Pharmaceutical Testing in the Incompetent Patient
The issue of the ethics involved in the pharmaceutical testing of the mentally incompetent patient (one who does not have the capacity to make medical decisions for himself or herself) was presented on my now inactive "Bioethics Discussion Pages". As with other topics on the "Pages", I would like to migrate them here to the blog and read what my current visitors might comment on them.
I recently got an e-mail from L.R. Booth (boteone@yahoo.com) who does not believe any surrogate has the right to make a decision for a mentally ill patient to participate in a drug experiment and believes that there are patients who could eventually make their own decision. He writes:
" I do not feel you can use the terms incompetent and mentally ill interchangeably. Someone who is incompetent cannot give consent, therefore, it is unethical.
I do not believe anyone has the right to make that decision for the Pt. It's a shame that too many DPOA's and legal guardians do not have the Pt.'s best interests at heart. If the Pt. has outlined this tx in the form of a Advanced Directive then it would be ethical. If someone is suffering from a mental illness that does not mean they are incompetent. Mental illness includes a wide variety of disease processes; depression, bi-polar etc. If treated properly these Pt.'s can make a informed decision on experimental drug txs"
I should explain my understanding of mental illness and capacity to make medical decision. Not every mentally ill patient has lost capacity to make their own medical decision. The loss of capacity must be determined by careful testing by the physician. It can be done successfully. A patient can have the capacity to make a medical decision in one context and not in another, so the testing should include the context in which the patient may be involved. Does the patient understand what drugs are and what they do, for what they are used, by whom and how drugs are developed and how they are tested, for what are they tested and upon whom they are tested? Does the patient understand that the patient might not get to take the drug that is being tested and might get another drug or a sugar pill? Does the patient understand that the drug being investigated might not be any more useful than a sugar pill or another drug? Does the patient understand that the patient might suffer complications from the testing either by bad effects of the drug or by the fact that their usual medication may have to be discontinued? If the patient passes all these questions by demonstrating understanding, then I would think the patient would have the mental capacity to make their own self-decision whether or not to participate in the study regardless of their established psychiatric diagnosis. For those who have no capacity to understand and give consent, the main question of this post is whether someone else should. But unlike surrogates giving consent for treatments that are not experimental and are known to be effective, balanced against the risks, in the case of experimental drugs tha effectiveness is unknown and the risks may only be partially known. Is the altruistic properties of being a subject in a test that might help oneself and many others sufficient to override the inability of the patient to understand and agree with the surrogate's decision?
In the comments below, the oldest replies are at the bottom of the posting. ..Maurice.
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Pharmaceutical companies must test new drugs for the treatment of mental illness on patients with the illnesses for which the drugs were developed to treat. This seems a very clear statement. The ethical concern is how can these patients who may have lost the capacity to understand the purpose, nature, risks, benefits and alternatives (including nonparticipation) of the research, to make a decision about participation? Should a family member or other surrogate make the decision for such a patient? Ordinarily, surrogate medical decisions deal with therapeutic issues. In the case of drug testing, the testing itself may not prove to be therapeutic, may be painful or even harmful for the patient. Should surrogates be given the power to allow the patient to be subjected to medications which have not been proven therapeutic but may be harmful? If there is no surrogate, who should make the decision or should the patient be eliminated as a candidate for the study?
Here are the questions:
How can the patient's rights be protected and still provide for necessary testing of drugs in the mentally ill? Who, if anyone, should make the decision for an incompetent patient regarding participation in a drug testing experiment?
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Date: Tue, Mar 9, 2004 7:06 PM From: khmaio@earthlink.net To: DoktorMo@aol.com
Please do not employ the term, "the" mentally ill. No group is generic.How to obtain informed consent when a person is not capable of giving it? Stop.If I know someone is not competent, proceeding is unethical. Only greed motivates past knowing the person cannot consent. The greed for an answer or for a recognition.More the latter than the former. Harold A. Maio
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Date: Wed, Jan 21, 2004 11:20 AM From: khmaio@earthlink.net To: DoktorMo@aol.com
How can the patient's rights be protected and still provide for necessary testing of drugs in the mentally ill? Who, if anyone, should make the decision for an incompetent patient regarding participation in a drug testing experiment?
There is no generic "the" mentally ill. There is however a commodity, "the" mentally ill, which is widely exploited. There have been many such "commodities" in history. Once one has retreated to an abstract "the", societies seem to offer that group to be expolited. Generally the exploited group has no political power, ergo the Tuskegee "study". Even the Salk vaccine was tested on people unable to consent.
If one is a "patient" are there not already ethics in place, or is the term just a convenient empty metaphor?
Should a person unable to consent be forced to participate? No. Whatever term someone wishes to employ, it amounts to force since consent cannot be obtained. Florida law accepts that infomed consent has been obtained when "sufficient" explanation has been given. "Sufficient" is a metaphor of force, since it will be defined by the person intent on forcing, not by the person forced.
Harold A. Maio,Consulting Editor Psychiatric Rehabilitation Journal Boston University
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Date: Tue, Apr 8, 2003 3:52 PM From: bpspiper@msn.com To: DoktorMo@aol.com
I believe that it is wrong to conduct experimental testing for unapproved drugs on the mentally ill without express consent from a legal guardian, power of attorney, or judgment of the state. As a nursing student we have been taught that our highest priority is to protect the rights of our patients. Through education we can help the families and guardians come to a better understanding of how pharmaceutical companies work to improve and or create new drugs that could better serve the people. With this education now comes the power of the families and guardians to decide what is in the best interest of the patient. We cannot arbitrarily stand by while others decide our fate. We have to stand up for the rights of those who cannot stand up for themselves. If we don't who will stand up for us if the time comes?
Becki Price
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Date: Mon, Oct 22, 2001 8:52 AM From: CBlades@JPMC.ORG To: DoktorMo@aol.com
Not all mentally ill people are incompetent. I think that has to be determined before you can make a blanket statement as to who can make the decision for their participation in a drug trial. Many mentally ill patients would welcome the chance even during stable periods, if it meant decreasing the effects that their illness has on their lives. Look at the Clozaril trials for instance...while there are great risks associated with this medication the benefits for the majority of the patients outweighed the risk. I believe we allow the patient to make the choice unless the court has declared them incompetent and if that is the case, give the information to the legal guardian and assist them in make the appropriate decision as needed.
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Date: Thu, Jan 11, 2001 5:46 PM From: mlammers3@home.com To: DoktorMo@aol.com
Using experimental drugs on persons who are mentally incompetent because of illness is not a clear cut issue. However, if the drugs are being designed to specifically treat their disease or disorder, and this disease or disorder often or always leads to mental incompetence, the treating physicians are really left with no choice but to test the drugs on these people. Certainly the drugs cannot be used on healthy people. I think the decision of whether or not these patients should be used in experimental drug testing should be left up to their relatives, who will hopefully act in the best interest of the patient.
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Date: Tue, May 19, 1998 3:44 PM From: sheilac@kalama.doe.Hawaii.Edu To: DoktorMo@aol.com
Pharmaceutical testing in the incompetent patients? This is a really tough issue. It's like a gamble, you test the drug on a person like a guinea pig, if it lives and does its purpose it works, but if the patient gets worse or dies it's a failure and you loose. I say let a family member make the decision for him or her. Discuss the drugs purpose and whats expected to happen, Also explain it's risk and possible side effects. Also explain what the patient may feel physically and mentally.
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Date: Sat, Jul 26, 1997 1:35 PM From: DocReading@sprintmail.com To: DoktorMo@aol.com
Mentally ill patients are not by definition incompetent to consent to drug testing. Many mentally ill patients do not lack the capacity to understand the purpose, nature, risks, benefits, and alternatives of the research. As a matter of fact, I have many patients (I am a Psychiatrist) who are more altruistic than their non-mentally ill designated counterparts. If a drug can be tested on willing and factually competent individuals, it should. Only if it can be proved that an illness renders all people who contract it incompetent to consent then legislation could be enacted to appoint a committee to decide based on the individual's premorbid preferences if possible whether or not to allow the person into the study. The principle of autonomy should rule whenever possible.
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Date: Wed, Apr 16, 1997 2:41 AM From: gottlieb@hp380.ist.unige.it (Prof. Alberto Gottlieb) To: DoktorMo@aol.com
The problem of consent to diagnostic and therapeutic procedures of incompetent individuals has not yet been solved adequately and you already ask about the consent relative to experimental therapy ?! It seems evident that caring for, let's say, a demented Alzheimer patient is quite easy when benefits prevail over risks by far :e.g.in case of arterial hypertension or acute appendicitis. If, on the contrary, performing diagnostic and therapeutic procedure entails a certain morbidity (annoying side effects) or mortality e.g. coronary disease, then every person deciding for the incompetent patient will be criticized , and perhaps also legally sued by relatives with conflicting interests , if things don't go straight. Deciding about new diagnostic or therapeutical procedures (namely drugs) to be applied in incompetent patients should start from the same point: the benefits either real or awaited (on serious scientific grounds)should prevail by far over risks. It must brought in mind however that only at the beginning of the dementing process, such as Alzheimer or Multiinfarctual dementia, a real benefit may be awaited from a therapy and it will be, when it will be, a stop to mental deterioration. It seems actually unbelievable to restore mental abilities that have been lost because the corresponding neuronal centers are atrophic and millions of neural cells and their fibers are absent. This stimulates drug researchers to focalize their efforts on the beginning of the dementia when the best resuls are perhaps attainable and, if attained, best measurable. But it is just the moment when patients usually are still competent and may be asked their consent about new drug treatments. I think morevover that in this period of initial restriction of mental capacity which does not intefere yet with the ability of caring about theirselves patients may be asked advanced directives about the future behaviors of the caregivers (deciding substitute) and the medical staff.
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Date: Thu, Dec 19, 1996 2:43 AM EDT From: BBrodie960@aol.com To: DoktorMo@aol.com
Society provides a surrogate decision maker for its immature and mentally incompetent members. To an extent, the rights of this unfortunate class are transferred to those close enough to them to act in a manner as similar as possible to the incompetent person. Usually, this is a family member, but it might be a friend, or even the state when that's the best society can come up with. It's not a perfect system, but more often than not, the designated decision maker acts in the incompetent individual's best interest and in a way that is reasonably similar to the way that individual would act if he or she were competent.
I think the testing of psychotropic drugs is so important that the risk of unnecessarily violating a person's right to make an informed decision is significantly outweighed by the benefit of making appropriately tested and effective drugs available to those who need them. (Not only does the mentally ill patient benefit from the drug, but society benefits from him or her taking the drug.)
I say, let the party designated to make any important healthcare decision on behalf ot the incompetent individual make the decision regarding participation in a drug study. The only exception I would make to this rule would be when the incompetent individual's guardian is the state because the state is least likely to know how the incompetent individual would act if he or she were competent.
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posted by Maurice Bernstein, M.D. @ 10:18:00 AM
6 comments
6 Comments:
Hi Maurice
I sit on a NHS research ethics committee over in Northern Ireland, so we consider this sort of question not infrequently when assessing applications that come before us.
In assessing whether or not someone is competent to consent for themselves in this sort of research you are correct to say that it depends on both them and the nature of the research. Personally if there is any doubt about their competency and the research involves risks then I prefer to play it safe by asking for their assent and the consent of someone else as well.
When they aren't competent at a minimum appropriate consent should be used. But I do think there is a fine line here, and certainly some worthwhile research should not be carried out because it imposes risks that the participants have not consented to.
It is of course a case by case decision.
What concerns me is a patient who has no capacity to give either consent or ability even to provide assent. Equipoise, where neither arm of a research project is known to be therapeutically superior in terms of efficacy or risks compared with eachother, is the type of research under consideration. One would think that direct and contemporary patient informed consent is necessary. Or on the other hand, in such a case, should any surrogate be given decision-making power for a research study where there may be no personal proven benefit despite significant risks being present? When the issue is simply deciding about providing an established drug with known history of efficacy and a known risk history, then certainly the surrogate should decide for that non-capacitated patient's best interest. I see that patient's best interest as a decision for non-participation in a study where equipoise is present. ..Maurice.
I see your point and agree that particularly in a situation of equipoise research with those unable to consent for themselves is difficult. But sometimes it is even difficult to determine whether equipoise is present.
To give one example (suitably altered) we recieved an application to try a drug that was used for another application with car crash victims who had had lung injuries. (Of whom 60% die) There was some evidence that the drug may be helpful, those who happened to be already on this drug when they had a car crash had significantly reduced death rates (30%) but it was unclear whether this was simply a statistical anomaly, a long term effect of the drug or something which could be gained by giving them the drug immediately after the crash.
This was particularly difficult because the nature of the study was such that getting consent from anyone would almost certainly jeopardise the study (due to timing) and getting informed consent would be impossible given the situation their next of kin would be in.
I should add that of course the drug did rarely have side effects that could be quite significant and include liver damage.
This was a tough case to decide upon, because there was some evidence that it may be beneficial to the patients, and they in many cases had little to lose, but consent was for all intents and purposes unobtainable...
Cheers
David
In the United States, we have regulations allowing emergency room research without consent but because of the burden of requirements, it is not applied much. I am sure if used, it would apply equally to the unconscious and the mentally ill patient who was unable to consent but it would have to be practiced in an life-threatenng emergency. Routine pharmacologic testing in the patient who is unable to consent of course is another matter. ..Maurice.
Dr. Bernstein, you certainly do know which questions to ask ...
First of all, I don't believe that experimental drugs should be used on anyone who doesn't stand a chance of benefiting from their usage.
Beyond that, I think that if the person can demonstrate an understanding of what is happening, then yes, of course they should be able to make that decision for themselves.
For those who are beyond the point of making that sort of decision, then I believe that if the physician feels that there's a chance it could help the patient, then he should use his best judgment ... just as he would do if the drug were not experimental.
I believe that "Routine Experimental Testing" should not be done at all without a patient's full understanding of what is being done, and of the possible consequences ...
Moof, you write "I don't believe that experimental drugs should be used on anyone who doesn't stand a chance of benefiting from their usage." Experimental drugs, I presume, means drugs whose efficacy and toxicity has not been fully established and that is why they are being tested in an experiment. In fact, in human studies, there should be equipoise between the two arms of an experiment (for example, the new drug vs placebo or the new drug vs old drug). Equipoise as defined in above comment is where neither arm of a research project is known to be therapeutically superior in terms of efficacy or risks compared with eachother. That means especially in a randomly controlled blinded trial where neither investigators nor subject know which arm is assigned to a subject, there is no intention for any subject to be benefitted from the drugs usage and no subject should ever be told that there would be personal therapeutic benefit from being a subject. Unfortunately, many patients, especially those with poorly treatable conditions, make the assumption they will be benefitted. It would be unethical for a physician or the researcher to make such a suggestion.
Because of the lack of benefit for the subject and the risk of complications or toxicity, all potential subjects should be given all the information available to decide if they want to participate. Participation would only be for altruistic reasons though occasionally there might be some nominal payment. ..Maurice.
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