The criticism of the Clovers sepsis clinical trial is that the the treatment and placebo arms of the trial each require rigid adherence to a protocol, and such adherence rules out personalizing individual treatment based on individual differences among patients and doctors’ clinical judgment based on past experiences. That criticism seems plausible and also seems to apply, not just to the Clovers sepsis clinical trial, but to all< randomized double-blind clinical trials.
(p. D1) A large government trial comparing treatments for a life-threatening condition called sepsis is putting participants at risk of organ failure and even death, critics charge, and should be immediately shut down.A detailed analysis of the trial design prepared by senior investigators at the National Institutes of Health Clinical Center in Bethesda, Md., concluded that the study “places seriously ill patients at risk without the possibility of gaining information that can provide benefits either to the subjects or to future patients.”
In a letter to the federal Office for Human Research Protection, representatives of Public Citizen’s Health Research Group compared the study, called Clovers, to “an experiment that would be conducted on laboratory animals.”
“The human subjects of the Clovers trial, as designed and currently conducted, are unwitting guinea pigs in a physiology experiment,” Dr. Michael Carome and Dr. Sidney M. Wolfe wrote in their letter.
Begun in March, Clovers is funded by the N.I.H. — despite the criticism of its own investigators — and aims to enroll 2,320 pa-(p. D3)tients at 44 hospitals around the country.
. . .
At issue is whether patients participating in Clovers are being given treatment that deviates from usual care — so much so that lives may be endangered by the research. . . .
When patients experience septic shock, current guidelines call for raising blood pressure by administering fluids within the first three hours of care, and then administering vasopressors within the first six hours if patients do not respond to fluids.
Vasopressors can be administered early on, during or after the infusion of fluids; a new treatment guideline for hospitals says the drugs should be started within the first hour if patients aren’t responding to intravenous fluids.
Many physicians have been critical of rigid guidelines like this one because they don’t allow for individualizing treatment and appear to discount the doctor’s clinical judgment.
Both fluids in large amounts and vasopressors can cause serious complications, but when a patient’s condition continues to deteriorate, doctors use both interventions, adjusting them depending on the severity of illness.
They generally start with fluids, which in small amounts are considered less toxic than vasopressors.
But participants in Clovers are randomly assigned to a “liberal fluids” group who receive large infusions of fluids in a very short time but limits the use of vasopressors, or to a “restrictive fluids” group in which fluids are minimized and drug treatment begun earlier.
For the full story see:
(Note: ellipses added.)
(Note: the online version of the story has the date Sept. 24, 2018 [sic], and has the title “Trial by Fire: Critics Demand That a Huge Sepsis Study Be Stopped.”)