Mary Collins has had type 1 diabetes for half her lifetime. The autoimmune disease, while manageable, is costly and unpleasant for the 55-year-old self-employed seamstress from Mountain Rest, S.C. So Collins, who lacks health insurance and hates the insulin shots she has to give herself before every meal, jumped at a chance a few years ago to join a research study. It provided her with free medical supplies, reimbursed her for travel to her appointments at the study site, paid her $1,200 outright, and—most appealingly—let her try out an inhaled form of the medication she'd always had to take by needle.
Collins was to participate in the industry-sponsored trial, which was designed to test a company's unproven delivery device for inhaled insulin, for a year. After 6 months, however, she dropped out of the study, concerned that her blood glucose levels were fluctuating to an unhealthy degree. Despite that outcome—and a hassle she experienced while seeking compensation that was due her—she has no regrets about giving the clinical experiment a try. "Even though I did have a problem," she says, "it would not stop me from doing it again." Medical research is an enormous—and enormously important—enterprise. Without a steady stream of volunteers like Collins, it would grind to a halt, making new therapies impossible to develop. "The reason we have [today's] standard-of-care drugs . . . is because people went into clinical trials and proved their efficacy," says Michael Caligiuri, a medical oncologist and CEO of the James Cancer Hospital at Ohio State University.
That doesn't mean everyone should join a clinical trial, however. For one thing, no trial is completely risk free. Ten years ago this month, in one of the most infamous research disasters in modern times, Jesse Gelsinger had a fatal reaction to an experimental gene therapy. The 18-year-old's death led to allegations of ethical misconduct directed at the study's leaders and the University of Pennsylvania, which ran the trial. (The parties involved reached an out-of-court settlement.)
Even ethically unassailable studies have risks. "Bad things can happen even when [trials] are done well," says Christine Grady, a bioethicist at the National Institutes of Health's research hospital, known as the NIH Clinical Center. In a 2005 analysis of 460 early stage cancer trials, researchers led by Grady found that 1 in every 7 participating cancer patients suffered serious side effects from drug toxicity. One in every 200 volunteers died from it. (That kind of trial may be particularly risky because of the nasty nature of many cancer medications.) And while many volunteers hope participating in a research study will improve their health, there's no evidence that that's likely. In the same 2005 study, doctors observed clinical improvements in only 4.4 percent of patients receiving the most unproven therapies; more patients were harmed than helped. And although a trial might give a patient access to a new drug, that drug isn't necessarily better than (or even as good as) standard therapies that have already been tested and proved.
Whether a particular medical study is right for a particular patient depends on the person's health condition, personal priorities, what alternative treatments are available, and how thoroughly the experimental therapy has been studied so far, among other factors. Here are nine tips for people considering volunteering for a clinical trial:
Understand the researchers' goals. A doctor's sole purpose is to help you get better, right? Not when she's wearing the hat of a medical researcher. A researcher's foremost responsibility, unlike that of a typical physician, is to ensure the scientific and ethical integrity of a medical experiment. Yet many patients wrongly hold a "presumption that being in a trial is [automatically] good for you," says Deborah Zarin, head of clinicaltrials.gov, a government database of clinical trials. That misunderstanding, called the therapeutic misconception, may lead some patients to agree to tests and procedures that they'd refuse if they really thought about the implications for their health.
Know how participating would alter your care. If you enroll in a trial, how will the treatment you get differ from the care you'd otherwise receive for the same health problem? That's a question that Kevin Weinfurt, a psychologist who's in charge of assessing trial volunteers' experiences at Duke University Medical Center, recommends asking before deciding whether to sign up. Researchers are required to give all patients at least standard-of-care treatment, whether or not they get an experimental treatment as well. But while some trials give patients drugs that aren't available to the general public, others simply test two or more readily available medications against one another.
In the former scenario, patients stand to gain more if they have either run out of mainstream treatment options or if existing treatments' side effects are unacceptable, says Gunn Elisabeth Vist, an evidence quality researcher at the Norwegian Knowledge Centre for Health Services in Oslo. In the latter instance, a patient's decision to join the trial may have no impact on his health; Vist's research indicates that trial volunteers typically fare no better (nor any worse) than patients who receive similar care outside the context of a trial.
Anticipate the risks. Some studies involve only negligible risks. Letting researchers draw an extra vial of blood and review your medical chart, for example, probably isn't a big deal. Others—like the cancer trials that Grady studied and many of the trials that recruit healthy volunteers rather than patients with a disease—are inherently more hazardous. And health risks aren't the only dangers to be considered. Weinfurt recommends that would-be volunteers ask study leaders about who would have access to their personal medical data and how the data will be protected from unauthorized eyes. HIV patients, for example, "want to be confident that the data they supply will not be available to a whole bunch of people who might potentially be able to identify [them]," he says.
[See Medical Identity Theft Turns Patients into Victims.]
Consider the potential benefits. Certain studies are known as therapeutic studies, meaning that researchers hope the experiment will help participants. Nontherapeutic studies, by contrast, have little if any chance of improving volunteers' health. Each trial is also designated as a phase 1 study, which primarily examines a treatment's safety; phase 2, which in most cases investigates a treatment's most effective dose; or phase 3, which generally compares the treatment's efficacy against the best available alternative. Harmful or ineffective treatments are sometimes identified and abandoned at phase 1. That's one reason phase 3 trials are more often therapeutic and, according to some experts, more likely to be safe. "In general," Vist says, "the worst [treatments] are weeded out before they get to phase 3."
Don't get stuck with a whopping bill. An experimental treatment provided as part of a clinical trial should always be free to the patient, says Caligiuri. If a patient also receives conventional tests or treatments in the course of the trial, her health insurance should cover as much of that care as it would outside a trial. But insurers sometimes refuse to cover even the nonexperimental portion of volunteers' care, Caligiuri says. About 30 percent of the insured volunteers participating in trials at his hospital run into such insurance claims denials, he says. Denials tend to occur with Medicare Advantage HMO and PPO plans and with insurance plans that are based outside the state where the trial is taking place. To protect yourself, make sure your insurer is committed in advance to reimbursing appropriate costs.
Look for opportunities to save money. On the flip side, says Caligiuri, uninsured patients can sometimes get cutting-edge care for free by joining a clinical trial. A small fraction of cancer trials, for example, are conducted by community-based physicians rather than researchers at academic medical centers. Community-based trials tend to be funded by pharmaceutical companies that have a stake in getting results as quickly as possible—and may be loath to turn away willing volunteers for lack of complete insurance coverage. "It is often the case [that] the industrial sponsor will cover what is not covered by insurance," he says.
Look out for financial conflicts of interest. Researchers who pour hundreds of hours into a study need to be compensated. Some forms of compensation—such as payments made to researchers for each volunteer they take the time to enroll—are commonplace and generally noncontroversial. But certain financial relationships raise red flags in the eyes of some experts. Weinfurt advises patients to avoid trials in which a participating researcher holds a patent on the experiment drug or medical device or owns stock in the company that makes it. Those kinds of "equity relationships are more worrisome than are other financial relationships," he and several colleagues wrote in a paper that appeared last month in the New England Journal of Medicine.
Consider getting an independent medical opinion, especially if the doctor who suggests you join the trial is directly involved in it. Researchers have incentives to expeditiously fill all the volunteer slots in their trials, and while they're forbidden from pressuring patients to participate, a doctor with unbridled enthusiasm for the research might unconsciously influence a patient's decision. If a researcher will treat only patients who join his trial, says Weinfurt, "I personally would feel more comfortable getting a second opinion." To bring an independent doctor up to speed, adds Zarin, "print out the study record [available on clinicaltrials.gov] and bring it to your provider."
Know your motivation. Why are you considering a trial? You might be driven by a sense of altruism. Perhaps you want the money or the free medical attention that comes with participation in certain studies. Or maybe you're driven by a hope, however slight, that the experimental treatment will improve your health. No one motivation is inherently more valid than another. But being aware of what your objective is will help you evaluate whether a particular trial is a good fit.
Jovona Neal of Nashville recently signed up for a flu vaccine trial she saw advertised on Facebook because, she says, "it's a good way . . . to do something charitable." She had already received a conventional flu shot and figures the experimental one won't give her any additional immunity. But she also knows enough about flu vaccines to realize that developing a faster manufacturing process, which is a goal of the trial, could help millions of people, especially in years, like this one, when a pandemic strain breaks out.
Neal also carefully gauged her risk before signing up. She knows and trusts the company conducting the study, and she learned that the vaccine had already undergone uneventful preliminary testing in people. "This particular study was in its second phase," she says. If the shot had been unsafe, she figures, "it would never have made it to the second stage."
Since joining the flu study, Neal has been offered the chance to participate in another trial. That study needs volunteers willing to follow a low-cholesterol diet and take an experimental anticholesterol drug. "I'm not sure I'm going to do that one," she says. "I happen to be happy with my cholesterol medication. If I wasn't, I think I'd be more tempted."
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