Platform optimises drug dose combinations

The researchers, from the UCLA schools of dentistry, engineering and medicine, developed a technology platform called phenotypic personalised medicine, or PPM, which can accurately identify a person's optimal drug and dose combinations throughout an entire course of treatment.

Their research is the cover article of the peer-reviewed journal Science Translational Medicine, a publication of the American Association for the Advancement of Science.

Unlike other approaches to personalised medicine currently being tested, PPM doesn't require complex, time-consuming analysis of a patient's genetic information or of the disease's cellular makeup. Instead, it produces a personalised drug regimen based on information about a person's phenotype—biological traits that could include anything from blood pressure to the size of a tumor or the health of a specific organ.

Dean Ho, UCLA School of Dentistry and UCLA Henry Samueli School of Engineering and Applied Science, said one of the platform's remarkable capabilities is its ability to produce graphs personalised for each individual patient that represent precisely how they respond to treatment.

The graphs plot the drug dose along the horizontal axis and the patient's response to treatment on the vertical axis. Remarkably, every person produces a graph in the shape of a parabola and that parabola dictates how doctors should proceed with the treatment.

Each person's unique curve provides doctors with a visual guide to determine the exact doses of medicine they should prescribe as the treatment continues, which Ho said is the key to achieving truly personalised medicine.

Among other things, the approach will allow doctors to prescribe the precise amount of medicine needed to shrink a tumor or ensure the body doesn't reject an organ, for example, as opposed to using a higher, "standard" dose that's recommended based on an average of how all patients have responded in the past.

Another benefit of PPM is that it can be recalibrated in real time to adapt to changes during treatment—for example if a person undergoes surgery or develops an infection, or if their organ function changes over time, any of which could mean that drug dosages or combinations need to be modified.

The new study evaluated eight people who had recently received liver transplants. Most transplant patients take an immunosuppressive drug called tacrolimus to prevent their bodies from rejecting the organ.

In general, doctors prescribe dosages of the drug based on how other patients have responded in the past, and they adjust those amounts if and when complications arise. In the UCLA research, four patients received care followed the traditional approach and four received treatment that was guided by PPM.

To know whether the PPM approach was successful, researchers wanted to see the amount of tacrolimus in each patient's body stay within the "ideal" range, as dictated by each patient's unique parabola-shaped graph. They found that those who were treated following PPM spent as much as 50% less time outside of that range than the patients whose treatment followed the traditional approach.

The team is using PPM in several other clinical trials, some of which are already underway, including for treating cancer and infectious diseases.