How Precision Medicine is Changing Clinical Trials

Medically Reviewed by Laura J. Martin, MD on June 09, 2019
5 min read

Brandie Jefferson has been in a half-dozen clinical trials since she was diagnosed with multiple sclerosis (MS) in 2005. She feels she benefited most from a vitamin D trial that she had to quit after high doses caused her blood calcium levels to soar. Now her doctor can better tailor her vitamin D prescription, the Baltimore resident says.

As clinical trials evolve in the age of precision medicine, Jefferson may benefit from them even more. Rather than being chosen for a trial just because she has MS, she may get the nod based on a genetic feature that makes her more likely to respond well. 

Precision medicine isn’t the norm for most diseases. But these cutting-edge treatments are already helping treat conditions that have a strong genetic link, like epilepsy, cystic fibrosis, and some forms of cancer. One-person trials, known as “n of 1 trials,” are now happening, along with a limited group of larger clinical trials.

The National Cancer Institute’s MATCH project is another new form of trial spawned by the quest for precision treatments. It will check tumor DNA from about 6,000 people whose tumors don’t respond to standard treatments. Those with gene changes (doctors call them "mutations") for which targeted treatments exist will be assigned to those drugs in different parts of the trial.

There are more than 105,000 registered clinical trials in the United States and more than 300,000 worldwide. These studies find out if drugs, medical devices, and other types of treatment (like using vitamin D for MS symptoms) work and are safe. Clinical trials are done on people. They usually follow successful tests on animals.

Most clinical trials have four phases.

  • Phase I tests if a new drug or device is safe, and it looks at side effects in a small group of people.
  • Phase II checks how the drug or device works for a larger number of people. Researchers compare results with a standard treatment or no medication at all (they’ll call this "placebo").
  • Phase III is similar to phase II but on a large scale. Some involve several thousand patients. After phase III testing, a drug company can request approval from the FDA.
  • Phase IV occurs after FDA approval, in part to keep tabs on the treatment’s long-term effects.

Even after all this research and testing, many drugs still don’t get the job done for many people. Precision medicine might change that.

These treatments can have powerful results. Consider the example of a toddler with a rare neurological disease. It “stumped the child’s medical team,” says David Goldstein, PhD, director of the Institute for Genomic Medicine at Columbia University Medical Center in New York.

But when Goldstein’s team sequenced her genome, “we found out she had a devastating disease that results from a transporter of a vitamin not working.” The girl was successfully diagnosed and treated, thanks to precision medicine.

Goldstein sees two ways precision medicine will change clinical trials. First, more trials will test targeted treatments on patients with specific genetic mutations -- the same thing the MATCH trial is doing.

Second, gene testing (doctors often call it "sequencing") will help create subtypes of diseases, like HER2-positive or triple-negative breast cancer. Currently, an epilepsy clinical trial might test one drug on a big group of patients with different types of the disease.

“You can find out: Does ‘Y’ treatment work in subgroup A or subgroup B or subgroup C?” Goldstein says.

Genetics isn’t the only thing that determines if a drug will or won’t work for you. What precision medicine does that conventional medicine often doesn’t is to take into account your lifestyle and environment. Do you smoke? Do you exercise? Was the water clean where you grew up? How about the air? These things may affect your response to medication and can make you more or less likely to get certain diseases.

In a few years, researchers should have access to lifestyle and health information on thousands of Americans. That data can help them as they design a clinical trial, and perhaps narrow the scope to people most likely to respond.

How will they get this information? Much of it will come via the National Institute of Health’s All of Us project. This nationwide effort to gather health data began in 2017. It’s looking for volunteers -- check online at Those who take part can submit data there or join up at a Precision Medicine Center. You’ll give a blood and urine sample, answer some questions, and provide access to your electronic health records.

Over the next 5 years, a group of research institutions called the Data and Research Support Center will comb through this wealth of information to figure out what keeps us healthy and what makes us sick.  That information, in turn, will be made available to researchers. 

Today’s phase III clinical trials tend to be large and involve thousands of people with one disease. The response rate can be surprisingly low, even for drugs that get approved. A precision medicine trial lets researchers study treatments that target just one aspect of disease -- say, a genetic mutation or lifestyle trait -- that only some people have.

You only study people who can respond. If you have responders, and you’ve eliminated nonresponders, the effect is much larger, says Robert Temple, MD, the deputy center director for clinical science at the FDA's Center for Drug Evaluation and Research. “We call that predictive enrichment.”

In contrast, he says, when a drug can only help a small group of people, it won’t have great results in a regular clinical trial. An example here would be the cystic fibrosis drug ivacaftor (Kalydeco), approved in 2012 for patients with a specific gene mutation that affects only about 4% of people with cystic fibrosis.

Will smaller trials with better results mean faster drug approvals? That part of the puzzle is still unknown. “We always weigh benefits against risks. If you do something spectacular, you can get away with smaller numbers [in trials], but it doesn’t change the fundamental process. You’re still demonstrating effectiveness, still demonstrating safety,” Temple says. And that can still take years.