April 11, 2023

What Exactly *Is* a Clinical Trial — And Should You Apply for One?

This piece originally appeared on katiecouric.com.

We asked an expert to explain it all, from who gets a placebo to why the process seems to take so long.

During the Covid-19 pandemic, we heard a lot about clinical trials and their importance in the development of a vaccine. If you’ve ever dealt with a cancer diagnosis, you’ve probably heard of them, too. But what exactly are clinical trials, and what purpose do they serve? Who gets to be part of them? Are they safe? And what’s the deal with placebo groups? We asked Ali Massoud, Vice President of Clinical Affairs at Exact Sciences, to break down this important step in the development of new drugs and medical tests.

What is a clinical trial?

In the most basic terms, a clinical trial is a study that seeks to answer a research question using human participants. Ms. Massoud explains, “That research question may involve an investigational drug, medical device, or diagnostic test, meaning one that is not yet approved for commercial use for sale.” Investigational drug trials seek to answer many questions about a treatment, like how safe it is and what doses have an effect. Ms. Massoud explains that these trials are an integral part of the product approval process: “They’re how we determine if a new drug, medical device, or diagnostic test will work for patients, and they’re done in a highly controlled and regulated setting.”

While there are always risks with any treatment, there are many different laws, guidelines, and agencies involved in clinical trials with the express purpose of minimizing those risks for clinical trial participants.

How long do clinical trials take?

Although the Covid-19 vaccines were approved in less than a year, this type of emergency authorization is far from the norm. In most cases, it takes years or even decades of research and monitoring for a new drug or device to get approved by the FDA for general use. That might seem frustrating, but once a drug is approved, you can be certain its safety and performance have been reviewed, along with its balance of risks versus benefits.

What are the phases of a clinical trial?

There are four general phases for clinical trials. Ms. Massoud explains, “In an oncology study, phase one is typically very small, usually between around five and 20 participants, and they’ll receive a very low dose of the treatment. These people have the type of cancer the drug is aiming to treat since you’d never want to give a healthy person a cancer drug.” She explains, “In phase one, the study is measuring what’s called a ‘dose-limiting toxicity.’ If any patient in the trial hits that, it means the drug may not be tolerated in higher doses.” Phase two is similar: it helps determine what dose of the drug can be tolerated, how effective it is, and what side effects are.

Phase three is where things get exciting. “This phase has a much larger sample size, and is really the pivotal point in the FDA approval process,” says Ms. Massoud. “Phase four happens after a drug is approved, and might compare the data that’s already been collected to a different drug, or look at longer-term patient outcomes that weren’t collected in previous trials.” If you’re part of one phase of a trial, it’s unlikely you’ll be in the next phase, because prior exposure to the drug could impact the new results.

How are patients selected for a clinical trial?

It depends on what the trial is for and the phase of the trial. For a new cancer drug or device, physicians select a group of people who could best answer the research question being asked. For something like Cologuard®, that would be a diverse group of people who are 45 and older and at average risk for colon cancer.

Maybe you’ve seen a TV ad or billboard asking people to sign up for a clinical trial — this is a way to reach people who might be good candidates to represent the population the drug or test is designed to treat. So if the trial targets the general U.S. population, they’d probably look at the demographic breakdown of people nationwide and try to represent those statistics as closely as possible in the trial.

Why can it be hard to find the right participants?

The problem is that some populations are more likely to sign up for clinical trials than others. For example, historical atrocities like the Tuskegee Syphilis study, which unethically experimented on Black patients in the American South, have understandably left many Black Americans wary of participating in clinical trials. A way to combat this, Ms. Massoud says, is to engage a community with practitioners they can rely on: “We try to recruit physicians and employees at clinical sites that are from the population we need for a representative trial. Since all patients need to give their informed consent, it’s crucial they trust the person asking them to participate. We don’t want participants to just sign a form. We want coordinators of the study to explain in detail the potential risks and benefits of a trial, the importance of confidentiality to protect the patient, and to answer any questions to put the patient at ease.” Clinical trial sponsors sometimes work closely with patient advocacy groups to diversify participants and get feedback on how to make potential participants feel comfortable and confident in participating in a new trial.

Does everyone in the study receive the drug being tested?

In later phases of a clinical trial, usually, one group will receive a drug and the other will receive a placebo. A placebo has no physiological impact on the patient and is used as a control to compare the results of the group getting the new drug to those of the participants who aren’t getting it.

There’s a misconception that if you’re getting a placebo in a pharma clinical trial, you’re not going to get proper care. This is false, says Ms. Massoud. “Even if you’re assigned to a placebo group, you’ll never get less than the standard of care that you would get if you were not enrolled in a placebo group.” Cancer drugs are a perfect example: If you’re in a phase three clinical trial for breast cancer, and the protocol’s treatment is chemotherapy plus radiotherapy, everyone in the trial will get that. If the trial is investigating a new form of immunotherapy, one group is also going to get the new drug in addition to the study’s standard care.

High school statistics class might’ve introduced you to the term, “double-blind.” In case you’re a little rusty, this means that almost everyone, even the doctor doesn’t know who is getting the placebo or the drug, avoiding bias when they report a patient’s outcome.

How can you learn about new clinical trials?

The best thing to do is tell your doctor you’re interested in enrolling in one. There’s also a government website that lists ongoing trials, including those sponsored or conducted by drug and device companies. Once you find one, you’ll likely have an interview with the clinical trial physician to make sure that you qualify and find out what it will mean for your ongoing care, and learn about any other inclusionary or exclusionary factors.

If you are interested in participating, make sure to bring a list of questions to ask your doctor and the clinical trial staff. Try using the following as a starting point: What is this trial trying to accomplish? How long does it last? What are the possible risks or side effects? Where does the study take place? Will there be any costs to me? What will my responsibilities be? Talking to your provider, getting answers to your questions, and learning more about the trial can help you decide if joining a trial is right for you — it’s a decision that is ultimately the patient’s to make.