in the published report.... Sources of disagreement included the introduction of an entirely new primary outcome in the published report (in the case of 6 trials); failure to distinguish between primary and secondary outcomes in the published report, even though the protocol did distinguish between them (2 trials); relegation of a primary outcome in the protocol to a secondary outcome in the published report (2 trials); and failure to include in the published report one or more primary outcomes specified in the protocol (5 trials).

Furthermore, it appeared that failure of published articles to clearly and fully report results in terms of the original, pre-specified primary outcome variables occurred when these comparisons were not favorable to gabapentin. As the authors summarized:

Thus, trials with findings that were not statistically significant (P≥0.05) for the protocol-defined primary outcome, according to the internal documents, either were not published in full or were published with a changed primary outcome.

As shown in Figure 3, all the changes that took place between what was specified in the protocol, what was known before publication (as presented in the internal company research reports), and what was reported to the public led to a more favorable presentation in the medical literature of gabapentin's efficacy for unapproved indications.

They concluded:

We are concerned that the reporting practices observed in our analysis do not meet the ethical standards for clinical research or maintain the integrity of scientific knowledge. Fair and honest treatment of patients enrolled in clinical trials of any kind requires full, open, and unbiased reporting. Journal publication, a formalized platform for scientific discourse and dissemination of knowledge, should not be used as a marketing tool for off-label drug use.

Reporting biases such as those we describe here increase the likelihood that interventions will appear to be effective when they are not. Such biases can lead to the omission of negative findings in systematic reviews of intervention effectiveness and in evidence-based guidelines. For example, the 2005 Cochrane systematic review regarding the effectiveness of gabapentin for acute and chronic pain concluded that it is effective on the basis of published findings and should now be updated with the inclusion of unpublished information made available through litigation.

I believe that the article by Vedula et al is particularly important because it shows what appears to be systematic manipulation of the analysis and reporting of multiple clinical trials of the same drug (but for different indications) that had the effect of making the drug appear efficacious when it likely was not. Furthermore, the manipulation was concealed. The published research articles did not completely describe what the intended primary efficacy outcome variables were, did not provide results in terms of these variables, and instead provided results only in terms of variables that were chosen post-hoc as new primary outcome variables.

To address that latter point, I independently reviewed three of the research publications cited by Vedula et al.(2,3,4) All three were noted to have reported significant results favoring gabapentin in terms of a primary efficacy outcome variable that was not identified as such in the corresponding studies' original research protocols or reports (see the supplementary data provided with the New England Journal article.) Per my review, none of the three published articles offered any hint that what they reported as primary outcome variables were not the variables originally chosen in that capacity, nor did they identify what those original primary outcome variables were, or how comparisons made using them turned out.

The implications of the article by Vedula et al are very important. Hence, I was surprised that the article appeared without an accompanying editorial to discuss these implications, and that its publication did not generate much media interest.

So that gives me an opportunity to comment further.

One could start with the implications for evidence-based medicine. As noted above, a short description of the evidence-based medicine is medicine whose practice is informed by critical, rigorous review of the best available evidence from clinical research as revealed by systematic search of the published research literature, as well as by the clinician's understanding of biology and the medical and biopsychosocial context, and by the patient's own values. Evidence-based medicine depends on critical, rigorous review, but the review process is generally done under the assumptions that research publications honestly describe what was done and what its results were. The review process was never designed to detect dishonest reporting or find information that was deliberately concealed. Manipulation of research (design, analysis, and implementation), concealment of that manipulation, and outright suppression of research threaten the foundations of evidence-based medicine. Yet the article by Vedula et al is part of a growing body of evidence that such manipulation, concealment and suppression are widespread, and done to serve vested interests, often commercial.

That is a huge problem for proponents of evidence-based medicine, but also for physicians who want their practices to be based on science, for patients who want their care to be based on science, and for all those in society who see the advancement of medical science as a way to improve peoples' lives.

As senior author Professor Kay Dickersin noted in an interview with Bloomberg "The trouble is, as a scientist, the publication has always been held up to me as the truth. It's the scientific record. What this study indicated is we can't believe that record."

Furthermore, to be a bit more concrete, most physicians, patients, and policy makers depend on what appears to be honest clinical research to make decisions about individual care and health policy. Deliberate and deceitful manipulation of clinical research to favor sponsors' products has likely lead to excessive use of and payments for drugs and devices that are less effective than advertised, if not useless or dangerous. Thus, it is likely that such manipulation is partially responsible for ever increasing health costs and poor health outcomes.

Finally, we need to start thinking about how we can detect and compensate for manipulation of clinical research in the past, and deter such manipulation in the future. One possible deterrent would be, as was noted by Vedula et al, detailed clinical trials registries that contain complete information about trial protocols.  For this to be effective, there need to be mechanisms to assure compliance, and penalties for non-compliance.  Moreover, since clinical research is now global, the registries must have global scope, and enforced assurance of compliance must also be global.

Registries might decrease future manipulation and suppression of research.   No one has suggested, as far as I know, a systematic way to detect and correct for previous manipulation. It would require a major, global investigative effort to uncover manipulation, and it would be a major scientific and policy endeavor to reveal most suppressed research and correct most manipulations.

However, before anything is done, patients, physicians and policy makers must acknowledge and understand the problem.  Yet it seems that even discussing these may be topics that are very uncomfortable for some of us. The longer we shrink from addressing them, however, the worse will be the results for patients, physicians, science and society.

References


1. Vedula SS, Bero L, Scherer RW, Dickersin K. Outcome reporting in industry-sponsored tirals of gabapentin for off-label use. N Engl J Med 2009; 361: 1963-1971. Link here.


2. Mathew NT, Rapoport A, Saper J et al. Efficacy of gabapentin in migraine prophylaxis. Headache 2001; 41: 119-128. Link here.


3. Vieta E, Goikolea JM, Martinea-Aran A et al. A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive gabapentin for bipolar disorder. J Clin Psychiatr 2006; 67: 473-477.  Link here.


4. Caraceni A, Zecca E, Bonezzi C et al. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the gabapentin cancer pain study group. J Clin Oncol 2004; 22: 2909-2917. Link here.

Post Title → The Editorial that Wasn't: Evidence for Systematic Research Manipulation Undetectable by Critical Review

Did Pfizer Marketers Suppress and Manipulate Clinical Studies of Neurontin?

Here we go again. Multiple media sources reported on allegations that Pfizer Inc, the world's largest pharmaceutical company, attempted to manipulate and suppress clinical research results unfavorable to one of its products. Per the Wall Street Journal,

Pfizer Inc. marketers urged the suppression of medical studies that reached unfavorable conclusions about the effectiveness of the company's big-selling drug Neurontin [gabapentin], according to internal Pfizer documents submitted in a lawsuit against the company.

In 2004, Pfizer's Warner-Lambert unit pleaded guilty to felony charges that it promoted Neurontin for uses not approved by the Food and Drug Administration, including bipolar disorder and chronic nerve pain. The FDA originally approved the drug as an antiseizure treatment for epilepsy and in 2002 for one kind of pain related to shingles.

Pfizer paid $430 million to resolve the charges and reimburse state Medicaid programs for unapproved, or off-label, uses of Neurontin. Pfizer said it made sure there was no improper marketing after it purchased Warner-Lambert in 2000. Pfizer has booked about $12 billion in Neurontin sales since then and, though the drug is now subject to generic competition, it remains a strong seller.

Documents and emails released this week in the case in U.S. District Court in Boston suggest Pfizer's marketers influenced the drug's scientific record to boost sales at least until 2003 by declining to release or altering the conclusions of studies that found no beneficial effect from Neurontin for various off-label conditions.

Here are the details about how one study of gabapentin was allegedly suppressed.

According to documents in the Boston case, a European study done in the late 1990s by Warner-Lambert to measure Neurontin's use for diabetic nerve pain produced consternation at Pfizer after it failed to find a significant effect. 'I think we can limit the potential downsides of the ... study by delaying the publication for as long as possible,' wrote Michael Rowbothan, then Neurontin's marketing team leader, in a 2000 email sent after Pfizer bought Warner-Lambert. He added that 'it will be more important to how WE write up the study.'

The study's scientific manager, Beate Roder, wrote in an email to employees after Pfizer agreed to buy Warner-Lambert that she had been instructed "that we should take care not to publish anything that damages Neurontin's marketing success." Neurontin has been widely prescribed for diabetic nerve pain, according to market researchers.

In 2002, Angela Crespo, then Neurontin's senior marketing manager, emailed an outside firm that was contracted to write up the study's results: "We are not interested at all in having this paper published because it is negative!!" Pfizer declined to make the three employees in the emails available for interviews.

The company's writeup of the study was subsequently rejected by two medical journals. Some of the reviewers for these journals said the company was putting too rosy a spin on the results, the court documents show. The paper was never published, although Pfizer later summarized some of the study's results in a broad review published in 2003 in an obscure medical journal, Clinical Therapeutics.

The New York Times had some more detail,

In one example, the experts concluded that Pfizer had deliberately delayed release of a study that showed the drug had little effect against pain that is a complication of long-term diabetes, even as the outside researcher who was a lead investigator for the study, Dr. John Reckless of Bath, England, pushed to publish the unflattering findings on his own. Dr. Reckless’s office said Tuesday that he could not be reached for comment.

According to one September 2000 e-mail message by a Neurontin team leader at Pfizer, “The main investigator in the U.K. (Dr. Reckless) is keen to publish but this will have several ramifications.” The team leader later wrote, “I think we can limit the potential downside of the 224 study by delaying publication for as long as possible.”

Another series of e-mail messages had the subject line “Spinning Serpell,” a reference to an investigator on the study, Dr. Michael Serpell of Glasgow, Scotland. In the e-mail exchange a senior marketing manager for Pfizer and a professional medical writer discussed how to cast the results in a more favorable light for a poster presentation at a medical conference, the experts concluded.

“If Pfizer wants to use, present and publish this comparative data analysis in which two of the five studies compared make the overall picture look bad, how do we make it sound better than it looks on the graphs?” the medical writer asked.

In summary,

One of the experts who reviewed the documents, Dr. Kay Dickersin of the Johns Hopkins Bloomberg School of Public Health, concluded that the Pfizer documents spell out “a publication strategy meant to convince physicians of Neurontin’s effectiveness and misrepresent or suppress negative findings.”

Dr. Dickersin, the Johns Hopkins expert, said that of 21 studies she reviewed, five were positive and 16 negative, meaning they did not prove the drug was effective. Of the five positive studies, four were published in full journal articles, yet only six of the negative studies were published and, of those, two were published in abbreviated form.

This case is important in that it reveals the extent of involvement of Pfizer marketers in the how and whether clinical research is reported, and the effects of that involvement in terms of how often negative studies are suppressed. The specific tactics pushed by the marketers appeared to have included having professional ghost writers spin the data so that a negative study will "sound better than it looks," delaying unfavorable results, and when all else fails, suppressing the most unfavorable studies entirely. In the case of gabapentin, which does not seem to be a very good drug, this meant suppressing about two-thirds of the negative studies, which outnumbered the positive studies by a three to one ratio.

This unfortunately is another blow to the current paradigm of evidence-based medicine. The EBM paradigm calls for physicians to make optimal decisions for individual patients based on their knowledge of the clinical context, the patients' values and wishes, and a critical review of the best relevant evidence from clinical research. For the paradigm to work, the assumptions are that all relevant research can be found, and that the research studies, while imperfect, were not intentionally designed or reported to deceive the reader. Yet the case of gabapentin adds to fears that relevant evidence that is unfavorable to the interests of the drug, device, or biotechnology company which sponsored the work is likely to be suppressed by that sponsor, and that commercially sponsored research is often deliberately manipulated to make its results appear more favorable.

Also, as Professor Dickersin noted (reported by the WSJ), "in exchange for being experimented upon in trials, patients are told they are contributing to human knowledge. To withhold negative results from the public breaks that ethical obligation to such patients...."

The practical lessons:
- As we have said many times, physicians, patients, and policy-makers need to be extremely skeptical about the clinical research evidence base.
- On a policy level, if providers of health care goods and services are to continue to be allowed to sponsor clinical research that evaluates their products, no one from their marketing departments should be allowed any influence on such research
- However, since it may be impractical to prevent such influence, a more draconian but effective approach would be to ban such commercial firms from any direct involvement in human research meant to evaluate their products.

Post Title → Did Pfizer Marketers Suppress and Manipulate Clinical Studies of Neurontin?

A Multi-Dimensional Web

The important article in the Annals of Internal Medicine on the stealth marketing of Neurontin (see post here) was accompanied by an editorial (Henney JE. Safeguarding patient welfare: who's in charge. Ann Intern Med 2006; 145: 305-6.)

Its author, Dr Jane Henney, put the onus on physicians to address conflicts of interest involving pharmaceutical companies.

Steinman and colleagues' article provides numerous examples of conflicts that arise when physicians receive compensation or other benefits from manufacturers in exchange for assistance with the marketing of drugs for off-label uses. The burden of managing these conflicts is the responsibility of the physician. The first and foremost principle of conflict management is disclosure. Whether the audience is a single patient or a group of fellow physicians, when the physician has accepted financial or other support (for example, slide preparation) from a manufacturer and has not told the audience about the arrangement, then that physician has gone over the line.

Steinman and colleagues' article on gabapentin marketing and promotion points out in stark detail that no patient is well-served when a manufacturer engages in practices, whether inside or outside the law, that involve physicians in activities in which conflicts are present. But physicians are not passive participants: They can say 'No.'

We have recently posted about arguments that disclosing conflicts of interest in health care may not be sufficient to manage all their ill effects, and could possibly even enhance such effects.

Ironically (a word that I seem to be using a lot), Henney's editorial itself illustrates the ambiguities created by disclosure. In her introduction, she discloses, "I have been privileged to serve in a variety of roles, including that of oncologist, principal investigator, study manager, senior academic administrator, Commissioner of Food and Drugs at the U.S. Food and Drug Administration (FDA), and as board member for 3 Fortune 500 and Global 500 companies (AstraZeneca PLC, 2001 to present; AmerisourceBergen Corporation, 2002 to present; and Cigna Corporation, 2004 to present). "

This disclosure immediately raises questions about why the solution she advocated for the problem of stealth marketing indicated by the Neurontin case was merely disclosure, rather the abolition of particularly important conflicts of interest. Was she speaking as an academic leader of a medical center, or as someone with ficuciary responsibility to the stock-holders of a large pharmaceutical company (Astra-Zeneca), a company that acts as a middle-man between pharmaceutical manufacturers and patients and providers, including hospitals and academic medical centers (AmerisourceBergen), and/or a health insurer/ managed care organization (Cigna)?

Furthermore, all the organizations she leads ostensibly have conflicting interests, forming a multi-dimensional web. The role of these conflicting interests in controllling costs is at the heart of arguments for market based health care. In theory, pharmaceutical companies to maximize their profits want to maximize drug prices and prescribing volume. Companies that convey drugs to users and providers want to maximize profits by minimizing drug prices. Academic medical centers want to maximize their surpluses by minimizing the prices they pay for drugs and other goods and services, while maximizing their reimbursement from insurers. Insurers want to minimize reimbursements for drugs and reimbursements provided to hospitals. In theory, the competition resulting from these competing interests should control costs.

However, Dr Henney is one example of how the leadership of organizations with such ostensibly competing interests overlap. Does this mean that these organizations are not likely to negotiate as vigorously as the theory suggests? Does this suggest a reason why health care costs have not been controlled by the market model? And does this suggest that US health care diverges even more from an ideal free market than was heretofore believed?

Inquiring minds want to know.

Post Title → A Multi-Dimensional Web

The Stealth Marketing of Neurontin

The Annals of Internal Medicine just published an important paper on pharmaceutical company marketing practices. (Steinman MA, Bero LA, Chen MM, Landefeld CS. Narrative review: the promotion of gabapentin: an anlysis of internal industry documents. Ann Intern Med 2006; 145: 284-293.)

The background is that gabapentin (Neurontin) was approved as adjunctive treatment for complex partial seizures, and later for post-herpetic neuralgia. "In 2004 the Pfizer subsidiary Warner-Lambert settled litigation and admitted guilt in connection to charges that during the 1990s it violated federal regulations by promoting the drug for pain, psychiatric conditions, migraine, and other unapproved uses." As a consequence of the related litigation, a large number of documents about how Parke-Davis (the original manufacturer) marketed gabapentin became available, and were reviewed by Steinman et al.

Notable marketing practices employed are summarized below.

Continuing Medical Education

Teleconferences - "'Medical education drives this market!!' noted the author of a Parke-Davis business plan." Specific tactics included setting up "educational" teleconferences whose real goal was "to increase Neurontin new prescriptions by convincing non-prescribers to begin prescribing and current prescribers to increase their new prescription behavior." Furthermore, "In some cases, Parke-Davis helped establish the agenda and was able to surreptitiously monitor teleconferences in progress." Physician moderators were given, in at least one instance, an agenda which emphasized "how Neurontin evolved into a first line therapy option in your practice." Moderators were paid directly by Parke-Davis.

Speakers Bureaus - "Sales employees were encouraged to 'expand the speaker base—identify and train strong Neurontin advocates and users to speak locally for Neurontin'" A lecture series was meant to improve "public relations within the neurology community, etc., as well as [to impact] the volume of Neurontin new prescriptions" Speakers included department chairs and directors of clinical programs. "Members of the speakers bureau were invited to special meetings, where, in addition to lectures on the clinical use of gabapentin, they were updated on promotional strategies for the drug."

Programs Funded Through "Unrestricted Educational Grants" - These grants were made to "medical education and communication companies" [MECCs]. Although officially Parke-Davis did not control the content of resulting activities, "these same medical education companies also worked for Parke-Davis in several other roles, such as organizing teleconferences, coordinating advisory boards and consultants meetings, and conducting tactical planning to promote gabapentin. Because of these relationships, medical education companies had incentive to develop educational programs that were consistent with Parke-Davis's marketing goals and to control content in a way that reflected favorably on the sponsor." Furthermore, in one instance, "Parke-Davis representatives were invited to a curricular development meeting , recruited physicians to participate in the course , and followed attendance counts at each program meeting." Also, "Parke-Davis also sought to provide unrestricted educational grants to locally organized symposia at which it expected gabapentin to be favorably discussed. One memo recommended the following: 'Assist in the organization of a [major university hospital's] pain symposium ... .We will probably write them an unrestricted educational grant to help fund the project. In return, they will discuss the role of Neurontin in neuropathic pain, among other topics. They do have a very favorable outlook toward Neurontin.'"

Advisory Boards and Consultants Meetings - Although the ostensible purpose of such activities were to obtain feedback from physicians, for which they were paid, "other aspects of meetings were conducted in a manner more suggestive of promotional intent. For example, attendees at one consultants meeting were invited largely because of their high rates of anticonvulsant prescribing, and sales representatives were given 'trending worksheets' to track prescribing behavior before and after the event; at the meeting, 'participants were delivered a hard-hitting message about Neurontin'. Some meetings resembled educational conferences, with dozens of participants and an agenda dominated by lectures from physician 'faculty'. Other meetings seemed to focus on cultivating relationships with thought leaders, as in one meeting at which lecture notes for the regional business director notified attendees that 'we would like to develop a close business relationship with you'. Attendees were carefully selected. "As described by a medical education company that organized meetings, 'it is [our] policy to complete a literature search to determine who authors favorable articles on the topics outlined'".

Publications Strategy

"Parke-Davis employed a 'publication strategy,' the goal of which was to use research not as a means to gain FDA approval for new indications but 'to disseminate the information as widely as possible through the world's medical literature', generating excitement in the market and stimulating off-label prescribing despite the lack of FDA approval. This strategy focused primarily on expanding gabapentin use in neuropathic pain and bipolar disorders, for which detailed decision analyses projected the greatest revenue potential."

This strategy included suppression of research whose results were unfavorable to Parke-Davis interests. "As stated in a marketing assessment, 'The results of the recommended exploratory trials in neuropathic pain, if positive, will be publicized in medical congresses and published'. Similarly, in discussing 2 nearly identical trials that yielded conflicting results on gabapentin as seizure monotherapy, the 'core marketing team' concluded that 'the results of [the negative trial] will not be published'. (The positive trial was published, but we could not locate the negative trial on a PubMed search.)"

The strategy also included ghost-writing. "Beyond publishing its own clinical trials, Parke-Davis expanded the literature on gabapentin by contracting with medical education companies to develop review papers, original articles, and letters to the editor about gabapentin for $13 375 to $18 000 per article, including a $1000 honorarium for the physician or pharmacist author. For example, one 'grant request' from a medical education company to Parke-Davis proposed a series of 12 articles, each with a prespecified topic, target journal, title, and list of potential authors (to be 'chosen at the discretion of Parke-Davis'). This proposal noted that 'all articles submitted will include a consistent message ... with particular interest in proper dosing and titration as well as emerging [off-label] uses,' mirroring Parke-Davis promotional goals for the drug. In this case Parke-Davis requested that authors prepare articles and submit them for peer review. However, in another instance the medical education company offered substantial assistance in the development of manuscripts, reporting in a status report that at [the author's] request, we did an extensive literature search and submitted selected articles to him for reference ... . We have offered him help in identifying and collecting his appropriate cases, analyzing data, writing a manuscript, or whatever he needs'." Furthermore, "article sponsorship was often not disclosed, with 6 of 7 articles not acknowledging receipt of an honorarium from the medical education company (although 1 of these acknowledged support from Parke-Davis)."

Key Opinion Leaders and Clinical Trials as Marketing Opportunities

"Engaging physicians in the research process had potential benefits for Parke-Davis beyond the publications themselves, providing an opportunity to engage thought leaders, reward key physician customers, or influence prescribing. Marketing strategy documents stated that 'the list of key influencers should be ... kept aware of the availability of research opportunities in clinical trials' and recommended the 'funding of smaller studies ... with our key customers for investigation of Neurontin and pain'. Among the 40 thought leaders described, 5 requested or were allocated research funding ranging from $32 000 to $75 000 per person. "

"One notable example of the confluence between promotion and research was STEPS (Study of Neurontin: Titration to Effectiveness and Profile of Safety), an uncontrolled open-label study in which physicians were instructed to begin adjunctive gabapentin therapy in their patients with epilepsy and to keep increasing the dose until their patients were seizure-free, or until a maximum dosage of 3600 mg/d (twice the maximum FDA-approved limit) was achieved. More than 700 physicians were enlisted to participate, enrolling an average of 3 patients each (with a $300 payment for each patient enrolled). The published report of the study stated that it 'examined the effectiveness of gabapentin' in this dose range. However, company documents described the goal of the study as to 'teach physicians to titrate Neurontin to clinical effect' and 'to give neurologists the opportunity to titrate to higher doses (>1800 mg) when needed', central promotional goals at the time. Described as a 'key activity' for the implementation and support of marketing goals, 'indicators of success' for the study included increases in market share and use of higher doses of gabapentin. At least 6 of 9 authors of the published report had substantial financial relationships with Parke-Davis; they had participated in a total of 263 activities sponsored by Parke-Davis between 1993 and 1997, with requested or allocated payments ranging from $11 450 to $69 000 per author."

In summary, the documents reviewed showed how one pharmaceutical company (now merged into Pfizer Inc) disguised marketing activities as communications between physicians, continuing medical education programs, publication of scholarly articles, and clinical research. Although many of the activities involved physicians, often academic physicians, who were selected because of their favorable opinions of Neurontin, and/or encouraged to convey the company's marketing themes, that the company was involved in these activities, or that the physicians were paid or coached by the drug company was not made clear to the physicians who were the activities' targets.

Although this story involves only one company marketing one drug, it fits with other accounts of stealthy and deceptive marketing practices used by pharmaceutical companies and other health care organizations, and with other accounts of the willingness of some academic physicians to participate in such marketing activities while holding themselves out to be disinterested academics, not paid marketers.

For example, we have previously discussed how pharmaceutical companies have used MECCs to develop ghost-written articles that were later published as if they were disinterested scholarship. (See, for example, posts here and here.)

The additional evidence provided by Steinman et al suggests that deceptive marketing practices implemented with the assistance of academic physicians are more common than previously thought.

Physicians must be increasingly skeptical about educational and scholarly activities that may be disguised efforts at drug marketing.

Shame on the companies that have implemented such stealth marketing programs. Shame on the academic physicians who have taken money to help them out without revealing their financial interests to their physicians colleagues.

WHAT WE CAN DO?

I realize that sometimes the "bad news" conveyed on Health Care Renewal can be numbing, especially in the absence of a clear idea of what one can do in response to the bad news.

In this case, I have some opinions on what physicians can do.

Physicians should avoid any continuing medical education activity that appears to be biased in favor of particular products or in the interests of particular manufacturers. Physicians who end up attending such activities should at least aggressively challenge any bias they perceive.

Academic physicians, at a minimum, should disclose any financial ties they have to commercial firms that may affect their professional or scholarly communication. Ideally, physicians should refuse any financial arrangements that could convey even the appearance of participating in stealth marketing efforts. Academic physicians need to remember that their goals are honest teaching and research. If they want to go into marketing, they should go to work honestly for firms engaged in marketing.

Post Title → The Stealth Marketing of Neurontin