Summary Points -/- Some 1500 documents revealed in litigation provide unprecedented insights into how pharmaceutical companies promote drugs, including the use of vendors to produce ghostwritten manuscripts and place them into medical journals. Dozens of ghostwritten reviews and commentaries published in medical journals and supplements were used to promote unproven benefits and downplay harms of menopausal hormone therapy (HT), and to cast raloxifene and other competing therapies in a negative light. Specifically, the pharmaceutical company Wyeth used ghostwritten articles to mitigate (...) the perceived risks of breast cancer associated with HT, to defend the unsupported cardiovascular “benefits” of HT, and to promote off-label, unproven uses of HT such as the prevention of dementia, Parkinson's disease, vision problems, and wrinkles. Given the growing evidence that ghostwriting has been used to promote HT and other highly promoted drugs, the medical profession must take steps to ensure that prescribers renounce participation in ghostwriting, and to ensure that unscrupulous relationships between industry and academia are avoided rather than courted. (shrink)

Pharmaceutical companies fund the bulk of clinical research that is carried out on medications. Poor outcomes from these studies can have negative effects on sales of medicines. Previous research has shown that company funded research is much more likely to yield positive outcomes than research with any other sponsorship. The aim of this article is to investigate the possible ways in which bias can be introduced into research outcomes by drawing on concrete examples from the published literature. Poorer methodology in (...) industry-funded research is not likely to account for the biases seen. Biases are introduced through a variety of measures including the choice of comparator agents, multiple publication of positive trials and non-publication of negative trials, reinterpreting data submitted to regulatory agencies, discordance between results and conclusions, conflict-of-interest leading to more positive conclusions, ghostwriting and the use of seeding trials. Thus far, efforts to contain bias have largely focused on more stringent rules regarding conflict-of-interest (COI) and clinical trial registries. There is no evidence that any measures that have been taken so far have stopped the biasing of clinical research and it’s not clear that they have even slowed down the process. Economic theory predicts that firms will try to bias the evidence base wherever its benefits exceed its costs. The examples given here confirm what theory predicts. What will be needed to curb and ultimately stop the bias that we have seen is a paradigm change in the way that we treat the relationship between pharmaceutical companies and the conduct and reporting of clinical trials. (shrink)

It is by now no secret that some scientific articles are ghost authored – that is, written by someone other than the person whose name appears at the top of the article. Ghost authorship, however, is only one sort of ghosting. In this article, we present evidence that pharmaceutical companies engage in the ghost management of the scientific literature, by controlling or shaping several crucial steps in the research, writing, and publication of scientific articles. Ghost management allows the pharmaceutical industry (...) to shape the literature in ways that serve its interests. This article aims to reinforce and expand publication ethics as an important area of concern for bioethics. Since ghost-managed research is primarily undertaken in the interests of marketing, large quantities of medical research violate not just publication norms but also research ethics. Much of this research involves human subjects, and yet is performed not primarily to increase knowledge for broad human benefit, but to disseminate results in the service of profits. Those who sponsor, manage, conduct, and publish such research therefore behave unethically, since they put patients at risk without justification. This leads us to a strong conclusion: if medical journals want to ensure that the research they publish is ethically sound, they should not publish articles that are commercially sponsored. (shrink)

Leopards break into the temple and drink to the dregs what is in the sacrificial pitchers; this is repeated over and over again; finally it can be calculated in advance, and it becomes part of the ceremony.–Franz KaflaFor more than two decades, significant controversies have been brewing over the efficacy and safety of Selective Serotonin Reuptake Inhibitors and other treatments for depression, and also over the expansion of their use for the treatment of a variety of other conditions. These controversies (...) culminated, in June 2004, with alawsuit intended by Eliot Spitzer, Attorney General of the State of New York. The lawsuit accused pharmaceutical giant GlaxoSmith-Kline of “repeated and persistent fraud by misrepresentation, concealing and otherwise failing to disclose to physicians information in its control concerning the safety and effectiveness of its antidepressant medication paroxetine” in treating children and adolescents suffering from depression. (shrink)

Leopards break into the temple and drink to the dregs what is in the sacrificial pitchers; this is repeated over and over again; finally it can be calculated in advance, and it becomes part of the ceremony.–Franz KaflaFor more than two decades, significant controversies have been brewing over the efficacy and safety of Selective Serotonin Reuptake Inhibitors and other treatments for depression, and also over the expansion of their use for the treatment of a variety of other conditions. These controversies (...) culminated, in June 2004, with alawsuit intended by Eliot Spitzer, Attorney General of the State of New York. The lawsuit accused pharmaceutical giant GlaxoSmith-Kline of “repeated and persistent fraud by misrepresentation, concealing and otherwise failing to disclose to physicians information in its control concerning the safety and effectiveness of its antidepressant medication paroxetine” in treating children and adolescents suffering from depression. (shrink)

In this case study from litigation, we show how ghostwriting of clinical trial results can contribute to the manipulation of data to favor the study medication. Study 329 for paroxetine pediatric use was negative for efficacy and positive for harm. Yet the ghostwritten publication from this study concluded that paroxetine provided evidence of efficacy and safety and continues to be influential. Despite the role of named authors in revisions of the manuscript, the sponsor company remained in control of the message.