Clinical trials are studies designed to test the benefits and side effects of experimental therapies such as potential drugs, products or treatments on people. It's estimated there are about 50,000 clinical trials taking place at any given time worldwide. And every year, 10 million healthy people are needed as participants in these medical studies in just the U.S. alone [sources: McHugh, Abboud]. These types of studies are often sponsored by pharmaceutical companies, but may also be funded through academic institutions, such as teaching hospitals, or government agencies, such as the National Institutes of Health. Clinical trials are usually carried out by teams of doctors, nurses and other health care professionals at hospitals or health centers, inside research centers, at universities, or even conducted through your doctor's office.
Before a human trial can be conducted, though, lab experiments first take place in animals and in human cells. If the results of those studies are promising, a written plan called a protocol is designed by clinical research specialists and statisticians, and reviewed and monitored by an Institutional Review Board (IRB) to ensure the study is both ethically and scientifically sound (both in concept and in execution) and protects participants.
But it wasn't always so. It wasn't until the 1962 Drug Amendments were passed that the U.S. Food and Drug Administration (FDA) gained authority to regulate and approve drugs in the United States. Prior to FDA regulation, in fact prior to modern evidence-based medical practices, there were no clinical trials. Early medical studies were more like trial and error. Consider it more like observation than anything else. On top of that, participants weren't necessarily volunteers, or if they did volunteer, the odds weren't good they were told what they were really signing themselves up for.
By the beginning of the 20th century, as many as 92 percent of drugs sold in the U.S. were fraudulent, ineffective, unproven or unsafe. Because of the risks associated with what some call "snake oil" treatments, in 1905 the American Medical Association announced a drug certification program and seal of approval for drugs that had been evaluated for quality control and safety [source: FDA]. Still, it wasn't common to conduct any pre-market safety or efficacy evaluation on experimental (or any, for that matter) drugs before the U.S. Food, Drug and Cosmetic Act of 1938 went into effect. It wouldn't be until after WWII when biomedical and clinical research projects became well-funded and the National Institutes of Health opened that statistically-based studies became the new standard in clinical trials.
Today the FDA regulates clinical trials for biologics (those are such things as vaccinations or gene therapy), drugs, and medical device products; any studies that fall outside of the FDA's authority are overseen by the organization (such as a research center) conducting the study.
Before we talk about the people who participate in clinical trials, how they're recruited and how much they're compensated, let's look at the basics of what clinical trials are and what happens during these studies.
Clinical Trial Process
Clinical trials are broken into four phases, and in total one individual study may last for more than a decade. The first phase, which spans about a year, is usually the first time that the treatment under evaluation has been used on humans. The number of participants is kept intentionally small. Generally, between 20 and 80 healthy volunteers are selected to participate at this early stage (rarely, but sometimes, individuals with advanced or untreatable disease may participate in phase I studies, too, depending on the circumstance). Phase I trials are designed to evaluate a drug's toxicity. Researchers use this stage to determine what the drug does to the human body, called pharmacodynamics (Can the body tolerate the drug?), and what the body does to the drug, called pharmacokinetics (How fast is the drug absorbed?). Safe dosage is determined during this phase, and acute effects are also identified and evaluated; there is almost never any therapeutic benefit to treatments tested on phase I participants.
If a drug is successful in phase I, phase II trials begin; and at this stage, patients suffering from the condition being studied are recruited as participants, rather than the healthy volunteers important to phase I. These studies typically last between several months to as long as two years, and are used to determine how well the therapy works in people who would benefit from its effects (its efficacy), and to further evaluate safety and side effects [source: CenterWatch]. Making it to the long-term testing of phase III, however, isn't in the cards for most experimental therapies. Out of every three phase I clinical trials conducted, one therapy will fail. Add in those therapies that fail during phase II studies, and the failure rate in early clinical trials rises to 85 percent [source: Pfizer New Haven Clinical Research Unit, Ledford].
Thousands of patient-volunteers around the world generally participate in phase III clinical trials, which may last over several years. Phase III studies are designed to confirm that the experimental treatment has a clear benefit, and compares it to similar treatments (if, in fact, there are similar treatments). During this phase the drug's side effects are also evaluated. Only about 50 percent of therapies studied in phase III will go on to be granted FDA approval [source: Ledford].
Phase IV of clinical trials happens actually after the therapy has been approved and marketed, and are called Post Marketing Surveillance Trials. This stage focuses on evaluating the drug's long-term benefits and side effects when used in the population at large.
Clinical Trial Participants
The first known written account of a participant actually being compensated for taking part in an early version of a clinical trial occurred in late 1667 in the diaries of Samuel Pepys. During this study the subject, a homeless man, allowed himself to be injected with sheep's blood (your guess is as good as ours regarding why, but the point is that man got paid for it) [source: Junod].
Recruiting participants for clinical trials can be, well, trying. More than 90 percent of all clinical trials are delayed or are never completed because volunteers are either not appropriately matched for the study or because there are simply too few volunteers.
The first three phases require a couple flavors of recruits; people with chronic or incurable illness who may benefit from the treatment, healthy people volunteering to help advance medical research, and healthy people volunteering for the paycheck.
Anyone can apply for any study that appeals to them, but the protocol written for each clinical trial outlines who can and cannot participate during each phase -- known as inclusion and exclusion criteria. These criteria cover specifics such as age and gender, current or past medical conditions, and anything else relevant to the specific study.
During most phases of clinical trials, participants are patients seeking new treatment, prevention or cure, but during phase I, participants are healthy test subjects with no known health issues. Phase I trials offer no therapeutic benefit to the volunteer, but participation helps in advancing cures, treatments and preventative therapies for chronic or fatal conditions. It can also be a lucrative endeavor for those in good health who have the time, flexibility and inclination to take part, such as college students or those who are unemployed (or underemployed).
Medical study participants are also compensated for their time based on a per-study rate, plus a per-study determined sum based on the duration of the study, the level of hardship, and the level of risk involved. Subjects could be paid a few hundred dollars or as much as $10,000 for just one study. The best-paying studies are typically those with the strictest requirements, such as a long duration, an in-patient stay, or invasive or uncomfortable procedures [sources: McHugh, Abboud]. Participants who volunteered to stay in bed for NASA's bed-rest study, designed for researchers to learn how microgravity effects the human body, for example, got a pretty sweet deal: $18,000 for a 70-day study (which turns out to be $1,200 weekly), over a total of 15 weeks at the Johnson Space Center in Houston, Texas [source: Ziegler]. In comparison, if you worked a 40-hour-per-week minimum-wage job (at $7.25 per hour) you'd take home $267.80 each week, a financial difference not lost on repeat volunteers, known as professional lab rats or "human guinea pigs" (a term coined by George Bernard Shaw), some of whom make upwards of $50,000 annually [source: Wing, McHugh].
The higher the risk of a phase I study, the higher the compensation, but sometimes, it comes at a physical cost. In London in 2006, for example, volunteers in a phase I trial of an experimental treatment for rheumatoid arthritis were paid £2,000 for their time, but six participants suffered life-threatening organ failure and went home with long-term disabilities [source: Elliot].
Volunteer Recruitment and Ethics in Clinical Trials
During the recruitment process, every human test subject must answer medical questions as well as questions appropriate to the study at hand. They must sign an informed consent form, an up-front document explaining the volunteer's rights and responsibilities during the study, the potential benefits as well as the potential risks of the experimental treatment, and the purpose, details and duration of the study itself, before a clinical trial can begin.
Human trials are ethically difficult to navigate, and while pharmaceutical companies and research units are often an easy target, volunteers sometimes act unscrupulously. There's nothing stopping a candidate from withholding information during the review process or being outright dishonest. For instance, as many as 10 percent of volunteers admit they've participated in simultaneous studies without telling researchers or recruiters. That's a problem because the overlapping experimental therapies may interfere with the final results of the studies (and may increase the risk of serious side effects, too) [source: Newsome]. Among professional test subjects it's common to fudge a medical history or age to appear as an attractive candidates for multiple studies. When being a test subject is your career, the more gigs per year the better the annual income, despite the potential risks.
And here's where things get a little gray -- well, grayer. Just as recently as 20 to 25 years ago, about 80 percent of all biotechnological and pharmaceutical trials were conducted in academic medical settings. Around 2000, though, pharmaceutical companies began to shift from non-profit academia to for-profit research units, and the majority (more than 60 percent) of studies shifted to third-party contract research organizations (CROs) [source: Newsome].
These for-profit companies, as part of the clinical trial process, pay for volunteer recruitment -- think of it like a finders' fee for physicians who recruit patients for appropriate studies. And those who do participate in scouting are paid additionally for their volunteer-recruitment services -- and not pocket change. CROs may offer health care professionals deals such as $12,000 for each patient who enrolls in a study, plus bonuses (including those based on enrollment numbers) [source: Elliott]. So far that adds up to a for-profit clinical trial research unit compensating doctors for their participation in patient recruitment, and then compensating those patients for their participation; a setup many describe as more of a business arrangement than volunteering as an act of kindness or generosity. What many ethicists and regulators would prefer is an arrangement not of monetary compensation and financial benefit -- rife with potential for exploitation -- but rather one with a sense of humanitarianism and altruism on the behalf of those who volunteer.
Author's Note: How much do pharmaceutical test subjects get paid?
There are actually five phases to clinical trials, not four, but phase zero isn't an official stage in trials and not required before clinical testing phase I can begin. It's an interesting stage nonetheless. Phase zero trials are pharmacological studies designed to find out some very basic information about how a drug and human body respond to each other -- for instance, does the drug reach the desired target (such as an organ or tumor)? That's good information to have before beginning years of clinical studies. In this stage, researchers use microdoses of experimental drugs in very small numbers of human volunteers (only 10 to 15 people at most) instead of relying on animal studies. The doses are so small the risk involved here is lower for participants than those in phase I studies.
More Great Links
- Abboud, Patrick. "What's the cost of being a human lab rat?" SBS. Nov. 6, 2013. (Dec. 19, 2014) http://www.sbs.com.au/news/article/2013/11/06/whats-cost-being-human-lab-rat
- American Cancer Society. "Phase 0 Clinical Trials: Exploring If and How a New Drug May Work." Oct. 31, 2014. (Dec. 29, 2014) http://www.cancer.org/treatment/treatmentsandsideeffects/clinicaltrials/whatyouneedtoknowaboutclinicaltrials/clinical-trials-what-you-need-to-know-phase0
- CenterWatch. "Overview of Clinical Trials." (Dec. 19, 2014) http://www.centerwatch.com/clinical-trials/overview.aspx
- ClinicalTrials.gov. 2014. (Dec. 19, 2014) https://clinicaltrials.gov/
- Elliott, Carl. "Guinea-pigging." The New Yorker. Jan. 7, 2008. (Dec. 19, 2014) http://www.newyorker.com/magazine/2008/01/07/guinea-pigging
- Grady, Christine. "Payment of Clinical Research Subjects." The Journal of Clinical Investigation. Vol. 115, no. 7. Pages 1681-1687. July 1, 2005. (Dec. 19, 2014) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1159153/
- Junod, Suzanne White. "FDA and Clinical Drug Trials: A Short History." U.S. Food and Drug Administration (FDA). July 7, 2014. (Dec. 19, 2014) http://www.fda.gov/AboutFDA/WhatWeDo/History/Overviews/ucm304485.htm
- Le, Jennifer. "Clinical Pharmacology: Pharmacokinetics." The Merck Manuals - Professional Edition. May 2014. (Dec. 19, 2014) http://www.merckmanuals.com/professional/clinical_pharmacology/pharmacokinetics/overview_of_pharmacokinetics.html
- Ledford, Heidi. "Translational research: 4 ways to fix the clinical trial." Nature. Vol. 477. Pages 526-528. Sept. 28, 2011. (Dec. 19. 2014) http://www.nature.com/news/2011/110928/full/477526a.html
- McHugh, Josh. "Drug Test Cowboys: The Secret World of Pharmaceutical Trial Subjects." Wired Magazine. Vol. 15, no. 5. April 24, 2007. (Dec. 19, 2014) http://archive.wired.com/wired/archive/15.05/feat_drugtest.html
- Moroney, Angela Cafiero. "Clinical Pharmacology: Pharmacodynamics." The Merck Manuals - Professional Edition. September 2013. (Dec. 19, 2014) http://www.merckmanuals.com/professional/clinical_pharmacology/pharmacodynamics/overview_of_pharmacodynamics.html
- National Institutes of Health (NIH). "Clinical Center: FAQs About Clinical Studies." Nov. 10, 2014. (Dec. 19, 2014) http://clinicalcenter.nih.gov/participate/faqaboutcs.shtml
- Newsome, Melba. "Human lab rats loan bodies to science for cash." NBC News. April 27, 2008. (Dec. 19, 2014) http://www.nbcnews.com/id/23727874/ns/health-health_care/t/human-lab-rats-loan-bodies-science-cash/
- Pfizer New Haven Clinical Research Unit. "What is drug development?" (Dec. 19,2 014) http://www.newhavencru.com/sites/NewHavenCru/Pages/what_is_drug_development.aspx
- The Hastings Center. "Clinical Trial Phases." (Dec. 19, 2014) http://www.thehastingscenter.org/uploadedImages/Publications/Briefing_Book/clinicaltrials_phases.gif
- U.S. Food and Drug Administration (FDA). "Inside Clinical Trials: Testing Medical Products in People." Nov. 6, 2014. (Dec. 19, 2014) http://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm143531.htm
- U.S. National Library of Medicine. "FAQ: ClinicalTrials.gov Questions." Oct. 24, 2009 (Dec. 19, 2014) http://www.nlm.nih.gov/services/faqctgov.html
- Wendler, David. "The Stanford Encyclopedia of Philosophy - the Ethics of Clinical Research." Stanford University - The Metaphysics Research Lab. Sept. 20, 2012. (Dec. 19, 2014) http://plato.stanford.edu/entries/clinical-research/
- Wing, Nick. "17 Numbers That Will Make You Realize Just How Pathetic The Federal Minimum Wage Is." HuffPo. september 24, 2014. (Dec. 19, 2014) http://www.huffingtonpost.com/2014/09/24/minimum-wage-increase-numbers_n_5868848.html
- Ziegler, Maseena. "NASA Will Pay $18,000 To Watch You Rest In Bed--Really." Forbes. Sept. 18, 2013. (Dec. 19, 2014) http://www.forbes.com/sites/crossingborders/2013/09/18/nasa-will-pay-18000-to-watch-you-rest-in-bed-for-real/