Human Subject: An Investigational Memoir

Contents | Next chapter | References | Contact

1. No Pain, No Brain

“C'est par la méthode analytique ou expérimentale seule que nous pouvons arriver à cette détermination des conditions des phénomènes, aussi bien dans les corps vivants que dans les corps bruts; car nous raisonnons de même pour expérimenter dans toutes les sciences.”

“Here’s the device.”

By my rough calculation, Lisa had said that sentence to me 20 times during the course of my two visits with her. The calculation was understandably rough, because I was impaired by the painkiller oxycodone.

On my previous visit I had been impaired by a placebo; in both cases I had been told not to drive myself home. The real reason for issuing this precaution was that neither I nor the research staff officially knew whether I'd had the drug or the harmless sugar pill. But studies have confirmed the existence of a placebo effect, in which people experience the benefits and the side effects of a drug even when they only think they've taken it. I wondered, after walking home that first day, if anyone has ever been arrested for driving under the influence of a placebo.

Lisa and I were at the general clinical research center (CRC) of a large medical center affiliated with a huge university, which I'll call Big U. I was participating in a study designed to test the cognitive effects of oxycodone in older adults. In plain English, this meant giving a prescription painkiller to geezers and then testing their thought processes and reaction times. I found it reassuring that, at age 52, I was not in the geezer group, but rather in the control group of 35- to 55-year-olds. The “older adults” were all at least 65.

The principal investigator (PI) on this study, a psychologist, had previously published a research report that revealed, among other findings, that pain itself can cause cognitive impairment. (This does not surprise me, as my brain was never so impaired as during the hours when my daughter was trying not to be born.) In that earlier paper, the PI had pointed out the lack of data on how narcotics like oxycodone affect old folks’ cognitive abilities; the current study was an attempt to begin filling that gap in clinical knowledge.

“The device” that Lisa wielded was a pupillometer, which she used to measure my left pupil every half hour to see how the pill I had taken was affecting it (narcotics tend to reduce pupil size). The lights had to be out for seven minutes before each measurement, and Lisa didn’t want to stand around in the dark that long. When she came in, she needed my help to guide the pupillometer to my eye.

That morning I had thought I was getting the hang of staring into the device at just the right angle so that she could get a good read on the size of my pupil, but with the drug in my system my eye had become uncontrollable--darting about, blinking rapidly, and nearly closing at times. At times today it had taken more than a minute for Lisa to get a reading. This last time, however, the eye had resumed its sober ways, as the drug diminished in my system, so the measurement took just a few seconds.

Immediately following the pupillometry, a nurse took my blood pressure and pulse and drew a few cc’s of blood from the IV planted in my arm. Having been told by a nurse several decades ago that I have “a funny little blood pressure,” I hadn’t been surprised the first day to see a reading of 85/58. The nurse, however, had found it troubling, so I walked around and tried to think upsetting thoughts in order to increase the pressure. It worked. Today’s nurse didn’t seem at all concerned by the low numbers, so I was able to remain lethargic and complacent. Later I would learn that such a low BP could really be a cause for concern.

Three times during each visit I underwent a series of cognitive tests, some of which were extremely boring and repetitive. At my screening visit, Lisa had told me that one person quit in the middle of his first study visit, because he couldn't stand the tedium. The worst test for me was the one where I was presented with a sheet of paper containing rows and rows of 'd’s and 'p’s, with various combinations of one or two tick marks above and below each letter. My task was to cross out all the d’s that had some combination adding up to two tick marks. It looked a bit like this . . .

Cognitive test

. . . except that each line was about three times that long and there were at least a dozen lines on each page. That’s how I remember it anyway. I was supposed to work as fast as I could, and Lisa would tell me when it was time to move on to the next row, so not only did I feel incompetent and inaccurate, because surely I’d missed a lot of the target items, but I felt incredibly slow, because I always left each row less than 90 percent complete.

Slightly more satisfying were the memory tests. One involved a list of words—all of them concrete nouns—that Lisa read to me very slowly and then asked me to recall. “Airplane . . . pig . . . letter . . . ” and so on. I always tried to construct a mnemonic story using most of the words (“A pig flew in an airplane, which also carried letters . . .”), but there were always a few words I forgot, and some groups of words just didn’t fit together very well. She would read the list three times, and each time, when she had finished reading, I would recite the words I remembered.

In another test, each of the digits from 0 to 9 had been assigned an arbitrary symbol, such as a greater-than sign (>), an X, or some other simple pictogram. One side of the paper was filled with a random series of digits, with the symbol-mapping key at the top of the page. I was able to look at the key while filling in the symbol for each digit as quickly as I could. Afterward, I had to turn over the paper and try to reconstruct the code from memory, recalling the symbol for each digit. I was never very good at this test (which, I learned later, was called Symbol Digit Modalities). At most I could remember six or seven of the symbols for sure, and I made wild guesses at the rest.

After the paper tests came “the computer task,” which sounds challenging and rigorous, but was really just a test of my reaction time: I pressed a Yes button when I saw the word Yes on the screen, and a No button when I saw the word No. After this stimulating interlude, Lisa would again ask me how many words I could remember from the list she'd read. Then she would read a mixture of some words from the list with various new words and have me identify the imposters.

Another memory test involved listening to a tape recording of a man reading numbers and letters. There were seven difficulty levels, with three trials at each level. At the first level he would read two or three numbers and letters (“9 . . . E . . . 4”); by the last trials, he was reading three or four of each (“G . . . 7 . . . Q . . . 5 . . . 2 . . . A . . . M . . . 9”). My task was to paraphrase the list he gave, reciting first the numbers in numerical order and then the letters in alphabetical order.

At first I had thought this test would be the most boring and annoying of all, but I discovered that I could do it well if I concentrated hard enough. It was just a matter of keeping two running, ordered lists in my head. Even on the second day, while under the influence of oxycodone, I was able to keep my mind from wandering too much from the task.

The cognitive tests were followed by questions about how I felt. Depressed? Happy? Floating? Itchy? (That one always made me itch.) Hungry? Headachy? Nauseous? I had to rate each sensation on a scale, 0 to 4 for some, 1 to 10 for others. I'm not sure why some feelings were presumed to have more nuances than others.

I had been strictly admonished not to have any caffeine for 24 hours prior to each visit. There were other prohibited substances, including alcohol, aspirin, and garlic, but coffee was by far the toughest to do without.

The day before the first visit, I didn't wake up until 9 a.m., 23 hours before my appointment. Wanting to stick to the letter of the instructions, I abstained from coffee throughout the day. By 8 the following morning, when I reported for duty at the CRC, the blood vessels in my head had become painfully dilated. (Later I learned that the dilation lowers one's blood pressure, which could partially explain the low BP readings I'd had that first day). My head continued to throb incessantly; the persistent, unvanquishable headache was one reason that I suspected I hadn't gotten the actual drug that day.

The following week, I awoke 25 hours before my CRC visit, so I was able to swallow a hefty dose of caffeine before eight o’clock. I had no headache on the morning of that second visit, which was quite ironic given the fact that the pill I'd taken that time was the real deal and would therefore have squelched any pain.

The last task in each series was a measurement of the effect the drug was having. Since they couldn't count on all subjects to be in agony from caffeine withdrawal, the researchers had their own means of inflicting pain: immersion of my hand in a bath of near-icy water. Lisa wouldn't tell me the temperature of the water, but I had read about similar procedures in other research reports, and the temperatures ranged from 1 to 4 degrees Centigrade.

I was instructed to say “now” when I first felt pain in the submerged hand; then when I couldn't stand the pain any longer I was to remove it. There was a lukewarm bath that I could then place my hand in (Lisa had told me that some people preferred not to put the cold hand in the warm water, because it was painful for them, but I found it a relief). It was important, Lisa said, to concentrate on the sensations I was feeling and to remove my hand at precisely the same level of painfulness each time. I tried hard to do this, but it wasn't easy to be that consistent.

On my previous visit, and during the screening visit, I had been able to keep my hand in the cold water for about three seconds. Today, with oxycodone in my system, I felt as if I could have kept my hand submerged forever. I didn't feel a lot of pain, but I suspected that I could be doing permanent damage to nerves or tissues, so I removed my hand after about eight seconds. (Weeks later I contemplated an extension of this experiment: taking a couple of oxycodone tablets and then walking into the ocean. For more on suicidal thoughts, see chapters 3 and 7.)

The pupillometry, BP reading, and blood-letting usually occurred while I was sitting up in a hospital bed. I would move to a chair for the cognitive and other tests. I got to keep most of my clothes on, so it wasn’t as demeaning a situation as most hospital patients find themselves in. The room had a television set for my entertainment between procedures, but I never turned it on. Instead I read a book or worked on homework for the last course I ever planned to take (having realized by this time that I was no longer course-taking material).

During my participation in this study, I never met the PI. In fact, the only health professional connected with the study that I had any contact with was the doctor who had performed a very brief medical exam during the screening visit. It seemed odd to me that Lisa, a research assistant with a bachelor's degree, had so much responsibility. Not only did she administer all the cognitive-function tests, as well as the ice-cold water test, but she even assisted the nurses with taking my vital signs.

Lisa seemed perfectly competent and conscientious, and she revealed to me during the second visit that she planned to attend nursing school. Still, she seemed underqualified, and was definitely underpaid, to have full responsibility for screening subjects, conducting tests, and gathering all the data for this study. Later I found the job description for Research Study Assistant, Lisa’s position, and was surprised to see that the duties could include drawing blood, administering ECGs, and measuring vital signs. The starting pay for the job was about $12.50 per hour. Since she’d been there for over a year, Lisa was probably making close to $13.

My own compensation for participating in the study was less than even Lisa's hourly wage, but there were other, less tangible rewards, like getting to watch blood being siphoned out of me at regular intervals. Plus I got two free lunches. Yes, they were hospital lunches, but they weren't half bad. On the previous visit, a Wednesday, I had feasted on a fishwich and lentil soup. Today, the first Friday of Lent, there were no vegetarian or seafood entrees on the menu—proof, if any were needed, that this was a secular facility rather than one with “Saint” or “Sisters” in its name. (No, I’m not Catholic, but I pay attention to when Mardi Gras is.)

When I commented on the dearth of mammal-free selections, Lisa brought me a previously undisclosed vegetarian menu. So that day I had veggie lasagna, spinach salad (a bowl of tightly compacted spinach leaves with a single-serving pouch of Italian dressing on the side), and two peach halves (why didn't they call it a peach whole? my foggy mind wondered).

After lunch both days I was allowed about 90 minutes of bed rest. During the previous, unmedicated visit, I had slept for a while. This time I didn’t want to miss a minute of the narcotic high, so I stayed awake. Alas, five hours after I’d gotten the pill, the effects began to wear off.

After my vital signs and blood were taken for the last time, I was free to go. Lisa had one last question for me, which I'm sure was not part of the study protocol: How had I managed to do so well on the memory task involving numbers and letters? I told her about the running lists I kept in my head, and I speculated that maybe I was able to keep them in order so well because of my years of working with call numbers in a library.

A few days later I received a check in the mail for $200, my compensation for the screening visit ($25), the first study visit ($75), and the second study visit ($100). A few weeks after that, I read in Robert Helms’s anthology Guinea Pig Zero (Helms, 2002) that his first “No-No” in grading research facilities is that the study subjects should never receive less than $200 per day. Thank goodness I wasn't in it for the money.

To insist on living wages for guinea pigs may strike some people as selfish and greedy, but in the early stages of research, healthy volunteers often assume a lot more risk than the patients who stand to benefit from the treatment. Medical research, particularly in the area of drug testing, has become a source of great wealth for many private companies, and it's only fair that those who make this wealth possible should be paid a decent wage. However, I think that all who participate in research are entitled to just compensation, not just the healthy subjects. I strongly disagree with drawing a distinction between those who are suffering from the condition being treated and those who are professional study participants. “But patients are in situations fundamentally different from those of healthy volunteers,” write Trudo Lemmens and Carl Elliott. “Often they are vulnerable because of their illnesses. . . . To import commercial considerations into this already fragile relationship would be to court the risk of serious exploitation.” (Lemmens & Elliott, 2001)

Hogwash! If anything, the afflicted patients deserve more compensation, because they stand to suffer the most if the product being tested doesn't alleviate their condition, or if they get a placebo instead of the actual drug. As I would soon see, however, this paternalistic attitude is the foundation for an entire government-mandated industry of human-subject “protection.”

Contents | Next chapter | References | Contact