Patients in randomized clinical trials of antibiotics are rarely informed of the purposes of the studies, researchers said.
Protocols for noninferiority trials also failed to explain acceptable decreases in efficacy, they wrote in JAMA Internal Medicine.
“Patients enrolling in clinical trials of antibiotics are not accurately informed of study purpose,” researcher Peter Doshi, PhD, of the University of Maryland School of Pharmacy, and colleagues wrote. “Because noninferiority trials do not intend to demonstrate superior efficacy of new interventions and entail tradeoffs of lesser efficacy for other benefits, this study raises fundamental questions of the ethics of consent in antibiotic trials.”
Of all the trials included in their analysis, six were superiority trials, which are designed to determine whether an investigational drug is more effective than an older one. The rest were noninferiority trials, which accept less efficacy in the investigational drug when there is a tradeoff benefit like decreased adverse effects. All trials were conducted between 1991 and 2011.
The researchers enrolled three patient investigators and two methodologists to review the informed consent forms (ICFs) of 50 antibiotic trials.
For each ICF, the patients were asked, “Is the primary purpose of this trial to see whether the new drug is more effective than the control drug, or is the primary purpose to see whether the new drug is not substantially worse than the control drug? Or can you not tell?”
The methodologists were asked if ICFs explained study purposes well enough to determine whether the trials were testing superiority or noninferiority.
The patients found that 11 of the 50 ICFs conveyed a study purpose, the researchers said. Of those, seven conveyed the study purpose accurately and four did not when compared with a reference standard, the patients determined. The methodologists found that only one of the ICFs conveyed a study purpose.
No ICF conveyed a study purpose in the opinion of both the patients and the methodologists.
The researchers themselves assessed the protocol or statistical analysis plan (SAP) in each of 72 noninferiority trials. They found that only one provided a justification for noninferiority.
Doshi and colleagues stressed that a failure to explain noninferiority in trials to patients can mislead investigators, resulting in ethical concerns.
“If potential research participants assume that they are enrolled in superiority trials that are actually noninferiority trials or vice versa, they may incorrectly assess the balance of benefits and harms to which they may be exposed based on the study’s intended purpose,” they wrote. – by Joe Green
Disclosure: Please see the study for all authors’ relevant financial disclosures.