I am a heavy sleeper, so my alarm clock is set to the local news radio station to help wake me. Sometimes, when I'm still pretty deep in sleep, I incorporate the stories into a little bit of my dreams. When I woke this morning, I was sure that this story had to be a nightmare - but it is completely true.
At two hospitals in the city of Detroit and several urban hospitals in 19 other states, doctors secretly injected "randomly selected" trauma patients with a blood substitute called PolyHeme. Secret clinical trials of PolyHeme have been conducted on unknowing patients since 2004. The patients and their families never gave consent for the testing. 49 people, including a Detroit man, died after receiving the controversial treatment. The FDA approved the secret tests on humans.
The trial of this drug raises many ethical issues. The trial parameters state that the blood substitute is to be given to subjects even if the traditional treatment can be given, violating FDA and HHS rules. Earlier trials showed recipients of PolyHeme suffered heart attacks, a fact quietly ignored by the manufacturer in information provided to trial Q&A websites. Also, this isn't the first time a drug of this type has secretly been tested in American trauma centers, leaving a trail of dead victims in its wake.
The Detroit Free Press has an outstanding article on the PolyHeme scandal and the local man's death:
Secret test gave patients a substitute for blood
Steve Neavling of the Freep (local slang for the Detroit Free Press, our left-leaning newspaper) described the situation artfully:
You're in a car crash, unconscious and bleeding profusely.
Without your consent, you are injected with an experimental blood substitute being randomly tested on victims of car crashes, shootings and other trauma. That's exactly what happened to nine trauma patients -- one of whom died -- at two Detroit hospitals last year.
I am not a medical professional - just an average American who found this concept stunning and frightening. While I'm sure the medical professionals testing this blood substitute are trying to help save lives, I wondered what risks there were to patients, why consent could not be obtained before using an experimental procedure when traditional methods for blood replacement are available. I did a few hours of internet research, and I was surprised at what I learned.
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Questions About PolyHeme's Safety
There have been many questions about the safety of PolyHeme and the ethics of their no-consent trials. Citizens for Responsible Care and Research (CIRCR) has done extensive research on the controversy regarding PolyHeme Research here. Most notable of interest is that the individual hospitals that provide information about the trial on websites do not note the prevalence of heart attack or other medical issues by patients who have used PolyHeme in clinical trials. For example, check out the Q&A about the safety of PolyHeme on UC-San Diego's PolyHeme trial website:
Is PolyHeme® safe?
In clinical trials to date, PolyHeme® has demonstrated no "clinically relevant" adverse effects. That is, they didn’t impact the patient’s safety or recovery.
Past studies have shown that PolyHeme® carries as much oxygen as blood, has not caused organ damage, keeps people alive who have lost all of their own blood, and can be infused up to two times a person’s entire blood volume.
Has PolyHeme® been tested on humans before?
There have been 5 human clinical trials of PolyHeme®.
How many patients have been treated with PolyHeme®?
Over 300 patients have been treated, including patients in a hospital-based trauma trial.
What happened to them?
In the Phase II hospital trauma trial, PolyHeme® significantly increased survival compared with historical controls.
This is rather deceiving. The Freep article noted that a higher percentage of those given PolyHeme have died than those who received the standard treatment in trial studies (13% versus 9%). Also, the Wall Street Journal published an article in February 2006 revealing that the makers of PolyHeme quietly shut down a clinical study years ago that showed a large percentage of heart attacks after use of this blood substitute.
(diarist's note: the full WSJ article is viewable by subscribers only. This link provides access to the entire article).
Several years ago a clinical trial of a blood substitute called PolyHeme finished with worrisome results. Ten of 81 patients who received the fake blood suffered a heart attack within seven days, and two of those died. None of the 71 patients in the trial who received real blood were found to have had a heart attack.
PolyHeme's maker, Northfield Laboratories Inc., quietly shut down the trial and didn't publicly disclose the results, which are described in internal documents viewed by The Wall Street Journal. It decided the heart attacks might have been due to doctor inexperience in using PolyHeme, not a problem with the product itself.
Now Northfield is in the middle of a new trial. A Food and Drug Administration official, Jay Epstein, calls the earlier data "alarming" but not sufficient to stop Northfield from trying out its product on hundreds of trauma patients.
According to the Free Press article cited earlier, Northfield Laboratories of Evanston, Illinois, claims that the reason they have had a high number of deaths after the drug was used was because many patients would have died anyway. If they excluded a large number of patients that probably had no chance of living with standard treatment, they claim the survival rate would be increased. Wow, what a great PR department they have.
PolyHeme's maker also gives a curious reason why the drug is tested without consent on patients. Again, from the Free Press:
Northfield Laboratories... contends there was no other way to test the product. Trauma patients are generally unconscious and cannot give consent.
Gee, there must be some way to try the drug on people with consent of them or their families. Couldn't they limit the testing of this drug on patients that consent is available (either through the patient or a family member), especially since there are serious concerns about the drug's safety?
Other nagging questions arise: were the patients informed that they were the subject of a secret medical test after they recovered (if they recovered)? Are they getting follow-up care to monitor the safety of the blood substitute on their health? I can't seem to find answers to those questions in my online investigation.
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Tuskegee again? The FDA's Approval of No-Consent Testing
In 1996, the FDA approved testing unapproved drugs on hospital patients without their consent. This Boston.com article from 2005 gives a little background on the FDAs decision:
All new drugs and medical devices require advanced safety tests before they can be approved for general marketing. However, subjecting patients to medical tests without their consent has led to notorious abuses like the Tuskegee Study, a 40-year experiment in which 399 black syphilis patients in Alabama weren't told they had the disease or offered treatment until the trial was exposed in 1972.
In 1996, the FDA passed rules that allow waivers for research where there is no realistic chance of getting patient approval and the treatment offered major benefits such as in trauma care. The FDA said about 20 trials involving waivers from consent have been approved since that time, though not all of those trials were actually conducted.
Federal regulations spell out the parameters in which no-consent clinical trials may be conducted in emergency situations. Note this section of the rules:
- The human subjects are in a life-threatening situation, available treatments are unproven or unsatisfactory, and the collection of valid scientific evidence, which may include evidence obtained through randomized placebo-controlled investigations, is necessary to determine the safety and effectiveness of particular interventions.
- Obtaining informed consent is not feasible because:
i) the subjects will not be able to give their informed consent as a result of their medical condition;
ii) the intervention involved in the research must be administered before consent from the subjects' legally authorized representatives is feasible; and
iii) there is no reasonable way to identify prospectively the individuals likely to become eligible for participation in the research.
- Participation in the research holds out the prospect of direct benefit to the subjects because:
i) subjects are facing a life-threatening situation that necessitates intervention;
ii) appropriate animal and other preclinical studies have been conducted, and the information derived from those studies and related evidence support the potential for the intervention to provide a direct benefit to the individual subjects; and
iii) risks associated with the research are reasonable in relation to what is known about the medical condition of the potential class of subjects, the risks and benefits of standard therapy, if any, and what is known about the risks and benefits of the proposed intervention or activity.
- The research could not practicably be carried out without the waiver.
(diarist's note: my emphasis added to highlight areas that seem interesting in regards to the PolyHeme trial)
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The Ethics of No-Consent Testing: Prioritizing Big Pharma's Scientific Research Above Patient Welfare?
Not all hospitals presented with the PolyHeme no-consent trial opportunity were comfortable with this drug or testing parameters. The requirements of the trial seem to conflict with the legal requirements stated by the HHS above. Per the Boston.com story cited earlier, three New England hospitals rejected the no-consent trial of PolyHeme on patients. One of the primary concerns, according to Alaisdair Conn, Chief of Emergency Medicine at Massachusetts General Hospital, is regarding the ethics of non-consent trials on patients who could receive traditional treatment. "The trial was designed to keep patients on the experimental PolyHeme hours after they could have been switched to blood transfusions." How would this fit the HHS provision stating this type of trial can only be conducted when "available treatments are unproven or unsatisfactory"?
Leonard Glantz is a professor of health law at Boston University and member of the Boston Medical Center board that rejected the trial of PolyHeme. He expressed concerns how some blood substitutes used in no-consent trials are often given to patients by first responders on-site of an emergency by first responders, but also continue to be given the blood substitutes after they arrive at a hospital. In 2005, he expressed concern about the reasoning behind using a blood substitute instead of traditional treatments. Again, from the earlier cited 2005 Boston.com story:
''There might be a good reason. But if the reason is solely a scientific one, and not related to the welfare of the subject, then I wouldn't be convinced," Glantz said.
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No-Consent Testing of Blood Substitutes is Not Uncommon. Neither are Heart Attacks.
PolyHeme isn't the only blood substitute drug that has been secretly tested on hospital patients - and it's not the only no-consent test trial drug that has resulted in patient deaths. Hemopure, a blood substitute manufactured by a different company, was used for no-consent testing by the US Navy before a high number of heart attacks in patients caused the clinical trial to be halted late last year. (diarist's note: this link is to a press release by Hemopure's manufacturer, which notes the trial and decision to halt testing until further negotiations with the Navy reach an agreement. The amount of information on the internet seems to be dominated by official Hemopure PR.)
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Summary of My Thoughts
I'm a strong believer in the importance of medical testing to find new treatments, but I also have concerns about bioethics. There may be very sound medical reasons to test possibly life-saving drugs on patients who cannot give consent. However, when previous medical tests indicate serious concerns, and traditional treatments are available to patients, why should doctors and hospitals prioritize Big Pharma's scientific curiosity over patient health?
To me, this story presents many questions that beg for answers. Is there evidence that those who received PolyHeme without consent were kept on the blood substitute after transfusions were available? Have the patients and families of those who received no-consent trial drugs always been informed of the procedure and risks after they have been subjected to the trials? Is adequate follow-up care provided to these individuals?
I hope we'll get more answers about this unsettling program of no-consent testing of medical treatments with dangerous side effects.
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Additional links for those interested in more information:
An Open Letter to the ISB regarding ethical problems in the PolyHeme trial:
PDF
A list of the 31 hospitals conducting PolyHeme no-consent trials are here
(diarist's note: while this document says the trial is no longer recruiting patients, it appears that the trial is being conducted on new patients at the participating hospitals. My interpretation of this is that the trial is closed to new hospitals).