Questions surrounding the motivations and personalities of the repeat volunteers are not just academic. The answers could alter the validity and reliability of thousands of studies, past and future. There are, for example, the four studies, soon to be a fifth, in which Della Malone is now enrolled. The 74-year-old Baltimore administrative assistant has undergone brain scans for a study of Parkinson's and CT scans for a study of lung function, swallowed concentrated broccoli with mango juice for months in a study of cancer prevention, and is planning to take selenium in a study of aging and dementia.
Psychologist Carl Tishler, a colleague of Bartholomae's at Ohio State, has found that personality characteristics of veteran NHRVs do differ from those of non-volunteers. And that may alter their response to medication, to give but one example. "Differences in personalities and psychologies have been shown to affect metabolic and immune responses, which can throw real doubt on the outcomes of clinical trials that use these volunteers," Tishler says. He contends that experimenters need to do more to understand how such differences influence brain, mind, and body reactions in drug tests or psychological research.
So little research has been conducted specifically about NHRV physiology, motivation, and personality variation that some psychologists openly suggest that the research industry and the volunteers may prefer to keep that Pandora's box closed. Nancy Kass, a bioethicist at Johns Hopkins, says she's unaware of any standard screening tool "that rules out psychopathology in 'normal' volunteers." Kass has the impression that "people have determined it's rare for someone with alarming pathology to volunteer and that it's a waste of resources to screen." It may, she notes, be "in the best interests of everyone involved to avoid the subject out of concern for eliminating volunteers even if a few are wacky."
How Normal Is "Normal"?
As far back as the late 1950s, studies have suggested that some substantial number of NHRVs have medical or psychological conditions or personality traits different from those in the general population. In a 2003 essay, Tishler and Bartholomae conclude—after reviewing the medical literature—that a substantial proportion of NHRVs "have been found to have a history of serious psychiatric illness or medical or neurological conditions, as well as characteristics, temperaments, or personality dimensions that differ from the norm of the population."
This is not to say NHRVs represent a population of Munchausen syndrome sufferers, who seek to become ill and gain sympathy and care. They may actually be more akin to bungee jumpers, or medical Evel Knievels, with temperaments that make them particularly tolerant of certain risks.
In the early 1990s, Spanish investigators assessed the relationship between personality factors and volunteering for phase-1 trials using the Sensation Seeking Scale and the Eysenck Personality Questionnaire, in 48 healthy male university student volunteers and 43 similar men who did not volunteer. "Significant differences" were found in thrill- , adventure-, and experience-seeking, boredom susceptibility, extroversion, and psychoticism, the researchers found. Overall, the personalities of volunteers were "characterized by a higher sensation-seeking trait and extroversion."
Similarly, a classic study of Army recruits decades ago found that volunteers who signed on for the most risky tasks were "significantly less anxious" than non-volunteers. And studies of prisoners, who once were allowed without limit to sign up for risky clinical trials, showed that volunteers also tended to be people who didn't see risk the way most of us do. In bioethicist Kass's study of 60 healthy volunteers, only 12 mentioned potential risks to health as a concern—and only when prompted.
There may be other significant psychological differences between NHRVs and non-volunteers besides their perception of risk and susceptibility to anxiety. Tishler and Bartholomae, among others, looked at personality characteristics of 28 male NHRVs participating in a phase-1 trial of three drugs. The drug trial required extended inpatient confinement. On the eleventh day of confinement Tishler and his team gave the volunteers questionnaires including the Minnesota Multiphasic Personality Inventory.
Among this group of very experienced subjects—who reported up to $80,000 in volunteer service income over their lifetimes—50 percent had "clinically significant elevations" on at least one of the MMPI personality scales. Findings ranged from some psychopathic deviation, to paranoia, to hysteria, to hypochondria, to depression. Tishler says, "The findings tell me that scientists might not really learn much [about the responses of the general population] if the only people signing up for a seclusion study are those whose psychological or physical makeup, temperaments, or brain chemistries are significantly different from the vast majority of those who eventually will take the drugs that were tested."
Why do such differences matter? Personality factors have deep biological roots in the brain. New Zealand investigators have shown that personality factors such as novelty-seeking, harm avoidance, and reward dependence are better than medical factors at predicting response to antidepressant drugs. Japanese scientists have found that the rate of drug absorption into the bloodstream is faster in highly neurotic volunteers than in less neurotic ones.
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