The idea behind this study is that pain and sleep problems often go hand in hand. Addressing one problem may help the other. But it will also help UCSD researchers in a quest to understand how the machine itself can be used as a tool to match patients with the right treatment for anxiety, depression or, in this case, pain.
The first brain scan will shoot a video of the blood flow to the amygdala and the insula, parts of my brain that are involved in processing emotions, anxiety, and pain perception. The second scan will take images of the same areas after one week of taking an insomnia drug, eszopiclone, better known as Lunesta.
I might receive a placebo, a sugar pill, as some call imposter drugs used for comparison in clinical research. But I have an equal chance of receiving Lunesta, an FDA-approved drug, to see if it helps me sleep. Either way, the study will be relatively quick and easy: only three visits of about three hours each, a couple of brain scans, and a week of taking pills.
The brain scans do not loom large as a problem. Over the past year I have had two MRIs. They weren’t fun, but they were over quickly. The pay, $275, is not bad — about $30 per hour if I get through all three sessions. I will also receive a picture of my brain.
But I am not yet in. The final judge will be the lead investigator, Dr. Martin Paulus, professor of psychiatry, Department of Psychiatry and the Laboratory of Biological Dynamics and Theoretical Medicine at UCSD. Kosheleva tells me she will email me shortly to let me know if I have made it to the next round, the assessment.
Google “human guinea pig,” and you’ll find plenty of reasons to have second thoughts about this line of work. Over the past few years, a steady stream of articles and columns has raised old and new ethical questions triggered by the increasing concentration of trials in the hands of industry and has assailed the lack of independent oversight.
The primary focus remains on the pharmaceutical industry, which, in 2006, spent a reported $55 million on research and development. About two-thirds of research-and-development funds are spent on clinical trials, making them the most expensive element of the R&D process, particularly when you consider that only one in five drugs that goes into these trials is actually approved by the FDA.
As recently as the early 1990s, academic institutions conducted over 80 percent of the clinical research for new pharmaceutical products. Today, more than 70 percent of trials are conducted in company-owned clinics or subcontracted to clinical research organizations, physicians, or hospitals. Academic institutions typically use their own internal review boards to oversee the rights and safety of human volunteers. For studies conducted in the private sector, this responsibility is assumed by companies called central internal review boards. These are paid directly or indirectly by the pharmaceutical companies sponsoring the research.
Among the lowlights: controversy over Eli Lilly’s reliance on homeless alcoholics to test its products in the 1990s. In 2006, SFBC International, then one of the country’s largest clinical research organizations, was charged with extensive violations of research volunteer rights, including paying undocumented workers to participate in clinical trials. Then there are the six volunteers at a British research site who in 2006 suffered multiple organ failure and lapsed into comas after being injected with a drug intended to treat leukemia and autoimmune diseases. Until that time, the drug had been tested only in animals. One man has reportedly since been diagnosed with cancer, and new safety guidelines for testing high-risk drugs are in place in Europe.
In the summer of 2005, controversy hit closer to home when Matt Potter raised questions on these pages regarding the testing in San Diego of PolyHeme, a blood substitute intended for use in trauma victims. Study sponsors did not appear to follow guidelines intended to inform the public and ensure that the risk was spread over a representative group, not just the poorest. These guidelines were established because guinea pigs in this study could not give permission; they were unconscious. Results of the nationwide trial, announced in late 2007, show a significantly higher death rate among people who had received PolyHeme than those who had received blood.
The fact remains that clinical trials represent the only way for millions to receive new drugs and procedures that can help them. Those willing to go first do not fall into convenient, easy-to-peg niches. Surveys of research volunteers identify a mix of factors that go into the decision to sign on for studies, including money, referrals from trusted doctors or friends, access to free or cutting-edge treatment, and the desire to help others while helping themselves.
The relative importance of each factor is not always clear. One 2005 survey conducted by Harris Interactive reports that 72 percent of adults would be “very likely” to consider a trial if they had a terminal illness. However, only about 5 percent of cancer patients in the United States, terminal or not, participate in clinical trials.
Money will have more impact on the decision of an unemployed or uninsured person than it might on someone like Lisa, a 37-year-old mother of two and one of several local lab rats willing to share their insights.
“My husband thought I was crazy. He thinks trials are a really risky thing to do,” she says.
This might be something any husband would say, but it has particular resonance coming from a man who works for a local drug-discovery company. His livelihood is tied to the successful outcomes of human trials involving drugs his company develops. So is Lisa’s, for that matter. At her company, she tests new drug formulations on animals, but the winners among them go on to be tested in humans.
We chat while blood flows from her forearm into one of four vials. Nearby, her study coordinator takes notes. The vials will go to a lab, and in a week or so she will find out if she makes it into her second clinical trial. This is Lisa’s assessment, and she wants in.