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'".
"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.
FDA is making progress inspecting foreign drug plants, but could do better - By some measures, the FDA has reduced the number of facilities that have gone without an inspection history to 33 percent of foreign plants.
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