Bias, Corruption & Accountability

The University of Minnesota announced a change to its research ethics policies this month after coming under criticism “following the recruitment of a schizophrenia...

In an Op-ed for the Times Union, Madeleine Ringwald explains how the Helping Families in Mental Health Crisis Act “would severely disable protection and advocacy organizations from protecting the civil, legal and human rights of people in mental health services.” “Whether you examine it through a scientific, civil rights or bottom-line lens, Murphy's bill should appall you,” she writes. “Any legislation that bolsters institutionalization at the cost of community-based services seeks not to help those with mental health needs, but help society find ways to hide, suppress and silence them.”

In the Atlantic, Cari Romm describes “what it is like to earn a living as a research subject in clinical trials.” “Phase 1 trials are almost always where the money is,” she writes, but they are “also the least regulated” and “companies aren’t legally required to register a trial with Clinicaltrials.gov.” “It seems to me like if you were considering signing up for one of these things, you would at least want to know the data that’s out there about [safety],” said Carl Elliott, an author for MIA and expert on the ethics of human subject research.

Yesterday, the Journal of the American Medical Association (JAMA) released an editorial entitled “Confluence, Not Conflict of Interest: Name Change Necessary.” The authors argue that the phrase “conflict of interest is pejorative,” and a better term “would be confluence of interest, implying an alingnment of primary and secondary interests.”

Hundreds of people have been given remote control deep brain stimulation implants for psychiatric disorders such as depression, OCD and Tourette’s. Yet DBS specialists still have no clue about its mechanisms of action and research suggests its hefty health and safety risks far outweigh benefits.

Bloomberg reports that the FDA asked Pfizer in August “to modify safety warnings for its antidepressant Zoloft (sertraline) and acknowledge for the first time that some studies linked the mood-altering medication to heart defects in newborns.”

Writing for the Atlantic, David Dobbs examines how much harm has been done in the 14 years since Paxil was wrongly determined to be safe and effective. “Study 329, as it became known, helped spur a huge increase in Paxil prescriptions,” Dobbs writes. “In 2002 alone, over 2 million prescriptions were written for children and teens, and many more for adults.” “Thousands of children, teens, and young adults attempted or committed suicide while on Paxil,” and the reanalysis of Study 329 in BMJ makes it seem “more likely than ever” that many did because of the drug.

In Saturday’s New York Times, Sabrina Tavernise describes the close industry ties of Dr. Robert Califf, a cardiologist and researcher recently tapped by the Obama administration to head the FDA. In a conflict of interest statement published last year, Califf “declared financial support from more than 20 companies,” leading some public health advocates to “question whether his background could tilt him in the direction of an industry he would be in charge of supervising.” Tavernise points to a presentation Califf gave on “Disrupting Clinical Research: Transforming a System” in 2014 where he singled out regulation as a barrier to research and innovation. “I think it illuminates his thinking,” Daniel Carpenter, a Harvard professor who studies the FDA, said of the slide. “In a sense, he’s the ultimate industry insider.”

It is appropriate to hold a company or doctors who may be aiming to make money out of vulnerable people to a high standard when it comes to efficacy, but for those interested to advance the treatment of patients with any medical condition it is not appropriate to deny the likely existence of harms on the basis of a failure to reach a significance threshold that the very process of conducting an RCT will mean cannot be met, as investigators' attention is systematically diverted elsewhere.

On Tuesday, the Obama administration nominated Dr. Robert Califf to be the new commissioner of the Food and Drug Administration (FDA). In a statement, director of the Public Citizen’s Health Research Group, Dr. Michael Carome called on the Senate to reject the nomination. He contends that Califf “racked up a long history of extensive financial ties to multiple drug and medical device companies, including Amgen, AstraZeneca, Eli Lilly, Johnson & Johnson, Merck Sharp & Dohme and Sanofi-Aventis, to name a few.”

In a major story, the New York Times presents the re-analysis by David Healy, Jon Jureidini, Mickey Nardo and others of Study 329, published in...

The authors of Study 329 began recruiting adolescents for a comparative study of Paxil, imipramine and placebo in 1994 and finished their investigations in 1997. They dropped a large number of their original cohort, so the randomness element in the study must be open to question. Late in 1998, SmithKline Beecham, the marketers of Paxil, acknowledged in an internal document that the study had shown that Paxil didn’t work for adolescents in terms of the two primary and six secondary outcomes they had established at the start of the study. In a nutshell, Study 329 was negative for efficacy and positive for harm, contrary to their succinct upbeat conclusion.

In 1980, the British Medical Journal published a “Systematic Review of the Benzodiazepines” by the Committee on the Review of Medicines. The committee denied the addictive potential of Benzodiazepines and limited their suggestions to short term use. The results have been devastating.

Antipsychotics are being prescribed to people who may have challenging behaviors but no mental disorder, according to new research published in this month’s issue of BMJ. “Excessive use of psychotropic drugs has individual and systemic implications,” the researchers write. “Antipsychotics, in particular, are associated with several adverse side effects that can impair quality of life and lead to deleterious health outcomes.”

In the September issue of The Journal of the American Medical Association (JAMA) three FDA advisory committee members describe the convergence of factors that made the committee’s recommendation to approve flibanserin especially challenging and politically charged.

In addition to hosting the Panorama programs and The Famous Grouse history of Study 329, Study329.org has a comprehensive timeline on the origins of concerns about the SSRIs and the risk of suicide, initially with Prozac and subsequently with Paxil/Seroxat. The hope is to provide a comprehensive repository for anyone who wants to study SSRIs, RCTs, and Study 329 in particular.

MedPageToday reports that Janssen Pharmaceuticals omitted data from a 2003 study that connected Risperdal with serious side effects. Janssen was previously sued by the FDA for marketing Risperdal for off-label uses and settled for $2.2 billion in 2013. Earlier this year, a man with autism was awarded $2.5 million after growing breasts while on Risperdal. According to MedPage, documents from this latest case reveal missing data tables from a 2003 study “designed to ferret out potential adverse effects of long-term risperidone use.” The missing tables were related to elevated prolactin levels and side effects, including gynecomastia in men.

Writing for Forbes, Matthew Herper documents the FDA’s increasing drug approval rates. “In 2008, BioMedTracker says the FDA approved 20 new molecular entities (NMEs) and rejected 20, for an approval rate of 50%.” So far this year, he writes, “the FDA approval rate is more like 96%.”

The International Business Times covers a new study showing “trials for new antidepressant medications may not be applicable to the population at large.” “The finding, published in the Mayo Clinic Proceedings, shows recent trials are less generalizable than the prior studies, as researchers excluded most depressed patients from drug company-sponsored treatment studies.”

Today’s NY Times front page featured a story on the problem reproducibility poses for many psychology studies. The story is based on the results of a year-long study where the researchers found they were unable to reproduce 60 out of 100 studies published in three leading psychology journals. “The overall ‘effect size,’ a measure of the strength of a finding, dropped by about half across all of the studies.”

Despite updated standards requiring preregistration of clinical trials aimed at improving transparency, most studies published in the top-5 psychiatry journals from 2009 to 2013 do not meet the new guidelines, according to an analysis published in PloS one.

Paul Thacker and Charles Seife provide an update on the ongoing battles over transparency in science, writing for the PLOS Biologue blog. While transparency is important for accountability and the public trust, some have begun to argue that requests for personal communications between companies and researchers have gone too far.

On Tuesday, the U.S. Food and Drug Administration (FDA) approved Flibanserin (Addyi) to treat low sexual desire in women despite concerns about the drug's limited efficacy and doubts over its clinical relevance. That the drug is being called the "pink Viagra" can be misleading as Viagra treats erectile dysfunction by improving blood flow while Flibanserin targets the brain, and must be taken daily.

A study in PLoS One shows that the number of National Heart Lung, and Blood Institute (NHLBI) funded drug trials reporting positive results declined precipitously after the implementation of the clinicaltrials.gov registry, which requires researchers to record their trial methods and outcome measures before collecting data. Of the 55 studies examined, 57% percent of those published before the implementation of clinicaltrials.gov in 2000 yielded a positive result. After 2000, only eight percent of trials claimed a significant benefit to the intervention examined.

Robert Whitaker and Lisa Cosgrove discuss their new book Psychiatry Under the Influence in an interview with psychologist and social critic Bruce Levine for Truthout. In the book, Whitaker and Cosgrove apply the institutional corruption framework, developed by Larry Lessig, to psychiatry and determine that “just as elected officials develop dependency on special interests and become beholden to these funders instead of the citizenry,” psychiatry has “had its social mission subverted by drug companies as well as by the psychiatry guild's self-preservation and expansionism needs.”