Tag: Pfizer

Cytotec misoprostol dans le déclenchement de l’accouchement : arrêt de commercialisation proche

Le Cytotec, médicament détourné de son usage, va être retiré du marché

… Malgré les différentes mises en garde de l’ANSM, le Cytotec reste majoritairement utilisé hors AMM dans des indications en obstétrique, soit pour déclencher l’accouchement à partir de 37 semaines d’aménorrhée soit dans l’interruption volontaire de grossesse médicamenteuse (IVG).

L’ANSM rappelle que cette utilisation hors AMM peut entraîner des effets indésirables graves pour la mère et l’enfant, comme la survenue d’une rupture utérine (déchirure du muscle utérin), d’hémorragies ou d’anomalies du rythme cardiaque fœtal.

Aussi, le laboratoire Pfizer a décidé d’arrêter la commercialisation de Cytotec. En accord avec l’ANSM, cet arrêt sera effectif le 1er mars 2018…

Communiqué ANSM
  • Cytotec (misoprostol) : arrêt de commercialisation à compter du 1er mars 2018 – Communiqué, ANSM, 20/10/2017.
  • Mise en garde sur les risques potentiels liés à l’utilisation hors AMM du Cytotec (misoprostol) dans le déclenchement de l’accouchement et toute autre utilisation gynécologique (25/02/2013) – Point d’information, ANSM, 25/02/2013.
Articles de Presse:
  • Le Cytotec, médicament détourné de son usage, va être retiré du marché, lemonde, 19/10/2017
  • Le Cytotec® sera retiré du marché en 2018, Allodocteurs, 19/10/2017.
  • Cytotec : “On a considéré mon bébé comme un produit à rentabiliser”, francetvinfo, 19/10/2017

Medical, scientific organisations panel members problematic financial relationships with industry

A Comparison of DSM-IV and DSM-5 Panel Members’ Financial Associations with Industry: A Pernicious Problem Persists, 2012

Summary Points

  • The American Psychiatric Association (APA) instituted a financial conflict of interest disclosure policy for the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM).
  • The new disclosure policy has not been accompanied by a reduction in the financial conflicts of interest of DSM panel members.
  • Transparency alone cannot mitigate the potential for bias and is an insufficient solution for protecting the integrity of the revision process.
  • Gaps in APA’s disclosure policy are identified and recommendations for more stringent safeguards are offered.

Introduction

A Comparison of DSM-IV and DSM-5 Panel Members’ Financial Associations with Industry: A Pernicious Problem Persists, PLOS Medicine, dx.doi.org/10.1371/journal.pmed.1001190, March 13, 2012.

All medical subspecialties have been subject to increased scrutiny about the ways by which their financial associations with industry, such as pharmaceutical companies, may influence, or give the appearance of influencing, recommendations in review articles and clinical practice guidelines. Psychiatry has been at the epicenter of these concerns, in part because of high-profile cases involving ghostwriting and failure to report industry-related income, and studies highlighting conflicts of interest in promoting psychotropic drugs. The revised Diagnostic and Statistical Manual of Mental Disorders (DSM), scheduled for publication in May 2013 by the American Psychiatric Association (APA), has created a firestorm of controversy because of questions about undue industry influence. Some have questioned whether the inclusion of new disorders (e.g., Attenuated Psychotic Risk Syndrome) and widening of the boundaries of current disorders (e.g., Adjustment Disorder Related to Bereavement) reflects corporate interests. These concerns have been raised because the nomenclature, criteria, and standardization of psychiatric disorders codified in the DSM have a large public impact in a diverse set of areas ranging from insurance claims to jurisprudence. Moreover, through its relationship to the International Classification of Diseases, the system used for classification by many countries around the world, the DSM has a global reach.

After receiving criticism that DSM-IV had no financial disclosure of panel members, to its credit the APA instituted a mandatory disclosure policy. The DSM-5 panel members are required to file financial disclosure statements, which are expected to be listed in the publication, and the APA has made a commitment to improve its management of financial conflicts of interest (FCOIs).

This new APA requirement makes the DSM’s disclosure policy more congruent with most leading medical journals and federal policies on FCOI. FCOIs are widely recognized as problematic because of the data showing a clear connection between funding source and study outcome whereby results are favorably biased toward the interests of the funder —what has been referred to as the “funding effect”. Some have argued that greater transparency of financial interests may facilitate a decline in FCOIs and a decrease in the potential bias that accompanies them, and that it may encourage professionals and consumers to more critically evaluate medical information. Others are not sure that disclosure will reduce FCOIs and the potential for bias, because transparency alone just “shifts the problem from one of ‘secrecy of bias’ to ‘openness of bias’”. Additionally, there is the concern that disclosure may open the door for subterfuge. That is, when researchers or panel members list every affiliation that they have ever had, including funding from federal agencies, it can create a “signal-to-noise problem,” thereby obscuring the truth about deeply problematic financial relationships with industry.

We have reported elsewhere on industry relationships with DSM-5 task force members. Although the composition of the task force has changed slightly since its formation in 2007 (e.g., Pilecki et al. found 72% of the members had ties in early 2011) industry relationships persist despite increased transparency. Currently, 69% of the DSM-5 task force members report having ties to the pharmaceutical industry. This represents a relative increase of 21% over the proportion of DSM-IV task force members with such ties (57% of DSM-IV task force members had ties). This finding is congruent with emerging data from fields outside of psychiatry suggesting that transparency of funding source alone is an insufficient solution for eliminating bias.

In 2006 we analyzed all DSM-IV panel members’ financial associations with industry. We have undertaken a similar analysis for DSM-5 panels, which allowed us to compare the proportions of DSM-IV and -5 panel members who have industry ties. There are 141 panel members on the 13 DSM-5 panels and 29 task force members. The members of these 13 panels are responsible for revisions to diagnostic categories and for inclusion of new disorders within a diagnostic category.

Three-fourths of the work groups continue to have a majority of their members with financial ties to the pharmaceutical industry. It is also noteworthy that, as with the DSM-IV, the most conflicted panels are those for which pharmacological treatment is the first-line intervention. For example, 67% (N = 12) of the panel for Mood Disorders, 83% (N = 12) of the panel for Psychotic Disorders, and 100% (N = 7) of the Sleep/Wake Disorders (which now includes “Restless Leg Syndrome”) have ties to the pharmaceutical companies that manufacture the medications used to treat these disorders or to companies that service the pharmaceutical industry.

Gaps in APA’s Disclosure Policy

Although the APA has made the disclosure of FCOIs of DSM panel members more transparent, there are important gaps in the current policy that need to be addressed:

  1. The current APA disclosure policy does not require panel members to specifically identify speakers’ bureau membership but rather cloaks it under “honoraria.” (A speakers’ bureau usually refers to an arrangement between a commercial entity or its agent whereby an individual is hired to give a presentation about the company’s product. The company typically has the contractual right to create and/or control the content of the presentation.) Therefore, despite increased transparency, it remains unclear how many individuals participate on speakers bureaus, because panel members may simply list “honoraria.” None of the DSM panel members identified participation on a speakers bureau. When we did an internet search of the 141 panel members, we found that 15% had disclosed elsewhere that they were members of drug companies’ speakers bureaus or advisory boards. These internet searches were conducted for sources published in the years 2006 (1 year before the task force was appointed) to 2011, a time period congruent with published research on financial conflicts of interest. Searches included peer-reviewed articles, conferences, participation in continuing medical education events (i.e., courses and/or seminars for health professionals) and self-reporting of any industry ties following interviews with the media. Speakers bureau and advisory board participation were included in our analysis only when there was unambiguous information (e.g., “Dr. Smith discloses that he serves on the speakers bureau for Eli Lilly and Pfizer”) and both authors (LC, SK) were in agreement. The nature of these relationships needs to be spelled out more precisely; speakers bureau participation is usually prohibited elsewhere (e.g., for faculty in medical schools), as it is widely recognized to constitute a significant FCOI. Pharmaceutical companies refer to individuals who serve on speakers bureaus as “key opinion leaders” (KOLs) because they are seen as essential to the marketing of diseases as well as drugs.
  2. Exclusions to the APA DSM-5 disclosure policy include unrestricted research grants; that is, panel members are not required to disclose unrestricted research grants from industry. However, we would argue that this exclusion allows for commercial interests to be reflected in the revision process: there is no evidence to suggest that simply because money comes in the form of a large “unrestricted” research grant it does not create an obligation to reciprocate or invoke an implicit bias.
  3. The current policy places high and arbitrary threshold limits on monies allowed from industry: DSM panel members are allowed to receive US$10,000 per year from industry (e.g., for consultancies), and panel members are allowed to have up to US$50,000 in stock holdings in pharmaceutical companies.
  4. In contrast to other disclosure policies (e.g., the Physician Payments Sunshine Act of 2007 and the 2011 US National Institutes of Health policy on conflicts of interest), APA’s policy does not require disclosure of the amount of money received from industry.

However, transparency alone cannot mitigate bias. Because industry relationships can create a “pro-industry habit of thought”, having financial ties to industry such as honoraria, consultation, or grant funding is as pernicious a problem as speaker’s bureau participation. Over four decades of research from social psychology clearly demonstrates that gifts—even small ones—create obligations to reciprocate. Also, because of the enormous influences of diagnostic and treatment guidelines, the standards for participation on a guideline development panel should be higher than those set for an average faculty member.

Conclusion

The DSM-5 will be published in about 14 months, enough time for the APA to institute important changes that would allow the organization to achieve its stated goal of a “… transparent process of development for the DSM, and …an unbiased, evidence-based DSM, free from any conflicts of interest” . Toward that goal we believe it is essential that:

  1. As an eventual gold standard and because of their actual and perceived influence, all DSM task force members should be free of FCOIs.
  2. Individuals who have participated on pharmaceutical companies’ Speakers Bureaus should be prohibited from DSM panel membership.
  3. There should be a rebuttable presumption of prohibiting FCOIs among the DSM work groups. When no independent individuals with the requisite expertise are available, individuals with associations to industry could consult to the DSM panels, but they would not have decision-making authority on revisions or inclusion of new disorders.

These changes would accommodate the participation of needed experts as well as provide more stringent safeguards to protect the revision process from either the reality of or the perception of undue industry influence.

There is no such thing as “free” vaccines…

Why Médecins Sans Frontières (MSF) rejected Pfizer’s donation offer of pneumonia vaccine (PCV) doses for the children they serve

Abstract

… “Free is not always better.

Donations often involve numerous conditions and strings attached, including restrictions on which patient populations and what geographic areas are allowed to receive the benefits. This process can delay starting vaccination campaigns, which would be an untenable situation in emergency settings, or grossly limit who you’re able to reach with the vaccine.

Donations can also undermine long-term efforts to increase access to affordable vaccines and medicines. They remove incentives for new manufacturers to enter a market when it’s absorbed through a donation arrangement. We need competition from new companies to bring down prices overall — something we don’t have currently for the pneumonia vaccine.

Donations are often used as a way to make others ‘pay up.’ By giving the pneumonia vaccine away for free, pharmaceutical corporations can use this as justification for why prices remain high for others, including other humanitarian organizations and developing countries that also can’t afford the vaccine. Countries, which continue to voice their frustration at being unable to afford new and costly vaccines such as PCV, need lower prices as well to protect children’s health.

Critically, donation offers can disappear as quickly as they come. The donor has ultimate control over when and how they choose to give their products away, risking interruption of programs should the company decide it’s no longer to their advantage. For example, Uganda is now facing a nationwide shortage of Diflucan, an essential crytpococcal meningitis drug, in spite of Pfizer’s commitment to donate the drugs to the government. There are other similar examples of companies’ donation programs leaving governments and health organizations in a lurch without the medical tools they need to treat patients.” …

… Read the full paper – There is no such thing as “free” vaccines: Why we rejected Pfizer’s donation offer of pneumonia vaccines, by Jason Cone, Executive Director of Doctors Without Borders in the United States, on medium.

  • More about the MSF Access Campaign, “pushing for access to & the development of life-saving and life prolonging medicines, diagnostic tests & vaccines for patients in MSF programmes and beyond“.
  • The Needle image by ps_sahana.

Why off-label marketing is irresistible to Big Pharma

If off-label marketing is ‘speech,’ why even have the FDA?

This post content is written by Martha Rosenberg and published by Reporting on Health, a nonprofit, nonpartisan and educational offering resources & community for journalists covering health

off-label-marketing
It has always been legal for U.S. doctors to prescribe drugs for off-label uses but marketing of off-label uses has been illegal. Image via pharmamkting.blogspot.

It has always been legal for U.S. doctors to prescribe drugs for off-label uses but marketing of off-label uses has been illegal. In August, U.S. District Judge Paul A. Engelmayer ruled that the First Amendment allows a drug company to “engage in truthful and non-misleading speech promoting the off-label use” of drugs and that the FDA cannot bar such “speech.” The ruling, pertaining to the drug Amarin, which targets high triglyceride levels, is likely to be appealed and only applies to the 2nd U.S. Circuit Court of Appeals, which includes New York, Connecticut and Vermont. But patients had better beware.

Off-label marketing is irresistible to Big Pharma because it saves years and millions spent on clinical trials which may not assure FDA approval anyway. It allows drug companies to circumvent the pesky and slow FDA altogether and get on with the business of making money– bringing their sales pitch to doctors and patients directly. Almost all major drug companies—GSK, Eli Lilly, Abbott, AstraZeneca, Pfizer, Johnson & Johnson, Amgen, Allergen, Bristol-Myers Squibb, Cephalon, Novartis and Purdue (which makes Oxycontin)––have agreed to huge settlements which include charges of off-label marketing.

In court-released confidential memos, Pfizer (then Parke-Davis) admits why it chose to off-label market Neurontin (only approved for postherpetic neuralgia and adjunctive seizure therapy) for the unapproved indication of bipolar disorder. “The U.S. market for Bipolar Disorders is an attractive commercial opportunity that warrants clinical development of Neurontin. Based on the current patent situation, an investment in full clinical development is not recommended at this time since completion of two pivotal trials and regulatory filing and approval would occur close to patent expiration,” says the memo. Translation: It would take too long to get legal approval—our patent would expire. Instead, says the memo, “it is recommended to implement only an exploratory study in outpatients with bipolar disorders with the results highlighted through a peer reviewed publication.” Translation: Let’s not do the studies and plant some info in medical journals that looks like we did.

Pfizer paid a $430 million fine and signed a corporate integrity agreement for off-label marketing of Neurontin which was linked to wrongful deaths and suicides. But that did not stop Pfizer from off-label marketing Lyrica, sometimes called “son of Neurontin,” soon afterward. Who can say incorrigible?

Nor did Eli Lilly’s guilty plea in 2009 to the off-label promotion of the antipsychotic Zyprexa deter it from requesting permission from the FDA to market Zyprexa to children three months later. The FDA said—yes! At the same time, Pfizer and AstraZeneca also requested permission to market their antipsychotics, Geodon and Seroquel respectively, to kids though both agreed to off-label marketing those exact drugs months later.

Another off-label marketing scheme centered around the selective estrogen receptor modulator Evista. Eli Lilly, its manufacturer, had noted fewer incidences of breast cancer in an Evista trial and wanted to market it not just for its approved treatment of prevention of osteoporosis but for prevention of breast cancer. A group of doctors told Lilly the anticancer marketing claims were “an egregious stretch” and that Evista’s high risk of stroke canceled out any anticancer benefits.

Undaunted, Lilly armed 1000 of its drug reps with an off-label Evista sales plan to sell the unapproved use of breast cancer prevention. Drug reps were told to hide a disclosure page that said, “The effectiveness of [Evista] in reducing the risk of breast cancer has not yet been established,” and “All of the authors were either employees or paid consultants of Eli Lilly at the time this article was written,” according to the Department of Justice.

Lilly was charged with a violation of the Food, Drug, and Cosmetic Act and ordered to pay a $36 million settlement for the off-label marketing. But Evista did receive approval to reduce the “risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer.” The problem was the drug, marketed so freely for off-label uses, was far from safe. Prescribing information warned “Serious and life-threatening side effects can occur while taking EVISTA” and ads warned about “death due to stroke.” Its effectiveness was also not impressive. Patients were warned that Evista doesn’t “completely prevent breast cancer,” and “Breast examinations and mammograms should be done before starting Evista and regularly thereafter.”

Clearly, forgiveness is cheaper than permission for drug makers who consider such settlements the cost of doing business. But are drug sales pitches really “speech?” Can a “truthful and not misleading” determination really be made by the for-profit company selling the product? If drug companies’ product claims are protected under the First Amendment and they can sell directly to doctors and patients why even have an FDA?

Over 50 years ago, Big Pharma was also annoyed with the slow-paced FDA whose efforts to ensure drugs were safe cut into profits. One company even complained to an FDA official’s bosses that she was a petty bureaucrat. The company made thalidomide.

The Whistleblower

A shocking expose of the healthcare industry by one of its most successful executives

The-Whistleblower book cover image
A shocking expose of the healthcare industry by one of its most successful executives.

Confessions of a Healthcare Hitman

This is a shocking expose of the healthcare industry by one of its most successful executives. “The Whistle Blower” will shock everyone. It begins in 2003 when Pfizer takes over Pharmacia and details the insidious techniques Pfizer used to terminate more than 10,000 Pharmacia employees. It reveals illegal, and even criminal business practices at Pharmacia, which the author brought to light during the Pfizer acquisition, resulting in the FBI, the FDA’s Enforcement Division, the Justice Department, the New York State Attorney General and the Securities and Exchange Commission all calling him in for questioning over the course of the following year. However, in the post-Enron world of federal sanctions for retaliation against whistleblowers, he couldn’t be fired or demoted, although he lost his department and was moved to an office next to corporate security. This is the story of one senior industry executive who set out to change the entire pharmaceutical industry for the better, fighting on the behalf of American consumers for lower priced drugs. To win this battle, he testified before congress and wrote this book, which exposes the drug industry’s darkest and most closely guarded secrets.