Lawsuit Over a Suicide Points to a Risk of Antidepressants

Roni Caryn Rabin
The New York Times
Originally published September 11, 2017

Here is an excerpt:

The case is a rare instance in which a lawsuit over a suicide involving antidepressants actually went to trial; many such cases are either dismissed or settled out of court, said Brent Wisner, of the law firm Baum Hedlund Aristei Goldman, which represented Ms. Dolin.

The verdict is also unusual because Glaxo, which has asked the court to overturn the verdict or to grant a new trial, no longer sells Paxil in the United States and did not manufacture the generic form of the medication Mr. Dolin was taking. The company argues that it should not be held liable for a pill it did not make.

Concerns about safety have long dogged antidepressants, though many doctors and patients consider the medications lifesavers.

Ever since they were linked to an increase in suicidal behaviors in young people more than a decade ago, all antidepressants, including Paxil, have carried a “black box” warning label, reviewed and approved by the Food and Drug Administration, saying that they increase the risk of suicidal thinking and behavior in children, teens and young adults under age 25.

The warning labels also stipulate that the suicide risk has not been seen in short-term studies in anyone over age 24, but urges close monitoring of all patients initiating drug treatment.

The article is here.

An NYU Study Gone Wrong, and a Top Researcher Dismissed

By Benedict Carey
The New York Times
Originally posted June 27, 2016

New York University’s medical school has quietly shut down eight studies at its prominent psychiatric research center and parted ways with a top researcher after discovering a series of violations in a study of an experimental, mind-altering drug.

A subsequent federal investigation found lax oversight of study participants, most of whom had serious mental issues. The Food and Drug Administration investigators also found that records had been falsified and researchers had failed to keep accurate case histories.

In one of the shuttered studies, people with a diagnosis of post-traumatic stress caused by childhood abuse took a relatively untested drug intended to mimic the effects of marijuana, to see if it relieved symptoms.

The article is here.

Expansion of ‘Right to Try’ legislation raises ethical, safety concerns

By HemOnc Today
Originally published April 25, 2015

Early access to experimental drugs has historically been reserved for patients enrolled on clinical trials.

In 2009, the FDA revamped its 1980’s expanded access program, which allows terminally ill patients ineligible for clinical trials and for whom no alternative, approved therapies exist to ask pharmaceutical companies for access to an investigational drug in their pipeline. More than 1,500 patients received an experimental treatment through the FDA’s program in 2014.

Now, some legislatures are going a step further by adopting so-called “Right to Try” legislation, intended to give terminally ill patients comparable access to investigational drugs but removing the FDA from the process.

Since 2014, thirteen states have passed Right to Try laws, and legislators in 20 more states have plans to introduce similar legislation this year.

The entire article is here.

Pharmaceutical firms paid to attend meetings of panel that advises FDA

By Peter Whoriskey
The Washington Post
Originally published October 8, 2013

A scientific panel that shaped the federal government’s policy for testing the safety and effectiveness of painkillers was funded by major pharmaceutical companies that paid hundreds of thousands of dollars for the chance to affect the thinking of the Food and Drug Administration, according to hundreds of e-mails obtained by a public records request.

The e-mails show that the companies paid as much as $25,000 to attend any given meeting of the panel, which had been set up by two academics to provide advice to the FDA on how to weigh the evidence from clinical trials. A leading FDA official later called the group “an essential collaborative effort.”

Patient advocacy groups said the electronic communications suggest that the regulators had become too close to the companies trying to crack into the $9 billion painkiller market in the United States.

The entire article is here.

Institutional Corruption and Pharmaceutical Policy

Institutional Corruption and Pharmaceutical Policy
An Edmond J. Safra Center Symposium
(forthcoming)
Journal of Law, Medicine and Ethics 
Vol. 14, No. 3 (2013)

The goals of pharmaceutical policy and medical practice are often undermined due to institutional corruption — that is, widespread or systemic practices, usually legal, that undermine an institution’s objectives or integrity. The pharmaceutical industry’s own purposes are often undermined. In addition, pharmaceutical industry funding of election campaigns and lobbying skews the legislative process that sets pharmaceutical policy. Moreover, certain practices have corrupted medical research, the production of medical knowledge, the practice of medicine, drug safety, and the Food and Drug Administration’s oversight of pharmaceutical marketing.

As a result, practitioners may think they are using reliable information to engage in sound medical practice while actually relying on misleading information and therefore prescribe drugs that are unnecessary or harmful to patients, or more costly than equivalent medications. At the same time, patients and the public may believe that patient advocacy organizations effectively represent their interests while these organizations actually neglect their interests.

The entire journal is here.

The articles are organized into five topics: (1) systemic problems, (2) medical research, (3) medical knowledge and practice, (4) marketing, and (5) patient advocacy organizations.

Breaking the Seal on Drug Research

By KATIE THOMAS
The New York Times
Published: June 29, 2013

Here are som excerpts:

For years, researchers have talked about the problem of publication bias, or selectively publishing results of trials. Concern about such bias gathered force in the 1990s and early 2000s, when researchers documented how, time and again, positive results were published while negative ones were not. Taken together, studies have shown that results of only about half of clinical trials make their way into medical journals.

Problems with data about high-profile drugs have led to scandals over the past decade, like one involving contentions that the number of heart attacks was underreported in research about the painkiller Vioxx. Another involved accusations of misleading data about links between the antidepressant Paxil and the risk of suicide among teenagers.

To those who have followed this issue for years, the moves toward openness are unfolding with surprising speed.

“This problem has been very well documented for at least three decades now in medicine, with no substantive fix,” said Dr. Ben Goldacre, a British author and an ally of Dr. Doshi. “Things have changed almost unimaginably fast over the past six months.”

Much of that change is happening because of what Dr. Goldacre calls an “accident of history.” In 2009, Dr. Doshi and his colleagues set out to answer a simple question about the anti-flu drug Tamiflu: Does it work? Resolving that question has been far harder than they ever envisioned, and, four years later, there is still no definitive answer. But the quest to determine Tamiflu’s efficacy transformed Dr. Doshi and others into activists for transparency — and turned the tables on drug makers. Until recently, the idea that companies should routinely hand over detailed data about their clinical trials might have sounded far-fetched. Now, the onus is on the industry to explain why it shouldn’t.

(cut)

Earlier this month, Dr. Doshi opened what he hopes will be a new chapter in his quest for greater understanding of clinical trials. He and several other researchers published what amounted to an ultimatum to drug companies: publish your data, or we’ll do it for you.

The entire story is here.

Prescription drug-related deaths continue to rise in U.S.

By Scott Glover and Lisa Girion
The Los Angeles Times
March 29, 2013

Despite efforts by law enforcement and public health officials to curb prescription drug abuse, drug-related deaths in the United States have continued to rise, the latest data show.

Figures from the U.S. Centers for Disease Control and Prevention reveal that drug fatalities increased 3% in 2010, the most recent year for which complete data are available. Preliminary data for 2011 indicate the trend has continued.

The figures reflect all drug deaths, but the increase was propelled largely by prescription painkillers such as OxyContin and Vicodin, according to just-released analyses by CDC researchers.

The numbers were a disappointment for public health officials, who had expressed hope that educational and enforcement programs would stem the rise in fatal overdoses.

“While most things are getting better in the health world, this isn’t,” CDC director Tom Frieden said in an interview. “It’s a big problem, and it’s getting worse.”

Drugs overtook traffic accidents as a cause of death in the country in 2009, and the gap has continued to widen. (Italics and color added).

The entire story is here.

Four Common Antipsychotic Drugs Found to Lack Safety and Effectiveness in Older Adults

Science Daily
Originally published November 27, 2012

In older adults, antipsychotic drugs are commonly prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications -- schizophrenia and bipolar disorder. The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia, some of which carry FDA warnings on prescription information for these drugs.

In a new study -- led by researchers at the University of California, San Diego School of Medicine, Stanford University and the University of Iowa, and funded by the National Institute of Mental Health -- four of the antipsychotics most commonly prescribed off label for use in patients over 40 were found to lack both safety and effectiveness. The results will be published November 27 in The Journal of Clinical Psychiatry.

The study looked at four atypical antipsychotics (AAPs) -- aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) -- in 332 patients over the age of 40 diagnosed with psychosis associated with schizophrenia, mood disorders, PTSD, or dementia.

"Our study suggests that off-label use of these drugs in older people should be short-term, and undertaken with caution," said Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of the Stein Institute for Research on Aging at UC San Diego.

The entire story is here.

Thanks to Tom Fink for this information.

Creation of a Central Management Plan for Every New Drug Needed to Strengthen FDA's Oversight of Approved Drugs' Safety

National Academies of Sciences
Released May 1, 2012

Although the approval of a new drug is based on evidence that its benefits outweigh its risks, the full range of a medication's effects may not become apparent until a product has been used by a larger, more diverse population over an extended period of time.  Problems associated with the anti-diabetes drug Avandia, pain reliever Vioxx, and cholesterol-reducing drug Crestor illustrate the challenges and underscore the need for a more systematic and transparent process to collect, assess, and act on data about a medication's benefit-risk profile throughout its entire "life cycle" from approval until it is no longer marketed, says a new report by the Institute of Medicine. 

According to recent estimates, nearly half of all Americans take at least one prescription drug daily and many older people use five or more, noted the committee that wrote the report.  The report's recommendations build on the new authorities and tools provided to the U.S. Food and Drug Administration through the Food and Drug Administration Amendments Act of 2007, which increased the agency's capacity to monitor drugs after approval and act if signs of safety problems appear. 

One of the committee's key recommendations is that FDA should create a benefit and risk assessment and management plan for each drug.  This would be a single, comprehensive, publicly available document that serves as a central repository of information for each product from its approval throughout its entire time on the market.  The document should include a description of any safety questions that exist when a drug is approved or that emerge over the course of the product's use, as well as benefit and risk assessments specific to these questions.  It should also include details on regulatory actions taken on the medication, such as restrictions on its use or the decision to require further research, as well as the results of these actions.  Much of this information is already being gathered by FDA, but it is currently scattered across multiple records.  Putting the information into an accessible format in a single document would make FDA's commitment to the life-cycle approach concrete and improve its transparency by giving the public easier access to useful data.

The entire news release is here.

Ghostwritten medical articles called fraud

CBC News

It's fraudulent for academics to give their names to medical articles ghostwritten by pharmaceutical industry writers, say two Canadian law professors who call for potential legal sanctions.

Studies suggest that industry-driven drug trials and industry-sponsored publications are more likely to downplay a drug's harms and exaggerate a drug's virtues, said Trudo Lemmens, a law professor at the University of Toronto. The integrity of medical research is also harmed by ghostwritten articles, he said.

Ghostwriting is part of marketing that can distort the evidence on a drug, Lemmens said. Industry authors are concealed to insert marketing messages and academic experts are recruited as "guest" authors to lend credibility despite not fulfilling criteria for authorship, such as participating in the design of the study, gathering data, analyzing the results and writing up of the findings.

Class actions involving drugs such as Vioxx, hormone replacement therapy and antidepressants suggest guest authors often fail to meet criteria for authorship, according to the policy paper in Tuesday's issue of Public Library of Science's journal PloS Medicine.

In the article, Lemmens and his colleague Prof. Simon Stern argue that legal remedies are needed for medical ghostwriting since medical journals, academic institutions and professional disciplinary bodies haven't succeeded in enforcing sanctions against the practice.

The institutions have divided loyalties, the authors say, which may explain why they've been slow to act. For example, universities wish to protect academic integrity while also protecting their employees from unjust accusation.

A legal response could act as a powerful deterrent, Stern said.

"Our theory does not depend on the accuracy of the data," Lemmens said in an email. "False representation of authorship is in our view fraud, regardless of the accuracy of the reporting."

Doctors and patients perceive published studies to be independent assessments made by academic experts, the authors noted.

Ghostwritten publications are used in court to support a manufacturer's arguments about a drug's safety and effectiveness, and academic experts who appear as witnesses for pharmaceutical and medical device companies also boost their credibility with the publications on their CV, Lemmens said.

The entire story can be found here.