A consumer advocacy group is asking the federal government to halt a clinical trial that will involve patients at the University of Kentucky. The nonprofit group Public Citizen sent a letter Tuesday to the federal Office for Human Research Protections, raising concerns about a trial to measure two treatments for sepsis, the tenth leading cause of death in Kentucky.
Sepsis is a serious illness that happens when a person has an infection and their immune system causes widespread inflammation. That inflammation can cause blood clots, poor blood flow and a big drop in blood pressure. Kentucky has the nation’s 5th highest mortality rate from the disease.
Kyle Brothers, a pediatrician and bioethicist at the University of Louisville, said that might be because the illness is usually treated in an intensive care unit, and for many in Kentucky that means a long drive to the medical hubs in Louisville and Lexington. He added that Kentucky’s high sepsis death rate is likely a reason the clinical trial’s investigators wanted to come to Kentucky.
“It means that the science coming out of this is of particular interest to our state,” Brothers said. “We have to look at the different ways of managing this problem and compare them.”
In its letter, Public Citizen wrote there are two main issues with the national clinical trial. The first is that there is no control group, which helps researchers measure the impact of an experimental treatment on patients against the care patients would normally receive.
“Without a control group, you can’t know whether one or both groups might be harming subjects in the trial compared to what they would have gotten had they just received usual care outside of the trial,” said Michael Carome, the director of Public Citizen’s health research group.
The University of Kentucky forwarded a statement in response for comment on this story. In the statement, Harvard Medical School co-principal investigator Nathan Shapiro defended the study’s methodology, saying the two treatments being used in the clinical trial are currently used widely.
“Our study will provide clinicians with authoritative data on which approach leads to better patient outcomes,” Shapiro said in the statement. “The study protocol was designed by expert clinicians in emergency and critical care medicine representing nearly 50 hospitals in the United States and follows a well-accepted design.”
Do Studies Need A Control Group?
Typically, treating sepsis involves giving a patient intravenous fluids, which help to increase blood flow. Blood pressure medication is also used to prevent the heart from stopping. But doctors disagree about the appropriate balance between IV fluids and medication, and treatment can be a guessing game.
“The problem here is that, according to the investigators, what qualifies as usual care is all over the place,” said Brothers of U of L. “They’re saying, ‘there are number of different ways of handling this. We came up with two protocols and we’re comparing them to each other.’”
The clinical trial will separate the two treatments – one group will get a little more than a gallon of fluids before blood pressure medication is given. In the other group, patients will get fewer fluids and more blood pressure medication.
Public Citizen is arguing that two treatments are so vastly different that there should be a control group, too: a third group that receives some combination of fluids and drugs in moderation.
Brothers said having a control group is the gold standard in clinical trials. But he said when the groups are exposed to more similar treatments, the outcomes are closer, too. This means researchers need more people to participate–and it raises the costs and can delay results.
“When you can enroll smaller number of patients you can get the results out quicker, which helps people and it saves money, which is important to the taxpayer,” Brothers said.
But Public Citizen is arguing that without a control group, the study’s results will be hard to interpret.
“Suppose the subjects in one group, 30 percent of them die. And in the other group, 20 percent of them die. But had we had a ‘usual care’ control group, ten percent would have died,” Carome said.
That could lead researchers to conclude the test treatment resulting in the 20 percent mortality rate is better.
“That’s what they start using in the care of sepsis,” Carome said. “But that would be misleading because they don’t know that it might have done worse than usual care.”
In scientific studies, if the experimental treatment shows early results of a higher number of deaths or complications, the study will be halted.