quote:

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Subj: PolyHeme
Date: 10/12/04 12:02:34 PM Central Daylight Time
From: BLOODSUBSTITUTE@lumc.edu (BLOODSUBSTITUTE)
To: sndrake@aol.com

If you need a bracelet so that you may decline participation in the PolyHeme study please send us name, address and number of bracelets needed as a reply to this email.

THank You,
(name deleted)
Clinical Research Nurse

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I talked to a few people at work about this. So far, the first any of them have heard of this is from ME. Interesting, considering the hospital was required to do community education and outreach.

It pisses me off that I have to wear a bracelet to avoid the possibility of being a guinea pig. It pisses me off that the ACLU is apparently too busy fighting for the rights of guardians to end the lives of people like Terri Schiavo to view this as a threat to indivdual autonomy and privacy.

I'll probably order around 20 - Diane wants one and two other coworkers also want one so far.

For more information on this particular study, check out this thread.

For more info on the earlier study and how the press initially missed the connection between the consent waiver and the discontinued blood substitute study, check out Media hasn't put 2 and 2 together
(It's the second article on the page, after Mike Ervin's "Guinea Pigs Don't Get to Say 'No'".
 

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Posted by Dagonee (Member # 5818) on :
 
Wouldn't it be better to try to convince people to wear the bracelets if they want to participate?

Holy crap, this isn't right.

Dagonee
 

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Posted by sndrake (Member # 4941) on :
 
Well, Dag, I think a true concern for informed consent and respect for individual autonomy would lead one to that approach.

But considering how low-key their "education" and "outreach" efforts were, they probably wouldn't have gotten many people wearing bracelets unless they did some real work in getting out to the community.

This is about money and prestige. The company manufacturing the product being tested is based in the Chicago area. It brings prestige and money to the University Hospital. And the financial windfall will be astounding to the first company to have a substitute blood product to market that has been approved by the FDA. Which will also mean jobs and an improvement in the economy.

All you have to do is cut some corners on some basic human rights considerations...
 

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Posted by Defenestraitor (Member # 6907) on :
 
[zombie] Northfield Laboratories Incorporated is a benevolent corporation with the public interest at heart. PolyHeme® will not harm you. Take your plasma substitute... Taaaake iiiiit... [/zombie]

Do they expect the public to just forget about the last trial in '96? This is shocking.
 

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Posted by Dagonee (Member # 5818) on :
 
Hey, it's probably pretty low liability for them. Someone needs blood or plasma in an abulance, they're probably pretty messed up to start with. Hard to lose a wrongful death suit when you can say the patient probably would have died anyway.

I know artifical blood replacement is critical, and I know it will be a huge lifesaver some day if they get it working. But frankly this doesn't sound like the way to do it.

For any doctors/scientists: Can trauma be accurately categorized enough to produce meaningful results in a comparison study? How big a sample do you need to do that?

It'd be interesting to see if FDA regulations allowing the test would preempt state battery law in tort. Probably, but it'd be an interesting case.

Dagonee
 

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Posted by sndrake (Member # 4941) on :
 

quote:

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Do they expect the public to just forget about the last trial in '96?

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quote:

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Intravenous access and fluid resuscitation are standard. However, this practice has become controversial.
For many years, aggressive fluid administration has been advocated to normalize hypotension associated with severe hemorrhagic shock. Recent studies of urban patients with penetrating trauma have shown that mortality increases with these interventions; these findings call these practices into question.

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quote:

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I am writing to request a copy of the methods section of your trauma trial description. In particular, I am interested in learning the particulars of:
1) Number of subjects planned and over what period of time
2) Method of randomization of control and treatment group assignment of subjects
3) Types of conditions/precipitating events resulting in "hemorrhagic shock" that will be used in stratifying the sample (if any).

In addition, I would like to have details on whether this is considered a single blind (patient not informed of treatment/control group ssignment) or double blind (both patient and the care-givers unaware of treatment/control group assignment).

If this is not a double-blind study, could you please give me further details of methods you will use to control for potential biases in the care-givers' treatment of subjects including, but not limited to, their decisions related to assignment of patients to treatment or control groups.

Thank you for any of the above information you can provide. If you cannot provide this information, please inform me as to the name and address of the
responsible party to whom I should make my request under the Freedom of Information Act. If it is your opinion that the requested details of this study are not subject to disclosure under the Freedom of Information Act, please inform me of that in writing at the address below.

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quote:

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At least I suspect they are giving up on random assignment to groups and there's no way this is a double blind study, in which case you have to assume that there are biases in group assignment, and then control for those biases in some manner.

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quote:

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Just as I don't offer medical advice anymore here at Hatrack, I also don't offer opinions on issues of medical ethics.

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[from my edit above]

I don't weigh in here anymore. I do weigh in elsewhere, though. [That is, I'm cool with clarifying or giving additional information in either circumstance, but not with presenting my personal opinions of what should or should not be done. It is a position of humility which gives me tremendously improved mental health and decreased burnout. But in other contexts, I do speak my mind, and with great passion. ]

It's an important issue for discussion, that's for sure.

[ October 19, 2004, 12:01 AM: Message edited by: Sara Sasse ]
 

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Posted by Goody Scrivener (Member # 6742) on :
 
Wow, Loyola's involved in PolyHeme. I better make sure my mother knows so she can get her opt-out bracelets. She's got a number of medical issues and doesn't want to risk it by being given the artificial stuff, in addition to being an infusion therapy nurse and just not trusting it from the beginning. But when I ask her about it she gets all vague and incoherent, so I can't manage to get any real information from her.

Thanks for the info, Stephen.
 

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Posted by Boris (Member # 6935) on :
 
It seems, to me at least, that this is a study that's trying to go too fast. I don't know anything about how the law works on this matter, but I do know a screwed up scientific process when I see it. Logically, using consent-only, you would severely limit the number of cases that would involve the use of the blood substitute, and it would take longer to get satisfactory results. The problem, as I see it, is that people running this test don't seem to realize that there are PEOPLE having this blood substitute, and not lab rats. I think, also, that in order for them to have a consent only study, they would have to offer some kind of reason for people to consent to it. That would cost them money. So what I'm seeing, and I think this is the problem, is that this company is trying to cut corners. That's always bad from a scientific point of view. But, I guess the lure of money and prestige makes people forget that they're dealing with people...<shrug> No point to this message. Just rambling as usual.
 

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Posted by Boris (Member # 6935) on :
 
And just as a side not, maybe you should order a bracelet for each person in Illinois just to protest I wonder what they'd do with an order for however-many-million bracelets...
 

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Posted by Sara Sasse (Member # 6804) on :
 

quote:

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Studies of human subject must be approved not only by the FDA but also by the local institutional review board.

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Some hospitals, like Boston Medical Center, have decided not to participate in the study for the very reason discussed so extensively here: namely, that the study requires treatment with the blood substitute for a full 12 hours despite access to whole blood or (packed red blood cells) once arriving at the hospital.

FWIW, the FDA's regulation regarding exception from informed consent requirements for emergency research. I'm not sure if this had been posted in its entirety yet. This link also details the relevant responsibilities of Internal Review Boards.

Additional info from NoBlood.org:
- The company manufacturing and testing this product is described as previously "unprofitable."
- Each unit of PolyHeme requires two units of blood to make, although it lasts for 12 months instead of 42 days (still, adoption of this as standard care might well put yet more strain on the nation's blood supply, and we might have to rely on paid-for blood, which is notoriously more problematic from an infectious disease standpoint)

[ October 19, 2004, 12:26 AM: Message edited by: Sara Sasse ]
 

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Posted by Kwea (Member # 2199) on :
 
Sorry Sara, I am on my parents computer, and they came in and started asking me questions while I was reading your post....I must have missed the last part of it, if I had seen it I wouldn't have asked.

Kwea
 

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Posted by sndrake (Member # 4941) on :
 
I'll post more tomorrow. I try not to get to get into posting stuff that gets me worked up emotionally and/or intellectually at night. That way lies insomnia.

Thanks to all so far. I was drawing on the protocols from memory. I don't know how much research time I'll have this week - I'm getting ready for a week of conference/workshop out of state and flying out Saturday.

I do know I'm going to order at least a hundred of these bracelets. I'll probably do some education with some of the people I know in the area - we're right next to Maywood, where the hospital is located.

It's obvious Loyola didn't do a very good job with the outreach. A couple of blurbs in the local news doesn't cut it. They also don't say how many churches they went to or how they went about it. (I watch the news, read the paper and I don't go to church. The only thing I ever saw was a mention of "planned" community outreach when the story broke.)

Besides, the real way to measure the effectiveness of outreach is by your turnout and response rate. Loyola doesn't seem to consider the low turnout rate to be an indication that their efforts were insufficient.

The product may or may not be safe. It doesn't matter. I was raised in that short period of time in our society when researchers were reined in by severe limitations on what they could do in the name of research. As an adult, I worked with people who were part of a population that were callously exploited by medical professionals when the restrictions were less severe.

And whether it's justified or not is not a decision that belongs in the hands of a relatively few professionals with similar interests. Something that touches on the right to say "no" should involve the whole community - not just a bunch of bioethicists, big Pharma reps and FDA bureaucrats.
 

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Posted by Sara Sasse (Member # 6804) on :
 
No worries, Kwea.

[I misread your post as stating your computer crashed. Regardless, I was probably editing as you were reading.]

I put on my information-hat here regarding medical matters. Otherwise, I work myself up into a lather in the most unproductive of ways.

[ October 19, 2004, 12:39 AM: Message edited by: Sara Sasse ]
 

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Posted by Bob the Lawyer (Member # 3278) on :
 
Let's just cut the crap here, Boris. Of course the scientists realize that these are real people getting the treatment. Having been involved in pharmaceutical development and been involved in clinical trials (on artificial blood products, among other things) the notion that scientists (and the company) don't care is absurd. Even if it suits your cynical purpose to abstract away their humanity the simple cost of killing people is enough to close a project (not necessarily enough to close a product already on the market, but enough to shut down development of one that isn't currently brining in profit).

So many issues in this thread...

I agree with Steven that people should be able to opt out and that a greater effort should have been made to alert the public. But how do you do that in this day and age that has no central meeting place for a community? Post flyers? Deliver them door to door? Door to door might have been the best approach although most costly.

Dags, determining the statistical significance of this would be a nightmare, no matter what method you used. While I don’t know how the product is intended to be used (dosages, half-life, time after injury that it needs to be administered, etc.) I’d be that the sample size would be obscene. Most tests are small, 5 or 6 rats, 2-dozen people, things like that. This would probably be up to the hundreds range? Honestly, that’s total guesswork and pulling a number out of me arse. Without seeing their prelim data and knowing more about this product I can’t offer you anything meaningful.

I don’t agree with you, Bob, that this is necessarily "bad" science. I would certainly agree that it isn’t "ideal" science (so blasting them back to stats 101 probably won’t do much good. Second or third year stats at least ) but what else would you have them do? Since you’re doing the blasting I’m curious to hear how you will design the test for them. Or would you just can it completely?

The usual treatments are available, rivka. Read the study. There is a saline+control sample that will be administered to women who are pregnant and people who are already receiving CPR. The control will be there. So if you’re Jane paramedic and you use the FauxBlood and lo, the patient’s blood pressure is still crashing you can switch out. It’s unlikely that paramedics will make the decision to switch, however, as the currently accepted immediate threat from blood loss is a severe drop in blood volume (which this would treat). Once you get to the hospital you can shunt blood to critical areas and fill ‘er up with blood (be it whole blood or (much more rarely) washed RBCs+rejuvesol) if deemed necessary. Further, ambulances don’t carry blood products anyway (to the best of my knowledge. Why would they?) And using saline isn't all that contested. As in, it's still extremely common and while data may be coming in that suggests it may not be the optimal treatment there isn't enough to instigate a wholesale shift in treatment. The Canadian article, in fact, seems to agree with this (in their stepwise treatment they suggest a crystalloid/colloid via IV taking place before an actual blood transfusion. I admit I only skimmed the review, there may have been contradicting this later, but it would come after their suggested treatment section).

Rabbit, the FAQ clearly states that rescue measures are allowed and that there have been 5 previous clinical trials where I assume it passed all necessary tox/carc tests as well as showed a statistically significant increase in patient survival in a small test sample.

Well I understand the dubious ethics, Steven, what's you're alternative? Tagging the hundreds of thousands of people necessary to ensure enough people wearing armbands of consent wind up in ambulances would be prohibitively costly and every study that requires uninformed consent would have to be canned. That's a lot more studies than just blood replacement therapies. Of course, it's fine and consistent if you're pro cancelling them all, I'm just making sure that's what you're calling for.
 

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Posted by rivka (Member # 4859) on :
 
*sighs* *resets BtL's sarcasmometer*

My point was (or was meant to be), that I don't see how this study can possibly meet that guideline. That is, clearly proven treatments ARE available. But the guideline says, "In accordance with the regulations, an exception can be granted if patients are in a life-threatening situation, available treatments are unproven or unsatisfactory, and the collection of valid scientific evidence is necessary to determine the safety and effectiveness of the particular intervention."

Life-threatening, check; collecting evidence necessary to determine safety and effectiveness, check; available treatments unproven or unsatisfactory? sure doesn't sound like it.
 

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Posted by Bob the Lawyer (Member # 3278) on :
 
I would disagree with you on that point. Current treatments are unsatisfactory. There's a lot of room for improvement in the treatment of trauma victims (leading cause of death for those <45 and all) and having an alternative to blood with this long a shelf life would have staggeringly positive effects.

I assume you're arguing that the current number of people dying is acceptable and there's no need to decrease that number. How then, do we decide how far is enough progress?
 

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Posted by rivka (Member # 4859) on :
 
I see your point. I'm not sure I agree . . . I need to think on it.
 

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Posted by Sara Sasse (Member # 6804) on :
 
I believe saline is considered "unsatisfactory" because it has no oxygen-carrying capability. That is, although it is the best we have, it is not good enough, because although it adds necessary volume*, it ends up diluting out the oxygen delivered to the brain, kidneys, and other critical organs. Lack of oxygen is a trigger for multiple organ system failure.

*Volume is key because the heart has to have something to pump against. The heart goes into "forward failure" when the volume of fluid in the circulatory system is too low, so even if the fluid can carry oxygen, it cannot be pumped. The heart fails. However, the saline makes what blood is left progressively ineffective, because it is the amount of oxygen in the circulatory fluid that primarily determines whether organs fail.

There are other reasons to focus on volume, such as the shunting processes triggered by baroreceptors which sense very low pressures. The kidneys kick into overdrive in order to save the brain, but this happens at the expense of other organs. Still, the heart failure is (I think) the biggest immediate issue. The rest of it adds up too, though.
 

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Posted by Bob the Lawyer (Member # 3278) on :
 
I think we're saying more or less the same thing here, Sara. That being, saline is the best we've got there aren't really any acceptable alternatives right now. It's better than nothing, anyway.

All of these posts have occurred post midnight. I'm deeply impressed by how coherent I'm being
 

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Posted by Sara Sasse (Member # 6804) on :
 
[Edit: just saw your post, BtL. Yes, I think we are covering some of the same ground.]

You end up giving saline because you have to give something -- without enough to fill it, the heart just ineffectively quivers and shakes, then stops.

But the saline overloads the system with fluid that can't do what you most need it to do -- deliver oxygen. And, after you have a messload of saline filling up the circulation, you cannot give too much more blood too quickly once you get to the hospital, because the heart and lungs can get overloaded with fluid and stop functioning.

You've already filled up the tank with somthing you can't really use. Getting it back out safely means doing an exchange transfusion, where you take out circulatory fluid from one IV while simultaneously replacing it through another -- and this is a much more complicated, arduous, and difficult manuever than it sounds. Takes forever, too. (Here is where the oxygen-carrying blood substitute might play a critical role -- if it carries oxygen effectively, then you wouldn't have the same pressure to jam a lot of blood in and throw the heart into congestive failure or the lungs into pulmonary edema, both of which happen a lot in current care.)

Status quo: Damned if you do, damned if you don't. Thus the "unsatisfactory."

Very complicated.

[I wonder why they are insisting on the 12 hour use of the PolyHeme if possible? At this point, wouldn't demonstrating effectiveness in the field be sufficient to establish that this would be a better alternative for paramedic use? Why not do trials just in the field for now, and then expand to additional care if it seems appropriate? True, they are trying to get a thorough assessment of the extremes one might encounter in the field, but why now? Hmmm.

I also wonder how difficult it would be to find out exactly what public outreach was done. I wonder if that information is readily accessible in more than a cursory format.]

[ October 19, 2004, 02:18 AM: Message edited by: Sara Sasse ]
 

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Posted by Sara Sasse (Member # 6804) on :
 
Paramedics don't carry blood in the ambulance because they can't type & cross for it without a laboratory, it requires too specific an environment to maintain in a vehicle, there is not enough O negative to go around, and the current regulation of blood (doublechecks and triplechecks of ID for safety's sake) isn't feasible in the field.
 

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Posted by Bob_Scopatz (Member # 1227) on :
 
Sara,
Thanks!

I couldn't find those details on the PolyHeme Trauma Trial website, so thanks very much for the info and links.

Multivariate analyses on what variables? This gets at my question about stratifying the sample. Surely they are after a decent mix of causal conditions/events. So, they probably have some sort of selection criterion in place as well, not just post analysis and leave it to "chance" in the field.

The alternate days thing doesn't really do it for me if there's any part of the decision left to the discretion of the EMTs/paramedics, as I'm sure there must be. I mean, if I'm in hemorrhagic shock but have any obvious contraindication, I figure they'll play it safe. But do they know about my elevated blood pressure (PolyHeme's website says it may cause extreme high BPs or something like that, right?)? Do they know who is a pack-a-day smoker and who isn't?

Certainly, this product may save lives. What I may have an objection to is the methodology. I'm not going to comment on the ethics either.

At this point I'm just interested in how they think this is a good methodology.

Treatment bias in single bind experiments is a pretty well documented phenomenon. Do they really believe that because it's medical practitioners doing the treatments that this experiment is immune from such factors?
 

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Posted by Sara Sasse (Member # 6804) on :
 

quote:

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Multivariate analyses on what variables?

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quote:

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This gets at my question about stratifying the sample. Surely they are after a decent mix of causal conditions/events. So, they probably have some sort of selection criterion in place as well, not just post analysis and leave it to "chance" in the field.

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quote:

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Under the current standard of care, paramedics will start IVs for trauma patients with saline solutions that may replace the volume of blood, helping to raise the blood pressure but not the oxygen, which is needed to keep vital organs vital. At hospitals participating in the trial, paramedics will assess trauma patients and if they meet the criteria, a sealed envelope will be opened containing either PolyHeme or a saline solution. [from the NoBlood.org link above]

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Treatment bias in single bind experiments is a pretty well documented phenomenon. Do they really believe that because it's medical practitioners doing the treatments that this experiment is immune from such factors?

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I think it's a matter of doing the best they can. How else would one design a trauma study for the field? (Sometimes a less-than-ideal study is the only one feasible. Even if they could color the saline, it would have a different viscosity.) Having the package presealed and trackable by ID means that it would be clear if persons had been assigned to saline or PolyHeme, regardless of what they actually got. So the issue of assignment is randomized to the patient, and non-random treatment afterward would be documented.
 

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Posted by Hobbes (Member # 433) on :
 
Sara's on a posting rampage!

Hobbes
 

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Posted by Sara Sasse (Member # 6804) on :
 
I am avoiding work, Hobbes! I should be writing my article for the Wisconsin Medical Journal.

(In my defense, I considered detailing the oncotic benefits of PolyHeme as opposed to saline, but scrapped it for time and space reasons. Suffice it to say that there are many more reasons why saline would be considered "unsatisfactory" as a trauma volume replacement, all things considered.)

[Edit: deleted two items of the triple-post. How'd that happen?]

[ October 19, 2004, 08:34 AM: Message edited by: Sara Sasse ]
 

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Posted by Farmgirl (Member # 5567) on :
 

quote:

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I believe (and EMTs or similar can correct me if I am mistaken) that the standard of care in ambulances includes whole (O neg) blood.

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Okay, I haven't read ALL of the posts after this, so this may have already been answered...

But from my personal experience working on ambulances, we never carried blood or blood substitute at all. It as basic saline to increase blood volume, or nothing. There is no way I can see where we would have a way to 1) properly store blood products on an ambulance, and 2) know which type to use, in the time given. Usually you just add fluids to keep their volume up until you can make it to the hospital.
Now, this may be different on things like air ambulances traveling from one hospital to another that have time to preparation for the patient. I don't know.

Don't Jehovah's witnesses, who don't believe in blood transfusions, have to wear a bracelet saying as much? I always wondered about that.

I agree that they should only have you wear a bracelet if you CHOOSE to participate, and anyone not wearing one would get the whole blood as before.

FG
 

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Posted by Sara Sasse (Member # 6804) on :
 
O negative wouldn't need to be type & crossed, as it can be given to anyone, but it is always in verrry short supply. The storage requirements are also a real issue, for O neg and for the other types (which would require a full type & cross).

BTW, Jehovah's Witnesses can be given PolyHeme; i.e., it is deemed a matter of personal choice by the associate director of Jehovah's Witnesses hospital information services.

[ October 19, 2004, 09:56 AM: Message edited by: Sara Sasse ]
 

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Posted by Farmgirl (Member # 5567) on :
 
Seven more, Sara -- you can post your first landmark under this username!

FG
 

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Posted by sndrake (Member # 4941) on :
 
I respect the desire to refrain from commentary on the ethics of this project, but here at "ground zero" the ethics/rights aspects are the central ones. The other issues around safety, study design, etc. are secondary. Not just me, but for others I've talked to.

We all resent the fact that an Institutional Review Board has the power to foist this on us and has the power to put the burden on us to provide proof we don't want to "participate." And the fact that their "community education" looks like it was pretty half-assed makes it look like they wanted to minimize the number of people who would order bracelets.

I'm going to try to get material together for people here at work, but I have told them that the product may very well turn out to be both safe and beneficial. But they don't call it an "experiment" for nothing, do they?

I have been unable to find any mention of the start date of the study or its duration on Loyola's website - did anyone else see anything? That's pretty relevant information, I would think.

[ October 19, 2004, 10:17 AM: Message edited by: sndrake ]
 

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Posted by sndrake (Member # 4941) on :
 
I found a pretty comprehensive article on Wired News from April of this year. I really question one comment in it, though. It describes the ethics community as "divided" on the wisdom of this study. Here in Chicago, which is swarming with bioethicists, none came forward to criticize the study.

Here's a link to page one of Fake Blood, Real Controversy

The second page has quotes from an ethicist who was willing to criticize the study in particular and the consent waiver in general. The ethicist is George Annas, who is not someone I agree with on many things. But he does have a refreshing willingness to break from the herd now and then:

quote:

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In 1998, a company called Baxter Healthcare launched the first major study of a blood substitute using the loophole. According to news reports, nearly half of 52 patients died and the study was halted.

George Annas, a medical ethicist at Boston University, criticized that study and thinks the people behind PolyHeme are making the same ethical errors. It's wrong to "treat human beings like animals, like laboratory animals," he said. "People have a right not to be research subjects."

The right to opt out by wearing a bracelet isn't enough, he added, although he declined to offer a better system. "It should be up to the study sponsor to figure out how to do the study ethically, not the people who criticize the study."

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I really am curious, Steven, to know if you're pro cancelling all work on all drugs that circumvent informed consent. Like I said, that's a lot of drugs. If you want to can them all and you feel we've progressed as far as we need to in this field (and the question of how much progress is necessary is one that pops up a lot) than that's one thing. Otherwise it sounds a lot like "don't throw your junk in my back yard."

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The crux of the disagreement, I guess, is whether or not one believes that it's possible to get enough people wearing bracelets of consent that enough would be in amulances in trauma situations that the study could go forward.

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First, I am grateful to see that my email to your site wasn't trashed as I thought it must have been, although I think it's strange you didn't email me about any of the community forums you held.

Second, a number of my coworkers have expressed interest in the bracelet as well, our workplace is right next door to Maywood. Please give me the start date of this study, what the bracelets consist of (are they plastic ones we may need to replace from time to time?), and how long the study will last once it's started.

I sincerely hope the reply to this email is speedier than the reply to my last one.

Stephen Drake
Research Analyst
Not Dead Yet
7521 Madison St.
Forest Park, IL 60130
http://www.notdeadyet.org

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Sorry for badgering you, Steven (Steve?). It was neither fair nor did it really help the thread.

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BtL,

It's "Stephen" or "Steve" but I don't bother to go around correcting people unless they ask as you have.

In my work, one thing I can't afford to have is a thin skin. Variations on the argument you threw up have been used in all seriousness by ethicists of ill repute in articles defending this practice as well as in comments in the press.

The "straw man" is not a stranger in bioethics.

There are some other arguments that have been used to promote this waiver that are even more interesting and might make for an interesting discussion with Bob Scopatz the traffic safety guy, and might actually serve as an excuse to continue a brief discussion he and I had at KamaCon.
 

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Posted by Dan_raven (Member # 3383) on :
 
What I found strange about this whole thing.

This is for emergency services involving major loss of blood.

Like when you, say, slit your wrist?

What happens when you accidently gash your wrist and cut the freaking bracelet?

What are the odds of a temporary bracelet surviving a major auto accident where this service would be required?
 

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Posted by sndrake (Member # 4941) on :
 
Well, guess what? I did some more searching and found a release on the Loyola site announcing the study:

Loyola decides to test new blood substitute

quote:

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MAYWOOD, Ill. – Loyola University Health System plans to test PolyHeme®, an investigational oxygen-carrying blood substitute designed to increase survival of critically injured and bleeding trauma patients at the scene of injury, beginning July 1, 2004, as part of a national clinical trial.

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Got that? If this is true, the study has been going on since July. I submitted my objections to being a participant via the website many months ago.

They emailed me a week ago with an offer for a bracelet.

Are they being this thorough with the rest of the study?

I think this may be grounds for a formal complaint for noncompliance with their own protocol. More tomorrow - I have to talk to some folks about filing a formal complaint and maybe going to the press if this start date is true.
 

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Posted by Sara Sasse (Member # 6804) on :
 
Sure. Art Caplan from the last blood trial and from the current one (see quotes below).

quote:

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[January 18, 1999] Some say such notification cannot replace direct consent from patients or their relatives.

"Public notification means nothing," said Dr. Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania. "I know people are enamored of it, but it means nothing."

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[September 12, 2004] Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, said it makes sense to allow some research on people who can't give consent, but there should be a plan to compensate loved ones of study participants who die.

In the 1990s, research on a chemically different blood substitute was halted after recipients died at a higher rate than a control group.

Caplan also said meetings attracting a few hundred people don't seem to be enough to gain community consent, especially if hundreds of thousands are potential participants in the study.

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quote:

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[February 1999] Given the availability of human blood, it is not clear that the artificial blood research meets the requirement that the research offer similar benefit to standard care, so that subjects could be exposed to this level of research risk without consent. However this point is answered, the subjects were grievously harmed as a result of the research, pointing out the importance and difficulty of protecting the rights of research subjects who do not give their consent.

To do so, we must have even greater confidence that the risks are outweighed by potential benefits. We must not allow community notification to take the place of efforts to find family members who can consent to participation on behalf of their loved ones. And we must create ways to allow members of communities to make clear that they choose *not* to participate in "no-consent" research -- a sort of informed refusal, in advance. The model of advance directives for the end of life, such as living wills, serves as an example for how this could be accomplished.
...
There are important benefits to us all from the information gained by medical research. But carrying out research on our fellow citizens is a privilege -- a privilege that rests on trust. This trust is fostered when subjects and potential subjects understand what research entails, and when society believes that the rights and interests of subjects are served.

---

Some bioethicists have also published in opposition to nonconsensual blood substitute trials both as books and as academic articles. Amazon and Medline searches would probably find them, should you be interested.

[ October 19, 2004, 06:50 PM: Message edited by: Sara Sasse ]
 

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Posted by Sara Sasse (Member # 6804) on :
 
The study was put on hold for a while. I don't know the actual start date now.

Study of blood substitute put on hold to train paramedics

[ October 19, 2004, 06:47 PM: Message edited by: Sara Sasse ]
 

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Posted by TMedina (Member # 6649) on :
 
Ya know, paramedics are not doctors. I don't think they should be the ones to decide whether or not the standard of "conventional techniques would have been ineffective" has been met.

-Trevor
 

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Posted by Sara Sasse (Member # 6804) on :
 
I'm confused as to your specific reference, T?

(And I'm all tired and achy. But I've hit 1005. I dedicate the 1000th to Farmgirl! )

[ October 19, 2004, 07:13 PM: Message edited by: Sara Sasse ]
 

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Posted by Bob_Scopatz (Member # 1227) on :
 
Sara,

I don't think that any amount of multivariate analysis can correct for unknown/undocumented selection bias. That's my concern -- that the best methodology they could possibly come up with for this trial would still be bad from a scientific methodology point of view.

I understand the "do the best your can" approach to things, but is this truly the best that can be done, or is it simply the best that can be done within a specified cost parameter?

[ October 19, 2004, 08:29 PM: Message edited by: Bob_Scopatz ]
 

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Posted by rivka (Member # 4859) on :
 
While I am still undecided as to the ethics of the study, as is, not to mention its ability to get meaningful results . . . I have thought quite a bit about BtL and Sara's point as to the lack of a current good treatment alternative.

Too bad I don't live in the study area. I think I would actually be willing to wear a bracelet that said I would participate (at least, after I checked with my personal physician, to be sure there's no reason why I shouldn't).
 

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Posted by Dagonee (Member # 5818) on :
 
I'd likely wear a bracelet allowing the study as well, with the same caveat.

Dagonee
 

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Posted by Bob_Scopatz (Member # 1227) on :
 
I'd volunteer as well.

See, I think they'd actually have a fairly easy time of getting volunteers if they went out into the community and said "we're going to have this stuff available on ambulances. If you want to have the potentially life-saving treatment, wear this bright orange wrist band.

Oh well, it'd take longer and they'd have to canvass...
 

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Posted by Kwea (Member # 2199) on :
 
Or you could continue to test it using informed consent protocols, until more was known.

Kwea

[ October 19, 2004, 11:02 PM: Message edited by: Kwea ]
 

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Posted by Dagonee (Member # 5818) on :
 
I think that's what rivka, Bob, and I were talking about - a hypothetical opt-in study which would provide for consent.

Unless you're talking about posts above ours, in which case, never mind.

Dagonee
 

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Posted by Sara Sasse (Member # 6804) on :
 

quote:

---

I understand the "do the best your can" approach to things, but is this truly the best that can be done, or is it simply the best that can be done within a specified cost parameter?

---

quote:

---

I don't think that any amount of multivariate analysis can correct for unknown/undocumented selection bias. That's my concern -- that the best methodology they could possibly come up with for this trial would still be bad from a scientific methodology point of view.

---

I confess you have completely lost me here. If the factors are "unknown/undocumented," how could you use them to stratify the sample? But if they are known, why can't they be controlled for in the analysis?

You may not get the most representative sample, but that's the best you can do without going out an inflicting the trauma yourself. At least the limitations of the sample can be addressed, insofar as they are known. If they are not known, then they cannot be addressed anyway.

Yes?

[ October 20, 2004, 01:21 AM: Message edited by: Sara Sasse ]
 

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Posted by Bob_Scopatz (Member # 1227) on :
 
Hi Sara,

The purposeful stratification of the sample yields better control than post-facto multivariate analysis because you aren't looking at the data and saying "well, we got too few of those to test the influence, so combine with these others."

I am, of course, assuming they'll have small counts in some of the cells of a table of desired trauma types.

I would think they'd at least have an idea going into it of what they'd like to stratify on if they had the chance.

The problem with unknowns isn't that you can ignore them. It's that they have unknown/unknowable effects on your outcome. It's the same as the third-variable problem in correlation analysis. You're trying to make causal attributions between x and y, but you have some unknown "z" in there that's really the cause of all the differences you see between groups.

One such thing is selection bias. Sometimes selection bias is obvious, but in other cases, it's just there and you have no way of knowing whether it had an effect or how big that effect is.

That's why you have to avoid it methodologically.

From what I've heard so far, this study isn't going to be able to do that. If there's discretion in the initial administration of the fake blood, then there's selection bias. That's not questionable, I think. No matter how well they train the paramedics, it's going to end up that the choice of who got the treatment and who didn't was affected by things other than what the study sponsors told them.

Since that's the case, you have to always ask whether the differences between groups at the instant that decision was made might not have affected the outcome.

When the people choosing group assignment know the desired outcome of the study, for example, they almost always bias their choices in favor of having the study come out "positive."

This is not a double blind study, so assignmment bias is almost guaranteed.
 

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Posted by Sara Sasse (Member # 6804) on :
 
Hey, Bob.

quote:

---

If there's discretion in the initial administration of the fake blood, then there's selection bias.

---

quote:

---

The purposeful stratification of the sample yields better control than post-facto multivariate analysis because you aren't looking at the data and saying "well, we got too few of those to test the influence, so combine with these others."

---

quote:

---

The problem with unknowns isn't that you can ignore them. It's that they have unknown/unknowable effects on your outcome. It's the same as the third-variable problem in correlation analysis. You're trying to make causal attributions between x and y, but you have some unknown "z" in there that's really the cause of all the differences you see between groups.

---

quote:

---

I wonder if it could be argued that this stuff is actually safer than blood. Apart from blood types, there can be some really weird incompatibilities and fatal reactions with whole blood.

---

quote:

---

The viral risks associated with blood transfusions, already reduced by extensive donation screening tests, are greatly minimized during the haemoglobin therapeutic manufacturing process by rigorous viral-inactivation procedures. Some chemically stabilized haemoglobin solutions, such as diaspirin cross-linked haemoglobin (DCLHb or HemAssistâ„¢, Baxter Health-care Corporation, Chicago, Illinois, USA) are subjected to ultrafiltration and heat treatment during the manufacturing process to inactivate viruses [4]. Other human haemoglobin-based products are currently being developed, including pyridoxylated and glutaraldehyde polymerised haemoglobin (PolyHemeâ„¢, Northfield Laboratories Inc, Evanston, Illinois, USA)...
...
Furthermore, infectious agents present in animal blood, such as the bovine spongiform encephalopathy prion, are not as well characterized and therefore are more difficult to detect than those in human blood. ... [But] In addition, the specific purification techniques used may be able to eliminate the protein responsible for bovine spongiform encephalopathy transmission, even though the nature of the protein is unknown.
...
[And in further research:]
Recombinant technology is also being investigated to engineer oxygen-carrying solutions. These techniques allow flexibility in product design, enabling haemoglobin molecules to be modified to address specific clinical needs. In addition, many of the potential side effects of bovine-sourced products, or indeed the sourcing complications associated with human red blood cells, may be avoided by using recombinant technology.
...
The possibility of obtaining haemoglobin from transgenic tobacco plants was recently reported [10].

[4]Farmer M, Ebeling A, Marshall T, et al. Validation of virus inactivation by heat treatment in the manufacture of diaspirin crosslinked hemoglobin. Biomater Artif Cells Immobil Biotechnol 1992;20:429–433.

[10]Dieryck W, Pagnier J, Poyart C, et al. Human haemoglobin from transgenic tobacco. Nature 1997;386:29–30.

---

(Eventual blood substitute through the extraction of hemoglobin from tobacco leaves? It was in Nature 1997, apparently.)

[ October 20, 2004, 12:49 PM: Message edited by: Sara Sasse ]
 

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Posted by MrSquicky (Member # 1802) on :
 
pooka,
That's the idea that I was trying to determine with my blood/saline experiement above. I think that there are two separate ethical issues.

First, is it ever right to perform experiments on people without their prior knowledge or consent?

Second, if this is not absolutely wrong, what conditions make it ok or not ok?

If people are ethically opposed in the first condition (which is what many people's remarks seemed to me to be suggesting), then they are not going to agree with this. But they are also not going to agree with nearly all trauma research and research from a host of other situations.

If instead they aren't absolutely opposed to this research (which, despite what it seems that people are saying, I think is the actual truth), then what are the aspects of this situation that they think makes it ok/not ok?

I think that it comes down in large part to a question of risk and of good faith on the part of the peopel doing the testing. If the PolyHeme has been extensively tested and, from this testing, there is a reasonable expectation that it's use in trauma situations carries little risk and the people who are running the experiment are operating in good faith with respect to the subjects of the experiment, I'd most likely not have ethical issues with this being a non-consensual experiment.

However, as a social scientist, I have a definite bias. As most social science experiements lose their validity if the subject know what the research is about, social scientists, by necessity, don't regard informed consent an ethical necessity as long as there is rigorous good faith on the part of the experimenter. It's possible that my ethical standards differ from other peoples and that they affect the way I see this situation. So, I'm interested in where people's objections to this experiment rest.
 

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Posted by Sara Sasse (Member # 6804) on :
 
I'm not sure it would be feasible to get true informed consent on site at a trauma, regardless.

"Hi. You [or your husband, or daughter, or whoever] is in shock and needs IV fluids or will probably die. We have a study going on where we are comparing a blood substitute that we think is more effective to saline. Mind if we enroll you [or ...] in the study? You might get the new stuff or you might get standard saline, it just depends. Oh, and you have about 30 seconds to decide, so no time for questions."

I mean, you might have more than 30 seconds, but not much more.

The only tenable way to get real informed consent would seem to me to be through a much more extensive public information campaign so that people are really familiar with the study before being put in the crunch. And if you are going to do that extensive a public relations campaign, you might as well have opt-in bracelets, anyway. Otherwise, the "informed consent" you get before starting the protocol would be a joke. Who, if one's loved one or self is dying, can really process this kind of information?

"Informed"? "Consent"? Or just mind-numbed and unthinking desperation?
 

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Posted by sndrake (Member # 4941) on :
 
:kind of obsessing on the reality of having to wear a bracelet for a year if I want to make absolutely sure I don't end up a guinea pig:

I'll try to write more later, but I haven't had any reply to my email to Loyola. In regard to keeping the community informed, shouldn't there be something on the site announcing the start date??

The more I read about this, the more convinced I am that it's not just paranoia on my part that leads me to believe this "community education" stuff was designed to be a sham. I read the FDA regs and they are incredibly nonspecific about what the information campaign should consist of.

And no plan to evaluate its effectiveness...

Like, if you hired a pollster now to ask what people knew about the study, what would the response be? If the level of knowledge is low, it means the efforts were a failure.

But, as I said, evaluation isn't part of the FDA requirements.

Which leads me to believe it's all a meaningless CYA effort and was designed that way. (Art Caplan seemed to be saying the same thing, but he doesn't have to back up his statements or his reasoning. )

(In case y'all didn't notice, btw, this change in the FDA regs happened during the Clinton administration.)

PS: Any response to your request, Bob?

[ October 20, 2004, 04:11 PM: Message edited by: sndrake ]
 

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Posted by Sara Sasse (Member # 6804) on :
 
Caplan and others in the Project on Informed Consent criticized the changes on informed consent in an article in a late 1998 edition of JAMA. That might be a useful resource.

And in reading back through the thread, I picked up on this:

quote:

---

The others aren't really in the "mainstream" of bioethics, though - especially Shamoo.

---

Adil Shamoo, PhD, is the director of CIRCARE, the Citizens For Responsible Care and Research group. Shamoo himself has published more than 100 articles, including in the American Journal of Bioethics, Neuroscience, and the Cambridge Quarterly of Healthcare Ethics. He was previously the chair of the Department of Biochemistry and Molecular Biology at U Maryland as well as maintaining affiliation with its Center for Biomedical Ethics.

He has chaired nine international conferences on ethics in research. He has published and testified before both Congress and the National Bioethics Advisory Committee about research on those with mental and physical disabilities.

Jeez, Stephen, what are your requirements for being mainstream?

You need to meet some new bioethicists. There is a whole world out there beyond Leon Kass.

[ October 20, 2004, 05:06 PM: Message edited by: Sara Sasse ]
 

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Posted by sndrake (Member # 4941) on :
 

quote:

---

You need to meet some new bioethicists. There is a whole world out there beyond Leon Kass.

---

Not-so-oddly, I have never met Kass. He has about as much interest in and/or respect for the disability rights perspective as Caplan, Kahn, etc. Living here in the Chicago area for the past 8 years, I don't get a sense of him as a dominant presence, although that may have been true at one time.

I have met George Annas - several years ago. He seemed to appreciate - at the time - both NDY and some points I made during a Q&A during a euthanasia conference at Harvard (we were not part of the conference and protested it).
His enchantment with NDY was probably short-lived - and when it comes right down to it, he's probably more in sync with other bioethicists in terms of who he thinks should be heard.

I also have had contact with Jeff Kahn. If memory serves, he actually called me, because we were embarrassing him and his center when they allowed a pro-euthanasia group to co-opt their conference on assisted suicide. (Long story, but he was obviously more upset with me and NDY for highlighting what happened than what Death With Dignity National Center did.)

No direct contact with Caplan, except to see him glaring at us from his seat on a panel discussing Kevorkian. (in spite of the fact that Kevorkian's body count consisted of mostly nonterminally-ill people with disabilities, there were no disability advocates invited.) Everyone on that panel resented our presence and sometimes outspoken behavior - except for Clarence Page, who was also the only minority person on the panel. He ended up writing a column about us.
(That's the same event I shouted Mike Wallace down when he made a really outrageous statement, but that's another story.)

And, of course, you already know what kind of an impression I made on Catholic ethicist Kevin O'Rourke.

Edit to add: Peter Singer - how could I forget? I annoyed the heck out of him! (and more annoyance to come next month )

See, Sara, I get to meet all kinds of interesting people.

But not Leon Kass. And it's not likely it will happen, either.

Edit to add: Steven Miles doesn't like me very much, either.

[ October 20, 2004, 05:49 PM: Message edited by: sndrake ]
 

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Posted by Sara Sasse (Member # 6804) on :
 
Were you unfamiliar with Shamoo?
 

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Posted by sndrake (Member # 4941) on :
 
Two additions to the list:

Was up against Glenn McGee once on a now-defunt newstalk show. We did a good job of annoying each other.

Susan Wolf: she also called me in regard to the co-opted conference. I respect her work, but that almost puts her out of the mainstream by definition.

David Mayo: Debated him.

(Hmmm... I have more bioethics contacts in Minnesota than I do in Illinois)

Illinois bioethicists I have met:

Kathryn Montgomery
Mark Kuczewski
Todd Chambers

Kuczewski's an interesting case - he is carving out a niche for himself in "disability and bioethics" but has a great deal of disdain for disability advocates - not just me or NDY-affiliated people.
 

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Posted by sndrake (Member # 4941) on :
 
I remember Shamoo and his protests when the big push started for access to legally incompetent people for medical research. That was the first I had heard of him. (he's quoted in the Ervin article I linked to earlier.)

I've actually talked with Vera Hassner Sharav a couple times and exchanged email. She's with the Alliance for Human Research Protection.

[ October 20, 2004, 06:30 PM: Message edited by: sndrake ]
 

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Posted by Sara Sasse (Member # 6804) on :
 
I was using "meet" in the Information Age sense. I understand that the above are people you have debated directly, or talked with, or have seen in person, but I get the sense that you are not familiar with the bioethics academic literature or the work that is done behind the scenes.

That is a shame, since the academics who publically debate or otherwise cultivate the popular media are not generally predisposed to nuance or thoughtful critique. You can't get something carefully developed across in a matter of minutes -- you yourself have noted your frustration with trying to get your points across in the short time allotted. What you can get across are brief sound bites. From an academic standpoint, these soundbites have to be short, blunt, and easily understood. That isn't rigorous and it isn't good philosophy.

I understand that from the advocacy side, even getting soundbites across is a step forward. I don't fault that at all, and I've come to respect the different approach you must take in order to have an effect. But from a bioethics standpoint, soundbite-driven media tends to attract people who are happy with soundbites, which is usually people who are happy with the party line. It is also a huge drive to financial gain through selling one's popular books and oneself as a popular lecturer.

On the other hand, you have someone like Shamoo, who is testifying before Congress on your issues, on your side; writing amicus curiae briefs; teaching students at university (some of whom will be going on into positions of power themselves); and who is leaving an intellectual paper trail in his own quiet way. And it's a good, careful, thorough, rigorous path he creates.

That is a friendly ear in which to voice your concerns, and it is connected to someone who does more (quietly, but powerfully) to affect the actual lives of persons than a Big Name talking head. He also may be a good resource for information and further contacts.

I hear your frustration when you rail against bioethicists, as it seems you are exposed to the worst of the lot with distressing regularity. But it troubles me to hear the whole profession tarred with that same brush, as it slanders people who are doing good work, even if they are not media darlings. Just as the media loves the flamboyant aspect of the Gay Pride Parade, so does it love bioethicists who will reflect what America expects to see right back at it.

And I know that Hatrack is a venting place for you, but when you are categorical about sneering at bioethicists and physicians, you are also sneering at me. It does hurt my feelings, even if I do understand, and it makes threads like this uncomfortable for me. (Not weepy, not depressed, not enraged -- just that tired, why-am-I-bothering, burned-out feeling that drives any of us to vent here anyway.) Hatrack should be a good place for you to vent and feel welcome, but that shouldn't have to come at the expense of insulting others here, even unintentionally, as it does belong to all of us. IMHO.

I can see taking an extreme stance in a soundbite, but at Hatrack you don't have to be extreme or radical to get listened to. People here (including me) value you and your thoughts and opinions, and we will listen even if you tone down the rhetoric. Actually, I'd be delighted with the qualification of "some bioethicists," or even "many" or "most." You can rant and rave about most of them all you like, and I'd be happy to join in. Just, please, be clear that the sneer isn't directed at at all of them, okay? Especially when you have at least one known reader here who is doing her best to uphold the stronger standards.

Thanks.

[To clarify: I'm not mad, and I don't mean to take you to task for being irritated at those who are total dipshits. I'm just asking a favor as a friend, along with trying to be helpful to both of us. You for possible contacts, and me for my avoidance of burnout and exhausted passion.]

[And, of course, if any of this is offensive or over the top to you or others, I would of course edit or delete as requested. I have my own doubts about posting it anyway, and it is a bit of a down night for me. Probably fuels the frustration in good part.]

[I am also aware that I sound fantastically whiny. Ew.]

[ October 20, 2004, 07:32 PM: Message edited by: Sara Sasse ]
 

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Posted by sndrake (Member # 4941) on :
 

quote:

---

On the other hand, you have someone like Shamoo, who is testifying before Congress on your issues, on your side; writing amicus curiae briefs; teaching students at university (some of whom will be going on into positions of power themselves); and who is leaving an intellectual paper trail in his own quiet way. And it's a good, careful, thorough, rigorous path he creates.

---

quote:

---

but when you are categorical about sneering at bioethicists and physicians, you are also sneering at me.

---

I really don't understand where this comes from. I don't think I've been categorical - at times I've stressed the issue of "mainstream" bioethics. The same with physicians - there's a difference between individual physicians and the medical culture, and attacking the latter often leads to a misinterpretation - usually an honest one - that it's individual physicians being painted with one big brush.

I'm not a proponent of deletion for anything except - to use a real example - anti-semitic remarks (first and only time I used the whistle on this forum).

Meanwhile, I'm still sitting here at ground zero, and reading old articles that feature one of the Loyola docs conflating the presumed consent to "treatment" in emergency situations with presumed consent to be a "research subject." It's vile - and if I did something like that, I'd most likely be called to task for it.
Or at least called on to defend it.
 

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Posted by pooka (Member # 5003) on :
 
(((Sara))) you did challenge him with the [paraphrase] Pull your head out of your Kass[/paraphrase] remark

We are talking about something that isn't prejudiced against the differently-abled, right?

I understand the specific situation that they contracted to provide community education and failed. That can't be excused.

But the structure of opting-to-not raises another principle. Are some treatments so overwhelmingly beneficial that it is okay to...uh, deceive the patient population in order to bring them to the market? If a physician believes that deceiving the public will ultimately benefit the public, is that okay?

If penicillin had been marketed as mold excrement, how many people would have opted to use it?

I guess my weird take on this is based on the fact that I think many medical procedures are guinea-pig-like in their nature. Most things that are done to hospital patients are things they would not specifically give informed consent for. We trust that all these things are within the standard of care, I think. I'm assuming such a concept exists.

Childbirth for many years involved many standards of care that had no research to back up their benefit and were at best annoying and expensive. Nothing related to pregnancy and children really can be tested because everyone recognizes that such testing would be unethical. So when changes in care occur, it is pretty much a stab in the dark.
 

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Posted by Bob_Scopatz (Member # 1227) on :
 
I must not be clear on this study design.

Are you saying that the ambulance goes out into the field with a set of fluid replacement bags that are wrapped in brown paper or something so that when the paramedic decides to give fluids, they "discover" whether it's saline or fake blood they'll be putting into the patient?
 

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Posted by Sara Sasse (Member # 6804) on :
 

quote:

---

I don't think I've been categorical - at times I've stressed the issue of "mainstream" bioethics. The same with physicians - there's a difference between individual physicians and the medical culture, and attacking the latter often leads to a misinterpretation - usually an honest one - that it's individual physicians being painted with one big brush.

---

quote:

---

I really question one comment in it, though. It describes the ethics community as "divided" on the wisdom of this study. Here in Chicago, which is swarming with bioethicists, none came forward to criticize the study....

---

quote:

---

As a result, the public gets no sense of context, and I'm not sure they even want it.

Mainstream bioethics doesn't seem to have much interest in it, either. (yeah, I know, them's fighting words)

---

quote:

---

I'm charging him with intellectual dishonesty (not using the exact words, phrased a little softer) and letting him off the hook a little by saying that much that I have to say about him specifically can be applied to the field of bioethics as a whole.

---

quote:

---

So, to be fair, a lot of the complaints I have with Peter Singer can be leveled against mainstream bioethics as well.

---

quote:

---

Singer and his fellow bioethicists are very happy to have the debate on policy dominated by a small range of people in the professional class - themselves.

---

These are what I remember in particular about bioethicists, and there are others about what "doctors" do and say. Not just medical culture or a doctor, but "doctors" in general, which means me, too, in my eyes (even if not intended). I know, a lot of this is old stuff. It just adds up. "Mainstream" has to be very narrowly defined in order to be this bad, and that use of mainstream is one I was not using myself, except in trying to understand you. Maybe the semantics here led to confusion?

I have a lot of respect for your skills and knowledge I wouldn't care if you were just some yahoo blowhard, but I do care because I respect and like you.

You talk a lot about being annoying, and I've come to recognize it as something of a useful characteristic in the work you do. Being annoying means being seen, and being seen possibly means having peoples lives be saved. And I know you are under stress. I am, too, and I get it. I also am on the frontlines, just at a different part. And I feel overwhelmed and embittered at times, too, and I come here to destress and vent, too.

I don't think you can see Shamoo's impact from where you are, though, not if you cannot see that he is mainstream. And I realize, it isn't your job to know all the details of various academics lives! But to question whether the community is at all divided on something which is evil, given a limited perspective, triggers (for me) all the past comments about my field. I agree with you that it is true in many cases, just not in all. And it isn't fair to judge the all just by what you see, not when it is something tagged as vile, like this.

This is whining. I can see that quite clearly, actually, and I doubt it is helpful to either of us.

Hmmm. Maybe could you ask me to check for persons with a more sympathetic eye to your cause when it seems that mainstream bioethics is completely clueless? I'd be delighted and honored to try to step up to the plate.
 

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Posted by Sara Sasse (Member # 6804) on :
 

quote:

---

(((Sara))) you did challenge him with the [paraphrase] Pull your head out of your Kass[/paraphrase] remark :

---

quote:

---

I must not be clear on this study design.

Are you saying that the ambulance goes out into the field with a set of fluid replacement bags that are wrapped in brown paper or something so that when the paramedic decides to give fluids, they "discover" whether it's saline or fake blood they'll be putting into the patient?

---

Yeah, that's how it is designed to work. But even if they made opaque bags and tubing, they'd still be able to see the fluid when starting the IV, and so once the bag is opened, the assignment to ttreatment or control is clear.

Hey! We must've been talking at cross purposes.
 

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Posted by Bob_Scopatz (Member # 1227) on :
 
By the way, trauma research can stratify on type of injury without CAUSING the injuries. Yes, you take what comes your way, but you also select cases. For example, the NEXT gun shot wound that comes in get's the stuff. Unless contraindicated.

You set out knowing the general time frame that it will take to collect a certain number of cases of a given type. And you don't allow discretion (other than contraindications or "opt out") in the choice of who receives the treatment.

That way, the assignment is random but you aren't going around creating trauma.

It's simple, but it takes more coordination and planning.

Methodology in medical research "in the field" is problematic. I'm not arguing that it should rise to the level that is obtainable under laboratory conditions -- that would be inconceivable.

But I am arguing that this methodology unnecessarily relies on post-facto statistical analyses rather than careful selection processes at the outset.

I suspect my proposal would cost more money and that's why it isn't done. It might also require closer coordination with the EMS providers, and that's not all that easily accomplished either.

The problems I continue to have with the statistical solutions are:
1) No matter how much apportioning of variance you do after the fact, if you haven't controlled for selection bias, you haven't controlled for it. It doesn't matter what your ANOVA tells you -- that's just working the stats test -- you have unexplained variance that you've folded into some place in the treatment or control. Oops.

2) STandard practices in various fields of scientific study are often in violation of the rules of statistical methodology. Analysis of Variance, for example, has a set of rules that should be met prior to its application. This study doesn't come close, and yet the ANOVA will be used. It's the old "when all I have is a hammer, the entire world looks like a nail" problem in statistical testing. Just because medical journals will publish it doesn't make it valid or reliable.

3) There are ways to control this kind of thing better and rule out some potential confounds. I can see how it makes it tough on practitioners to do the studies better and how it would suck up research dollars to do so. So, I also recognize that my little diatribe isn't going to change anything. Medical studies in naturalistic settings will continue to be performed this way. And the result will be, every once in awhile, the researchers will guess wrong when they apportion the variance by tweaking their stats package. Will that result in deaths? Probably not so many that we'd be able to detect it.

In other words, I'm just being a crank from the sidelines.

But, to me, it raises an issue of reliability. If this is the study that will determine if this product is used nationwide, I think after the rollout, we'll still be using an experimental treatment.

Since the FDA and drug companies have taken it on the chin lately with treatments that made it through clinical trials and then years later were shown to increase the risk of death in selected groups of people, I think there's reason to suspect that the motto of "do no harm" has been sort of chucked out the window for the sake of convenient experimental design rather than scientific rigor.

I think it is perhaps time for the medical community to seriously question the research methods that pass for "standard practice."

Maybe the decision will indeed be "this is the best we can do." But I suspect the answer will be "we need to do better."
 

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Posted by Bob_Scopatz (Member # 1227) on :
 
Sara...

Church bus crash on a Tuesday, 14 patients all with similar cause of injury and type of injury get the fake blood.

Large N.

They're all drawn from a small demographic group.

I assume they've controlled for this.

But according to the protocols I now understand, this could happen.
 

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Posted by Bob_Scopatz (Member # 1227) on :
 
By the way, I'm feeling a little guilty here. I don't mean to pick on you, Sara. Medical research today is much better than it was 50 years ago, and we have some amazing treatments available because of it.

I also think that medical research is vitally important.

I'm not trying to be difficult. I find the methodological stuff fascinating.

Sorry for being so critical of your wonderful profession.
 

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Posted by MrSquicky (Member # 1802) on :
 
Bob,
They've been doing trauma efficacy studies for some time now and I'm willing to bet they have actually dealt with the issues that you're bringing up. It's not like this study is introducing any new complications into trauma experiments. The methodological issues you are mentioning are either already anticipated or are flaws in all research of this type. As I try to tell people when they start looking at reputable, established, peer-reviewed research, if you came up with your objection off the top of your head, it's reasonable to assume that it has already been investigated. The potential methodological flaws you are bringing up are pretty basic. If we assume that the people doing these experiments for the past 30 years or so aren't completely incompetent, I think they've almost definitely thought of them as well.

[ October 20, 2004, 10:19 PM: Message edited by: MrSquicky ]
 

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Posted by pooka (Member # 5003) on :
 
I posted and then deleted a really dumb question. Like "I already forgot items mentioned in the first post" dumb. Not like "I don't trust the medical-industrial establishment to always do the right thing" dumb.

P.S. I applaud the thread title change. At least as long as that "other white meat" thread is floating around.

[ October 20, 2004, 11:05 PM: Message edited by: pooka ]
 

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Posted by sndrake (Member # 4941) on :
 
pooka,

the title of this thread hasn't been changed. There's yet another thread with "guinea pig" in the title.

But I understand the confusion.
 

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Posted by sndrake (Member # 4941) on :
 

quote:

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I have a lot of respect for your skills and knowledge I wouldn't care if you were just some yahoo blowhard, but I do care because I respect and like you.

You talk a lot about being annoying, and I've come to recognize it as something of a useful characteristic in the work you do. Being annoying means being seen, and being seen possibly means having peoples lives be saved. And I know you are under stress. I am, too, and I get it. I also am on the frontlines, just at a different part. And I feel overwhelmed and embittered at times, too, and I come here to destress and vent, too.

---

A couple of points. I obviously haven't been clear about the "annoying" stuff. Being intentionally annoying is almost always done as part of a protest, part of theater - to get attention, as you say. And sometimes people like Clarence Page get it, even though folks like Art Caplan just turn red with agitation (he does that pretty easily though.)

Mostly, though, I annoy people like Singer, Mayo, and others by playing by a different set of rules. I insist on relating to the real world of medicine with our own documented stories of what happens to people in the health care arena. I don't soften my language when one of them is being sloppy or just plain misrepresenting facts.
I'm annoying because they don't have a ready answer for charges fairly laid.

And I think that's a place we differ. When it comes to policy, I believe we have far to much elaboration on philosophy and case examples and far too little about what's really going on in the system.

I don't know what to think of "diversity" in bioethics, frankly. In the case of Robert Wendland - a brain-damaged man never argued to be in PVS - 43 bioethicists signed onto a brief supporting the right of surrogates to withhold lifesaving treatment on a "good faith" standard.

In the Schiavo case, there were 55 bioethicists who signed onto the brief supporting Michael Schiavo.

Number of bioethics briefs opposing starvation in either case: 0

It's also harder to find bioethicists speaking out against futile care guidelines. There used to be quite a few, but the voices seem to be dwindling in both numbers and volume.

To use another example, I know for a fact that there are members of the "Aspen Group" that strongly disagree with Ron Cranford's advocacy with the newly classification of "minimally conscious state." Cranford advocates having people in that category thought of as being most like people in persistent vegetative state, and that the laws around cessation of lifesaving treatment should be similar.

They may be troubled by Cranford's advocacy, but they aren't getting their hands dirty publicly countering his agenda.

Who knows? Maybe if enough "good" bioethicists get annoyed at being lumped with the "not so good," maybe they'll be motivated enough to get as sophisticated about media and advocacy as the others.
 

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Posted by sndrake (Member # 4941) on :
 
Example (non-Singer one) of confronting someone with being less than honest:

A few years ago, I debated David Mayo, who was and is on the board of directors of both the Hemlock Society (which has now merged with another organization) and Death With Dignity National Center.

At one point, he tried to say that Hemlock was "divided" on Kevorkian. I just looked at him and said something along these lines:

"David, your own surveys show over 80% of your membership is extremely supportive of Kevorkian. As a board member, you authorized the raising and donating of over forty thousand dollars to Kevorkian's defense fund. Not only that, you won't find one single critical word about Kevorkian any issue your organization has put out. Who are you trying to kid here? Shame on you."

Edit to add: For obvious reasons - he's part of the Minnesota Bioethics Center - I suspect Mayo played a significant role in the assisted suicide conference fiasco.

[ October 21, 2004, 09:06 AM: Message edited by: sndrake ]
 

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Posted by BannaOj (Member # 3206) on :
 
FYI, I'm reading this thread with interest.

AJ
 

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Posted by Sara Sasse (Member # 6804) on :
 

quote:

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A couple of points. I obviously haven't been clear about the "annoying" stuff. Being intentionally annoying is almost always done as part of a protest, part of theater - to get attention, as you say. And sometimes people like Clarence Page get it, even though folks like Art Caplan just turn red with agitation (he does that pretty easily though.)

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quote:

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I don't soften my language when one of them is being sloppy or just plain misrepresenting facts.

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quote:

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And I think that's a place we differ. When it comes to policy, I believe we have far to much elaboration on philosophy and case examples and far too little about what's really going on in the system.

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quote:

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I don't know what to think of "diversity" in bioethics, frankly. In the case of Robert Wendland - a brain-damaged man never argued to be in PVS - 43 bioethicists signed onto a brief supporting the right of surrogates to withhold lifesaving treatment on a "good faith" standard.

In the Schiavo case, there were 55 bioethicists who signed onto the brief supporting Michael Schiavo.

Number of bioethics briefs opposing starvation in either case: 0

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quote:

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In a fairly substantial piece I am writing on Robert Wendland I state that the Amici Curiae brief submitted to the California Supreme Court supporting his extubation was badly written due to its adversarial legal setting and poorly informed by traditional Catholic medical ethics in spite of several “Catholic� institutional undersigners. My review of the Court's decision notes that it saw this case as a request to kill a conscious patient who was not even sick, who was making limited progress, and who would be likely to suffer distress, since he was conscious, from the prolonged process of dehydration. I suggest further that the Court may very well been aware that claiming that such an action was a legitimate "letting die" of a dying patient would sound like nonsense to objective observers.... My judgment of the case, as framed by the Court's language, is obviously negative about the Amici Curiae brief and completely in agreement with the Court.

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quote:

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They may be troubled by Cranford's advocacy, but they aren't getting their hands dirty publicly countering his agenda.

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quote:

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Who knows? Maybe if enough "good" bioethicists get annoyed at being lumped with the "not so good," maybe they'll be motivated enough to get as sophisticated about media and advocacy as the others.

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quote:

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By the way, trauma research can stratify on type of injury without CAUSING the injuries. Yes, you take what comes your way, but you also select cases. For example, the NEXT gun shot wound that comes in get's the stuff. Unless contraindicated.

You set out knowing the general time frame that it will take to collect a certain number of cases of a given type. And you don't allow discretion (other than contraindications or "opt out") in the choice of who receives the treatment.

That way, the assignment is random but you aren't going around creating trauma.

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quote:

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Methodology in medical research "in the field" is problematic. I'm not arguing that it should rise to the level that is obtainable under laboratory conditions -- that would be inconceivable.

But I am arguing that this methodology unnecessarily relies on post-facto statistical analyses rather than careful selection processes at the outset.

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quote:

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By the way, I'm feeling a little guilty here. I don't mean to pick on you, Sara. ... Sorry for being so critical of your wonderful profession.

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Not at all! I'm cool with criticizing a specific incident, action, or person. You raise thoughtful questions.

I am reminded, though, that I tend to have trouble with "all" in the implied or colloquial sense in many areas of my life. This literalism has been a sticking point between me and my husband -- he says something like, "Americans believe blah-blah-blah," and even if it is generally true, I perseverate on insisting that this is not "all" Americans. We've come to joke about it between us, but it has been a definite issue in the past.

It seems to be more than a pet peeve, as I don't seem to be able to get past it. I know for sure it is a clanging bell in my mind even in cases where that literal a meaning of the phrase is not intended by the speaker.

I'm sorry about this, Stephen. perhaps it is just me. Could you indulge me as a friend by using "many," "most," or "nearly all" (but just in those cases where it is indeed appropriate, that is) and I'll find something nice to do as a thank you back?
 

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Posted by sndrake (Member # 4941) on :
 
Sara,

I'd forgotten about Dundon. He contacted me a couple years ago asking thoughts from both me and Diane on his own thinking about the case. But it still comes as too little too late, frankly.

Wesley is kind of a special case. I've known him for about 8 or 9 years. But, while they were still posting, mainstream bioethicists on an email list I'm on were pretty clear as viewing Wesley as an outsider - a "spoiler," even.

My point, not made clearly, is that if colleagues of Cranford's are truly alarmed or object to his advocacy, then they have to be as public as he is or that opposition is nonexistent, for all practical purposes. It's weird - futility policies seem to have taken the quiet, backdoor approach. OTOH, the issues around ending the lives of people with cognitive disabilities are being handled through a very public discourse - with people like Jon Eisenberg, Peter Singer, Ron Cranford and others working to shape public perceptions.

I don't know what to say to you. I type on the fly not always taking the time to type every thought perfectly. If I had to do that, I'd probably be unable to post about my work stuff here any more, except for cutting and pasting things I've already written. That gets deadly dull.

I don't know how much I'll be on for the next week or two anyway. I have to leave town for a workshop on Saturday and I'll be gone for a week. Don't know how much time I'll have while I'm there. And I have a lot of stuff to get ready right now.
 

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Posted by BannaOj (Member # 3206) on :
 
Sara is *that* why I butt heads with your husband? It suddenly makes sense! (And I mean butting heads in the nicest sense because I enjoy a good discussion, but now I see where the disagreements probably often originate.)



AJ
 

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Posted by sndrake (Member # 4941) on :
 
Sara,

I'll try to post something later. Your last reply came in while I was typing. My office computer is crashed and I need to completely reformat the hard drive, which I don't have time for right now.

So for the past few days I've been having to type from a public room in the office, people going in and out - right now there's a radio going. All very distracting and not very pleasant when I'm already sleep-deprived.

I think maybe I better avoid posting until this situation gets better.
 

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Posted by Sara Sasse (Member # 6804) on :
 

quote:

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Wesley is kind of a special case. I've known him for about 8 or 9 years. But, while they were still posting, mainstream bioethicists on an email list I'm on were pretty clear as viewing Wesley as an outsider - a "spoiler," even.

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quote:

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I don't know what to say to you. I type on the fly not always taking the time to type every thought perfectly. If I had to do that, I'd probably be unable to post about my work stuff here any more, except for cutting and pasting things I've already written. That gets deadly dull.

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Yeah, I get that. I guess my plea would be to remember me as a fellow Hatrack eye when you speak about physicians or ethicists as a whole. Like I said, just a "many" or a "most" (or even an "it seems") when you speak about the whole bunch of them together would set my heart a'flutterin.'

quote:

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I don't know how much I'll be on for the next week or two anyway. I have to leave town for a workshop on Saturday and I'll be gone for a week. Don't know how much time I'll have while I'm there. And I have a lot of stuff to get ready right now.

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I hear you. I think I've likely made this venue uncomfortable for you, though, and that wasn't my intent, although it is a logical consequence of witchy whining about my feelings in public like this. Looking back, if I wanted to be effective and respectful, this should have been dealt with over email instead at a public forum, with a great deal more good humor and less self-indulgence, and in a short "hey, could you do this" format rather than beating it into the ground in agonizing detail.

I think it's called "social skills." I promise to work on it. Really, I will, and I'll be creative about addressing the issues in myself.

quote:

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Sara is *that* why I butt heads with your husband? It suddenly makes sense! (And I mean butting heads in the nicest sense because I enjoy a good discussion, but now I see where the disagreements probably often originate.)

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AJ, I have no idea. I'm guessing you mean over at GreNME, where I'm not following things carefully, or really following at all lately. It might well be that you and he get stuck at an impasse if you have the same perseveration over categoricals that I do. Dave calls it "seeing the leaf instead of the tree." I, on the other hand, can't make sense of a categorical that isn't true for all members of the group.

Once when I was about four, my mother assigned me the aftenoon chore of "picking up all the sticks in the yard so that your brother can mow tomorrow." [actually, I might have told this story here before -- can't remember. But it's illustrative.] Although intially happy about the task, I ended up at sundown sitting in the grass and crying. I'd cleared all the sticks and twigs and little tiny dried hard bits of grass from around me in a few yards' width circle, but I'd run out of time with most of the yard left. I panicked and stressed out because no one could have picked up all the sticks in the whole yard, but I felt like I was supposed to and failed.

Actually, that's developmentally appropriate literalism for a four-year old. It isn't developmentally appropriate for a thirty-four-year-old, but -- even though I work around it -- looks like I'm still stuck in the same place. There is definitely a strong personal component to this for me.

quote:

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So for the past few days I've been having to type from a public room in the office, people going in and out - right now there's a radio going. All very distracting and not very pleasant when I'm already sleep-deprived.

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quote:

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I think maybe I better avoid posting until this situation gets better.

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quote:

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Don't know if anyone who has met me ftf noticed, but I don't wear anything in the way of jewelry - no ring, nothing on my neck, no even a wristwatch. I don't like wearing nonclothing items.

Shutting up is not an option.

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quote:

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Bob,
They've been doing trauma efficacy studies for some time now and I'm willing to bet they have actually dealt with the issues that you're bringing up. It's not like this study is introducing any new complications into trauma experiments. The methodological issues you are mentioning are either already anticipated or are flaws in all research of this type. As I try to tell people when they start looking at reputable, established, peer-reviewed research, if you came up with your objection off the top of your head, it's reasonable to assume that it has already been investigated. The potential methodological flaws you are bringing up are pretty basic. If we assume that the people doing these experiments for the past 30 years or so aren't completely incompetent, I think they've almost definitely thought of them as well.

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quote:

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We have not had any community meetings in Forest Park yet. We have been in the towns of Hillside, Northlake, and Berwyn. They will be the first to enroll patients along with Loyola's Lifestar. We will be starting this study on November 1st 2004. Request for bracelets can be directed to this email address. The bracelets are plastic. Length of study is not known. Please provide name, address and number of bracelets required with request.
Thanks,
(Name deleted)
Clinical Research Nurse

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OK - there are a number of possible interpretations here. One is that the study will only start in the three towns named on November 1, along with "Lifestar" (?). Forest Park will be "enrolled" (gotta love the language) only after a community forum is held.

OR it could be that it's starting and there will be no community forum until after the study has already begun.

One thing is clear - there were no forums *before* the decided to do the study. I wonder if they have a list of how many information sessions they held before approving the study.

Ya know, these studies almost depend on the ignorance of the population. The kinds of trauma they're looking at aren't that frequent. The best way to make sure that they have full access to as many qualified "enrollees" as possible is to have people ignorant. They know the numbers who would wear bracelets to volunteer would never be sufficient to meet their needs.

(This isn't helping my anger issues, btw. And I don't even have a "happy place" to retreat to. )

btw, in the interests of preserving relationships, I took a golden opportunity to turn some of this hostile energy toward a listserv I'm on that's heavily populated with psychologists in the dev. disabilities field. Kinda stomped on one of the psychologists, but he was stomping on a woman with autism who says things annoying to applied behavior specialists.

*Recovering Behaviorist*

[ October 21, 2004, 05:20 PM: Message edited by: sndrake ]
 

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Posted by Bob_Scopatz (Member # 1227) on :
 

quote:

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Bob,
I wasn't trying to get into a pissing match here (edit: not that you were/are either. I'm just trying to say that I wasn't trying to disagree with your credentials or authority, both of which are greater than mine). I don't really know much at all about the statistical methodologies used in medical research, but I do know about those used in psych research and about methodology in general. The problems you brought up seem to be very basic to me. Perhaps they aren't actually recognized in medical research of this type, but I would be greatly suprised and discomfitted by this. As I said, I have no atual evidence that they are recognized, so, if you do look it up, I'd be interested in seeing what is said.

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quote:

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Hillside, Northlake, and Berwyn

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quote:

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Chicago Hospital Joins Fake Blood Study

By LINDSEY TANNER
AP Medical Writer
Published November 4, 2004, 7:09 AM CST

CHICAGO -- Loyola University Medical Center has joined a nationwide study of a potentially revolutionary artificial blood product that's being tested in trauma patients without prior consent, authorities said Wednesday.

Doctors say the product called Polyheme could transform trauma care if it saves lives by quickly replacing blood loss at the scene or en route to the hospital.

After months of preparation, including efforts to give local residents a chance to refuse participation, Loyola began the study Monday by equipping its medical helicopter with Polyheme. Hospital spokesman Stephen Davidow said in coming weeks Polyheme will be used in as many as six ambulances in three Chicago suburbs.

Because trauma patients often are unconscious or in shock, they are unable to give the consent required for experimental treatment. As a result, the Polyheme researchers are being allowed to bypass the consent rules under a 1996 federal exemption that applies to emergency, potentially lifesaving research.

Polyheme's maker, Northfield Laboratories, is the second Illinois company to test a blood substitute without obtaining prior patient consent. The first, Baxter Laboratories, halted research on its own artificial blood in 1998 after the deaths of more than 20 patients who received the product.

While there's evidence that Polyheme can be safely used in hospital patients, the study is "bringing it closer to the time of insult and injury by testing it in the field," said co-researcher Dr. Mark Cichon, director of Loyola's emergency medical services. He said there hasn't been a similar advance since World War I research on saline fluids that are now standard procedure for trauma victims.

"If the study proves that this is a safe product, it will in some ways revolutionize what we are doing for trauma patients," Cichon said.

Ambulances do not carry human blood, which has a short shelf life. Instead, patients get an intravenous saline solution to restore fluid volume and blood pressure. But unlike blood, the fluid does not contain tissue-nourishing oxygen, so patients risk organ damage.

Polyheme has that blood-like ability and is made by extracting oxygen-carrying hemoglobin from human red blood cells. It can be used in patients with any blood type and lasts longer than blood.

Loyola hopes to test Polyheme on about 20 patients, and results will be compared with 20 patients given saline fluids, Cichon said.

Davidow said as of Wednesday, no patients had been tested because none had met the study qualifications.

Criteria include severe blood loss, and participants must be older than 18. People excluded include pregnant women, people with severe brain injuries and those who require cardiopulmonary resuscitation to maintain their heartbeat.

More than 700 patients nationwide are expected to participate in Polyheme research at more than 20 centers. Loyola is the 16th center to join and the only hospital in Illinois involved, according to a Northfield spokesperson.

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quote:

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Yes, this is a tragedy. Yes, this woman is likely dead because someone screwed up. No, this isn't an indictment of the clinical trial process as a whole.

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Yeah, but it's one more piece of evidence pointing to a system that could do with a lot more oversight and accountability. The issue of informed consent raises its head here, as well as the more obvious routine medical competency questions.

I didn't post anything about it (at least I can't find anything), but there's been some press coverage devoted to the way in which universities have abandoned ethics in their research contracts with pharmaceutical companies. The pharmaceutical companies, as part of the contract, have the right to prevent publication and sharing of data - and they exercise that option regularly for research findings that aren't what they're wanting to find.

These contracts played a role in the delayed findings of potential dangers in Vioxx and in the use of some anti-depressants in children.
 

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Posted by Tatiana (Member # 6776) on :
 
Wow, what a great discussion! I'm sorry I didn't follow this thread all along.

As for this particular study, the main reason I would opt out is that once you get to the hospital where whole blood is available, they continue treatment with polyheme anyway. That's very wrong, in my view. I would certainly opt out for that reason.

As for the informed consent question, it hinges on trusting them to work against their own interests by publicizing the study as widely as possible and making the process of opting out as easy as possible, which clearly we can't trust them to do. The task of mailing out bracelets will clearly be given last priority behind every other task. I wonder if they even have the bracelets made yet, and how many they made up?
 

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Posted by Tatiana (Member # 6776) on :
 
The issue of trusting medical professionals in general is also an interesting one, to me. Obviously many doctors like Sara, and my doctors Joey and Bob, are awesome and excellent. But from working at a hospital for a number of years, and from my 2 year experience with my father's illness and death, and other experiences, I've come to know that you MUST take ownership yourself of your own treatment. It's not a failing of any individual, but rather the system as a whole. There is just not any way that a huge system such as a hospital can care individually about a single patient in the way that you care about your own father. And they will not be straight with you about mistakes they make.

My father had a reaction to heparin. It was causing coaggulation all over his body. They ignored the signs of this. Fever spikes to 107 were dismissed as post surgery fever. Or the machine not reading right. His increasing difficulty in breathing from blood clots in his lungs was called ARD, Adult Respiratory Dysfunction (basically means the patient can't breathe for unknown reasons). His O2 saturation was in the 80s and the resident on duty said to keep him from getting so much oxygen, that "80s, 90s, it's not that different" (which caused Dr. Bob to say he needed to go back to med school.) The night of my father's surgery he was alert and strong, and in the next two weeks he declined rapidly, and nearly died. We managed to save him when we insisted on them consulting a medical pulmonary specialist. I had to threaten with lawyers and so on to make them do it. They still were not going to do it. Finally I got a friend who was a retired surgeon at that hospital to talk to the resident, and then he agreed to call in the consulting doc. The consulting doc immediately diagnosed the problem and saved my father's life.

Oh wow, I need to post this whole story someday. There's so much more. It needs to be written down. One CPU nurse nearly killed my father of a morphine overdose on Thanksgiving day when she didn't want to be disturbed by restive patients. She wrote "morphine" on the chart 4 or 5 times, but didn't write the dose she gave. When I pointed out that his blood pressure was reading 30, she said the machine wasn't reading right. If this were a rare thing it might be of little concern. But it's not rare. Something is wrong that needs to be fixed. Hospitals are being stressed to the breaking point by all the changes in the payment system over the past 20 years.

Here are some of the huge red flags I saw that were systemwide.

1) Whenever a measurement machine gave alarming data, they dismissed it as a faulty reading. Even when the data was consistent with other signs and symptoms. 107 fever, for instance. 85 oxygen saturation. 30 blood pressure. They would take the reading 10 times, and if 9 readings were alarming but 1 looked a bit better, they'd write down the least alarming number. (You'd better believe that 30 blood pressure never made it onto my father's chart.)

2) They ordered so many tests and never looked at the results unless and until I asked them what the result had been and what it indicated to them. I've found this to be true even in good doctor's offices. They order tests and then they never look at the results until I ask.

3) The doctor in charge of the case, when things were stabilized finally and gradually improving, got rotated out. To me this is a huge problem! If the project engineer on a project gets changed midstream it throws the whole project into confusion and delays. The arguments that claim one doctor can just pick up and carry on for another are exceedingly weak! I don't know how to fix this but it MUST BE FIXED!

[ December 16, 2004, 11:17 AM: Message edited by: Tatiana ]
 

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Posted by Dagonee (Member # 5818) on :
 
The situation that happened here is exactly the kind of situation that can occur whenever a drug with potentially bad side effects is administered. The fact that this was a clinical trial added nothing to the mix:

1.) The drug was known to cause liver problems.
2.) The doctor failed to either adequately test or to adequately respond to the test results.
3.) The drug-induced liver problems killed the patient.

Nothing in this series of events depends on this being a clinical trial. There are many approved drugs with potential liver effects. I've taken several, and been stuck monthly to test for the problems.

In fact, had this drug already been on the market, it's likely the woman's family would never know about this. Because it was a clinical trial, the adverse event was reported to NIH, which is the source of the information.

This death was caused by breakdowns in the way medicine was practiced in this case, not by the way clinical trials are administered.

Edit: To be clear, I'm not saying there aren't problems with the clinical trial system. I am saying the death in this incident was not caused by any risk present in clinical trials that is not present in standard medical practice.

Dagonee

[ December 16, 2004, 10:58 AM: Message edited by: Dagonee ]
 

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Posted by Tatiana (Member # 6776) on :
 
As for what I would recommend a patient do, it is this.

1) Don't even go to the hospital unless the thing you have is life threatening. There is a fair chance (not miniscule by any means) that they will kill you in the hospital. So just don't go there, never have surgery, unless what you have already is life threatening and worth the risk.

2) Never leave a loved one who is sick or incapacitated alone in the hospital without someone who loves them looking out for them. If the nurse comes in and calls them by the wrong name, for instance, they could correct that mistake before a wrong drug was given.

3) Check the labels on all medicines and IV bags to be sure they are actually for the right patient. Know what treatment the patient is supposed to get, understand the reason for each medicine and procedure and what is expected to be accomplished.

4) Know what tests are ordered and why, and what we expect to learn from them. Check back and ask about the results and what we discovered or ruled out. Ask all these things. Good caregivers love for the patient and family to be involved and interested. Those who are less good prefer that there be no questions asked.

5) Know what all the machines are, what the readings mean, and how they are supposed to read. Nurses are all overworked. Help them out whenever you can by monitoring the patient's condition more frequently than they can. You improve the level of care greatly this way, while easing the burden on the nurses.

6) Read and study online about the patient's condition, the treatment options, all the drugs being given, etc. Check drugs for interactions. Read the side effects of drugs. Often a question like, "We're seeing x symptom. Might this be a side effect of y drug?" could trigger a doctor to make an association that might otherwise be missed.

Diagnosis is extremely tricky. Doctors have dozens of patients at any one time. You just have the one. Obviously you have more time to ponder and observe and figure out what is going on, though of course they have much more knowledge and experience. If you work together you can pool your time with their knowledge and improve the level of care that the patient receives.

Good doctors, though always pressed for time, are delighted when people take so much interest.
 

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Posted by Tatiana (Member # 6776) on :
 
While I'm going off on a tangent about medical and hospital care, I want to talk about hospice as well.

The hospice people were great but the whole focus of the hospice system alarmed me because they were all about "how can we kill this patient as quickly as possible?" It was just weird, when I asked if he didn't need fluids they gave me a brochure about how death of dehydration is so much more pleasant than other deaths. If I could have gotten him to drink and swallow, in those first couple of days, he might have revived. Partly the problem was that his morphine was oral drops, and I think it deadened his throat muscles so they wouldn't work.

Of course, by that point he was going to die of the cancer in his liver eventually anyway, but the doctor from looking at the CAT scan thought he had a couple of more months on that.

So how do you decide? It seems to me that life is a terminal disease, and the fact that we're going to die eventually doesn't stop us from taking care of people.

The hospice people were great, and yet, they weren't wanting him to get better. They were wanting him to go as quickly and with as little trouble as possible. That didn't feel right to me in my guts. At one point my father asked my mother to call 911. She didn't. A few days later a much weaker father looked at me in desperation and said "Help, help help! Quick, quick, quick!" ... and I ... made soothing noises and did nothing. How was that a help?

I don't know what I think about hospice. Something about it felt very wrong to me.
 

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Posted by ketchupqueen (Member # 6877) on :
 
I've had cases where I was having a bad reaction to a drug, reported it, and was dismissed. When I presented them with research I had done, it was still dismissed. I finally refused the medication, and (surprise!), the reaction went away. At that point, they implied that the reaction had been all in my head...

What I want to know is, if Polyheme is contraindicated in pregnant women, what steps are in place to make sure they don't get it? Are they going to track down every woman who is pregnant or may become pregnant, inform them of the risks, and provide them with an opt-out bracelet? Are they going to administer a pregnancy test before they give the treatment to any woman of childbearing age? Because you can't always tell by looking, and if the patient is unconscious and no one on the scene knows she's pregnant, how are they going to know?

[ December 16, 2004, 11:37 AM: Message edited by: ketchupqueen ]
 

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Posted by rivka (Member # 4859) on :
 
*BUMP*

Here we go again -- or at least, that's what they're attempting.
 

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Posted by sndrake (Member # 4941) on :
 
Every bit of reason to be outraged. FDA Waivers continue in spite of the latest:

Blood substitute 'a disaster' in trials

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In a potential blow to the future of an Evanston-based biotech company, a clinical trial showed Tuesday that its key product, an experimental blood substitute, performed worse than standard treatments in patients who suffered traumatic injuries.

In a trial of 712 patients, Northfield Laboratories Inc. reported 13.2 percent of the 349 who had been given Northfield's product died, compared with deaths of 9.6 percent in the control group of 363 who received either saline solution in the ambulance or blood in the hospital.

"No matter how they slice it, it's a disaster," said Martin Shkreli, a hedge-fund manager at New York-based Elea Capital, which invests in health-care companies and sold its Northfield shares earlier this year. "If you look at the absolute number of deaths, it kills more patients than saline does."

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Or was it such a blind study that they have no way of knowing if their loved one was given the real blood or the blood substitute, and thus have no recourse?

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Just who are lawyers supposed to go after? This was all sanctioned by the FDA. The feds signed away these people's rights.

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From the Blood substitute 'a disaster' in trials article:

Gould hopes the FDA will review Northfield's data carefully, considering that the trial was complicated and involved a complex group of patients who had suffered traumatic injuries that were treated by emergency workers under intense pressure at accident scenes or while being transported by ambulance.

"This was a logistically complex study with many variables and a high incidence of protocol violations," Gould said. "We believe that there is an unmet medical need for a hemogloblin-based, oxygen-carrying red-blood-cell substitute, and that Polyheme is that product."

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Originally posted by Anshi:
Is one to believe that Northfield didn't already know, and accepted, the fact that protocol violations would inevitably happen given that they occur in "controlled" settings as well?

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Actually, I'm quite curious as to what these protocol violations might have been since this 3.6% difference between the experimental group versus control shows a marked 'inferiority'. (Northfield promised the FDA a 3.8% increase in lives saved in the experiemental group as the FDA required that to show superiority. I would say this is ironic, except that people died because of this.)

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Originally posted by Bob_Scopatz:

The design as I understand it so far simply cannot be a double blind study. In such a case it is flat impossible to control for selection bias unless you have a strict "no discretion" policy for assigning people to treatment and control. I personally can't imagine any medical director of pre-hospital care signing off on taking away the discretion of the paramedics who are dealing with the patient in the field.

Hence, selection bias.

I don't think the study design can deal with this.

I'm reserving judgement, though, because I don't have the methods section yet.

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Easing of FDA rules may have led to deaths
Media hasn't put 2 and 2 together, says Steve Drake

Last April 1, an Associated Press article that was not a joke began, "A pharmaceutical company abruptly halted its study of a blood substitute in U.S. emergency room patients after discovering they were dying at a higher rate than expected."

"This news was of interest to me because of another story, from November 5, 1996," says Steve Drake of Not Dead Yet. On that day, the New York Times's Gina Kolata had reported on the U.S. Food and Drug Administration's easing of requirements that informed consent be obtained for enrollment in trials of experimental medical procedures.

"For the first time in a half century, new federal regulations allow investigators to enroll patients in some medical research studies without their consent," wrote Kolata. "The Food and Drug Administration regulations, which took effect on Friday, apply only in carefully circumscribed situations. The patients must have a life-threatening condition, like a severe head injury, and must be unable to say whether they want to be part of a study. They would be selected only if it was not feasible to obtain consent from a relative."

"TV coverage of this FDA change at the time indicated that experimental use of artificial blood would be one of the first applications of this rollback of the Nuremberg Code," said Drake. In her article, Kolata explains that this Code "dates back to the Nuremberg trials of Nazi doctors after World War II, when American judges were agonizing over rules that might prevent doctors from ever again using human subjects in horrendous experiments.

"The judges wrote a code of ethics, the Nuremberg Code, whose first principle was that no one should ever be forced to take part in a medical experiment," wrote Kolata.

"The voluntary consent of the human subject is essential," says the Nuremburg Code.

"The leader of the group of bioethicists who quietly lobbied and won the FDA changes," says Drake, "was Norman Fost, the first recipient of the funded chair at Princeton that Peter Singer will now hold." (See "Peter Singer appointment draws warning," D.R. Nation, September/ October). At the time of the FDA change, Fost was Director of the Center for Clinical Ethics at the University of Wisconsin.

"We are seeing a worldwide trend in the use of 'nonconsenting subjects,'"says Drake. "A few years ago, most of the European community signed onto a new set of research guidelines that allows incapacitated people (people with mental retardation, in 'persistent vegetative states' or in comas) to be 'enlisted' in research not of direct benefit to the subjects."

"No press coverage seems to have put the earlier story together with the April 1 news," says Drake, "but it seems highly likely that the people in the artificial blood experiment gone bad were 'enrolled' in this research project without their consent--and that a number of people may have died as a result of getting the artificial blood."

"Given that the subjects are now dead (and evidently do not have next of kin), it is unlikely there's worry of lawsuits regarding wrongful deaths in this scenario," says Drake. "Convenient, isn¹t it?

"Is there going to be a re-evaluation of the wisdom of this exception to the requirement of informed consent?" asks Drake. "Or is it still ethical, due to the fact that the press hasn't caught on and there will probably be little danger of litigation resulting from the deaths of unwitting participants?"

"One would think that the early termination of studies involving nonconsenting subjects would have been newsworthy--yet it received scant attention from the press," Drake continues. "No coverage of the discontinued study tied it to the FDA informed consent exemption."

"According to investigative reports from a couple of years ago, the FDA's own data indicate that about half the medical researchers they have monitored (after the fact) had significant problems in terms of documenting informed consent or giving enough information so that consent could be truly informed," Drake adds. "It seems we are giving further powers to a group that has a s____y track record of obeying already existing rules."
(edited for PG Compliance)

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Originally posted by rivka:


To me, there is something worse than the fact that some patients will (unknowingly and with no choice in the matter) get blood substitute. It is that NO patients will get whole blood! I believe (and EMTs or similar can correct me if I am mistaken) that the standard of care in ambulances includes whole (O neg) blood. But because of this study, that will not be available to ANY patients.

[Addit: The web site says saline, not plasma, and claims this is standard for hemorrhagic shock. I will have to look more.]

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