Human Subject: An Investigational Memoir

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15. No Brain, No Pain

“Les coïncidences, dit-on, peuvent jouer dans les causes d'erreurs de la statistique un si grand rôle, qu'il ne faut conclure que d'après des grands nombres.”

After I’d been rejected by PsychoPharm, I began looking around for other opportunities to volunteer. I still hadn’t found a replacement for Evista, the drug that was known to prevent osteoporosis and was suspected of preventing breast cancer. At the only studies of osteoporosis prevention required that you have cancer or some other disease already. I gave up on that angle and looked instead for studies aimed at cancer prevention, theorizing that if Evista could prevent cancer, then something that prevents cancer might also prevent bone loss.

There was only one breast cancer prevention study for which I was possibly eligible. It was comparing a drug called exemestane with placebo in high-risk post-menopausal women. To be eligible for the study, one needed something called a “Gale score” greater than 1.66. I found a Web site that said I could get such a score by using a certain risk assessment calculator, which was somewhat similar to the one I used in chapter 9. My results didn’t include a numerical score, but I did get this warning: “You are at high risk of getting breast cancer.” Surely that was good enough.

I thought that perhaps, before taking the plunge into the study, I should look for confirmation of my theory about the bone-breast connection. I found many articles linking exemestane to bone mineral density, but they mainly offered evidence for its producing, not preventing, bone loss. Curious, I checked to see what exactly the drug does, and I learned that it reduces the amount of estrogen and progesterone produced by the body. Well, no wonder, since low levels of these hormones can lead to bone loss. My literary career certainly wasn’t worth a hip fracture.

During my research on exemestane, I came across, a nonprofit organization that provides information about the disease. The site has a Celebrity Talking Dictionary, where you can listen to famous people reading words and their definitions. The celebrity for the word “exemestane” was Dr. Andrew von Eschenbach. When I learned that he was the current FDA commissioner, after about four years as head of the National Cancer Institute, I felt embarrassed that I hadn’t recognized the name. Wondering if the rest of the celebrities were equally illustrious, I clicked on the “See all the celebrities” link. There I found about 55 people I’d heard of, mostly entertainers, and about 15 I hadn’t (including two other M.D.s). I clicked on someone named Amy Jo Johnson and heard her define “radiologist”; I clicked on someone named Anastacia and heard her define “bacterial toxin.”

With no possibility of preventing osteoporosis pharmaceutically, I resolved that I would just eat more cheese and ice cream. Then I turned to a page at Big U’s Web site that listed studies that were supposedly seeking healthy volunteers. Most of those studies, however, required that you have a particular condition, or at least a risk of getting a disease, or else you had to be young or old or overweight. This seemed to confirm what I’d read about Phase I studies, i.e., that they were no longer limited to healthy subjects.

So I gave up on being a healthy volunteer and looked instead for any depression studies that I might have better luck with than I’d had at PsychoPharm. The most intriguing one I found involved the use of repetitive transcranial magnetic stimulation, or rTMS, to treat depression. In this technique, a magnetic field is used to induce electrical currents in the cortex of the brain. The study was being conducted at another affiliate of Big U, which I’ll call UniPsych.

I could have paid for this treatment if I’d traveled to Canada (our neighbors to the north tend to be way ahead of us on health care). In the U.S. it was still an experimental technique, but some TMS devices had FDA approval for treating some other conditions. Physicians were therefore allowed to use the devices “off-label,” just as when they prescribe approved drugs for an unapproved purpose or population (see chapter 19). Apparently they were cautious, or at least quiet, about doing so, because I didn’t find any doctors advertising the service in the U.S.

I didn’t have much hope that I would qualify for the study, because they only wanted people who hadn’t gotten “full relief” from antidepressants. Of course, I wondered if anyone with major depression ever gets “full relief,” but what they meant, I learned from reading more about the treatment, was that they wanted people whose depression wasn’t really helped at all, i.e., it was resistant to medication. I thought that my trouble with side effects, including the low blood pressure that had excluded me from the desvenlafaxine study, might give me a reasonable chance at qualifying, so I called and volunteered.

Alas, my drug history didn’t quite qualify me, but the UniPsych study coordinator told me that if I stayed on the duloxetine for two more weeks (a total of four weeks) without getting totally better, I might be eligible. She said that the criteria included intolerance of, not just resistance to, medication. So I planned to call her back if, at the end of four weeks, I still had low blood pressure and was in a perpetual stupor, which seemed very likely.

Meanwhile, I had easily qualified for another study involving electricity and the brain. For that one I just needed to be right-handed and a native English speaker, and the study would only take a few hours of my time. It wouldn’t cure any illness I had, but it would contribute to research in cognitive neuroscience.

This research relied on a phenomenon called event-related potentials (ERPs), which are electrical responses in the brain to thoughts or perceptions. The researchers were collecting data on how parts of the brain respond to standard and nonstandard sentences. ERPs seem to be all the rage these days, not just for linguistic research but also in studying a lot of psychological disorders, including cognitive impairment, attention problems, and schizophrenia. To detect ERPs, researchers stick multiple electrodes on a person’s scalp, with each electrode connected by wire to a device that converts electrical impulses into wavy lines on a piece of graph paper. The system of detecting and recording brain impulses is called electroencephalography, or EEG.

Even after quite a bit of reading on the subject, I have only a vague understanding of what ERPs are and how they work. Apparently they’re designated by a letter and number, e.g., P300 or N100. The letter is always either ‘N’ for negative or ‘P’ for positive, and the number usually refers to the time, in milliseconds, from the triggering event to the peak of something called a wave or a component. Then there’s some kind of voodoo that involves averaging all the ERPs and also averaging everything that isn’t an ERP in order to get a final picture of how the brain reacted to a stimulus. Sorry, but that’s the best I can do by way of explanation.

This study would require a one-time commitment of a few hours in the lab, with no pay. The only risk was that I might end up with my hair full of conductivity gel. This seemed like a risk I could handle, so I happily volunteered. But apparently they didn’t need me after all, because no one from the cognitive neuroscience lab ever contacted me.

When I mentioned the study to my daughter, “Emily,” she reminded me that she had been a research assistant in that very neuroscience lab during her brief stint as a psychology major. As you know from reading chapter 10, psychologists are notoriously deceitful, so she wouldn’t tell me the real point of the experiment as long as there was a chance that I might be a subject. When I told her that they weren’t going to use me after all, she revealed all.

It seems that the cognitive neuroscientists have identified particular ERPs that occur when people read or hear sentences with certain anomalies in them. There’s a P600 effect associated with syntactic anomalies (e.g., “He am reading a book.”) and an N400 effect associated with semantic anomalies (e.g., “He is feeding a book.”). In this study, or at least in the one that Emily helped with, people would see a mixture of sentences, most with either a syntactic or semantic error but some that were deemed OK and some that contained both types of anomaly (e.g., “He am feeding a book.”) The researchers would observe which effect, P600 or N400, was elicited by the combination sentences. At least that’s how I understood Emily’s explanation.

I was sorry that I never got to take part in that study. It seemed like it would have been one of the easiest and most enjoyable, despite the need for extra hair washing.

On a warm summer morning I had my eighth and last visit as a PsychoPharm subject. As Dr. J read through the tedious and senseless checklist of withdrawal symptoms, he stopped at “unusual sweating” and joked, “That may happen when you go back outside.”

My blood pressure was back to normal (for me), and there was no change between lying and standing, which made me question whether duloxetine was indeed what I’d had during the study. My weight had gone down two pounds, which warmed the cockles of my anorexic heart.

I made an appointment to go back in two weeks, so that Dr. J could monitor what the study coordinator called my “two AEs.” Two? I didn’t ask what she was counting as an adverse event besides the low blood pressure. It could have been the gastrointestinal discomfort I had mentioned. (I was pretty sure that was due to a plate of Indian food I’d eaten at an outdoor festival a few days earlier. I probably shouldn’t have mentioned it.) Or it could have been the decreased libido that Dr. J seemed to enjoy quizzing me about at each visit.

One problem with tracking adverse events is that they may or may not be related to a particular treatment. Robert Helms writes in his introduction to Guinea Pig Zero: “No one will ever know how many people have been lied to, manipulated, poisoned, and killed by unethical medical researchers.” One reason we’ll never know is that many unpleasant or injurious experiences, including some reported by GPZ writers, have a poorly substantiated link to the procedures or medications involved in the study.

It’s hard to take any drug warnings seriously when you know that (1) they’re based on researchers’ imperfect interpretations of subjects’ imperfect descriptions of their symptoms and (2) adverse events, ranging from mild headache to suicide, could have many different causes. My sex drive, for example, probably wasn’t any stronger before I started taking the drug, and even if it were, plenty of other conditions could have caused it to diminish, including menopause and a guilty conscience.

If enough people report an upset stomach or headache while taking an experimental drug, it goes down in the literature as a side effect, no matter how mild or severe it is and whether or not the drug caused it. If the researchers think the event is adverse enough, like my low blood pressure, the drug company won’t let you continue taking the drug (at least not with their blessing and on their dime). By stopping the study at the first sign of trouble, researchers may never find out just how adverse an event might become.

I rode down in the elevator with Dr. K, whom I hadn’t seen for a few weeks. I told her what I had learned about low blood pressure and cognitive impairment. She said that as a fellow hypotensive, she was relieved to have an excuse for her bad memory.

Meanwhile, in the herpes study, I had reached the washout period that preceded the switch from Valtrex to acyclovir. Once that week was over (with no viral outbreaks if I was lucky and stress-free), I had to start taking three 800 mg pills a day instead of just the one 500 mg Valtrex. I could also look forward to seven more weeks of four swabs a day. It was natural at this point in the study, Donna said, to resent the seemingly constant sampling. She called this feeling of resentment “swabbing fatigue.”

I had recently started applying for full-time jobs, but I hoped no one wanted to hire me before those seven weeks were over. Even with my fashionable black insulated lunch container to hold the paraphernalia I would need, I didn’t look forward to swabbing during my first days at a new job.

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