a better choice…

Posted on Friday 23 December 2011

In the fall of 2010, I was on a vacation trip driving through New York State – an unexplored and previously unknown world for this southern boy who’d trained in New York City, but was unprepared for the beauty of the rest of the State. It was on that trip that I first read Carl Elliot’s The Deadly Corruption of Clinical Trials in the Mother Jones magazine – the story of Dan Markinson’s suicide during the CAFE Trial, an AstraZeneca funded Trial designed to show the wonders of their Seroquel after its poor showing in the NIMH CATIE Trial. He was floridly psychotic and under a form of commitment, yet he was allowed to volunteer for a study that both inadequately treated him and gave him the freedom to kill himself under the full sway of an intense paranoid psychosis. The story haunted me for the remainder of the trip. While I hadn’t seen that kind of case in the latter part of my career, I’d seen plenty enough early on to know what a tragedy that story represented. Those cases are dramatic and once seen, never go away. It was that article that ultimately lead me to begin looking at Seroquel [seroquel I: introduction to an “atypical”…] last winter and then on to a painful refresher course in what had happened in my specialty, psychiatry, in the modern era. That was less than a year ago, but I was incredibly naive and had no idea about the Contract Research  Organizations or the Clinical Trials Industry. I actually wrote a friend asking, "What’s a CRO?"

Then earlier this year, I received Carl Elliot’s book, White Coat Black Hat. Even though he writes in a easy way, it was hard for me to take it all in. It covers the invasion of the pharmaceutical industry into medicine and research over the last twenty-five years. Before reading that book, I think I had begun to see that medical science had been heavily corrupted by industry, but his book added a level of darkness to the story that took me a while to absorb. I guess I just wasn’t ready to see all the specifics of the Clinical Research Industry that has replaced clinical research I knew in the past in academic centers. It had been easy for me to see that the "Placebo Effect" was increasing geometrically in studies, but a lot more uncomfortable to look at why.

This morning, Carl sent me a link to an earlier article of his in the New Yorker back in 2008 [Guinea-pigging: Healthy human subjects for drug-safety trials are in demand. But is it a living?] in response to my last post mentioning "fake patients" and professional patients. I hadn’t read it before. I think I’d considered Phase III Trials mostly, the trials for efficacy and safety required by the FDA for approval. I hadn’t thought much about the Phase I and Phase II trials that come earlier and are more dangerous. It is also a difficult story to read – a seedy story. Here’s a sampler:
    In May of 2006, Miami-Dade County ordered the demolition of a former Holiday Inn, citing various fire and safety violations. It had been the largest drug-testing site in North America, with six hundred and seventy-five beds. The operation closed down that year, shortly after the financial magazine Bloomberg Markets reported that the building’s owner, SFBC International, was paying undocumented immigrants to participate in drug trials under ethically dubious conditions. The medical director of the clinic got her degree from a school in the Caribbean and was not licensed to practice. Some of the studies had been approved by a commercial ethical-review board owned by the wife of an SFBC vice-president. [The company, which has since changed its name to PharmaNet Development Group, says that it required subjects to provide proof of their legal status, and that the practice of medicine wasn’t part of the medical director’s duties. Last August, the company paid $28.5 million to settle a class-action lawsuit.]

    “It was a human-subjects bazaar,” says Kenneth Goodman, a bioethicist at the University of Miami who visited the site. The motel was in a downtrodden neighborhood; according to later reports, paint was peeling from the walls, and there were seven or eight subjects in a room. Goodman says that the waiting area was filled with potential subjects, mainly African-American and Hispanic; administrative staff members worked behind a window, like gas-station attendants, passing documents through a hole in the glass.

    The SFBC scandal was not the first of its kind. In 1996, the Wall Street Journal reported that the Eli Lilly company was using homeless alcoholics from a local shelter to test experimental drugs at budget rates at its testing site in Indianapolis. [Lilly’s executive director of clinical pharmacology told the Journal that the homeless people were driven by “altruism,” and that they enrolled in trials because they “want to help society.” The company says that it now requires subjects to provide proof of residence.] The Lilly clinic, the Journal reported, had developed such a reputation for admitting the down-and-out that subjects travelled to Indianapolis from all over the country to participate in studies.

    How did the largest clinical-trial unit on the continent recruit undocumented immigrants to a dilapidated motel for ten years without anyone noticing? Part of the answer has to do with our system of oversight. Before the nineteen-seventies, medical research was poorly regulated; many Phase I subjects were prisoners. Reforms were instituted after congressional investigations into abuses like the four-decade Tuskegee syphilis studies, in which researchers studied, instead of treating, syphilis infections in African-American men. For the past three decades, institutional review boards, or I.R.B.s, have been the primary mechanism for protecting subjects in drug trials. F.D.A. regulations require that any study in support of a new drug be approved by an I.R.B. Until recently, I.R.B.s were based in universities and teaching hospitals, and were made up primarily of faculty members who volunteered to review the research studies being conducted in their own institutions. Now that most drug studies take place outside academic settings, research sponsors can submit their proposed studies to for-profit I.R.B.s, which will review the ethics of a study in exchange for a fee. These boards are subject to the same financial pressures faced by virtually everyone in the business. They compete for clients by promising a fast review. And if one for-profit I.R.B. concludes that a study is unethical the sponsor can simply take it to another.

    Moreover, because I.R.B.s scrutinize studies only on paper, they are seldom in a position to comment on conditions at a study site. Most of the standards that SFBC violated in Miami, for example, would not be covered in an ordinary off-site ethics review. I.R.B.s ask questions like “Have the subjects been adequately informed of what the study involves?” They do not generally ask if the sponsors are recruiting undocumented immigrants or if the study site poses a fire hazard. At some trial sites, guinea pigs are housed in circumstances that would drive away anyone with better options. Guinea pigs told me about sites that skimp on meals and hot water, or that require subjects to bring their own towels and blankets. A few sites have a reputation for recruiting subjects who are threatening or dangerous but work cheaply…

There are many more [and worse] examples. At every level, the Clinical Research enterprise seems to be a study in illusion. The well coiffed articles appearing in our shiny journals with massaged graphs and tables evoke images far removed from the Bowery-like conditions Elliot describes [that move into areas of exploitation more regularly than we know]. Ultimately, physicians become agents of those illusions when we write the prescriptions for drugs approved based on jury-rigged data from non-patient subjects. Elliot’s research and commentary like that in the last post stand in stark contrast to the writings of Dr. Tom Insel at the NIMH who talks about streamlining the processes to ease the burden on the drug companies so as to deal with the perceived crises in new drug development. A moratorium might be a better choice than streamlining…
  1.  
    December 23, 2011 | 7:55 PM
     

    A moratorium would get the job done, alright.

    Duane

  2.  
    Autistic Lurker
    December 24, 2011 | 4:19 AM
     

    thanks, I’m speechless.

    A.L.

  3.  
    Melody
    December 24, 2011 | 11:34 AM
     

    Mickey–

    You’ve brought eye-opening material to the uninitiated, for which I offer thanks. The Eli Lilly story (referenced above) has long been in my consciousness. As hubby researched material for his self-published, mostly-unsold book, “Too Profitable to Cure”, he found just how heinous Lilly behavior was. I know they have ‘tested’ many more drugs than just their genetically-engineered insulin; and though my anger has lessened, it is merely because outrageous behaviors continue to grow. To illustrate the consequences of their “altruistic” drug trials, today’s diabetics have been forced to inject themselves daily (multiple times) with GE insulin or insulin-like products, each being the ‘latest and greatest’ till patents expire. Now, after more than 30 years, claims of cost containment and/or better outcomes can be determined to be false . . . yet the product(s) and treatment methodology remains. That has to be a big SUCCESS for the pharma industry. (If you read the NDA for synthetic insulin you would be amazed at the miniscule size of the studies. As you continue to expose the wrongdoings of pharma in the field of psychotropic medicines, until you prove me wrong, I still contend that Lilly–with their studies in support of rDNA insulins–were the trailblazers in creative clinical trialing.)

    Melody

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