PolyHeme - Artificial Blood & Emergency Medicine Research
WASHINGTON, March 14, 2006 (UPI) -- U.S. Sen. Charles Grassley, R-Iowa, says the Food and Drug Administration has made patients into "potential guinea pigs" in a blood substitute study. Grassley says a patient-safety office within the Department of Health and Human Services has been expressing ethical concerns about the study to the FDA for nearly two years, The Wall Street Journal reported Tuesday. The concerns centered on the design and implementation of a study of the blood substitute PolyHeme, made by Northfield Laboratories Inc.
Summary & Timeline
December 2003: Phase III Trial of Polyheme begins enrolling patients in a study investigating the “ Safety and Efficacy of PolyHeme ® in Hemorrhagic Shock Following Traumatic Injuries Beginning in the Pre-Hospital Setting.” The study starts at the injury scene and continues through ambulatory transport and up to 12 hours of inpatient hospital stay or 6 units of PolyHeme. Trauma victims are automatically enrolled unless they wear a blue bracelet that indicates their desire to “opt out” of the study.
As of March 2006, more than 600 patients at 31 trauma centers in 18 states have been enrolled. Northfield Laboratories has reported that a total of 2000 people have requested the blue bracelets, and 11 victims who initially received the blood substitute declined to continue participation once in the hospital.
An earlier non-randomized trial (October 2004) has been published in the Journal of the American College of Surgery.
- What is PolyHeme?
Created by Northfield Laboratories, this blood substitute is an oxygen-carrying resuscitative fluid. PolyHeme uses hemoglobin extracted from red blood cells and then modifies the hemoglobin into a polymerized from. This is a chemical reaction in which two or more small molecules combine to form larger molecules that contain repeating structural units. The polymerized hemoglobin is then put into solution in approximately the same concentration that hemoglobin is found in natural blood.
Official Study Title “A Phase III, Randomized, Controlled, Open-Label, Multicenter, Parallel Group Study Using Provisions for Exception From Informed Consent Requirements Designed to Evaluate the Safety and Efficacy of Poly SFH-P Injection [Polymerized Human Hemoglobin (Pyridoxylated), PolyHeme ® ] When Used to Treat Patients in Hemorrhagic Shock Following Traumatic Injuries Beginning in the Prehospital Setting.”
This study has not been required to obtain the informed consent of trauma victims under FDA regulation 21 CFR 50.24 – the emergency research exception. This exception allows a waiver of informed consent requirements under emergency therapy conditions in which it is not possible to obtain standard consent.
March – June 2004: The Office of Human Research Protections (OHRP) raises concerns to the FDA regarding the PolyHeme study based on a complaint that alleging inappropriate use of the emergency informed consent waiver once subjects arrive as the hospital. In order for the waiver to be applicable, other available treatments must be unproven or unsatisfactory (21 CFR 50.24a, 1). Yet once in the hospital, trauma victims are usually able to receive matched blood within 45 minutes – 1 hour.
A discussion of the ethics of this type of artificial blood experiment took place on NPR in March 2004.
It is among the duties of the OHRP director to advise the Secretary of Health and Human Services on issues of human subject protections. Both the FDA and the OHRP fall within the purview of the Department of Health and Human Services.
July – November 2004: The Director of the OHRP makes multiple requests to meet with the various FDA officials to discuss concerns over the PolyHeme trial. In August, a meeting took place between OHRP and FDA officials, but this did not resolve the concerns over the PolyHeme study. The Director ultimately writes to the acting commissioner of the FDA, Dr. Lester Crawford, to urge that a review of the PolyHeme study (and other uses of the emergency waiver) be conducted.
March 2005: The FDA finally replies to concerns raised by the OHRP, claiming that FDA had requested more information from Northfield Laboratories on details of the PolyHeme study. They also agreed on the need for a clearer description whenever the PolyHeme study was added to a new community.
May 2005: OHRP again requests a joint review with the FDA to investigate implementation of use of the emergency waiver.
December 2005: OHRP finally receives a response to their requests for a review – the FDA conducts an internal review of the use of the emergency waiver in studies submitted to it.
February 2006: (2-22-06) The Wall Street Journal publishes a story on a previous PolyHeme study from 2000 which is no longer in progress. The WSJ questioned whether Northfield Laboratories were secretive about negative side effects such as heart attack in patients exposed to PolyHeme. In response, Northfield Laboratories' stock plunges by as much as 27 percent.
Northfield Laboratories issues a statement contradicting the claims in the WSJ story.
March 2006: The March-April issue of the journal IRB: Ethics and Human Research will publish an article entitled “ Trials and Errors: Barriers to Oversight of Research Conducted under the Emergency Research Consent Waiver” in which criticism is made of the PolyHeme trial's use of emergency consent waivers.
Also, these same authors have written an open letter to IRBs concerning the Northfield PolyHeme. This letter is forthcoming in the American Journal of Bioethics .
- Northfield issues a statement countering claims made in the IRB: Ethics and Human Research article.
(3-13-06) Senator Charles Grassley (R, Iowa; Chair of the Senate Finance Committee) writes a letter to Secretary of Health and Human Services Michael Leavitt indicating his disapproval of the PolyHeme study and requesting attention to “problems that continue to plague the FDA” and a particular intervention into the PolyHeme study to address concerns of informed consent. He also requests that clear information about this study be made public by the FDA.
- Northfield also issues a response to concerns raised by Senator Grassley.
Northfield Laboratories has dedicated a large portion of their website to addressing concerns over the Phase III PolyHeme trial. This includes a Northfield Laboratories to liquidate under Chapter 11, June 2, 2009.], and also a section. [Note: Northfield Labs filed for bankruptcy; it's website and FAQs on PolyHeme are no longer online. See: