By Stacey Kusterbeck
Researchers at Massachusetts General Hospital are seeking to validate a new technology to isolate and identify bacteria in the bloodstream of very sick patients — something that takes more than 24 hours using traditional blood cultures. To validate this new diagnostic, it was necessary to get a blood sample from emergency department (ED) patients at the same time the clinical blood culture was obtained and before antibiotics were given.
“We needed to enroll sick patients in time to get a research sample at the same time as the clinical blood culture — which is, for the most part, directly after arrival to the ED. We were failing to do this with traditional informed consent,” says Michael Filbin, MD, director of clinical research in emergency medicine.
Researchers only enrolled 52 patients at three hospitals in 18 months. Only 20.7% of these had positive blood cultures, which are needed to confirm the validity of the diagnostic. “This is simply too low and too slow to enable the development of new, important diagnostics that could significantly change how we practice medicine,” notes Filbin. Obtaining standard informed consent during the initial resuscitation of these sick patients was simply not practical.
Filbin and colleagues wanted to determine if using alternative procedures to obtain informed consent could be effective for clinical studies that are looking at novel diagnostic products. The researchers compared two forms of informed consent used in study recruitment of adult patients at risk for bacteremia.1
As part of their diagnostic workup, patients with potential bloodstream infections had blood cultures drawn shortly after arrival to the ED, and the new diagnostic was compared to these cultures. Most patients are treated with intravenous antibiotics soon after this first blood draw, which means that if researchers wait until after the draw to initiate consent, the infection is partly treated. That makes a valid assessment of the new diagnostic impossible.
Participating in the clinical study meant patients would need to have extra blood drawn simultaneously with the clinical blood cultures. During the first phase of the study, researchers used a standard informed consent procedure and obtained the patient’s consent before drawing the research blood. In the second phase, researchers used an alteration of informed consent, which allows for consent to occur in a deferred fashion after research blood has been drawn. This approach is permissible for minimal risk studies (such as blood draw studies) that could not be practicably carried out without the alteration of informed consent.2 The researchers obtained the additional blood as part of the initial clinical blood draw, and then sought the patient’s consent later to use the blood in the study once the initial resuscitation and stabilization phase of care was completed.
Of 501 patients approached by the researchers, 353 consented to participate in the study (53.5% consented during the first phase using traditional consent, and 95.1% consented during the second phase using after-the-fact consent).
“It is feasible to implement an alteration of informed consent with deferred consent where an early blood sample is obtained with the initial clinical diagnostics, followed by consent later,” concludes Filbin.
The alteration of informed consent resulted in enrolling a sicker, more diverse population of patients, including older patients, patients with altered mental status, higher-acuity patients, and non-white patients. “This is more representative of the patients we see with severe bloodstream infections and precisely those who stand to benefit from a new diagnostic,” says Filbin.
The study’s findings suggest that deferred consent procedures can be acceptable to patients when applied in the appropriate situation. “It is always best for researchers to put themselves in the shoes of the patient when developing a research protocol, and do what would seem reasonable,” says Filbin. In this case, researchers took a small amount of additional blood that could be used to help test and develop a very important diagnostic that might help patients in the future. “Most patients seem to think this is reasonable,” observes Filbin.
- Mauermann A, Rogers Z, Hua R, Vyas A. 216 Alteration of informed consent in the emergency department has a significant impact on ability to effectively evaluate novel diagnostics for severe infection. Ann Emerg Med 2023;82:S98.
- Code of Federal Regulations. 45 CFR 46 subpart A. 2018.
