Clinical Trials 101 A Beginner s Guide Everyday Health
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A Consumer' s Guide to Clinical Trials
By Hilary MachtMedically Reviewed by Thomas Urban Marron, MD, PhDReviewed: December 12, 2018Medically ReviewedClinical trials are the best way to advance our understanding of medicine.iStockA clinical trial is a research study that involves human volunteers. Heralded as the best, if not the only way, to advance medicine, clinical trials are designed to evaluate new ways to prevent, detect, or treat disease. (1,2)
Every medicine on the market, every pill we swallow, every vaccine in use, was once the subject of a clinical trial; countless lives have been saved by penicillin and the smallpox vaccine, to reach back in history and name just two. Current advances include a long list of immunotherapies now approved for use by the U.S. Food & Drug Administration (FDA) to treat lung cancer, as well as other cancers.
The number of clinical trials being conducted in the United States and around the world is higher than it’s ever been. A total of 291,895 studies are currently registered with ClinicalTrials.gov, one of the largest databases of clinical trials in existence. Of these, 48,921 are actively recruiting participants. That’s up from just 1,255 trials, in total, when the National Institutes of Health (NIH) website first became available to the public in early 2000. (3,4)
Yet despite efforts by both pharmaceutical companies and public health agencies to educate people about the potential benefits of clinical trials and to recruit volunteers, public awareness about clinical trials remains relatively low — as does participation, particularly among women, children, and minorities, who tend to be underrepresented in research. (5,6,7)
A study published in May 2018 in the Journal of the American College of Cardiology found that while women were well-represented in trials of drugs for hypertension and atrial fibrillation, the numbers of those participating in studies involving heart failure, coronary artery disease, and acute coronary syndrome were significantly lower than the relative numbers of women affected by those conditions in the general population. (8) Cardiovascular disease continues to be the leading cause of death among women (and men) in the United States.
Indeed, recruitment in general is considered a major challenge for those leading these trials, and many studies never get off the ground due to a lack of volunteers. Studies involving cancer therapies are known for being hard hit. Over 12,000 cancer clinical trials are in the recruitment stage, but estimates put rate of participation among cancer patients at as low as 3 percent of potential trial candidates. A recent report found that a significant number of trials fail to enroll more than a single patient.
Among the most commonly cited reasons: simple lack of awareness among potential volunteers, mistrust of the process and fear of being a “guinea pig,” fear of not receiving the new therapy but rather the “standard of care” comparison therapy, restrictive inclusion criteria — for example, those who have had prior chemotherapy may be ineligible — and fear of side effects of new drugs. (9,10)
Clinical Trials Past and Present
The history of clinical trials is said to date back to 1747, when British physician James Lind conducted a systematic trial among British sailors with scurvy — a disease now known to be caused by a deficiency in vitamin C — by dosing some sailors on board a long sea voyage with a combination of orange and lemon juice to see if it helped cure the condition.
A variety of studies soon followed, but it wasn’t until the twentieth century, when randomized trials came into play, that things took a big leap forward. (11) Randomization involves dividing participants into separate groups by chance, not by selecting them for certain features, to compare different treatments. The first recognized randomized trial was carried out in the mid-1940s by the British Medical Research Council to test the efficacy of the antibiotic streptomycin against tuberculosis.
This trial also featured two other methodological advances in experimentation in that it was double-blind (neither investigators nor patients knew whether they were getting the active drug) and placebo-controlled (some patients received an inactive substance).
Today, most large clinical trials involving drugs that are likely en route to FDA approval are randomized, double-blind, and placebo-controlled — a combination known in medicine as the gold standard. Still, trials involving medical devices and surgeries are frequently not randomized, and many, if not most, devices aren’t subject to the same clinical rigor as drugs.
The vast majority of clinical trials involve drugs or biologics — medicinal preparations like vaccines and immunotherapies that stimulate the immune system to fight infection and disease. At last count, 133,007 such trials were registered with ClinicalTrials.gov, more than double the number of studies involving surgical procedures and medical devices combined. (4)
Related: 7 Myths About Clinical Trials for Advanced Breast Cancer
The Phases of Clinical Trials 1 2 3 and 4
Clinical trials are usually carried out in humans after laboratory and animal testing demonstrate that a treatment is promising, according to the NIH. The trials move through a series of phases and follow protocols including plans to balance potential risks with benefits. Trials are typically conducted in four phases:
Phase 1 Researchers test a treatment in a small group of people (about 20 to 80), for a period of several months. The main purpose is to learn about safety and to identify side effects, often as dosage levels are increased. About 70 percent of drugs pass this phase of testing.
Phase 2 Usually (but not always) a larger group of people (100 to 300) receive the treatment to further assess efficacy as well as safety and side effects. About one-third of experimental drugs successfully complete both phase 1 and phase 2.
Phase 3 The treatment is given to still larger numbers of people (1,000 to 3,000) and can last several years. This phase is intended to provide investigators — and, ultimately, the FDA — with more complete information on effectiveness and the range of possible adverse reactions. Between 70 and 90 percent of drugs entering phase 3 studies succeed. After a successful Phase 3 trial, a pharmaceutical company can request FDA approval to market the drug or biologic.
Phase 4 This phase, also referred to as post-marketing surveillance, occurs after a treatment has been approved by the FDA and is made available to the public. At this stage, researchers are supposed to track safety in the general population and gather information on benefits and optimal use. If problems occur, restrictions may be placed on the drug or result in its being taken off the market. (12,13)
Should You Participate in a Clinical Trial
People say they participate in clinical trials for a variety of reasons, including to play an active role in their healthcare; to help others by contributing to medical research; to gain access to treatments before they are widely available; to get medical attention and care they might not ordinarily receive; and even to earn money, according to CenterWatch. (14,15)
Satisfaction rates among people who have participated in a clinical trial run high: A report published in 2013 by the Center for Information & Study on Clinical Research Participation (CISCRP) found that 95 percent of those who had taken part in a trial in the past said they would consider joining another in the future. (16)
Still, many potential first-time volunteers never move forward. There are a number of reasons for that. Some, particularly minorities, are disturbed by memory of missteps in the past, primarily the Tuskegee Syphilis Experiment (1932–1972), in which African-American men were told by the U.S. Public Health Service that they were being treated (at no charge) for syphilis, but who in fact received no treatment at all for the communicable and often deadly disease. (17)
Still others are cognizant of past trials that resulted in products or treatments that subsequently turned out to be problematic for some reason, such as thalidomide, the sedative marketed to pregnant women in the late 1950s for morning sickness that caused thousands of severe birth defects; and the Dalkon Shield, the intrauterine device (IUD) used in the early 1970s that prompted more than 200,000 lawsuits by women harmed by the device.
Other commonly cited concerns include: fears about side effects; doubts that the therapy will be any better than the standard of care; and worry about receiving a placebo — as in, why would anyone want to risk getting a placebo, especially if they are very ill? (14)
While experts in the field acknowledge that the risks of enrolling in a clinical trial are real and entail many unknowns, they also say that some concerns are unfounded. For example, placebos are rarely used in trials involving patients with more advanced or serious illness, says Kenneth Getz, founder of CISCRP, explaining that most use an active comparison drug, typically the FDA-approved standard of care. In addition, volunteers are free to withdraw from a trial at any time and for any reason. (18)
Understanding Informed Consent
Over the years, and often in response to mistakes from the past, practices have been put into place to protect and inform patients. For example, the Tuskegee tragedy led to a process known as informed consent, which involves informing prospective volunteers about the intervention in question and the potential risks involved. Informed consent is now considered both a critical component of patients’ rights and clinical trials themselves. (6)
During the informed consent process, people should be provided with information that enables them to make an informed and educated decision about whether to enroll in the trial. That includes explaining to prospective subjects the purpose of the research, what their role would be and how the trial will work, and allowing them adequate time to ask questions and discuss things with family and friends. The FDA also notes that it’s important for people to understand their role as a “subject of research” — not as a patient.
Finding a Trial That Suits Your Needs
Clinical studies are conducted in a variety of types of locations, including hospitals, universities, doctors' offices, and community clinics. The location depends on who’s conducting the study. Funders can include governmental agencies, industry groups, individuals, universities, and other organizations, such as foundations and not-for-profits. Locations now exist in all 50 states and in more than 200 countries around the world, according to NIH. (4)
Trials can be found for virtually every condition imaginable. While many of the most commonly publicized trials often involve high-stakes therapies, such as those for late-stage cancer, lower-stakes trials are plentiful. Registered trials include treatments for everything from acne to insomnia to anxiety. (4)
And they’re not all about pharmaceuticals. Many clinical trials involve interventions with therapies such as botanicals, mineral supplements, and acupuncture — even aromatherapy and yoga for hot flashes, for example. (4)
People with a preference for lifestyle interventions to prevent or treat illness can help play a role in moving those disciplines forward as well. A number of trials involving diet and exercise have been registered.
These include studies assessing the effects of low-fat vegan versus Mediterranean diets on body weight and insulin sensitivity, run by the Physician’s Committee for Responsible Medicine, and the effects of intermittent fasting in subjects consuming a Mediterranean or Western diet, part of ongoing research at the Washington University School of Medicine on the prevention and treatment of age-related diseases. (4)
In the end, whether to participate in a trial is a personal decision, but perhaps the most important takeaway is that the decision be an informed one. Whether the thinking is "buyer beware" or "well-informed is well-armed," the consensus is that it’s best to gather as much information and input as possible from trusted and valued sources, including doctors and other health professionals as well as family and friends.
“Our motto is ‘education before participation,’” says Getz. “We encourage patients and their families and friends to gather the facts, speak with other patients and professionals, and ask a lot of questions.”
There are several searchable databases that offer listings of available clinical trials, including:ClinialTrials.govCISCRP.org
Additionally, you may find searchable listings at local healthcare centers, on the websites of disease specific organizations, and even advertised in local newspapers. (14,19,20,21,22)
Things to Keep in Mind When Considering a Clinical Trial
In most cases, participating will be at no cost to you. Sometimes, insurance may be billed for some devices, drugs, or services. These should be spelled out in the informed consent process.
What to Ask Can you spell out what the cost will be to me?
Some clinical trials will not require travel. Others will require regular check-ins. Find out what will be required of you beforehand.
What to Ask Will my travel costs be covered?
A treatment trial may be comparing a new treatment to one that is the standard, or to a placebo. You have no control over which arm of the trial you are assigned to.
What to Ask Am I willing to participate if I’m not getting the new treatment?
You can opt out of a trial at any time.
What to Ask How do I handle the situation if I decide to opt out part way through the trial?
Some trials involve years of follow-up.
What to Ask When does the trial end, and how long will my obligation last?
Resources We LoveClinialTrials.govU.S. Food & Drug AdministrationThe Center for Information & Study on Clinical Research ParticipationCenterWatchAmerican Cancer SocietyAmerican Heart AssociationNEWSLETTERS
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Editorial Sources and Fact-Checking
ReferencesNIH Research Clinical Research Trials And You. National Institutes of Health.What Are Clinical Trials and Studies? National Institute on Aging. May 17, 2017.Learn About Clinical Studies. ClinicalTrials.gov. January 2017.Trends, Charts, Maps. ClinicalTrials.gov. November 2018.Miseta E. Survey: 50% Of Americans Not Aware of Clinical Trials. Clinical Leader. April 20, 2017.FDA Encourages More Participation, Diversity in Clinical Trials. U.S. Food & Drug Administration. January 16, 2018.Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies: Volume I. National Institutes of Health. 1994.Scott PE, Unger EF, Jenkins MR, et al. Participation of Women in Clinical Trials Supporting FDA Approval of Cardiovascular Drugs. Journal of the American College of Cardiology. May 2018.Survey of Clinical Trial Awareness and Attitudes. SubjectWell.How to Maximize Patient Recruitment in Oncology Trials. BioPharmaDive.com. March 2017.Junod S. FDA and Clinical Drug Trials: A Short History. U.S. Food & Drug Administration.Glossary of Common Terms. National Institutes of Health. February 10, 2016.Overview of Clinical Trials. CenterWatch.Volunteering for a Clinical Trial. CenterWatch.Making the Decision About Clinical Trials. American Cancer Society. May 3, 2016.2017 Perceptions & Insights Study: The Participation Experience. The Center for Information & Study on Clinical Research Participation. November 10, 2017.Washington H. Medical Apartheid: The Dark History of Medical Experimentation on Black Americans from Colonial Times to the Present. 2008.Myths Vs. Facts About Clinical Studies. Seattle Cancer Care Alliance.Informed Consent for Clinical Trials. U.S. Food & Drug Administration. January 4, 2018.Questions to Ask Before Participating in a Clinical Trial. National Institute on Aging. May 17, 2017.Questions To Ask. The Center for Information & Study on Clinical Research Participation.Women in Clinical Trials = Hope. U.S. Food & Drug Administration. 2016.Show Less
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