The Basics of Clinical Trials
Clinical trials are studies in which people volunteer to test new drugs or devices. Doctors use clinical trials to learn whether a new treatment works and is safe for people. These kinds of studies are needed to develop new treatments for serious diseases like cancer.
Clinical trials are vital in studying all aspects of medicine, not just cancer. The stakes may seem higher when researching medicines to treat cancer, but all new treatments (drugs and medical devices) must go through clinical trials before being approved by the FDA.
Who can be in clinical trials?
For a child to be enrolled in a clinical trial, the parents or guardians must decide if they want their child to take part. If the parents give permission, older children are usually asked whether they wish to take part. This process is called assent. In most cases, a child can refuse, even if the parents are willing to permit it. The process of considering a clinical trial is much the same for the parents of a child as it is for an adult.
There’s always uncertainty when you’re thinking about a clinical trial. Part of it is that the doctors in charge of a clinical trial don’t know ahead of time how things will turn out. If they did, there would be no need for the study in the first place. So there’s no simple answer to the question, “Should I take part in a clinical trial?”
Most people don’t pay much attention to clinical trials until they have a serious illness. Medical breakthroughs (the results of clinical trials or other kinds of research) often make the news, but you usually don’t hear about clinical trials themselves unless something has gone wrong in one of them. For instance, the media quickly reports it any time a volunteer in a study is harmed.
What you usually don’t hear about in the news are the thousands of people who are helped each year because they decided to take part in a clinical trial. You also aren’t likely to hear about the millions who benefit from others’ participation in clinical trials.
Why do we need clinical trials?
Clinical trials show us what works (and what doesn’t) in medicine and health care. They are the best way to learn what works best in treating diseases like cancer. Clinical trials are designed to answer 2 important questions:
- Does the new treatment work in humans? If it does, doctors are also looking at how well it works. Is it better than what’s now being used to treat a certain disease? If it’s not better, is it at least as good, while perhaps causing fewer side effects? Or does it work in some people who aren’t helped by current treatments?
- Is the new treatment safe? No treatment or procedure – even one already in common use – is entirely without risk. But do the benefits of the new treatment outweigh the possible risks?
Answering these questions, while exposing as few people as possible to an unknown treatment, often requires several different clinical trials. They’re usually grouped into “phases.” Clinical trials in each phase are designed to answer certain questions, while trying to make sure the people taking part are kept as safe as possible. Every new treatment is tested in 3 or more phases of clinical trials before being considered reasonably safe and effective.
New treatments have to pass many tests before they get to you.
Clinical trials are only a small part of the research that goes into developing a new treatment. Drugs of the future, for example, first have to be discovered or created, purified, described, and tested in labs (in cell and animal studies) before ever reaching human clinical trials. Of all the substances that are tested in these early stages, very few are promising enough to be tested in humans.
On average, a new cancer drug has been studied for at least 6 years before it even makes it to clinical trials. But the major holdup in making new cancer drugs available is how long it takes to complete clinical trials themselves. It takes an average of about 8 years from the time a cancer drug enters clinical trials until it’s approved.
Why so long? To be sure it’s safe and effective, researchers look at each new treatment in several different studies. Only certain people are eligible (meet the requirements) to take part in each clinical trial. And cancer clinical trials take years to complete. It takes months, if not years, to see if a cancer treatment works in any one person. And figuring out if a drug really improves survival can take a very long time.
The biggest barrier to completing clinical trials is that not enough people take part in them. Fewer than 5% of adults (less than 1 in 20) with cancer will take part in a clinical trial. But clinical trials are much more commonly used to treat children with cancer. In fact, 60% of children under age 15 participate in clinical trials. This is one reason that survival rates for childhood cancer have increased so dramatically in the last few decades.
The main reason people give for not taking part in a clinical trial is that they didn’t know the studies were an option for them. But there are many other reasons. Some people want to take part but don’t meet the requirements. Some are uncomfortable with the idea of being a volunteer in a study. Others worry that they won’t be treated fairly or could be harmed by an unproven treatment.
How does a treatment qualify to be used in a clinical trial?
Before a clinical trial can be done it must be decided whether it’s ethical to ask patients to volunteer for the experimental treatment. Has the study been designed, as much as possible, to make sure the people in it will be safe? Will the volunteers get a treatment that’s at least as good as, and maybe even better than, what they would get if they didn’t volunteer for the study?
Scientific panels are set up to review and approve all clinical trials to make sure questions like these are answered before the researchers are allowed to sign up patients.
Pre-clinical (or laboratory) studies
Clinical trials are done only after pre-clinical studies suggest that the proposed treatment is likely to be safe and will work in people.
Pre-clinical studies, also called laboratory studies, include:
Cell studies: These are often the first tests done on a new treatment. To see if it might work, researchers look for effects of the new treatment on cancer cells that are grown in a lab dish or a test tube. These studies may be done on human cancer cells or animal cancer cells.
Animal studies: Treatments that look promising in cell studies are tested next on cancers in live animals. This gives researchers an idea of how safe the new treatment is in a living creature.
Pre-clinical studies give a lot of useful information, but they don’t give all the answers that are needed. After all, humans and mice can be very different in the way they absorb, process, and get rid of substances. A treatment that works against cancer in a mouse may or may not work in people. And there could be side effects and other problems that didn’t show up when the treatment was used in mice.
If the pre-clinical studies are completed and the treatment still seems promising, the US Food and Drug Administration (FDA) must give permission to test it in humans.
The investigational new drug (IND) application
Before a clinical trial can be started, the research must be approved. An investigational new drug or IND application or request must be filed with the FDA when researchers want to study a drug in humans. The IND application must contain certain information, as described below. The FDA reviews this information before human clinical trials start. Here’s some of the information required on an IND request:
Pre-clinical studies: Results from studies, including those on animals, allow the FDA to decide whether the product is reasonably safe for testing in humans. This part may also include any experience with the drug in humans (if the drug has been used or studied in another country, for example).
Manufacturing information: This explains how the drug is made, who makes it, what’s in it, how stable it is, and more about the physical qualities of the drug. The FDA uses this information to decide whether the company can make batches of the drug that will always be exactly the same.
Clinical protocols and investigator information: Detailed outlines for the planned clinical studies, called study protocols, are looked at to see if the study might expose subjects to unnecessary risks. Information on the clinical investigators who will supervise the study is reviewed to find out if they’re qualified to run clinical trials. Finally, the research sponsor must commit to getting informed consent from the research subjects, having the study reviewed by an institutional review board (IRB), and following all the rules required for studying investigational new drugs
Some facts about clinical trials to keep in mind
Taking part in any clinical trial is voluntary.
You always have the right to choose whether you will take part in a clinical trial for which you meet the criteria. The level of care you get should not be affected by your decision.
You also have the right to leave a clinical trial at any time, for any reason. If you decide to leave the study, talk to your doctor first. You’ll want to know how quitting the study might affect your health and what other treatment options you have. You should also tell the research group that you’re quitting and why. The clinical trials team may ask that you agree to continue to be watched for a certain length of time to look for any long-term effects of treatment.
Not all clinical trials study treatments.
Many clinical trials look at new ways to detect, diagnose, or learn the extent of disease. Some even look at ways to prevent diseases from happening in the first place. Researchers still use human volunteers to test these methods, and the same general rules apply.
Clinical trials are not all drug trials.
Many clinical trials test other forms of treatment, such as new surgery or radiation therapy techniques, or even complementary or alternative medicines or techniques.
Clinical trials are used to study approved drugs, too.
Even after a drug has been approved for use against a type of cancer, doctors sometimes find it works better when given a certain way or when combined with other treatments. It may even work on a different type of cancer. Clinical trials are needed to study these possibilities, too.
Clinical trials and placebos
A placebo is a sham pill, inactive ingredient, or fake treatment used in some types of clinical trials to help make sure results are unbiased. A placebo pill is sometimes called a “sugar pill.”
Over the years, doctors have found that some people begin to feel better even if they just think they’re being treated. Although this effect tends to be brief, and doesn’t really affect cancer, it can make a new treatment seem to help. Sometimes, people who know they’re getting placebo don’t report all the health problems that come up, while those on the treatment do. This can make the treatment look like it has worse side effects than it does. A placebo control group keeps people from knowing if they’re getting the treatment being studied, and makes the results more likely to be valid.
Placebos are rarely used alone in cancer research unless no known effective treatments exist. It’s not ethical to have someone take a placebo if there’s a treatment available that works. When cancer clinical trials compare treatments, they compare the new treatment against the current standard (proven) treatment. At times, a study may be designed so that patients don’t know which one they’re getting, but they know they’re getting treatment that at the very least meets the current standard of care.
In some clinical trials, the doctors want to learn if adding a new drug to the standard therapy makes it work better. In these studies, some patients get the standard drug(s) and the new one being tested, while other patients get the standard drug(s) and a placebo. But none of the patients would get only a placebo. Everyone gets standard treatment if there’s a standard treatment available. For more information about placebos and how they might be used in some studies, see Placebo Effect.
Who sponsors and runs clinical trials?
The National Cancer Institute (NCI) sponsors (pays for) a good portion of the thousands of cancer clinical trials going on in the US at any given time. The NCI is a part of the National Institutes of Health (NIH), which is funded by US tax dollars. These studies are often run through the NCI’s National Clinical Trials Network (NCTN), which are networks of doctors and institutions across the country that specialize in a certain aspect of cancer.
NCI Cancer Centers also conduct research at their facilities across the United States. Government agencies other than NCI, including parts of the Department of Veterans Affairs and the Department of Defense, often sponsor cancer clinical trials. And, there are doctors, academic medical centers, foundations, volunteer groups, and other non-profit organizations that sponsor clinical trials, too.
The other main sponsors of clinical trials are pharmaceutical and biotechnology companies, which must prove their medicines or devices are safe and effective before they can be marketed.
Researchers conduct clinical trials in many different settings. Major cancer centers are often the focal points of clinical trials research. Because they usually have the most advanced facilities and highly trained staffs, they can conduct all phases of clinical trials.
Community hospitals across the country also take part in clinical trials, although these are usually phase II or III studies. Many of these hospitals are part of the NCI’s Community Oncology Research Program (NCORP), which means they work with an NCI cancer center or the National Clinical Trials Network. NCORP members conduct the same clinical trials across the country. Community hospitals may conduct privately sponsored and other types of studies, too.
Doctors in private practice can also be involved in clinical trials, either as members of cooperative groups or by being actively involved in privately sponsored research.
What this may mean for you
At one time, clinical trials were done only at major medical centers. This often meant that patients had to travel long distances and were treated by doctors they didn’t know very well. This is sometimes still the case, especially with phase I and some phase II studies. Of course, this isn’t always a bad thing. Many people prefer to be treated in major cancer centers because of their experience, reputation, and resources. Ultimately, the hassles of traveling must be weighed against the chance of being helped by the treatment.
Today, patients have more options. This may include staying closer to home during a study or even staying with their own doctors. Your doctor may or may not be involved in clinical trials. If he or she is, you may be eligible for one of them. Whether this is the right study for you is, of course, a question worth asking. Keep in mind, each study also has its own requirements that a person must meet to take part.
Although clinical trials are now done in many different settings, the same rules are in place to protect patients.
Center for Information and Study on Clinical Research Participation. 2015 Perceptions & Insights Study: Report on the Decision to Participate. Consultado en www.ciscrp.org/download/2015-perceptions-insights-study-decision-to-participate/?wpdmdl=5734 en mayo 5, 2016.
Dilts DM, Sandler A, Cheng S, et al. Steps and time to process clinical trials at the Cancer Therapy Evaluation Program. J Clin Oncol. 2009;27(11):1761-1766.
Friedman LM, Furberg CD, DeMets DL. Fundamentals of Clinical Trials, 4ta ed. 2010. New York, NY: Springer Science + Business Media, LLC.
National Cancer Institute: Children’s Assent to Clinical Trial Participation. Consultado en www.cancer.gov/clinicaltrials/learningabout/patientsafety/childrensassent en mayo 4, 2016.
National Cancer Institute: Resumen del NCI’s National Clinical Trials Network consultado en www.cancer.gov/research/areas/clinical-trials en mayo 2, 2016.
National Cancer Institute: Clinical Trials Information for Patients and Caregivers. Consultado en www.cancer.gov/about-cancer/treatment/clinical-trials en mayo 4, 2016.
National Cancer Institute Community Oncology Research Program (NCORP) consultado en www.ncopr.cancer.gov/about en Mayo 2, 2016.
National Cancer Institute: NCI’s Clinical Trials Programs and Initiatives. Consultado en www. Cancer.gov/research/areas/clinical-trials en mayo 2, 2016.
National Cancer Institute: Patient Safety in Clinical Trials. Consultado en www.cancer.gov/clinicaltrials/learningabout/patientsafety/ en mayo 2, 2016.
US Food and Drug Administration Investigational New Drug Application. Consultado www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/default.htm en mayo 2, 2016.
Last Medical Review: May 3, 2016 Last Revised: May 3, 2016