Trauma Care Patients: Exceptions to the Informed Consent Rule

Informed consent, the heart of the Nuremberg Code, is no longer applicable to certain trauma care patients receiving treatment in the U.S. The Nuremberg Code states unequivocally that:

the voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him/her to make an understanding and enlightened decision.

Rules were changed in 1996 to allow emergency research physicians the option of intervening with experimental therapies. The following directives, under 21 CFR 50.24 , currently govern trauma care research:

• The research study must involve participants suffering from a life-threatening disease process or injury for which the current standard of care is associated with a very high failure or mortality rate.
• In addition, there must be reasonable evidence that the research has the potential to provide real and direct benefit to the patient.
• Furthermore, studies must be held to the highest ethical standards. These clinical trials undergo multiple independent rigorous reviews to ensure that they meet these standards.
• Before any patients are enrolled, communities are consulted about participation and made aware that informed consent will not be obtained for most study participants, as required by law.
• Surviving patients and/or their authorized representatives need to be informed about the trial as soon as feasible after the intervention has been given.

Emasculating the Nuremberg Code to serve scientific agendas is significant for it is the only principle protecting citizens from predatory research practices .

It is acknowledged that clinical trial subjects are vital resources for the research industry. But is there a valid defense for testing experimental products and procedures on unconscious, non-consenting patients?

The following three examples illustrate the conflict between the Nuremberg Code and scientific interests in the matter of Exception from Informed Consent rules.

PolyHeme , an artificial blood substitute [ hemoglobin based oxygen carrier— HBOC ], was tested on an unknown number of emergency room entrants from 1991 to 2009. Phase III PolyHeme studies , involving 720 hemorrhagic shock victims in 32 trauma centers, were concluded in 2007. The FDA notified the manufacturer, Northfield Laboratories, after the close of Phase III that:

the administration of PolyHeme places the patients at a higher risk of significant adverse events, and therefore, in the absence of clinical benefit, the risk: benefit assessment of the product in trauma is unfavorable.

The Emergency Research Waiver granted to Northfield was controversial for many reasons but specifically because patients were denied whole blood transfusions, the standard course of treatment.

Hemopure, a HBOC product derived from bovine red blood cells, was tested both in the U.S. and South Africa. The Hemopure trials were halted due to high fatality rates. A 2008 analysis from the Journal of the American Medical Association found that HBOCs are potentially deadly and should not be tested in humans. The critical Journal study prompted a firestorm of complaints from the Naval Medical Research Center, other related parties and the manufacturer . One of the coauthors of the JAMA critique said the FDA's concerns are moot because the Navy will advance plans for using Hemopure in likely to die patients.

Patients entering the University of Pittsburgh Medical Center suffering from significant blood loss are being enrolled, also without consent, in a unique clinical trial. It is called emergency preservation and resuscitation [EPR]. If the presumed dying individual meets criteria, trauma surgeon Samuel Tisherman and his team will place the patient in a type of suspended animation. This is accomplished by exsanguinating the patient's remaining blood and replacing with freezing salt water. The researchers hope that this procedure will provide a window of opportunity to stabilize cardiac arrest patients. To test the theory, researchers will select ten subjects and apply EPR, another ten will receive conventional cardiopulmonary resuscitation treatment.

Terminally injured and diseased patients are subject to the Emergency Research Consent Waiver at any juncture during course of treatment because of the influence of the Declaration of Helsinki. The World Medical Association, an international research consortium, determined in 1964 under Helsinki that informed consent was not a mandatory code of conduct. Language was altered to secure consent "if at all possible" and by proxy consent was approved.

The World Medical Association was a favored U.S medical ethics trendsetter until 2000. The reasons for the schism are discussed here .

Modifications to the Helsinki guidance document in 1975 set the stage for the concept of independent medical research committees as overseers of clinical trials. Institutional Review Boards have managed clinical studies in the United States since 1981.

In the World Medical Association's opinion:

In the treatment of the sick person, the physician must be free to use a new diagnostic and therapeutic measure, if in his or her judgement, it offers hope of saving life, reestablishing health or alleviating suffering.

Contravening the Nuremberg Code and due process rights to achieve scientific prowess is necessary argue those who advocate for expedient clinical trials.

It should be remembered that it was Dr. John C. Cutler , director of the Guatemala syphilis trials and participant in the Tuskegee experiment who said , "Unless the law winks occasionally, you have no progress in medicine."

The Foster Children in Medical Research Debate

Foster Children's Rights—Congressional Amnesia

With scant public notice Congress authorized the employment of foster children in medical research in 1989. This decision was based on HHS Secretary Bowen's recommendation that:

State and local child welfare agencies should create systems to manage the participation of children in foster care in special medical treatment and experimental trials. (HHS/ASPE, 1989, p. 60).

Thus it came to be that foster children became exceptions to the informed consent rule and the research industry gained a valuable commodity. Supporters of the exception rule state that juvenile judges and welfare agencies are able to make consent decisions for their custodians but it can be argued under due process law that, excepting life-threatening situations, no wards of state may be enlisted in government-sponsored research experiments.

Lawmakers declare that they have established rules to protect children from clinical trial abuse but these assurances are suspect because Congress initiated and funds the foster children in medical research program. The Associated Press reported in 2005 that the majority of foster children utilized in AIDS research did not receive " basic legal protection ."

In 1974 Congress, by way of the National Research Act , mandated the creation of Institutional Review Boards to approve or decline medical research prospectuses based on the risk-benefit formula. The measure was passed to assuage public anger over the disclosed Tuskegee experiment.

A 2002 study found that fifty-eight percent of IRB chairpersons were fully knowledgeable of the child protection rules. Most importantly the inquiry showed that the evaluators could not agree on the risk levels of procedures common in clinical trial practices in healthy 11-year olds. There was no consensus on the part of the respondents on whether blood draws, MRIs, allergy skin tests, electromyography, pharmacokinetic studies and lumbar punctures were minimal risk, minor risk over minimal risk or more than minor risk over minimal risk. Results of the study may be found here .

There are more than 3,000 IRBs overseeing human clinical trials in 350,000 U.S. locations . Two-thirds of the research projects are privately-managed and 1% are reviewed by the FDA. HHS receives approximately 300 IRB registrations and 300 quality assurances each month. The GAO probe found that many of these filings are not reviewed. This is an unacceptable inspection record considering that Congress , the GAO and the DHHS inspector general have documented critical IRB operating deficiencies.

The 2009 GAO report determined that

The IRB system is vulnerable to unethical manipulation, which elevates the risk that experimental products are approved for human subject tests without full and appropriate review. Unfortunately the IRB system sometimes fails to protect research subjects. For example, in 2002, a 47-year-old man died after his heart stopped beating while participating in an experimental trial of antipsychotic medication at a Texas research center.

Daniel Dueber, Coast IRB Chief Executive Officer, testified during the INSTITUTIONAL REVIEW BOARDS THAT OVERSEE EXPERIMENTAL HUMAN TESTING FOR PROFIT hearing that he did not understand why his company was being investigated for approving the counterfeit Adhesiabloc clinical trial:

we have never at Coast ever had a fraudulent study submitted to us. There is no economic reason for anybody to do such a thing.

Mr. Dueber was equivocating because he certainly knows that money is the catalyst for misconduct.

The Fiddes faux research trials are another illustration of the ease of fraud within the IRB system. Family practitioner Fiddes, conductor of more than 170 clinical trials, deceived his pharmaceutical employers by substituting test samples. Dr. Fiddes' actions harmed test subjects and contaminated research results submitted to the FDA for new drug approvals. For these manipulations Dr. Fiddes was convicted of medical fraud and was sentenced to a fifteen-month prison term in 1998. The FDA did not initiate debarment proceedings against Dr. Fiddes and his accomplices until 2002.

More than seventy percent of clinical trials fail efficacy or safety markers by the close of phase II testing. The following two examples highlight the hazards of pharmacokinetic testing . In 2006 anti-inflammatory drug TGN1412 was tested on six volunteers. The experimental drug caused immediate organ failure in all drug recipients. A 1995 NIH-sponsored fialuridine phase II study caused the death of five participants. Post mortem investigation determined that fialuridine, a thymidine analog, caused mitochondrial injury.

The Taking of Justina Pelletier: A Sentinel Event

The Justina Pelletier case history, investigated by The Boston Globe, has brought unwelcome attention and perhaps congressional mitigation to the practice of using foster children in psychological and medical research. Justina Pelletier became a foster child as the result of an abuse complaint filed by Dr. Alice Newton of Boston Children's Hospital.

The Globe discovered that Justina was the sixth child whose parents were accused of medical abuse while their children were receiving treatment in BCH. In its successful state custody court petitions, Boston Children's Hospital was allowed to keep the children and proceed with parent-ectomy studies.

Dr. Newton and other professionals opine that taking questionably diagnosed children out of the parental sphere will improve their health. These severance studies were approved by the hospital's ethics committee. In a follow up article The Globe reported that some hospitals would cease these in-house decisions in view of the negative responses generated by Justina Pelletier's sixteen month psychiatric incarceration.

Parental medical child abuse complaints are profitable. BCH, for example, received more than $400,000 for Justina's confinement.

Some still believe that Dr. Newton's judgment in the Justina Pelletier affair was appropriate. The truth is Dr. Newton's medical child abuse allegations do not withstand scrutiny. The issue before Judge Joseph Johnston was whether Justina's entering mitochondrial diagnosis was valid and whether her Tufts cecostomy button surgery was a warranted procedure.

Dr. Newton, head of BCH's child protection team assured the court that she was certain that Justina's mitochondrial condition was induced by her parents' influence. Dr. Newton failed to advise the court that BCH treats mitochondrial conditions and performs cecostomy surgeries. Justina was referred to BCH to see her former gastroenterologist Dr. Alejandro Flores. Dr. Flores' opinion on the value of cecostomy surgery is positive .

Dr. Newton's court presentation was flawed but neither she nor her cohorts could not know that Justina's parents would violate the court's gag order and reveal the circumstances of their daughter's abduction.

Justina's Law, H.R. 4989, would reduce the use of foster children in medical research but the bill does not address the issue of consent.

Justina's Law as proposed:

Prohibits the use of federal funds to conduct or support treatment or research involving a ward of the state in which the individual's health is subjected to greater than minimal risk with no or minimal prospect of direct benefit.

Clinical trials involve unexplored terrain and they expose subjects to unquantifiable immediate and long term health risks. For this reason research volunteers have expressed safeguards: they are apprised of the potential impairments and may depart the clinical trial at any time.

Foster children became research captives by congressional fiat but this action violates equal protection laws. The exceptions to the consent rule is ripe for judicial review.