Outing Wyeth and Their Hired Ghosts

Margaret A. Winker, MD, Senior Research Editor for PLOS Medicine, reflects on the 2010 Policy Forum by Adriane Fugh-Berman that explored the medical literature manipulation behind hormone “replacement” therapy.

The results of the Heart Estrogen/progestin Replacement Study (HERS) and Women’s Health Initiative (WHI) randomized trials stand out as two of the most important and surprising findings in the recent medical literature. The trials showed that hormone “replacement” therapy (HT), which was touted to treat estrogen “deficiency” in menopausal women just as thyroxine is used to treat hypothyroidism, not only did not reduce risk of cardiovascular disease but even increased risk of coronary heart disease, breast cancer, stroke, and pulmonary embolism. These remarkable results were both public and personal: an obstetrics-gynecologist friend on vacation when the news broke was flooded with phone calls from patients who feared their increased risk and wanted to stop HT immediately. My mother, who I had strongly encouraged to take HT given its apparent benefits, had just stopped it after developing endometrial hyperplasia.  Of course, until the trials were published the evidence was observational with the known likelihood of confounding, but researchers had tried to control for those issues as best they could and had still found an association. The huge popularity of HT appeared to result from the available evidence, and the steady stream of papers supporting HT for a multitude of diseases including cardiovascular disease, Alzheimer’s disease, and stroke had seemed to indicate consensus around the importance of HT. Or did they?

Image Credit: David Merz, Flickr.

Image Credit: David Merz, Flickr.

The use of medical ghost writers by pharmaceutical companies was well established when Adriane Fugh-Berman’s paper was published in PLOS Medicine and the documents on which it was based posted (here and here). However, her revelations of Wyeth’s promotion of HT, culled from a collection of documents obtained from litigation brought by more than 14,000 plaintiffs who developed breast cancer while taking Prempro and made public when PLOS Medicine  and the New York Times intervened in the litigation, were remarkable for their breadth and impact, shocking even the most cynical reader. Wyeth used several medical writing firms, but one in particular, DesignWrite, developed and implemented a publication plan on behalf of Wyeth to promote “HRT… a drug in search of a disease” for a number of conditions, ultimately publishing four trial reports and 20 review articles, a total of “over 50 peer-reviewed publications, more than 50 scientific abstracts and posters, journal supplements, internal white papers, slide kits, and symposia.”

Fugh-Berman outlines in excruciating detail the lengths to which DesignWrite went to promote Wyeth’s product. Not only were “authors” enlisted to put their names on the ghostwritten pieces but the ghosts were careful to ensure the “authors’” hesitation about the lack of evidence or misleading messages did not undermine the underlying marketing messages. Responses to peer reviewers who challenged the flawed studies being cited implied that such criticisms were inappropriate: “The review of the current paper is not the appropriate place to criticize the methodologic flaws of published papers”, DesignWrite wrote for the authors.


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Category: 10th Anniversary | 4 Comments

PLOS Medicine’s Big Food Series: Shining a Spotlight on Industry’s Influence on Health

PLOS Medicine Deputy Editor, Paul Simpson, reflects on the PLOS Medicine Series on Big Food, which was published in 2012.

‘The Food Industry is Ripe for Scrutiny’ is the clarion call of the lead editorial that announced PLOS Medicine’s Big Food series. The series of eight commissioned articles was the brainchild of PLOS Medicine’s then Senior Magazine Editor, Jocalyn Clark (@jocalynclark), alongside guest editors for the series Marion Nestle (@marionnestle) and David Stuckler (@davidstuckler), and was published over three weeks in June and July 2012.

Image Credit: Todd Hryckowian, Flickr

Image Credit: Todd Hryckowian, Flickr

While the field of medicine has had a long interest in how global corporations influence human health, particularly the tobacco and pharmaceutical industries, the editors were inspired to commission the series because they noted a dearth of critical perspectives in the medical literature on the food industry’s role and competing interests in human health. This seemed especially pertinent as the global health community were and are increasingly focused on the health impact of two billion of the planets population being obese or overweight, while at the same time one billion people on the planet are hungry.

David Stuckler and Marion Nestle’s Essay, Big Food, Food Systems, and Global Health, clearly set the scene for the series by noting that, “food systems are not driven to deliver optimal human diets but to maximize profits.”  They highlighted three positions that public health advocates could adopt in relation to the food industry: The first is to do nothing and let the industry regulate itself; the second is to work in partnership with the industry; and the third is to take the view that there are inherent conflicts of interest between corporations that profit from unhealthy food and public health collaborations. Few in the field of public health would agree that self-regulation is likely to be optimal from a health perspective, others may see some merit in working alongside the food industry but in their essay the authors plant their flag firmly in the ground: “[W]e find no evidence for an alignment of public health interest in curbing obesity with that of the food and beverage industry.”


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Category: 10th Anniversary | 4 Comments

A Little Furry Test for Human Toxicity

PLOS Medicine Associate Editor Laureen Connell discusses a research article from 2014 in which Gary Peltz and colleagues described a new mouse model with a humanized liver that can replicate human-specific toxicity and improve safety of clinical trials.

Image credit: Rama, Wikimedia Commons.

Image credit: Rama, Wikimedia Commons.

In 1993, fialuridine (a nucleoside analogue used to treat hepatitis B virus infection) was tested in humans in a phase II trial after earlier preclinical testing in animals suggested the drug was safe. Some participants had a variety of severe reactions to the drug, including liver failure, lactic acidosis, and steatosis, which led to the death of five participants. Human-specific drug toxicity is a potential problem that requires screening early in drug development.  The development of accurate models in the lab to test drugs for toxicity before serious side effects arise during clinical trials in humans is an important part of developing therapeutics.  Also, more nucleoside analogues are being developed as therapeutics, and therefore improved screening tools are needed for human-specific toxicity. Peltz and colleagues recently explored this problem when they investigated whether testing fialuridine in a new mouse model would have predicted the problems found in humans during clinical trials.

Chimeric TK-NOG mice with humanized livers were generated in 2011 and have been used to predict human-specific drug metabolism and interactions with other drugs. These chimeric TK-NOG mice have been transplanted with human liver cells in order to establish a long-lived mature “human organ.” Previous mouse models used for testing drug toxicity in humans had many limitations and did not accurately predict toxicity in humans. The TK-NOG chimeric mouse was generated by expressing a herpes simplex virus type 1 thymidine kinase (TK) transgene within the liver of a highly immunodeficient mouse strain (NOG).  The mouse’s liver cells expressing the transgene were ablated by exposure to an antiviral drug, allowing transplanted human liver cells to develop into a humanized liver, with a three-dimensional architecture and gene expression pattern characteristic of mature human liver and containing only a small percentage of mouse liver cells.


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Category: 10th Anniversary | 2 Comments

Happy Birthday to PLOS Medicine

On the 10th anniversary of our first issue, the PLOS Medicine Editors reflect on some of our most interesting and influential articles.

Image Credit: Larry Peiperl

Image Credit: Larry Peiperl

This week PLOS Medicine celebrates the 10th anniversary of our first issue. Don’t worry, you don’t need to get us a present. Instead, you can celebrate with us by taking a stroll down memory lane and reading some of the most exciting and interesting articles from the past decade.

We’ve chosen eight articles and one collection that highlight the breadth and influence of PLOS Medicine, from publishing ethics to public health policy to translational medical advances and more.

Starting today and over the next week, Speaking of Medicine will be publishing posts written by the editors of PLOS Medicine explaining what each article is about, what makes it exciting and important, and reflecting on its influence on the field since it was published.

Post 1 of 8:

A little furry test for human toxicity” by Laureen Connell, about Fialuridine Induces Acute Liver Failure in Chimeric TK-NOG Mice: A Model for Detecting Hepatic Drug Toxicity Prior to Human Testing the 2014 translational study in which Gary Peltz and colleagues described how a new mouse model with a humanized liver can replicate human-specific toxicity and improve safety of clinical trials.

Post 2 of 8:

PLOS Medicine’s Big Food Series: Shining a Spotlight on Industry’s Influence on Health” by Paul Simpson, about the series of eight commissioned articles that considered the various ways food corporations influence global human health.

Post 3 of 8:

Outing Wyeth and Their Hired Ghosts” by Margaret Winker, about The Haunting of Medical Journals: How Ghostwriting Sold “HRT”, Adriane Fugh-Berman’s 2010 Policy Forum that explored a pharmaceutical company’s manipulation of the medical literature to promote a product.

Post 4 of 8:

Quantifying the dirty nature of war” by Amy Ross, about The Dirty War Index: A Public Health and Human Rights Tool for Examining and Monitoring Armed Conflict Outcomes, Madelyn Hsiao-Rei Hicks and Michael Spagat’s 2008 Policy Forum that proposed a new tool to quantify the harm done by certain weapons and warfare tactics on civilians.

Post 5 of 8:

Pulling back the curtain on lethal injection” by Thomas McBride, about Lethal Injection for Execution: Chemical Asphyxiation? the 2007 research article by Leonidas Koniaris and colleagues that investigated whether lethal injection actually produces a consistently painless death.

Post 6 of 8:

The truth about standardized packaging? Blow some my way” by Linda Nevin, about Representation and Misrepresentation of Scientific Evidence in Contemporary Tobacco Regulation: A Review of Tobacco Industry Submissions to the UK Government Consultation on Standardised Packaging, in which Selda Ulucanlar and colleagues deconstructed advocacy documents submitted to the UK and demonstrated a meaningful distinction between scientist and advocate.

Post 7 of 8:

Voluntary Male Circumcision as HIV Prevention in Africa” by Linda Nevin, about the first randomized controlled trial of voluntary medical male circumcision.

Post 8 of 8:

I’ve got a (lot of) little (check)lists” by Virginia Barbour, about CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomised Trials and Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. This pair of guidelines, published in 2009 and 2010, presented medical researchers and publishers with standards for reporting to improve the way we read, assess, test, and reproduce science.

 

Category: 10th Anniversary | 3 Comments

Improving the health of pre-adolescent children: The latest update to the Pediatric Medicine Collection

In celebration of PLOS Medicine’s 10th birthday, we announce an exciting update to the Pediatric Medicine Collection, highlighting new articles focusing on the health needs of 5 to 10 year old children globally.

In January 2014 PLOS Medicine launched a call requesting papers on the Health of Pre-Adolescent Children, and in light of PLOS Medicine’s own 10 year anniversary, the theme of the call was chosen with the aim to contribute to a better understanding of children who live beyond their 5th birthday but aren’t yet at adolescence. This resulting collection has brought together a broad range of research and commentary.

pediatric_medicineFeatured work in this latest update

Authors Angela Donin and colleagues invited 9-10 year old children to participate in a study examining risk factors for type 2 diabetes. By measuring the levels of insulin, glucose, and other markers, participants reported how often they ate breakfast. It was concluded that children who ate breakfast infrequently had higher fasting insulin levels and increased insulin resistance than children who ate breakfast every day who displayed a favourable type 2 diabetes profile in comparison.

A recent policy forum by Sumit Gupta and co-authors drew attention to the growing need for national childhood cancer strategies in low- and middle-income countries. Amongst severe resource constraints, deficits in infrastructure and other pressing health needs, pediatric oncology resourcing has yet to be translated through from high-income countries. The authors outline why pediatric cancer should now be considered a global child health priority.

Researchers from New Zealand attempted to evaluate the importance of using hand sanitizer for reducing illness in school children. Following a parallel-group cluster randomised trial across 68 primary schools, Patricia Priest and Joanne E McKenzie and colleagues discovered that the provision of hand sanitizer did not reduce the number of school absences due to a specific illness.

 

Through this collection we hope to provide a broad platform for the dissemination of new high-quality evidence and analysis of conditions that affect pre-adolescent children from around the world.

 

Please visit the collection at: www.ploscollections.org/pediatricmedicine

Or read the Flipboard version: http://flip.it/SzfOB

Category: 10th Anniversary, Collections | 2 Comments

Global Health Security and the NTDs

Peter Hotez, co-Editor in Chief of PLOS NTDs, comments on President Obama’s call for global action to prepare for future disease outbreaks and to treat biological threats as issues of national and global security.

globe light

Glyn Lowe

In a landmark White House summit last week President Barack Obama addressed health ministers from more than 40 countries, in addition to leaders from several international health organizations.  His welcomed message was that highly lethal and widespread epidemics such as the West African Ebola outbreak are more than public health threats.  Instead these devastating infections when they affect or threaten large populations also have dire economic consequences and themselves are highly destabilizing leading to further breakdowns in already fragile systems and infrastructures.  In this sense Ebola is a direct and serious threat to national and global securities.

This is not the first time we have seen epidemics threaten global security. We saw such connections during the SARS pandemic in 2002-03, again with the emergence of avian influenza, and especially during the H1N1 influenza pandemic of 2009.  These outbreaks together with concerns about bioterrorism were underlying reasons why BARDA (The Biomedical Advanced Research and Development Authority) was established within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services (DHHS).
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Category: General | 4 Comments

PLOS Medicine launches a new Collection on Universal Health Coverage

A new PLOS Medicine collection, Monitoring Universal Health Coverage, provides technical details and country-level experience of the implementation, monitoring, and evaluation of Universal Health Coverage, adding much needed insight to the global conversation on this topic.

Universal Health Coverage (UHC) is the desired outcome for health system performance, whereby all people who need the full spectrum of health services – promotion, prevention, treatment, rehabilitation and palliation – receive them according to need and without resulting in financial hardship.

Image Credit: PLOS

Image Credit: PLOS

The high-profile nature of the event held at The Rockefeller Center (more information here) at which the Collection will launch is fitting for the topic that has emerged as front-runner of the post-2015 development agenda. UHC has been the focus of much work and effort by the international community in order to turn its broad aims into an actionable framework.
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Category: General | 1 Comment

Ebola: a Blind Outbreak

Grazia Caleo of Médecins Sans Frontières (MSF) UK describes her experiences as a medical epidemiologist during the Ebola outbreak in Kailhun, Sierra Leone.

In José Saramago’s book, Blindness, he describes an epidemic of an unknown infection that causes people to lose their sight; a single person remains uninfected to bear witness to the anger, chaos, violence and death generated by the spread of disease.

In the novel, humanity’s descent into blindness represents the loss of reason, and shows how fear can cause dramatic social breakdown; at the same time, the clear vision of one person represents the opportunity to restore light.

What I saw in Sierra Leone as a medical epidemiologist reminded me of Saramago’s book.

I saw ‘blindness’ circulating in villages and amongst local and international Ebola ‘experts’; I saw wisdom among the patients who survived and the doctors and nurses who cared for them.

I saw the under-estimation of the risk and consequences of Ebola in an area bordering three countries; the fear caused by rumours; the late communication with villagers about Ebola and its spread; the huge numbers of patients dying in front of us without our being able to provide them with treatment; the missed opportunity to trace contacts and to apply the simple rule of previous outbreaks: ‘time, place, person’. All of these contributed to a blind response.

Image credit: MSF

Image credit: MSF


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Category: General, MSF | Tagged | 2 Comments

In Honor of Dr. Elisabetta Ullu

Kasturi Haldar, PLOS Pathogens Editor-in-Chief, reflects on Elisabetta Ullu’s pioneering contributions to the understanding of molecular mechanisms of RNAi in T. brucei.

Dr. Elisabetta Ullu.  Image credit: Yale

On the eve of 25th anniversary of the premier Molecular Parasitology Meeting (MPM) held at the Marine Biological laboratory at Woods Hole MA, we reflect on the tremendous accomplishments of the field presented at this meeting, ranging from leading therapeutics in global parasitic diseases as well as fundamental mechanisms enabling development of treatments in seemingly disparate disease states, like tumor biology and autoimmunity.  But the excitement is burdened with hearts full of sadness that Dr. Elisabetta Ullu, a beacon in the field and past MPM organizer, passed away on September 8, 2014 after a heroic battle against cancer.

Dr. Ullu joined the faculty of Yale University School of Medicine as an Assistant Professor in 1984, where she rose through the ranks to Professor of Medicine and Cell Biology.  Her laboratory pioneered in molecular mechanisms of RNA biology in the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness and a portal for RNA based mechanisms at cellular and organismal levels.  Professor Ullu and Prof. Chris Tschudi (her partner in science and life) discovered the novel mechanism of ‘RNA interference’ (RNAi) by which T. brucei blocks the expression of its genes.   Broad acceptance of the central role of RNAi for cells in general, was a 2006 Nobel Prize shared by Andrew Fire and Craig Mello, for their work in nematodes.  Ullu’s findings were transformational to determine functions of proteins encoded by parasite genes, which is key to the discovery of new therapies urgently needed for sleeping sickness. She received many honors and accolades for her work, the most recent being the American Society for Biochemistry and Molecular Biology’s inaugural Alice and C. C. Wang award in 2012, for seminal contribution to the field of Molecular Parasitology.
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Category: General, Trypanosomiasis | Tagged , , , , , , | 1 Comment

When Implementing Universal Health Coverage, Context Matters

As the WHO’s Millennium Development Goals reach their final phase, Sara Gorman reflects on what we have learned about how political, cultural and financial contexts impact the success of universal health coverage systems. 

Image Credit: Edith Soto, Flickr

Image Credit: Edith Soto, Flickr

In May of 2013, Margaret Chan affirmed the WHO’s commitment to achieving universal health coverage worldwide, proclaiming “universal health coverage is the single most powerful concept that public health has to offer”. For Chan, public health measures such as universal health coverage represent a key component of development work in the 21st century. As the Millennium Development Goals (MDGs) begin to wind down with their 2015 expiration date looming, the WHO has turned its attention toward the next set of goals for world health. With statistics revealing that more than 100 million are pushed into poverty each year due to excessive health care costs, it seems ever more urgent to advocate for universal health coverage, spreading the costs across entire populations.
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Category: General | 5 Comments