Creative Minds: Designing Personalized Clinical Trials

Posted on December 14, 2017 by Dr. Francis Collins

Karina Davidson/Jörg Meyer

It might have been 25 years ago, but Karina Davidson remembers that day like yesterday. She was an intern in clinical psychology, and two concerned parents walked into the hospital with their troubled, seven-year-old son. The boy was severely underweight at just 37 pounds and had been acting out violently toward himself and others. It seemed as though Ritalin, a drug commonly prescribed for Attention Deficit Disorder, might help. But would it?

To find out, the clinical team did something unconventional: they designed for the boy a clinical trial to test the benefit of Ritalin versus a placebo. The boy was randomly assigned to take either the drug or placebo each day for four weeks. As a controlled study, neither clinical staff nor the family knew whether he was taking the drug or placebo at any given time. The result: Ritalin wasn’t the answer. The boy was spared any side effects from long term administration of a medication that wouldn’t help him, and his doctors could turn to other potentially more beneficial approaches to his treatment.

Davidson, now an established clinical psychologist at the Columbia University Irving Medical Center, New York, wants to take the unconventional approach that helped this boy and make it more of the norm in medicine. With support from a 2017 NIH Director’s Transformative Research Award, she and her colleagues will develop three pilot computer applications—or digital platforms—to help doctors conduct one-person studies in their offices.

Large clinical trials are great at establishing which treatments work best for the average patient. But not all patients are average. That’s where personalized studies, called “N-of-1 trials,” can be helpful. Doctors can use them to compare how a person responds to two or more treatments before deciding on a prescription.

Though N-of-1 trials remain relatively uncommon, recent technological advances have now made them more feasible to pursue. For example, wearable health monitors and smartphones can make it easy to digitize and gather a wide array of data on individual patients.

What’s needed is the right electronic platform to enable doctors to order and manage N-of-1 trials along with their influx of data. Davidson and her colleagues including Ian Kronish, also at Columbia University, will use the grant to put their platforms to a rigorous, real-world test. To begin, doctors will enroll 60 patients with newly diagnosed high blood pressure, assigning each either to an N-of-1 trial or standard care.

In the N-of-1 group, each person will take one first-line blood pressure medication for two weeks followed by another for the same duration. Davidson and team will then collect data on the responses to the medications. For each patient, the team will try to ascertain the most-effective medication with the least side effects. Most importantly, the team will see whether patients who participate in N-of-1 trials ultimately have better treatment outcomes than those randomized to standard care.

The team will also use a similar N-of-1 trial design to determine which people battling depression will benefit from light therapy, a treatment that mimics natural outdoor light to influence mood. The researchers will also explore which patients with insomnia will sleep better with low doses of the natural hormone melatonin.

Davidson and team in addition will also test how well doctors can incorporate N-of-1 trials into their regular clinical workflow. If the N-of-1 approach proves beneficial to doctor and patient, Davidson and her colleagues hope one day to make the platform widely available to doctors for a range of other purposes. Some possibilities include managing diabetes, controlling pain, setting an exercise regimen, and developing more personalized weight loss programs.

Ultimately, Davidson’s goal is to change the very nature of a basic clinical encounter, as science is brought to bear on treatment decisions for each and every person. As we continue to learn even more about individual differences in health risks and treatment responses through the NIH’s All of Us Research Program and other efforts, the potential for such an N-of-1 approach to medicine is surely poised to grow.

Links:

All of Us (NIH)

Karina Davidson (Columbia University, New York)

Ian Kronish (Columbia University)

Davidson Project Information (NIH RePorter)

NIH Director’s Transformative Research Program (Common Fund)

NIH Support: National Library of Medicine; Common Fund