Everything You Need to Know About Clinical Trials

When you’re receiving treatment for cancer, your medical team will want to provide you with the best, most effective care. Sometimes those treatments will be part of a clinical trial. And while that phrase could make anyone feel like a guinea pig, participating in a clinical trial is a normal part of many, many people’s cancer treatment.

Clinical trials can provide you with a treatment beyond what’s called standard of care, which means the typical courses of treatment provided for a diagnosis. Clinical trials are a critical part of advancing cancer care and discovering new medicines; all the current standard treatments wouldn’t be possible without the clinical trials that initially tested them.

Sometimes people with cancer pursue clinical trials after they’ve attempted other treatments; sometimes they will start treatment in a clinical trial; sometimes they will do a clinical trial after the cancer is eradicated for survivorship needs like mental health or ongoing side effects. Experience will range widely depending on what phase the clinical is in, whether they’re testing a drug, procedure, or other health intervention–and that changes what participation may look like.

Maybe you’re worried about feeling like a test subject; or you’ve heard you might not get the treatment at all and may instead get a placebo. These concerns and questions are so normal. We’ve talked to doctors and experts about all this and more below.

Understanding what clinical trials do

Clinical trials are active research studies involving patients that seek to evaluate the efficacy of new drugs, doses, procedures, and other interventions. Trials are conducted by a team of researchers, typically led by a doctor. Some trials may also involve questionnaires or may involve collecting biospecimens, like blood or stool samples, to contribute to a research database.

Clinical trials testing a new treatment progress through different phases. Phase 1 trials are the first step and aim to identify the safest and most effective dose. They are also typically the smallest trials, involving around 15-50 participants.

“They're new drug trials being used in people for the first time. There's a lot of work that's gone behind that and regulations before it gets to that,” says Sarah Kotila, who is a registered nurse and leads the clinical trials navigation team at the University of Wisconsin’s Carbone Cancer Center.

Phase 2 trials are larger and focus on evaluating the efficacy of the treatment, as well as any side effects. Phase 3 trials are usually the last step before a new treatment is sent to the FDA to become officially approved and available for use as standard treatment. There are also Phase 4 trials, which study the drug over time.

Anytime you come to that fork in the road, whether it's a new diagnosis or the treatment is no longer working or you’re having side effects…it's a good time to pause and look at what all your options are out there, whether it's standard treatment options or clinical trials.

Are clinical trials a last resort?

Kotila says it’s a common misconception that clinical trials are a “last resort” for someone’s cancer care. In fact, there are trials that could help throughout the whole time you’re getting care.

“We have clinical trials at any stage of cancer treatment. It can be when you're first diagnosed for an early stage disease, pre- or post-surgery, and certainly we do have trials when the cancer has spread or when the other treatment options have been gone through,” Kotila says.

Also good to know: trials aren’t just available for treatment–but also for managing long-term side effects. Dr. N. Lynn Henry, a breast oncologist and clinical researcher at the University of Michigan Rogel Cancer Center says, “there might be trials that look at trying to help manage long term symptoms, whether it's neuropathy, numbness and tingling, fatigue. It might be trying to increase exercise levels or improve nutrition. There's a lot of trials that really span the entire spectrum.”

When should I start thinking about clinical trials?

Upon receiving a diagnosis, there’s already so much information coming at you, so perhaps you hadn’t even thought about clinical trials. It’s important to know clinical trials are a treatment option, not an experiment. That’s why experts suggest asking your doctor about clinical trials early on if they haven’t already brought it up themselves.

“The earlier you can explore clinical trials, the better, because it may give you more treatment options. You could still have those standard treatment options that are out there but also have the potential for clinical trials,” Kotila says.

“Anytime you come to that fork in the road, whether it's a new diagnosis or the treatment is no longer working or you’re having side effects…it's a good time to pause and look at what all your options are out there, whether it's standard treatment options or clinical trials.”

Lots of people start clinical trials as a way to access the most advanced, innovative treatment, or screenings, or post-treatment care. Or it could be that the side effects of your current treatment are miserable, or your body isn’t responding well to a drug, or maybe your current treatment plan just isn’t sitting right with you and you want to pursue something else.

How do I find a clinical trial?

All clinical trials that receive federal funding and assess an FDA-regulated drug or device have to be registered on ClinicalTrials.gov. This database can be very overwhelming. The National Cancer Institute also has a page of clinical trials and a hotline to help prescreen you and search for trials you may be eligible for. Drug companies and other cancer nonprofits may also have their own lists, especially for specific cancer types.

If you’re receiving care at a large hospital or academic medical center, they will likely have their own portfolio of clinical trials and a clinical trial navigation office to help search for one that fits your diagnosis, age, and your treatment plan. If there’s not a trial at your center that would be a good fit, your doctor may also be able to connect you with trials going on nearby.

Dr. Henry notes that even if you’re receiving care in a community setting or smaller clinic, academic medical centers may still be able to connect you to a clinical trial–and then you can go back to your usual oncologist after the trial.

“We try to make it as seamless as possible for patients to be able to have access to clinical trials but still maintain that continuity of care with the team that they're used to getting treatment from,” says Dr. Henry.

Trial descriptions can be hard to understand since they’re primarily designed for healthcare providers. If you find a trial online, it’s a good idea to bookmark or print out the page to share with your doctor, particularly the study’s protocol summary. This section describes the trial’s goal, treatments used, and locations.

It’s important to note that just because a clinical trial may seem like a good match to your diagnosis, there are so many moving parts in determining eligibility. For example, some trials have restrictions about how many or what types of prior treatments you can have had before starting. Eligibility criteria is also one of the reasons why experts encourage asking your doctor about trial options early and throughout your treatment process.

Getting a placebo alone is very rare in clinical trials related to cancer, primarily due to ethical concerns about not providing treatment to someone that needs it.

Is there a chance I won’t get any treatment?

Something you may have heard of in clinical trials is placebo (a placebo is a substance that looks and tastes like the actual drug being tested, like saline or a sugar pill, but has no true effect). Researchers sometimes use placebos as a control measure for comparing the efficacy of the treatment they are testing.

However, getting a placebo alone is very rare in clinical trials related to cancer, primarily due to ethical concerns about not providing treatment to someone that needs it.

“The truth is, in cancer care, placebos are rarely used because it would be illegal and unethical to not treat someone that needs cancer treatment,” Kotila says.

If a placebo is used, it is typically used in combination with standard treatment. For example, if chemo is the standard treatment for a type of cancer that a clinical trial is investigating a new drug for– they may have one group that receives chemotherapy plus the research medication and a control group that receives chemotherapy plus a placebo.

“I always try to reassure people that, at a minimum, you're getting what I would have been giving you anyway,” Dr. Henry says.

Usually the only time a placebo is used alone is when there is no existing standard treatment for the particular diagnosis.

While you will be getting treatment in a clinical trial, it’s also important to understand that you may not receive the new drug or procedure the trial is testing. Clinical trials involve a randomization process where participants are randomized to various different conditions. This randomization is also not always 50:50, so it’s important to understand what your chances are of getting the new treatment vs. standard of care options.

To maintain the integrity of the study, you might not be told what treatment you’re receiving. In “double-blind” trials, neither the researcher nor the participant knows who is receiving placebo or who is receiving the treatment that is being tested. In “single-blind” trials, the researcher is aware of who is in the placebo vs. non-placebo groups but the participants are not. Some trials, especially those where the difference between the two groups is obvious (e.g. one group is receiving an exercise training regiment but the other is not), are “non-blinded.” Double-blind trials are typically considered the most scientifically rigorous.

“There's a possibility that you might get something more [than standard treatment], which might be better or it might not be. We don't know – it's what we're testing, but at a minimum, you're going to get the basic [treatment] and so participating in a clinical trial does expand the possibility of getting to try a new treatment, but it's not a guarantee,” Dr. Henry says.

Before starting any trial, you’ll go through a thorough informed consent process where the team will explain the different study group conditions and how many participants will be involved in each, as well as the main goals of the study, risks and benefits, costs, and your rights. This is a great opportunity to ask any questions you have.

How are clinical trials measured for safety?

Federally funded clinical trials have to undergo a rigorous review process before getting started. This includes receiving approval from an institutional review board, or IRB, that is composed of at least five experts tasked with assessing the ethics, legality, design, and safety of the proposed study. They review the protocols annually and have the authority to change them or stop the study entirely if they have safety concerns.

Some later phase clinical trials also involve a data safety monitoring board. The monitoring board’s responsibility is to oversee enrollment and any unforeseen adverse events. In some cases, there will often be measures built in to stop the trial early if the new treatment seems to be significantly better than the standard, although the bar for this is quite high, Henry says. On the flipside, the bar for stopping a trial early if the new treatment is looking worse is quite low. This data isn’t made publicly available to the research team or the participants, but the data safety monitoring board is always keeping an eye on it.

Do I have to pay for a clinical trial? Do they pay me?

Clinical trials are considered treatment, and so the costs can vary. Typically, any elements of the trial that would be part of standard treatment, like routine scans or check-ups, are billed to your insurance. Any additional research costs, such as those of a new medication or more intense imaging, get billed to the researcher. What portions of the treatment will get billed to your insurance vs. the research team is also something that should be explicitly shared with you during the informed consent process.

It’s important to note that you likely will not get paid for participating in cancer treatment trials. This is due to ethical concerns about incentivizing people to participate in trials. There are some examples of non-treatment trials that require a lot from participants, like collecting biospecimen samples at home and mailing them or completing lengthy questionnaires, in which case some compensation may be provided.

While treatment trials do not pay participants, there are opportunities to be reimbursed for lodging and travel if you live far from the clinical trial site. Drug company funded trials typically have more cash to work with, whereas government supported trials and investigator initiated trials, which typically receive funding from companies, foundations, and academic institutions, may have fewer opportunities for support.

What should I ask my doctor about clinical trials?

It’s often a good idea to ask your doctor about clinical trial options throughout your treatment, and it’s never too early to ask. To address other concerns you might have, here are some other questions to consider asking about a clinical trial (Jadey’s list of general questions to ask your oncologist is here).

• “Why is this clinical trial being done? What are they studying?”
• “Do you think this trial is right for me?”
• “Are there any downsides?” or “What are the risks and benefits?” (For example, if blood tests and scans are stressful for you, maybe you’d want to ask if participation in the trial would increase the amount of testing you need to receive.)
• “What is the time commitment for the trial? How many visits will be involved?”
• “Will enrolling in the trial take a long time?” Sometimes safety checks can take a long time. This can delay starting a new treatment, resulting in additional stress and anxiety for some.
• “If I don't do a trial now, will it be an option in the future?” Different trials have different eligibility criteria for how far along you may be in your treatment or disease course, so check with your doctor what other types of trials may be available to you in the future.
• “What options for reimbursement are available, if any?”

Can I leave a clinical trial once I’ve already enrolled?

Yes, yes, yes. Participation in a clinical trial is completely voluntary. Even after going through the informed consent process and officially enrolling, you can leave the trial at any point.

“Clinical trials are always voluntary and optional, at any point. It can be when you're first told about them, you could sign a consent, you could go on a trial – you can come off at any point. It's not legally binding. It's always optional and always voluntary,” Kotila says.

Potentially joining a clinical trial could seem like a treatment option you had never even considered. It’s common–and normal–to feel reluctant to join a trial, but Dr. Henry says it’s good to keep an open mind.

“Some trials may directly benefit you by getting access to a drug that [you] wouldn't otherwise get to try against your cancer. Other times, you may not end up getting direct benefit. It may be that the new drug doesn't live up to the hope that we had for it, or maybe you get randomized to the standard of care arm, but you're still getting standard of care,” she says.

“All of that information that we get from those trials will help future patients as well,” says Dr. Henry. In fact, women (and minorities) weren’t even required to be included in clinical trials until 1993. This means that we have significantly less data on how women’s bodies work and respond to different treatments, an information gap that can only be improved through increased participation.

“With many of these trials, there's potential that you will directly benefit, but you'll also be helping generations in the future, and so I always appreciate when people participate in clinical trials.”