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A suicide draws attention to the ethics of psychiatric drug testing

This is a really important long read that we all need to pay attention to. It concerns how we treat people with who are suffering from paranoid delusions — and how we treat people whose families worry that they are a threat to others. It concerns the relationships between doctors and the pharmaceutical industry. It concerns the ethics of clinical trials — the risks we run as we test potential treatments that could help many, or hurt a few, or both. If we want to reform mental health care, this needs to be part of the discussion.

In 2004, Dan Markingson committed suicide. The story behind that death is complicated and depressing. At the Molecules to Medicine blog, Judy Stone documents the whole thing in three must-read chapters. Many people find help in psychiatric drugs, and credit those drugs with making their lives better. (Full disclosure, I'm one of them. I have used Ritalin for several years. I am temporarily on an anti-depressant.) But we have to pay attention to how those drugs get to us. This isn't just about treating people. It's about the process that gets us there. Because, if that process is compromised, the treatments we get won't be as effective and lives will be lost along the way.

Markingson began to show signs of paranoia and delusions in 2003, believing that he needed to murder his mother. He was committed to Fairview Hospital involuntarily after being evaluated by Dr. Stephen Olson, of the University of Minnesota. He was subsequently enrolled on a clinical trial of antipsychotic drugs—despite protests from his mother. This study was a comparison of atypical antipsychotics for the treatment of first episodes of schizophrenia (aka the CAFÉ study), sponsored by AstraZeneca. The study’s structure was that of a Phase 4 randomized, double-blind trial comparing the effectiveness of three different atypical antipsychotic drugs: Zyprexa (olanzapine), Risperdal (risperidone) and Seroquel (quetiapine), with each patient to be treated for a year.

After about two weeks on study treatment in the hospital, Markingson was discharged to a halfway house—again over his mother’s objections. Over the coming months, Dan’s mother, Mary Weiss, continued to express concerns about her son’s deterioration, even asking if her son might have to kill himself before anyone else would take notice…then, in fact, her son violently committed suicide on May 7, 2004, mutilating himself with a box cutter. The University of Minnesota and their IRB have maintained that the study was conducted appropriately and that they have no responsibility for Dan’s death. Dan’s mother and bioethicist Carl Elliott believe otherwise.

We’ll explore some of the major issues of contention in this case over several posts, as illustrative of basic clinical research principles, including adequacy of informed consent, IRB oversight, conflicts of interest, and coercion, including threats to a bioethicist whistleblower.

Read the first part of the story

Read the second part: How clinical trials should be done and how they were done in this case.

Read the third part: Conflicts of interest between the researchers and the pharmaceutical industry.

Image: Pills (white rabbit), a Creative Commons Attribution (2.0) image from erix's photostream

Meet Science: How clinical trials work

Did you know that, with a properly conducted series of clinical trials, it can take upwards of 20 years before a medical discovery makes it from the lab to the hospital?

Judy Stone, an infectious disease specialist who does clinical research, has a guest post on the Scientific American blog network today, explaining the basics of clinical trials—where they came from, and how they can go wrong.

She's going to be publishing a series of posts on this topic, and is looking for input on what you want to know about clinical trials. Disclaimer: As a clinical researcher, Stone has a goal here. She'd like to see more people volunteering for clinical research, and part of what she's interested in is the gaps in knowledge that make people wary of participating, or leave them unaware that they can participate. Your input would be helpful.

Image: Pills Phial, a Creative Commons Attribution Share-Alike (2.0) image from luca_volpi's photostream

Clinical trials seek to learn whether a drug (or device) works as expected—it’s unknown, until tested in people. That’s why early phase trials use only a few people, and more are added as experience is gained. Sometimes unexpected discoveries are made along the way. For example, Rogaine was discovered by an astute clinician researcher during a clinical trial studying high blood pressure. The drug, minoxidil, originally under study as an anti-hypertensive medication, was serendipitously found to have the unexpected side effect of stimulating hair growth, prompting a whole new line of products for baldness.

Similarly, Viagra was discovered by accident. Sildenafil, the generic form, was being studied as a treatment for angina, as it dilates blood vessels by blocking an enzyme, phosphodiesterase (PDE). While not very effective for angina, it was found to prolong erections, stimulating the whole “life-style drug” industry. Fortunately, PDE inhibitors are now being found useful for a host of important medical conditions, ranging from pulmonary hypertension to asthma and muscular dystrophy.

Of course, not all inadvertent discoveries have such rosy outcomes.

For example, Diethylstilbesterol (DES), a synthetic estrogen, was commonly prescribed in the US 1938-1971, to help prevent miscarriages. It was only after many years that DES was found to cause a rare type of vaginal cancer in daughters of exposed women. Later, other types of cancers showed up as well, in small numbers.

Via Aaron Rowe