New trial design accounts for patient behavior
Photo by Esther Dyson
New research suggests patient behavior can have a serious impact on the effectiveness of a treatment, and procedures used in double-blind randomized controlled trials (DBRCTs) may not allow researchers to assess the effects of behavior on treatment.
To solve this problem, a group of investigators has proposed a new trial design, called a two-by-two trial, that can account for behavior-treatment interactions.
They described this design in PLOS ONE.
Study rationale
The study authors pointed out that patient behaviors can directly relate to a trial. For example, a patient who believes in the drug might religiously stick to his or her treatment regimen, while someone more skeptical might skip a few doses.
Alternatively, patient behaviors may relate to how the person acts in general, such as preferences in diet, exercise, and social engagement. And in the design of today’s standard trials, these behaviors are not accounted for, said author Erik Snowberg, PhD, of the California Institute of Technology in Pasadena.
He noted that DBRCTs typically assign patients to an experimental group that receives the new treatment and a control group that does not. As the trial is double-blinded, neither the subjects nor their doctors know who falls into which group.
However, patients do know their probability of getting the treatment, and that 50% likelihood of getting the new treatment might not be enough to encourage a patient to change behaviors that could influence the efficacy of the drug, Dr Snowberg said.
For example, if a subject wants to lose weight and knows he has a high probability—a 70% chance—of being in the experimental group for a new weight loss drug, he may be more likely to take the drug as directed and to make other healthy lifestyle choices that can contribute to weight loss. As a result, he might lose more weight, boosting the apparent effectiveness of the drug.
However, if the subject knows he only has a 30% chance of being in the experimental group, he might be less motivated to both take the drug as directed and to make those other changes. As a result, he might lose less weight—even if he is in the treatment group—and the same drug would seem less effective.
“Most medical research just wants to know if a drug will work or not,” Dr Snowberg said. “We wanted to go a step further, designing new trials that would take into account the way people behave. As social scientists, we naturally turned to the mathematical tools of formal social science to do this.”
New trial design
Dr Snowberg and his colleagues found that, with the two-by-two trial, they can tease out the effects of behavior and the interaction of behavior and treatment, as well as the effects of treatment alone. The new trial design, which still randomizes treatment, also randomizes the probability of treatment, which can change a patient’s behavior.
In a two-by-two trial, instead of patients first being assigned to either the experimental or control groups, they are randomly assigned to either a “high probability of treatment” group or a “low probability of treatment” group.
The patients in the high probability group are then randomized to either the treatment or the control group, giving them a 70% chance of receiving the treatment. Patients in the low probability group are also randomized to treatment or control, and their likelihood of receiving the treatment is 30%. The patients are then informed of their probability of treatment.
By randomizing both the treatment and the probability of treatment, researchers can quantify the effects of treatment, the effects of behavior, and the effects of the interaction between treatment and behavior, Dr Snowberg said. And determining each is essential for understanding the overall efficacy of treatment.
