A great number of studies and several meta-analyses have shown that journal articles on industry-sponsored trials report results on efficacy and harm, and draw overall conclusions, that are all favorable to the sponsors (Lundh et al. 2012). For many areas of medicine, articles reporting industry-sponsored research are nearly certain to come to positive conclusions. A standard explanation of industry’s favorable position focuses on the conflicts of interest that academics involved in industry- sponsored
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research have. The concern is that more-or-less independent researchers act to align their studies with funders’ interests, through those studies’ design, implementation, interpretation, and/or publication.
Let us consider the common image of industry-sponsored research. First, an independent researcher designs and proposes a study. Then, looking for support, that researcher approaches one or more drug companies. A company may choose to fund the research, either out of interest in the results or to buy goodwill, or both.
Then, the researcher performs the study, writes up a few articles on it, and submits them to journals. Along the way, the researcher might bias the study to support the sponsor’s interests by, for example, testing the experimental drug against an inap- propriate comparator or in an unrepresentative population or choosing statistical tests with success in mind.
However much one believes in the power of conflict of interest, it seems ques- tionable that conflicts of interest stemming merely from research funding could produce fairly consistent positive results by independent researchers. Luckily, we do not have to believe that researchers are so easily influenced, because the common image of sponsored research is wrong on key details of the actual processes of phar- maceutical research production. One is that most clinical trials are not in any inter- esting sense performed by independent researchers. A second is that the independent researchers who act as named authors on journal articles often neither design the studies nor write the articles. Instead, the pharmaceutical industry manages the pro- cess of producing and publishing research about drugs, from start to finish, from behind the scenes. Two main sets of actors in the process are contract research organizations (CROs) and publication planners. Together, they intervene substan- tially in the production and dissemination of pharmaceutical knowledge, in ways superficially similar to but substantively different from typical scientific and aca- demic research and publishing activities. This whole process is the “ghost manage- ment” (Sismondo 2007, 2009) of pharmaceutical knowledge, and it is partly through this process that companies establish positive scientific profiles for their drugs.
Contract Research Organizations
Companies can now pick and choose populations…in order to get a most pronounced drug benefit signal as well as a ‘no-harm’ signal.—Former CRO chief executive (quoted in Petryna 2009: 17)
The pharmaceutical industry sponsors a majority of the 40,000 new clinical trials initiated each year and 60,000 trials ongoing at any one time and provides roughly half of all funding for clinical trial research (CenterWatch 2009). Of this research, 70–75% is done by CROs, for-profit companies that perform research and develop- ment (Fisher 2009; Mirowski and Van Horn 2005). An indicator of their rising sig- nificance is that CRO revenues increased from US$1 billion in 1992 to an estimated
$27 billion in 2010.
Hegemony of Knowledge and Pharmaceutical Industry Strategy
CROs are involved in all different aspects of pharmaceutical industry research, from preclinical work through all phases of clinical research, and they perform 95%
of laboratory services related to trials. According to a 2005 survey of pharmaceuti- cal company departments that hired CROs, outsourcing serves a number of pur- poses. It saves costs (74%), protects the sponsoring company from risk (70%), enhances quality (67%), saves time (59%), and increases productivity (52%) (CenterWatch 2009). In addition, though not arising in the survey, CROs provide something that academic researchers leading clinical trials will not: data to pharma- ceutical companies with no strings attached. The data from a CRO study is wholly owned and controlled by the sponsoring company.
CROs conduct trials with one eye to the drug approval process and the other to the marketing of products. For both purposes, the pharmaceutical companies spon- soring the research prefer, and often need, trials that meet high formal standards within medicine—often randomized, controlled trials, considered the “gold stan- dard” of medical science. This requires access to large populations and often popu- lations in multiple countries. Available populations are the result of a number of factors, and recently these have been pushing more trials to the developing world and Eastern Europe. Costs per patient are considerably lower in the developing world than in North America or Western Europe. Many people in the USA and Western Europe are unwilling to participate in trials, and many are ineligible because they are already being treated. Wealthier countries can be “treatment satu- rated,” whereas elsewhere there are many potential subjects who are “treatment naïve.” Thus countries like India, for example, are well positioned to provide sub- jects; India’s Economic Times wrote in 2004: “The opportunities are huge, the mul- tinationals are eager, and Indian companies are willing. We have the skills, we have the people …” (Shah 2006: 17).
Most important for the argument of this chapter, though, is a point mentioned above: CROs have no interest in publishing the results under their own names. They simply produce data for their clients, and clients can use it to best advantage.
Publication Planning
Adis Communications works in partnership with clients to position their products at the right place, at the right time through: Hundreds of well-respected, and high-impact factor journals …. (Adis Communications 2006)
Although industry-sponsored articles about drugs in medical journals are often
“authored” by academics, authorship does not necessarily represent significant con- tributions to the research, design, or writing of the articles. If a pharmaceutical company is behind it, an article on a drug is almost always part of a dedicated “pub- lication plan,” designed and implemented by “publication planners.” In this process, authors typically make only modest contributions to articles. Here’s one email from a pharmaceutical company to an eventual author: “It will not be you personally who will have to write those articles but a ghost writer will do this for us/you and you
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kind of give your good name for this publication!” This email was accidentally included in correspondence forwarded to a journal editor in 2010, who quoted it at a publication planning conference.
From the few cases where there is hard data, it appears that roughly 40% of medical journal articles mentioning major new in-patent drugs are parts of publica- tion plans (Healy and Cattell 2003; Ross et al. 2008). This includes not only articles reporting on company-led trials but also some reviews, meta-analyses, and com- mentaries. Some planners work within pharmaceutical companies, but more work in independent agencies: more than 50 agencies advertise publication planning on the Internet. Some of these boast that they have hundreds of employees and handle many hundreds of manuscripts per year (individual planners handle dozens of man- uscripts per year). There are two competing international associations of publication planners that organize meetings and seminars. One of those associations, the International Society of Medical Planning Professionals, has more than 1000 mem- bers. Both it and its competing association, The International Publication Planning Association, hold annual conferences, and the latter hosts regional conferences.
Publication planning, then, is a sizeable activity.
Publication plans aim to maximize the value of research, in terms that are simul- taneously commercial and scientific. Thus, plans lay out the terms for constructing articles that establish consistent profiles for drugs. The publication planning team should be put in place early, said one presenter at a 2007 workshop for new plan- ners, “before too much data has gone unpublished.” Ideally, it would be in place for research design, and this is especially important when there is “need to create [a]
market” or create an “understanding of unmet need.”
It is worth quoting at length one publication plan’s description of planning itself:
Strategic publication planning provides the tactical recommendations necessary to develop a scientific platform within the biomedical literature to support the mar- ket positioning of an established product or the launch of a new product. The pro- cess of publication planning includes:
• An analysis of the characteristics of the market into which the product will be launched
• An analysis of competitive issues
• The expected product profile
• Identification of issues relevant to the disease state or primary indication for the product
• Development of a series of key communication messages addressing the major issues
• The availability of clinical and preclinical data to support the key communication messages
• Recognition of appropriate target audiences for each of the recommended publi- cation tactics
• Recommendations for publication vehicles (e.g., journals, meetings, congresses, etc.) for each publication activity (Wyeth 2002)
Hegemony of Knowledge and Pharmaceutical Industry Strategy
On its standard self-presentation, publication planning should be, though isn’t always, independent of marketing. It should be in the service of scientific knowl- edge about results. However, in their interactions with each other and with the phar- maceutical industry, planners recognize that their work has marketing value. “How are we going to create publications that have the right message, and a memorable message, for prescribers?” asked a planner, addressing attendees at the introductory workshop mentioned above. The websites of publication planning firms promote their work on that basis. Watermeadow Medical says that its “mission is to ensure that…messages reach and energize…target customers,” including through “hard- core scientific writing” (Watermeadow Medical 2007). Envision Pharma’s site says that “data generated from clinical trials programs are the most powerful marketing tools available to a pharmaceutical company” (Envision Pharma 2006). Ultimately, publication planning needs to generate revenue by providing information that increases sales.
Publication plans exist to serve the marketers, and yet, to some extent planners see part of their job as constraining marketers’ influence. It is only by stifling the marketing department’s efforts to hype the product that publication planners can do effective marketing to scientific audiences. Thus planners have to convince the mar- keters that their more subtle approach, with its limited range of tools, is the right one. This is a version of a common tension occurring when the most persuasive rhetoric is not marked as an explicit attempt to persuade. As already mentioned, to
“sell without selling” is a sales and marketing ideal. At least some of the time, mar- keting is best done if it is invisible.
Science can indeed mesh smoothly with marketing. The director of one publica- tion planning agency writes in an article that science and marketing are equal part- ners (Bohdanowicz 2005). Therefore, “Where shall we publish this study?” is paired with “Who are our customers?” And “What can we claim from the results?” is paired with “What are our customers’ needs?” In this image, science and marketing together determine what the research says and how the products can be sold.
Scientific standards are important, though. Meeting them constitutes part of what is considered ethical behavior and underpins the distinction between doing publica- tion planning and doing public relations. After planners persuade their sponsors that their work will provide a good return on investment, they want to obey ethical guidelines in the hands-on work they do and to adopt high scientific standards for the writing of each paper. In addition, publication planners can only succeed if their work displays high standards, so that their papers will be published to best advan- tage. Medical journals have high rejection rates, as high as 95% in the case of jour- nals such as the Journal of the American Medical Association and the British Medical Journal. Meanwhile, publication planners claim to have very high success rates, for example, an “acceptance rate on first submission of 94% for abstracts and 78% for manuscripts” (Gardiner-Caldwell Group 2007).
Authorship problems represent a major ethical concern for publication planners, in particular because of difficulties meeting the International Committee of Medical Journal Editors’ (ICMJE) criteria for authorship (ICMJE 2014). Academic authors,
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often referred to as KOLs, are valuable to the credibility of the manuscript and therefore essential to the whole project of publication planning. To leave analysis and writing to authors, though, will often result in a manuscript that does not serve the company’s interests. One experienced planner addressing colleagues at a 2011 conference jokingly illustrates the point, waving an imaginary manuscript in the air:
“What is this? They’re promoting the competitor!” Another calmly affirms that “the approach of having an industry-authored [industry-written] first draft is a good one.” Moreover, as depicted by planners, authors typically make few substantial contributions to the manuscripts they author, are slow to respond, and miss dead- lines. Some expect prominence in authorship order and even try to violate ethical practices, for example, by trying to remove acknowledgment of medical writers.
While the planners complain about deadbeat authors, they create the conditions for those deadbeats. According to one speaker’s estimate, 50% of companies show only the penultimate manuscript to authors, to solicit their input. It is likely that authors will have little to add to a well-crafted manuscript essentially ready for publication. That becomes especially likely if authors are given tight deadlines.
According to one whistle-blowing medical researcher, part of the problem he faced was that he received abstracts only after they were submitted (and accepted) for meetings and received manuscripts only days before the planners’ deadlines for journal submission. The orderly and efficient rollout of presentations and papers means that authors are likely to contribute little.
To produce a manuscript, planners must coordinate work by multiple parties they do not want to become authors, such as company statisticians, company and agency researchers, and medical writers. Perhaps some of these would meet authorship criteria, or perhaps no single person would, because the ICMJE maintains a concept of authorship that does not easily apply to cases of corporate production of manu- scripts. On the whole, research as managed by publication planners is hard to fit into the ICMJE’s framework, although it directly opposes the implicit ethical stance adopted by those criteria.
In this largely unseen process, pharmaceutical companies initiate and fund the planning, research, analysis, writing, and the placing of papers, and typically main- tain control of data throughout. In the corporate production of knowledge, medical writers, authors, planners, company scientists and statisticians all play roles, with the end goal of supporting the marketing of products.