The Problem with POLST
Over the years, informed consent has been given short shrift. There is, however, a growing understanding of the importance of obtaining an actual and legitimate consent before having a patient accept or reject m…
Author Archive: Bernard Freedman
There have been a number of articles written by well-known physicians and bioethicists expressing great concern over the recent Office for Human Research Protection, OHRP, letter of criticism with respect to the SUPPORT clinical trial. This blog discussed this controversy in the post of May 23, 2013. This controversy has turned dark with efforts to intimidate the OHRP.. Not attractive in the arena of customarily well reasoned debates in the bioethics community.
The latest in this saga is a plea signed off on by, as they describe themselves, a group of scholars and leaders in bioethics that was published in the New England Journal of Medicine of June 5, 2013. Yet these otherwise noted scholars’ plea is remarkably devoid of academic integrity and disciplined analysis. They “protest too much” when they should be supportive of these criticisms issued by the OHRP for the safety and benefit of all research subjects.
The OHRP is absolutely correct in their findings and should stand fast in their criticism of the informed consent process in this clinical trial.
The parents of these research subjects, infants less than 28 weeks, were not provided with complete information or a clear understanding of the information available and the risks involved in this clinical trial. This group of scholars and leaders in bioethics, which indeed they are, accuses the OHRP of being “both foolish and risky” in their criticism. They say this while at the same time admitting that the consent forms could be improved. How? They don’t say.
They ignore the legally mandated full disclosure owed to the parents involved in this study. They instead assert that the criteria for disclosure should not be the full disclosure because it is unfair to the investigators and institutions involved in this clinical trial. Their worry that full disclosure will “impede the ongoing and future patient centered outcome studies. Such studies are crucial for advancing medial practice, reducing risks…” So, these scholars wish to sacrifice full disclosure and a legitimate informed consent process for the sake of conducting admittedly critically important research that might not be conducted if full disclosure is provided.
They argue that the informed consent process for human research subjects could be better dealt with by “relevant stakeholders” instead of the OHRP. It is, however, hard to imagine a greater “stakeholder” than the research subjects themselves. It is the job of the OHRP to protect research subjects. These scholars therefore want the OHRP to quiet themselves and allow researchers to decide what research subjects should or should not be told. It does not work that way, at least not ethically.
This august group of scholars did not raise or discuss – in any fashion whatsoever – the specific criticisms set forth by the OHRP. They do not factually challenge or quarrel with the conclusions of the OHRP as to the available information that should have been provided to the parents. They merely argue that the findings of the OHRP lack merit, and claim that the process of determining proper informed consent be left in the hands of “properly constituted IRBs” behind closed doors and if logic follows, have the Office of Human Research Protection close their doors.It is damning to note that in this clinical trial the IRB was told by the principle investigators in the clinical trial protocol that oxygen restriction could result in damage to neurodevelopment. They failed, seemingly by design, to tell the parents the same thing in the consent form given to the parents.
When explaining the proposed SUPPORT trial the investigators told the IRB:
“However, oxygen toxicity can result in increased risk for CLD, [chronic lung disease] retinopathy of prematurity (ROP) and other disorders. Alternatively, oxygen restriction may impair neurodevelopment.”(emphasis added).
Their argument that “properly constituted IRBs” will provide sufficient protection to research subjects is conspicuously contradicted in the purposeful failure in this same clinical trial. They apparently feel strongly that if full disclosure is demanded of them their research will be threatened. This is precisely why we need the OHRP for the protection of patients whom we try to recruit for research.
A Fight Against Providing Informed Consent and The Risk of Randomization: Informed Consent in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT)
by Bernard W. Freedman,JD, MPH
In their article Risk, Consent, and SUPPORT David Magnus and Arthur Caplan chastise the Office for Human Research Protections (OHRP) for their findings of a failure to provide adequate informed consent as required by federal regulations, in a clinical trial. The OHRP is right in their position.
The underlying clinical trial, Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT), published in 2010, sought to evaluate the effects of different levels of oxygenation provided to premature infants with extreme low birth weights (ELBW). Two groups were randomized, one to provide oxygen saturation levels from 85% to 89% and the second group from 91% to 95%. The purpose of the study was to find a percentage of oxygen saturation that would avoid reducing oxygen levels low enough to result in retinopathy of prematurity (ROP) but not so low to increase morbidity and mortality.
What I will discuss in this article is the difference in perception between the researchers and the parents; the negligent or purposeful withholding of crucial information from the parents. Magnus and Caplan, two stalwarts in the bioethics academic community, attempt to ride to the aid of the researchers but fail in their “we didn’t know” defense.
The controversy developed over whether or not parents were provided with adequate information before allowing their child to participate in the study. The researchers told one thing to the IRB and left out critical information in the consent form provided to the parents of infant research subjects who were being recruited.
Compare the explanation for the need for the study 1) placed in the Clinical Trial Protocol , with 2) the description provided to parents in the informed consent form.
Clinical Trial Protocol Statement:
“… there is no definite recommendation or standard teaching regarding the level of oxygenation that should be maintained in ELBW infants. Oxygen supplementation has to be used liberally as ELBW infants frequently have desaturation episodes and thus wide saturation ranges are tolerated clinically. However, oxygen toxicity can result in increased risk for CLD, [chronic lung disease] retinopathy of prematurity (ROP) and other disorders. Alternatively, oxygen restriction may impair neurodevelopment.”
“…ROP is increased by the prolonged use of supplemental oxygen from observations published in the 1950s, but the benefit of higher versus lower levels of oxygenation in infants, especially for premature infants, is not known. In going back and looking at how babies in the past were managed, is being suggested that the use of lower saturation ranges may result in a lower incidence of severe ROP.
The consent form uses the word “benefit” but does not discuss risks to individual infants and fails to mention any risk that oxygen restriction might impair “neurodevelopment” or death.
Specifically, the concerns and criticisms of the OHRP stem from their review of prior research reflecting known risk factors that might lead to differences in whether an infant survived or developed blindness in comparison to what might have happened to a child had that child not been enrolled in the study, i.e., the effects of oxygenation on (ROP) on the one hand and neurologic morbidity and mortality on the other. The OHRP suggested, in part, that the parents should have been told that:
… the study involves substantial risks, and that there is significant evidence from past research indicating that the level of oxygen provided to an infant can have an important effect on many outcomes, including whether the infant becomes blind, develops serious brain injury, and even possibly whether the infant dies…”[i]
The informed consent form did not mention any difference in risk in being assigned to one group or the other. The assignment, they were told, was the same as a “flip of a coin.” Parents were told, “Participation in this study does not involve any known risks to you or your child.” Here, however, the the risk of higher oxygen levels could lead to blindness while the risk of too low oxygen levels could lead to death.
The concept of “foreseeable risk” under the federal regulations is not limited to specific, direct, exacting scientific evidence. Indeed, the determination of actual, direct scientific evidence was the endpoint of this trial. “All foreseeable risk” encompasses all adverse effects that could occur. It is clear that as the OHRP wrote, “the level of oxygen provided to an infant can have an important effect on many outcomes, including whether the infant becomes blind, develops serious brain injury, and even possibly whether the infant dies.”
Magnus and Caplan, take issue with the OHRP. They declare that:
“…there is absolutely no evidence to support the claim that the infants enrolled in the study were exposed to greater risk than infants outside the study.”
This may be true from an epidemiologic, biostatistical standpoint as to the group of infant research subjects, but not true as to individual infants. Parents do not decide what is best for the group of the clinical trial participants, only what is best for their child. The consent they are asked to give means nothing without receiving and understanding all information.
Magnus and Caplan make the point that, “there was a variation in clinical practice…based upon random physician preference. ” Random physician preference is the risk of randomization. Medical treatment that is being randomly chosen is different from an individual physician’s medical decisions being made for an individual infant – a patient – not a group.
“Random physician” here means a statistical range of possible oxygen saturation levels, but not a clinical decision made by a physician for a unique patient. Not all physicians are the same. Their education and experience varies and so with it the efficacy of the decisions they make. The care of an ELBW infants nuanced and many parents make the effort to find a highly respected physician whose treatment decisions are based on the individual merits of the infant’s physician. So, being recruited into a trial without being fully informed of the risks of randomization is a breach of medical ethics as well as the federal regulations requiring that all information be provided.
There is a long history here leading up to the SUPPORT study. Research in early trials in the 1950s and 1960s demonstrated the possibility that although lower oxygen levels reduced ROP, it also threatened significant morbidity and mortality. In 1973, a study found that: “it would seem that each sighted baby gained [by limiting the use of oxygen] may have cost some 16 deaths.” A 2006 retrospective review noted that “lower oxygen for prolonged periods of hypoxemia may result in poor growth, cardiopulmonary complications of chronic lung disease, neurodevelopmental disabilities, or increased mortalities . . . Although maintaining ranges of hemoglobin oxygen saturation in the vulnerable preterm population in the proximity of 85% to 90% is gaining increasing acceptance, marked variability in opinion exists.” (SUPPORT ranges went to 95% saturation).
“Marked variability in opinion” means that different well-respected careful and prudent physicians in the medical community specializing in neonatology do, indeed, differ. Thus, in failing to explain that there has been a long- standing controversy in the community regarding the effects of increasing or reducing oxygen levels in ELBW patients and potential complications ranging from blindness to chronic lung disease to death is: a misrepresentation, at best, and a failure to obtain legitimate consent to enter the infant into the study protocol.
Magnus and Caplan, in an attempt to justify the withholding of information, argue that the ends justified the means. They say, in retrospect, “The study made clear that higher oxygen saturations within the then-recommended range increased the risk of retinopathy but decreased the risk of death.” Yet, it is clear that information obtained after a study has nothing whatsoever to do with the relevant and material information that must legally be provided to the parents before the study.
Magnus and Kaplan seek refuge behind the argument that the “standard of care” included the range of oxygen saturation of 85% to 95%. Yet, admittedly, the standard of care, if one can call it that, was unclear and controversial and differed among physicians. In fact, the principal investigators of the study do not say that there is a “standard of care.” Instead they explain in there protocol that:
“… there is no definite recommendation or standard teaching regarding the level of oxygenation that should be maintained in ELBW infants.”
Even if there is a range of oxygen saturation levels which some consider to be a standard it should be understood that under the law in most states a “standard of care” is not determinative of the adequacy of disclosure of information that a reasonable person would deem relevant and material to his or her decision-making process. Thus, failing to include all information will bear on any issues of liability that may arise.
The reality is that neonatologists make medical decisions as to what percent of oxygen saturation is best for an individual infant is based upon their experience, education and unique assessment of their individual patient. Individualized care was withdrawn when the infants were randomized. Before research subjects leave individualized care and enroll in randomized clinical trials, the highest amount of information and candor owed.
Accordingly, the action taken by the OHRP was proper and should be seen as a legitimate effort to protect the research subjects in this clinical trial.
[i] The OHRP stated: It would have been appropriate for the consent form to explain (i) that the study involves substantial risks, and that there is significant evidence from past research indicating that the level of oxygen provided to an infant can have an important effect on many outcomes, including whether the infant becomes blind, develops serious brain injury, and even possibly whether the infant dies; (ii) that by participating in this study, the level of oxygen an infant receives would in many instances be changed from what they would have otherwise received, though it is not possible to predict what that change will be; (iii) that some infants would receive more oxygen than they otherwise would have, in which case, if the researchers are correct in how they suppose oxygen affects eye development, those infants have a greater risk of going blind; and (iv) that the level of oxygen being provided to some infants, compared to the level they would have received had they not participated, could increase the risk of brain injury or death.
that the study involves substantial risks, and that there is significant evidence from past research indicating that the level of oxygen provided to an infant can have an important effect on many outcomes, including whether the infant becomes blind, develops serious brain injury, and even possibly whether the infant dies; (ii) that by participating in this study, the level of oxygen an infant receives would in many in stances be changed from what they would have otherwise received, though it is not possible to predict what that change will be; (iii) that some infants would receive more oxygen than they otherwise would have, in which case, if the researchers are correct in how they suppose oxygen affects eye development, those infants have a greater risk of going blind; and (iv) that the level of oxygen being provided to some infants, compared to the level they would have received had they not participated, could increase the risk of brain injury or death.”
Waiting for medical records “after discharge” is of no help.
Reviewing medical records in the hospital allows the patient and/or a surrogate decision maker to obtain the greatest amount of information pos…
The determination of a patient’s capacity to make decisions is based upon her understanding of her disease or illness and the risks and benefits of treatment. If she is unable to articulate a clear understanding it may be determined that she lacks the necessary capacity to make her own decision and is further taken out of the loop of information and adequate and legitimate updates on her condition. Concomitantly, surrogate decision makers are not always available to see the treating physicians and consults, and often get a cursory explanation of the patient’s condition.
Physicians remain exceedingly reluctant to confront the difficult subject of end of life care. The New York times, on January 11, 2009 published an article, by Denise Grady, – “Facing End-of-Life Talks, Doctors Choose to Wait.” Discussing a survey of 4,074 doctors who took care of cancer patients, who had only four to six months left, but was still feeling well. 65 percent said they would talk about the prognosis, but wait to discuss end of life preferences.
67%: Making sure family is not burdened financially by my care
66%: Being comfortable and without pain
61%: Being at peace spiritually
60%: Making sure family is not burdened by tough decisions about my care
60%: Having loved ones around me
58%: Being able to pay for the care I need
57%: Making sure my wishes for medical care are followed
55%: Not feeling alone
44%: Having doctors and nurses who will respect my cultural beliefs and values
36%: Living as long as possible
33%: Being at home
32%: Having a close relationship with my doctor
As time progresses and severity of illness increases, being able to say what she – the patient – actually wants is of paramount importance. Respecting person’s wishes is both ethically required and legally mandated because we recognize that each of us is owed the respect to decide what is done to our bodies, how we wish to live. These human rights are not relinquished when sever illness must be faced. The need to provide timely information to the patient must not be ignored. If the determination of the true wishes of the patient are, in fact paramount in decision making than the earlier information is provided then there is a greater probability of knowing – with confidence – the wishes and decisions of the patient. Moreover, be speaking early the patient has the opportunity to ask questions of her physicians that she deems important. All this is lost by waiting. When a patient loses capacity the physicians are forced to turn to the surrogate decision maker who may be reluctant to express the wishes of the patient or unable to face the harsh realities of the situation and delay decisions.
1 A surrogate cannot be permitted to cause a delay in decision making which will harm the patient by causing unnecessary suffering and costly delays.
2 If a surrogate cannot or will not be fully informed and understand the diagnosis and prognosis, he or she may not continue as surrogate
3 If a surrogate cannot or will not decide – find a new surrogate, or move to a best interest standard.
Often the surrogate is a family member suffering from fear and grief, often at odds with the views of other family members and friends. There is an understandable empathy for people in this position and the desire to help them through such a hard time in their lives is great. Yet, it is not the job of a physician or nurse or bioethicist to become involved with the surrogate to the point that the surrogate’s feelings seem more important than the need to uncover by the most reliable means possible under the circumstances to know the true perspective and intentions of the patient.
It must be of crucial importance to maintain focus on the patient’s wishes and not see the surrogate and family as a filter or as an easier method to arrive at a decision. The surrogate must make a decision, not based on a consensus of the family or the advice of the doctor or nurse, but on the best and clearest representation of the wishes of the patient.
From “Waiting for Godot” Samuel Beckett
Let’s wait till we know exactly how we stand.
On the other hand it might be better to strike the iron before it freezes.
I’m curious to hear what he has to offer. Then we’ll take it or leave it.
What exactly did we ask him for?
Were you not there?
I can’t have been listening.
Oh . . . Nothing very definite.
A kind of prayer.
A vague supplication.
And what did he reply?
That he’d see.
That he couldn’t promise anything.
That he’d have to think it over.
In the quiet of his home.
Consult his family.
His bank account.
Before taking a decision.
It’s the normal thing.
Is it not?
I think it is.
I think so too.
At the 2013 annual meeting on Women’s Cancer by The Society of Gynecologic Oncology (March 9 2012 – Los Angeles) Dr. Robert Bristow, the director of Gynecologic Oncology at the University of California – Irvine presented a retrospect…
“Be a good girl and take your medicine.” Part 1
This statement was made to a 60 year old end stage leukemia patient who demanded to be discharged from the hospital. The patient refused the prescribed medications. No attempt was made to discuss the risks attendant in not taking the prescribed medication. The patient was cogent and articulate – able to make medical decisions for herself. The physician walked out of the patient’s room in the ICU. No social worker, bioethicist had been called to assist. Patient Jane was merely told, “Be a good girl and take your medicine.”
What can we say about the physician who made this statement? One might speculate that perhaps the physician was elderly – old school, etc. He was not. Early forties, well trained, and well respected. Could it be a socioeconomic impasse in communication? Possibly, the pt was poor and black. There was family or friends to advocate on her behalf. Nevertheless the statement breached medical ethics and legal responsibilities. A patient has a fundamental right to determine what medical care she will accept. To ignore these requests constitutes battery and possibly false imprisonment.
The patient reported that she never really spoke with her doctor. He would come into the room briefly, she said, early in the morning. He spent a short time examining her. Often he was interrupted by cell phone calls. He would say he had to run. The pt reported that the nurses were giving her little attention, save saying that she should take the medicine the doctor proscribed. She told the ICU nurses she was refusing meds and wanted to be discharged. She called me.
I found her curled up in a fetal position shivering with no blanket calling for help. She told me her wishes; her refusal of meds and request to be discharged. She had voluntarily admitted herself to the hospital and saw no reason that she should be kept “like a prisoner” and with her “Constitutional Rights violated.” She implored me to help her; she said she had a brief time to live and did not want to remain in this hospital to wait out her days. She was feeling better and “wanted out.” I contacted the primary treating physician who said she was not competent to make decisions. I recommended a psychiatric consult to confront this issue. The psychiatrist responded within a few hours and found that Jane was clearly competent to make decisions for herself, but placed her on an involuntary 72 hour hold because he found her to be paranoid that people would not listen to her.
This was a misapplication of the purpose of the 72-hour psychiatric hold statute, used for the protection of a who may cause harm to herself or others. I contacted then psychiatrist to inquire why he felt she might cause harm to herself or others. He did not think she would but did not want to cause “a problem” for the primary treating physician.
The 9th Circuit Court of Appeals recently heard oral argument in the case of NATURAL RESOURCES DEFENSE COUNCIL,( NRDC), vs. ENVIRONMENTAL PROTECTION AGENCY, Case# 12-70268, regarding the EPA’s conditional approval of a nano-silver product made by a Swiss company HeiQ Materials. The Amicus briefs describe it as:
“ the EPA’s unprecedented decision to conditionally register the nano-silver pesticide products HeiQ AGS-20 …as unsupported by substantial evidence. EPA has failed to show that the conditional registration will not cause any unreasonable adverse effect” on human health and the environment. The limited studies to this point have raised significant red flags about nano-silver.”
The Product is HeiQ AGS-20, as described by its manufacturer, provides antimicrobial protection for textiles (e.g. blankets) and medical products … (wound dressings, implants) with unique durability and effectiveness… contribute to healing, increased safety and faster recovery.
The issue in this case is the legality of the EPA’s interpretation that the interest of the public and of business trumps the EPA’s administrative mandate to first determine the safety of pesticides and to affirmatively determine that a product does not have “unreasonable adverse effects.” In this case infants and children under 2 have not been studied regarding fabrics containing nano-silver if chewed by infants or children 1 or 2 years of age. The fear is an increased risk of injury or death. Although the EPA is required to evaluate risk, they did not do so in the group most likely to ingest nano-silver – infants and children 1 to 2 years old who chew on materials available to them.
During oral argument in the Court of Appeal, one Justice questioned counsel for the NRDC as to whether we should do away with stairs because babies fall down the stairs all the time – isn’t there a risk in everything that we do?
This joking cynicism fails to appreciate the unknown risks of nanotechnology and perhaps parallels the ignorance of the majority of the public as to dangers of working with substances of unknown nature. According to an amicus brief filed on behalf of various organizations, both private industry and governments are spending billions of dollars on research and development of nano technology. Nano-silver is the largest area with the greatest amount of new products at the present time. To date, however, no labeling with respect to unknown risks is required.
The EPA regulates nano-silver products, as pesticides because the intended purpose is antibacterial and antimicrobial. The risks involve potential toxicity from individual one time exposure to dose related effects from the aggregate expose to numerous products such as, sunscreens, food packaging, children’s toys and pacifiers, laundry detergent, personal hygiene products, jeweler, bedding and furniture, underwear, hair brushes, creams, lotions, pillows, and toothbrushes.
Nano materials can be absorbed into the brain (able to get across the blood brain barrier), liver, heart, kidney, spleen, bone marrow as well as the nervous system.
It is the EPA’s job, its burden of proof, to determine before registering a pesticide, that it will not cause any “unreasonable adverse effects” on human health and the environment. That is the EPA’s affirmative duty and thus cannot be delegated to the manufacturer or anyone else. The EPA has in this instance chosen to give a conditional approval permitting the manufacturer to market it for 4 years – and then see what happens.
The justification for giving HeiQ conditional approval, as stated by the EPA: “the Agency has considered the nature and its pattern of use, application methods and rates, and level and extent of potential exposure. Based on these reviews, the Agency was able to make basic health and safety determinations which show that use of HeiQ AGS-20 during the period of conditional registration will not cause any unreasonable adverse effect on the environment, and that use of the pesticide is, in the public interest. “
Whether this is a sufficient predicate to conditionally approve the product, or whether the EPA is shirking its duty under its administrative mandate, should be at the core of the Court of Appeals’ decision. The statute requires that “ The Agency will approve an application only if:… The Agency has determined that the product will perform its intended function without unreasonable adverse effects …”