by Markus Pohlmann
A lot is uncertain in Corona times. Many of us hope nolens volens that new medicines and vaccines will be developed. Thus, the door is wide open for speculation, charlatanism, influence peddling and big money. Reason for that is that the search for new active ingredients doesn’t always rely on scientific independence and the scientific integrity of decision-makers, researchers, and authors. Rather, it also hides manifested economic interests of the pharmaceutical industry and a covert “ghostly” system of influencing scientific research results and their dissemination. For example, Mucchielli recently tried to show that in the two most important bodies that decide on medication and clinical test procedures for Covid19 in France (the ‘Scientific Council’ (CS-COVID) and the ‘Committee for Analysis, Research and Expertise ‘(CARE)) there are a number of experts who have had close relationships with the pharmaceutical company Gilead in the past. The American pharmaceutical company has developed a license for Remdesivir, an antiviral drug used against Ebola (nonetheless never approved) that was promoted by these experts despite initially controversial and poor scientific results. Just recently a new study showed that it can significantly shorten the clinical treatment time by four days in more severe cases, but without influencing the mortality. The EU Commission then approved Remdesivir at the beginning of July 2020 as a medication for the pulmonary disease Covid-19.
With all the blessings of modern pharmaceuticals, the search for a Covid-19 medication or a vaccine falls also under the responsibility of a social system that has both beneficial and as well as harmful effects in science and in our health. Despite all regulatory efforts, scientific fraud, corruption and unauthorized interference are normal components of this system, and the red line between legitimate and illegitimate scientific support – even illegal ghostwriting and science fraud – is still blurred. This is partially because the social system operates largely covertly. Despite the constant effort for transparency, not a small part of the scientific production takes place in a dark field, which only legal processes – due to other offenses such as off-label marketing (see our blog dated May 24, 2019) – occasionally reveal.
Authorship in medical-pharmaceutical research
A crucial point in this instance are scientific authors and their scientific publications. When it comes to authorship in scientific journals, each subject has its own set of unwritten rules behind the facades of formal criteria. This also applies to the field of medical-pharmaceutical research. In many cases, as various studies show, the information on authorship does not consistently meet the criteria of the professional associations or magazines. Some of the authors who appear prominently on the articles have neither worked on them nor are they often aware of the details of the study. You are an author by status or position. This authorship, known as “gift, guest or honorary authorship”, is more common, for example, with the last authorship, which is nevertheless relevant for career, reputation and in appointment procedures. While the last authors are often “set” from the outset, there is a lively “gaming” when it comes to career-related mentions as the first author. You negotiate who is the first author of which publication and thus get the free ticket for a doctorate or a scientific career in the subject. At the same time, those who did actually prepare the results for an article in the background do not appear as authors.
In many countries, the “medical writers” are a widely accepted standard in the preparation and planning of publications. They write the articles, prepare them for submission in a specialist journal and – unnamed and unrecognized – often make a substantial contribution to the publication. Medical writing is often supported – especially in the USA – by outsourced companies, so-called MECCs (Medical Education and Communication Companies). These MECCs are largely profit-oriented and are largely financed by the pharmaceutical industry. In some cases, the MECCs also initiate clinical studies, the results of which are evaluated and professionally prepared for publication.
Easy to see, medical writing is a gateway for hidden marketing in the pharmaceutical industry and the boundary between scientific fraud and corruption is unclear. For example, the memorandum on the sentence against Pharmacia & Upjohn Company Inc. (Pfizer) in 2009 (in which a penalty of USD 2.3 billion was attributed) shows that the pharmaceutical companies commercialized their product “Bextra” through comprehensive and targeted “scientific” treatment strategies for treatment advertise for which it was not approved (approved indication: symptomatic treatment of rheumatoid arthritis and osteoarthritis also approval for the treatment of pain in primary dysmenorrhea). They initiated and funded articles on the curative effects of Bextra that were written by medical ghostwriters. The pharmaceutical company implemented a “manuscript development process”, the so-called “ghost management”, in which a core team planned potential publications and recruited authors for them. Well-known authors were sought, who then submitted the articles under their names in well-known journals. The role of the pharmaceutical company has not been adequately disclosed – a common practice in pharmaceutical knowledge production. This is exactly what ghostwriting means: A pharmaceutical manufacturer designs an article and pays a scientist (the “guest author”) a fee to put his name on it and to publish it in a peer reviewed journal. In addition, there can then be “goody” consulting and research assignments. The company is not buying his competencies, but his reputation. For example, in the case of the MSD (Merck, Sharpe and Dohm) pain reliever scandal surrounding Vioxx, one researcher had taken on a well-funded project, but the data analysis had already been completed by MSD. A senior researcher with a scientific article, says Marcia Angell, former editor-in-chief of the New England Journal of Medicine, brings more than 100,000 profit to a pharmaceutical company.
Similar tactics have also been used, for example, to convince doctors to prescribe and patients to take certain hormones during menopause. Doctors were paid by Wyeth, the manufacturer of the best-selling menopause hormone therapy, Prempro (equine estrogens and medroxyprogesterone acetate), to promote off-label use of the hormones. They explained that the preparation could prevent cardiovascular diseases and dementia in women. Speakers paid by Wyeth presented powerpoint slides at conferences, showing shrunken or dead brain cells in estrogen-free solutions. This is despite the fact that, according to a large-scale study, the administration of estrogens increased the risk of dementia and cognitive impairment in old age. This study, published in 2010, was part of the Women’s Health Initiative (WHI) and received funding from the United States Department of Health (NIH, National Institutes of Health). It referred to hormone therapies during the menopause and was based on data from 26,000 women aged 50 to 79. According to Fugh-Bergmann, experts associated with Wyeth swarmed out and criticized the study. They tried to demonstrate that estrogens prevented vascular damage in animal experiments. A large number of “ghostwritten” articles appeared (26 scientific articles were identified in the court documents alone), often coordinated by DesingWrite, an MECC. They explained that the WHI examination was a faulty study and that estrogen had a preventive effect. But the NIH commissions alone have been 70 members included who had received more than USD 1 million for advice, speeches, etc. from the pharmaceutical industry.
The results of the WHI study are still controversial today. In 2019, a meta-study published in “The Lancet” showed that permanent hormone doses not only increase the risk of heart attack and thrombosis, but also the risk of breast cancer. It evaluated individual data from over 500,000 women, including around 144,000 breast cancer patients and 425,000 women without breast cancer. But the scientific argument about advantages and disadvantages still continues. For us, however, the focus is not on who is scientifically right, but rather that the documents uncovered in many proceedings against Wyeth could show how aggressively the pharmaceutical industry is shaping the scientific knowledge process in accordance with its marketing interests. But medical ghostwriting has also been used in many other uncovered cases to promote the sale or off-label use of the supplements through ghost marketing. These include, to name a few, Zyprexa (olanzapine), Paxil (paroxetine), “Fen-Phen” (fenfluramine and phentermine, used for weight loss), Neurontin (gabapentin, approved for seizures), Vioxx (rofecoxib, an analgesic) and Zoloft (sertraline) Antidepressant).
Organizational deviance and crime in science
We are dealing with an environment that is conducive to deviance and crime, whose parties, despite the numerous lawsuits and high penalties, do not refrain from inadmissible influences and scientific fraud. The fact that science itself can be corrupted again and again has by no means only economic reasons. The competition in this field is fierce. A competition for reputation that works freely according to the Matthew effect: For to everyone who participate will moe be given; but from him who does not, even what he has will be taken away. At least, he’s running the risk of ending up on the substitute bench in a career game.
At the same time, science is not only a performance-oriented system in this area, but a primarily output-oriented system. As with papers and final theses, the time and effort required can be very different, but only the product delivered is graded. And this is no different with scientific articles. In the mills of article production, many would like to tread the path to the last author, to whom many articles are assigned by position and status, and for this it is beneficial to constantly increase the output. This hierarchically structured reputation competition opens up easy access for ghostwriting in the pharmaceutical industry. Sometimes, under great time pressure, what turns out to be appropriate is what appears to be simple and at the same time creates deadweight effects. And even if you are already an established last author: the reputation competition never ends. Socialized in this system, in which pharmaceutical companies make many things possible in a positive sense, a conflict of interest does not prevent a scientific publication, but is only required to be stated. And a justification of “medical ghostwriting” about the possible progress in knowledge is always very obvious. After all, the pharmaceutical industry in particular is bringing many drugs onto the market for which we are grateful in the event of illness or for which we, as in the case of Covid-19, are longing.
The merging of business and science?
This only becomes a problem for everyone if there is a fusion of business and science, i.e. the scientific cognitive process does not primarily follow truth criteria but economic interests. However, this is by no means always the case, and the frequent scandalization of connections that are too close shows how much the established social expectations are still aimed at separating the two spheres. However, this is becoming increasingly difficult to estimate if you not only know that negative results from clinical tests are published less often than positive ones. Rather, there is also the fact that negative results from industry-financed studies are published even less frequently than in any case, so this leads to an additional distortion of the knowledge process. As further evidence, an analysis of 1534 oncological studies came to the conclusion that studies with stated conflicts of interest (due to financing of the pharmaceutical industry) were significantly more likely to come to positive results regarding the treatment than studies without conflict of interest.
The exact proportions of articles based on medical ghostwriting are unknown. The data from various studies fluctuate between 7.9% and 27.6% of the articles published in established journals with peer review process. The large number of ethics, formal regulations and requirements laid down so far have not been able to solve the problem, as can be seen from the frequent scandals and fines paid by pharmaceutical companies. Rule violations are normal here, and serve to the benefit of the companies as well as the researchers, ghostwriters and scientists involved.
So, what can we do?
Here, as elsewhere, we advocate for setting-based prevention. We have to change the structures, the organizational forms. As demanded by the German Science Council in 2018, this may include expanding the funding of non-commercial clinical studies as well as the opportunities for permanent employment in medical-pharmaceutical research. In this way, it may be possible to mitigate the “rat race” with the “The Winner takes it all” effects.
But moreover, the separation of clinical and academic careers with the simultaneous formation of “bridges” in the form of a dual management structure of clinicians and researchers, as was demanded in Germany a long time ago, could somewhat alleviate the pressure that such unified model of clinical practice, research and teaching combined brings. In addition, the earning opportunities of the researchers would have to be adjusted to those of the clinically employed. (Haverich 2008).
But these are just a few ideas that have been under discussion for a long time. Perhaps the fight against Covid-19 now offers the opportunity to go one step further in this direction. In any case, given the prospect of huge profits in this ongoing struggle, more than enough commercial clinical trials can be expected.
Sources and further literature
Abraham, John. (2010) “The sociological concomitants of the pharmaceutical industry and medications.” Handbook of medical sociology 6: 290-308.
Bosch, Xavier, Bijan Esfandiari, and Leemon McHenry. (2012) “Challenging medical ghostwriting in US courts.” PLoS Med 9.1.
Chunlan, Zhao, and Rong Zhongkui. (2014) “Sociological Analysis on the Phenomenon of Ghostwriter.” Examinations Research 4: 2.
Coker LH, Espeland MA, Rapp SR, Legault C, Resnick SM, et al. (2010) “Postmenopausal hormone therapy and cognitive outcomes: the Women’s Health Initiative Memory Study (WHIMS)”. J Steroid Biochem Mol Biol 118: 304–10
da Silva, Jaime A. Teixeira, and Judit Dobránszki. (2016) “Multiple authorship in scientific manuscripts: ethical challenges, ghost and guest/gift authorship, and the cultural/disciplinary perspective.” Science and Engineering Ethics 22.5: 1457-1472.
Fugh-Berman, Adriane J. (2010) “The haunting of medical journals: how ghostwriting sold “HRT”.” PLoS Med 7.9 (2010): e1000335.
Halliburton, Murphy. (2018) “Ghost‐Managed Medicine: Big Pharma’s Invisible Hands. Sergio Sismondo, Manchester, UK: Mattering Press, 231 pp.” Medical Anthropology Quarterly 34.1 (2020): e1-e3.
Laskai, Anna. (2020) “Institutional Corruption Theory in Pharmaceutical Industry-Medicine Relationships: A Qualitative Analysis of Hungary and the Netherlands”. Springer Nature.
Lyon, Alexander, and Mark Ricci. “The Case of Wyeth, DesignWrite, and Premarin. (2012) ” Case Studies in Organizational Communication: Ethical Perspectives and Practices: 197.
Moffatt, Barton, and Carl Elliott. (2007). “Ghost marketing: pharmaceutical companies and ghostwritten journal articles.” Perspectives in biology and medicine 50.1: 18-31.
Mucchielli, Laurent. (2020) “Behind the French controversy over the medical treatment of Covid-19: The role of the drug industry.” Journal of Sociology.
Reshma Jagsi, Nathan Sheets, Aleksandra Jankovic, Amy R. Motomura, Sudha Amarnath, and Peter A. Ubel. Frequency, nature, effects, and correlates of conflicts of interest in published clinical cancer research. Cancer, Online May 11, 2009; Print Issue Date: June 15, 2009
Rothman, Sheila M., et al. (2013) “Medical communication companies and industry grants.” JAMA 310.23: 2554-2558.
Sismondo, Sergio. (2020) “Ghost-managing and gaming pharmaceutical knowledge. ” Gaming the Metrics: 123.
Sismondo, Sergio. (2007) “Ghost management: how much of the medical literature is shaped behind the scenes by the pharmaceutical industry?” PLoS Med 4.9: e286.
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Tonia, Thomai, Guido Schwarzer, and Julia Bohlius. (2013) “Cancer, meta-analysis and reporting biases: the case of erythropoiesis-stimulating agents.” Swiss medical weekly 143: w13776.