posted
I work in Forest Park, Illinois. The nearest trauma center is Loyola. Loyola received a waiver for informed consent from the FDA for a "study" they'll do with a new blood substitute. Anyone in an accident and who is unconscious will either receive plasma or the new product. Those who receive the experimental product will continue to receive it when they get to the hospital. Those who receive plasma will get whole blood if they need it.
The last time they tested one of these products under these rules, there was a higher than expected death rate and they had to discontinue the study. So people who never gave their permission to be guinea pigs died as a result of the nonvoluntary participation.
Here's the email I received a few days ago:
quote: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
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
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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[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
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.
quote:Do they expect the public to just forget about the last trial in '96?
Well, first of all, it was a different product made by a different company.
Second, they don't "expect" the public to forget about the '96 trial. The KNOW the public - with the exception of some malcontents such as myself - HAS forgotten.
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This is bad science. I'm imagining how this might work in an emergency medical response situation.
If you allow the EMT/paramedic to decide who gets which type of blood, you have to somehow control for their biases, conscious or subconscious. Really, the only way to do this right would be a double-blind study wherein they don't know whether they are giving the patient synthetic or human blood. But how could they do that?
So, guess what, they have to know. And then you have the biases that any human would bring to the situation. They give the real stuff to people who they think have a shot at making it? Do they give the synthetic stuff out only when they are running low on the real stuff? Do patients that remind them of their mothers get real blood, and the nasty smelling homeless people get the fake stuff?
This is just dumb.
And what do they mean by "accident?" Is this traffic crashes only, or all accidents?
Also, if you want to control for level of trauma, you either have to do some sort of scheduled administration like: - the next person from a motor vehicle accident with no visible injuries but complaining of abdominal pain and showing signs of internal bleeding, you give them the fake stuff. or - every 3rd person with a compound fracture and major blood loss...
Yeah right.
This just doesn't sound methodologically possible.
I'd like to read the methods section of this study, Stephen, if you can get ahold of it for me. If it is as bad as I fear it is, I will write a letter for you that would help blast these people back into stats/methods 101.
I have some medical friends who might help expose this too if it is as bad as all that.
Please let me help!!!
I hate bad science. Especially when it has the potential to get people killed.
Who approved this, anyway? It sounds amazingly ill considered.
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Its not quite as bad as it originally sounded...it has passed 5 clinical trials in humans. At some point they will be brining it into the mainstream...this is just the step right before that.
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While I agree that there are consent issues (I was convinced of that in the last thread), I don't think this is necessarily bad science (just bad ethics).
The simplest way to decide who gets which is to make it random -- even-odd; or, more likely (for reasons of space and less complexity), everyone served by ambulances A, B, and C gets plasma; everyone served by D, E, and F gets blood substitute. (Or everyone on Mondays and Wednesday gets plasma, and on Tuesdays and Thursdays ya get substitute.)
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.]
posted
(After having finished reading the Loyola FAQ)
GRRRRRRR! Wow, talk about spin! "Why was such an exception granted in connection with this study?
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." (emphasis mine)
Ya mean because you will have ensured that the usual treatments are NOT available? And how about when the patient gets to the hospital, where blood IS available, even type specific blood! and they are still kept on the substitute?
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posted
. . . and it turns out, according to eMedicine, that even giving saline is controversial!
quote: 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.
These official guidelines (from a Canadian OB/Gyn group) seem to disagree, as does the EMS Journal.
posted
And, oddly enough, for some things it is great ^^. Actually, I think that the Greeks used the little they knew to much greater effect than we use the vast amount we know.
I truly admire and respect the Greeks.
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posted
I serve on our University's institutional review board and I am absolutely shocked that this has been approved. Studies of human subject must be approved not only by the FDA but also by the local institutional review board.
I can understand the difficulty involved. This product is designed to treat trauma victims many but not all of whom are not conscious and able to consent. What's more, decisions must also be made in the field very rapidly. It is also a potential important contribution. If a blood substitute is found that performs as well as blood transfusions it could save many lives. What I see as unethical is that doctors are not require to get consent from the the patients or their next of kin to continue the treatment once the patient is in the hospital. This is simply unethical.
Also, is there a rescue method allowed in the study. If patients are not responding well to the substitute or have a bad reaction, will the doctors be allowed (required) to end the study and give whole blood.
I'd also like to know if any previous clinical trials of this product have been done. It would seem appropriate to begin clinical trials with some other population of patients who can give consent and for whom participation is less likely to be life threatening.
[ October 18, 2004, 09:26 PM: Message edited by: The Rabbit ]
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posted
Here's my e-mail I sent to the address given at the website:
quote: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.
by the way, you can't send the ambulances out with only one product (blood or fake blood -- or actually it's saline soln or fake blood). They have to be able to pick up other patients who might need the "normal" treatment. So, you have to have the ambulance fully stocked as normal, plus have this stuff on board too.
Then you have to see if they pick up a case that matches the treatment protocols. And then someone has to decide whether or not to give this stuff to this patient. Is that decision randomized? How?
Every 3rd person with the right vital signs?
I'm really not thinking this is going to work out the way they hope it will. 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.
One possibility is to have the decision of treatment/control assignment made by an off-site medical control person. The "doc" decides over the radio based on telemetry data and talking with the ambulance crew.
Is there pressure on the crew to find the right patient?
If they've got one last subject to fill a cell in their treatment table, does the doc tell them go for it in cases that are sort of borderline?
Seriously, I'd be concerned.
I assume they went through methodological and ethical review panels. But I'm just not seeing how they got this past a skeptical audience.
Maybe I'm missing something about medical treatment decisions in the field. I'll hope to get a response from them and let you all know.
posted
The Loyola protocol is to alternate days (saline v. PolyHeme). [press release] Patients are started on a fluid replacement protocol when they qualify as in a state of hemorrhagic shock -- essentially, unstable vital signs in the face of major blood loss from blunt or penetrating trauma.
PolyHeme has been used in hospitalized patients to replace all the blood in patients. The five clinical trials showed no significant adverse events.
PolyHeme is a different product than the Baxter blood substitute tested in the late 90s. Regarding that trial by Baxter in the 90s, the following additional information may help give more context. [Corrected statistics: Out of the 100 persons in the study, 52 had recieved the blood substitute. Out of those who were given the substitute, 24 died. This compares to the 22 persons expected to die out of 52 persons in similar circumstances] -- that is, the mortality rate was 46.2 compared to the expected [42.6]. Baxter voluntarily pulled the study in the US, but I am not certain why, as the increase of 2 unexpected deaths was not statistically significant (though there was increasing public resistance at that time). The product continued to be studied in Europe without problems.
"Since February, Loyola has been conducting a number of community outreach efforts, including meetings with community leadership; open forums with members of the public; placing public notices in community newspapers; and distributing flyers in schools, churches, grocery stores and public health centers." [press release] These meetings have been very sparsely attended, averaging 0-6 persons per meeting. I don't know how well they were publicized to non-television-watching public, but the story has been covered on Chicago's WGN and ABC7 and NBC5 and CBS2, CNN, and MSNBC, and there are weblinks to all of these.
"During the study, every effort will be made to receive consent from the patient or the patient's family. If there is an objection in advance from the patient or the patient's family, he or she will not receive the blood substitute." [press release]
If there is interest, I will try to find cites for the information above which is not linked already (e.g., the information about the Baxter trial in the 90s). I have summarized my notes from a Grand Rounds (by practitioners for practitioners) presentation on the topic of blood substitutes last year.
[BTW, I am not interested in defending the use of blood substitutes as part of non-consented clinical trials. Just as I don't offer medical advice anymore here at Hatrack, I also don't offer opinions on issues of medical ethics. However, detailed accurate information is always good, and this particular issue is complex enough to be tremendously confusing.]
[ October 19, 2004, 12:14 PM: Message edited by: Sara Sasse ]
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quote: 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.
It looks like alternate days are designated for each treatment. They will control for nonmatching in the groups through multivariate analysis.
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posted
Sara, do you belive that the study should go forward without informed consent?
I worked at USAMRIID for 3 years, and I had personal contact with members of Congress who were on the board that oversaw the MRVS protocols...Medical Research Volunteer Subjects....and this flies in the face of everything I learned from them regarding proper protocals for research studies.
quote:Just as I don't offer medical advice anymore here at Hatrack, I also don't offer opinions on issues of medical ethics.
[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
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
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
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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quote:Studies of human subject must be approved not only by the FDA but also by the local institutional review board.
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.
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
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.
posted
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
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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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
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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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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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 Posts: 3243 | Registered: Apr 2002
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[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
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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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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Variables like age, sex, weight, major chronic medical problems (diabetes, cardiovascular disease), etc.
quote: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.
Chance seems to be the only option, given that this is trauma. A multivariate analysis can correct for unbalanced variables (like the ones above) between the treatment and control groups.
I'm pretty sure the criteria are the basic ones stated. Paramedics generally work to stabilize en route and don't give medications unless under the direction of a physician, e.g. via radio. I think that given the training and given the understanding that PolyHeme improved survival in hospitalized patients (compared to saline) without clinically significant associated side effects, paramedics would be unlikely to remove patients from the protocol at their own discretion. There doesn't seem to be reason to.
I can't find mention of hypertension as a side effect at the product websiste, but the participating Eastern Virginia medical Schools has a PDF file that states "Favorable safety profile. No clinically significant drug-related adverse effects, specifically, no organ toxicities nor systemic or pulmonary hypertension have occurred in clinical trials to date [italics added]" I haven't heard of hypertension for PolyHeme apart from that that comes with volume replacement, which would be the same issue with saline. But since I don't work with it myself, there could well be problems I don't know about.
quote: 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]
If I remember correctly, the blood substitute is blood-colored, so once the sealed package is open, it should be clear that one is not using saline. If the package is opened but the patient is not continued on the protocol for some reason, it would be standard practice to log those reasons as part of the study.
quote: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?
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
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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quote: 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.
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.
posted
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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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.
posted
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.
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: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."
posted
My understanding is that the Chicagoland bioethics scene is dominated by Leon Kass, who is the Big Name appointed by Bush Jr to head a presidential council on bioethics. I have yet to be staggered by Kass' thoroughness, rigor, intellectual honesty, or willingness to support or develop a position contrary to the general trend of public opinion.
Other bioethicists are speaking out against this, just like Annas. Again, though, the media covers the Big Names who tend to toe the party line. But see, e.g.: - Adil E. Shamoo, PhD, co-founder of Citizens for Responsible Care & Research (a NY advocacy group), who is opposing the current study - Art Kaplan, PhD, director of the Center for Bioethics at UPenn, who has declared public notification to be "meaningless" even if we are "enamored of it" [Kaplan is also a Big Name, but he has called into serious question whether public notification strategies can ever be really effective to establish "implied consent" for these otherwise nonconsensual studies] - JD Bleich, PhD, Talmud professor, who opposes nonconsensual trials in general - Jeffrey Kahn, PhD, MPH, director of UMinn Center for Bioethics, who believes that nonconsensual research on blood substitutes destroys fundamental trust between the field of medicine and the public -Len Doyal, PhD from Great Britain, who essentially argues for the inviolability of consent laws and has opposed blood substitute trials for trauma victims in Britain -etc
I have never been particularly impressed with the bioethics hive at Chicago, it's true. There is a definite party line. Anytime there is a consistent lack of diversity of opinion in bioethics, something has gone wrong.
[ October 19, 2004, 12:13 PM: Message edited by: Sara Sasse ]
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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."
I wonder what would cause a bigger outcry? The widespread public announcement that these practices are going on or one saying that no more work on improved procedures for trauma victims will occur. Honest question. I really don't know (not being intimately familiar with the American social climate). The stem cell restrictions didn't seem to bother anyone but scientists, perhaps this would meet the same sort of reaction?
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quote: 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."
The answer is "yes." And the rest of your question is a "straw man," since we've seen a great deal of progress in medicine with the informed consent restrictions in place, so it's not an "either/or" situation. (There have been significant failures in following consent protocols, but that's another matter.)
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Yeah, it is a straw man. But it's so much more simple if it's a straw man. I guess that's the beauty of straw people.
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.
Edit: I guess you could just go to the military where there are frequently blood shortages anyway and use it as a "better than nothing" treatment?
[ October 19, 2004, 12:21 PM: Message edited by: Bob the Lawyer ]
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![[Eek!]](eek.gif)
Wouldn't it be better to try to convince people to wear the bracelets if they want to participate?![[Smile]](smile.gif)
]![[Wink]](wink.gif)
) 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?![[Cool]](cool.gif)
