Every year, more than 185,000 clinical trials are in progress worldwide, 40 percent of which take place in the United States, according to the National Institutes of Health (NIH). And one of the biggest challenges for researchers is attracting enough volunteers.

For someone with a life-altering disease, participating in a clinical trial may offer hope for a better treatment. For healthy friends and family, enrolling can help make a difference for someone they care about. For others, it means helping expand scientific knowledge and possibly being part of a breakthrough that benefits everyone.

No matter what your motivation, taking part in a study can be a meaningful way to make a significant contribution to science. We talked to experts to help you make a fully informed decision about whether and how to participate.

The Pre-Clinical Phase

A trial begins the moment a light bulb goes off in a researcher's head, says Dietrich Haubenberger, MD, director of the clinical trials unit in the intramural research program at the NIH in Bethesda, MD, and a member of the American Academy of Neurology (AAN). Then begins the long process of establishing safety before the first humans can be enrolled. In the pre-clinical phase, the drug or treatment is tested first in the laboratory, then in animals. Those results, as well as manufacturing and clinical protocols, are reviewed by the US Food and Drug Administration (FDA) to validate their safety.

If the FDA gives the green light, researchers then outline the details: the results they're after, what they're measuring, what changes they expect, and how many patients are required to prove the treatment works. Those details go before an institutional review board, a group composed of at least five members that includes scientists, doctors, and lay people, which is responsible for protecting the welfare of potential participants and ensuring that all medical, legal, and ethical requirements are met.

The Three Phases of Clinical Trials

Once the design is approved and subjects recruited, the researchers can begin a human trial. Generally, clinical trials are divided into three phases: Phase 1 is designed to define the maximum tolerated dose of the drug, phase 2 determines whether a drug may work in a specified illness, and phase 3 determines if a drug is better than the standard treatment for that illness or, if a standard treatment doesn't exist, better than placebo. With each phase, the number of volunteers increases, from 10 to 80 in phase 1 up to hundreds or thousands in phase 3. For conditions given "orphan disease" status by the FDA—meaning rare diseases that affect only a small percentage of the population—the FDA allows smaller-sized studies.

If a trial doesn't meet its designated goals at each phase, the FDA will rule out further testing and end the process. The FDA allows for certain side effects, but if a participant were to have a heart attack, develop a serious disease as a result of the drug, or die, the organization would intervene.

Trial Designs Vary

Study designs differ depending on what the researchers are trying to find out and may require different levels of involvement from study subjects. In observational studies, participants may be observed and monitored but receive no treatment, so researchers can learn how the disease progresses. For genetic studies, researchers screen certain groups of patients to look for links between their medical conditions and their genes for possible genetic targets for new treatments. In interventional trials, participants may be given an experimental drug or a placebo to determine whether a new treatment is effective.

The "gold standard" for testing new drugs in phase 3 trials is a randomized, placebo-controlled, and double-blind design, says Bruce H. Cohen, MD, director of pediatric neurology at Akron Children's Hospital in Ohio, a Fellow of the American Academy of Neurology (FAAN), and a member of the Neurology Now editorial advisory board. Participants are randomly divided into two or more groups, with some getting the drug and others getting a placebo. "Double-blind" means that no one knows who is getting the drug and who is receiving the placebo, which ensures that everyone is treated exactly the same and that researchers can objectively evaluate whether the new treatment is effective. It also allows for less biased reporting of symptoms and perceived benefits by participants.

For crossover studies, which are required for certain types of medications and illnesses, participants who start with a placebo are eventually switched to the real drug, and vice versa, allowing researchers to compare one treatment against another and ensuring that all participants experience the new treatment.

In open-label studies, which usually compare two treatments to see which is more effective, both researchers and participants know who is receiving the experimental or placebo therapy. If, for example, one treatment is physical therapy and another is a medication, patients and researchers would have to know who is getting which treatment.

Trials Take Time and Money

Trials receive funding from various sources, including the government (the NIH, the Department of Defense, and other agencies), the pharmaceutical industry, medical device manufacturers, private organizations such as research foundations, private grants, and patient support associations, says Dr. Haubenberger. And they aren't cheap or quick. It typically takes 15 years and a billion dollars to get a drug to market, says Claire Meunier, vice president of research engagement at the Michael J. Fox Foundation in New York.

Given those parameters, there's a lot of competition for funding, says Edward J. Kasarskis, MD, PhD, FAAN, chief of the Veterans Affairs neurology service and a professor of neurology at University of Kentucky HealthCare in Lexington.

As a result, some conditions get lost in the shuffle, says Catherine Rice, executive director of the International Essential Tremor Foundation. For instance, she says, "up to 10 million people in the United States have essential tremor, but less than $500,000 a year is spent on research for it." Because of that, very few clinical trials are planned for the disease and no drugs are in the pipeline.

And people are often surprised and frustrated by how long it takes for a treatment to gain approval and be released on the market after the trial is over. "Patients are impatient with the incremental process of research, made worse when you're dealing with diseases like amyotrophic lateral sclerosis (ALS), which have such short life expectancies," says Dr. Kasarskis. "Patients fear the treatment is going to pass them by."

Obstacles to Volunteering

There are several reasons why more people don't join clinical trials. One is a lack of awareness, says Meunier. Another is that physicians don't routinely refer patients to clinical trials, says Nathan Fountain, MD, a researcher with the epilepsy program at the University of Virginia in Charlottesville and a member of the AAN. Third, he says, many trials have eligibility requirements that may rule out potential participants. For example, epilepsy trials often need patients who experience at least four seizures a month. And some trials may ask patients to go off their standard medications. Plus, not all potential volunteers want to be test subjects, even when the need for a cure is great.

Then there are the practical matters, such as having to report to a clinic for regular assessment. "Some people, like those with epilepsy who have unpredictable seizures, aren't able to drive," Dr. Fountain says. And for those on the edge of poverty, enrolling in a trial is a luxury they can't afford. "If you're struggling to work one or two jobs and pay the bills, it may not be possible," says Dr. Kasarskis.

Perks of Participation

But there are benefits to participating in trials. Claudia Revilla, of Peoria, IL, who was diagnosed with Parkinson's disease five years ago at age 45, says volunteering for a trial is a way to take action against her disease. Over the past three years she's participated in five studies, even joining one during a trip to New York City. "I call it 'neuro-tourism,'" she says.

Enrolling in a trial means potential access to treatments not yet available, ones that may have fewer side effects or be more effective than current treatments. Another bonus is the careful medical monitoring and supervision participants receive for free.

While Revilla admits that volunteering can sometimes be difficult, she says it's worth it. "It gives me hope, keeps me motivated, and helps me fight my disease."

What to Expect When You Volunteer

The more informed you are before participating in a trial, the more likely you are to appreciate the process and stay enrolled. Here's what you need to know.

Your health is protected.

Many trials have a data safety monitoring board, which assesses the study results at different time points and can interrupt a trial if it becomes clear that the new treatment is much more or much less effective than expected. If it's more effective, the board may decide to allow everyone in the trial to get the superior treatment. They also can halt a trial for safety reasons.

You have rights.

Before participating, you will be asked to sign an informed consent document, which explains the purpose of the trial and the type or types of treatments being tested. The form also states that your participation is voluntary and you can leave at any time, for any reason. It also notes that your personal and medical information will be kept confidential and that you have the right to medical treatment for any trial-related injury. And you can continue to see your regular doctor throughout the trial.

There are potential downsides.

If you're in a trial that's testing a new drug, the treatment might not work or may have side effects or other risks that may be worse than your current treatment. Plus, you may find the frequent clinic visits and testing and travel requirements difficult. Because most studies are randomized, you also have no control over whether you get the active drug or a placebo.

Not all trials test drugs.

Plenty of trials require a simple cheek swab or a blood draw and don't involve extensive testing or regular clinic visits. "There are so many options," says Claudia Revilla, who has participated in five trials since being diagnosed with Parkinson's disease at age 45. "You can access trials through the Internet, phone, or mail. Some are just genetic testing; you do it yourself and mail it back. Every bit of information and every participant is important."

You're encouraged to ask questions.

No question is too silly to ask; it's important to know why the study is being done, what kinds of treatments and tests you'll receive and how often, and how these tests and treatments will affect your daily life. Ask if the treatment is free and, if it isn't, whether your insurance will cover it. Find out what you'll be entitled to if you're harmed as a result of the research. If the study involves long-term monitoring, know what that entails. If the treatment works for you, ask if you can keep taking it after the study ends. And always find out if and when you can learn the results.

Find a Trial

• ClinicalTrials.gov 
  This US government registry and results database includes information on publicly and privately supported clinical trials conducted worldwide. The site lists study requirements, risks, potential side effects, possible benefits, inclusion requirements, and more, and usually provides a contact number and email address where you can direct questions.
• ClinicalResearchTrials.NIH.gov 
  This section of the National Institutes of Health website offers lots of helpful information about finding and participating in clinical trials.
• Fox Trial Finder
  This site provides an easy-to-search system for anyone looking to join a Parkinson's disease trial, including people without Parkinson's who want to volunteer.
• Rare Diseases Clinical Research Network
  This site provides information on a range of trials for rare diseases, many of them neurologic in nature.
• ResearchKit
  This new Apple software allows researchers to design apps that make enrolling in clinical trials and collecting comprehensive data easier and faster. The apps provide patient surveys and informed consent forms through the touch of a button. Using existing iPhone hardware, such as motion sensors and voice recorders, the apps can also assess a person's health data, for instance, speech and walking patterns that may suggest Parkinson's disease.