Docs EMTS & others, ethical human medical experiments without patient consent?

Great Debates
1

I’m really hoping a couple of doctors or other medical professionals will drop in here to provide some fact-based commentary for the rest of us.

I was inspired to this question by this Reuters story about a product designed as a blood substitute.

Medical experiments without patient consent. Today, in America. There are some circumstances when the FDA allows such experiments. The story focuses on PolyHeme.

Here is a product description from the manufacurer.

Their words:

Interestingly, it is made from human red blood cells, the very item it is substituting for. My general impression is that Polyheme has mostly logistic advantages; long shelf life, possibly a more reliable supply because it would not be so dependent on fluctuating blood donation levels, no concerns about blood type mismatch, and I’m sure they have many more hopes for it as well.

And I can imagine this and products like it, IF they work, to be a trmendous boon to society. Reprocessing blood components to greatly increase their shelf life, and maybe decrease the chance of blood norn pathogen transmission, seems like a great idea.

But here’s the tricky part. From an NIH website, here are the inclusion and exclusion criteria for the study:

So you gotta be in shock to qualify for treatment, but you can’t give consent if you’re in shock. So they got an exception that the Reuter’s story in the first link discusses.

I have a lot of questions about this trial. The PolyHeme is being evaluated against a “standard” treatment of saline solution administered by EMTs until transport to a facility where blood is available. Is that the actual standard? Do ambulances carry plasma or anything else they they night use other than saline? And is it in any wat reasonable to call this standard treatment either unproven or unsatisfacctory? Does saline actually have any oxygen carrying capability, or is it just basically to maintain some minimal safe volume?

The trial may have been ethically challenged in another way. Not only did PolyHeme substitute for the saline in the ambulance, it also substituted for the real blood once the patient got to the trauma center. At some point the patient might become cogent enough to decline continuing in the study, But others were given the Polyheme instead of blood “as needed” for 30 days.

Should this test have been allowed?

I have to say no. The manufacturer’s website discusses other trails in which patients were able to give consent, such as elective surgeries. Even in cases whe there is unexected bleeding and the patient goes into shock and needs a transfusion – they could and did arrange informed consent.

So this testing may be more about expanding their market niche than saving more lives.

And right or wrong, Polyheme seems like just the kind of thing the military will buy in order into use in combat zones. Whether this should happrn is a whole nother debate in itself, but if the Pentagon buys in, good luck to the kids. Really, I hooe it will turn out to be a boon to the survival of the wounded, but if I woke up and found this stuff dripping into me, I’d have it removed.

2

I read it slightly differently than you. To me it says that Polyheme can be used in some trauma cases where the situation is dire (the person is badly injured and can’t communicate) but the person might still have a chance with effective treatment. The traditional EMT measures like saline solutions may not do that much good for some people so there is little to lose by giving Polyheme to a person in such a state.

All of that assumes that Polyheme has been shown to be safe and not countereffective through traditional testing. Field testing may provide a good alternative to certain victims and to research without much to lose. I don’t have much of a problem with that.

I do see the problem with continuing to give Polyheme for 30 days in the hospital if it isn’t the best option. I would hope that the doctors as well as the patient or at least the patient’s family would still do an honest review at the first opportunity.

3

I have to disagree. One of the EXclusionary criteria is “Patients who have sustained unsurvivable injuries”.

This is, I think, a real methology problem. There is an automatice exclusion of those with the very worst injuries, which would tend to make the product look better against standard treatment – ublees the standard would be to just pack up and let the patient die.

I have concept I’m hoping some EMT might validate or shoot down. I imagine that EMTs don’t often make a call that injuries are “unsurvivable” while there are still vital signs. Basically, they work on the patient until death or until they get to an ER. Maybe I’m wrong about this.

4

From the FDA discussion here:

See Slide #6:

from Slide #8

It’s creepy, but it seems acceptable, given the restrictions and circumstances involved.

5

The slide show is about the criteria that justifies experimenting without informed consent

The question is whether THIS study fits within these criteria. I would argue that, at the very least when real blood is available, providing the blood substitute takes it outside the bounds.

For EMTS to use it on the street is IMO less of an ethical stretch, but I don’t feel I have enough knowledge about medicine and trauma to be have a strong opinion about this.

6

I’m actually pretty familiar with this study. One of our neighboring services, whom we frequently back up is a part of this study, as is one of the local Level I Trauma Centers.

The logistical advantages are more significant than you make them sound. As of right now, there is no practical way to carry/use blood products on a ground ambulance. Most air medical services do not routinely carry blood products, either. There’s also some significant disadvantages to crystalloid (saline, Ringer’s Lactate, etc.) solution volume-replacement. Namely, as you increase the patient’s blood pressure, you can increase the rate of blood loss, and decrease the patients ability to perfuse vital organs since crystalloids have no oxygen-carrying capacity.

My understanding of the “unsurvivable injury” exclusion is that they did not want patients worked with PolyHeme that would have been pronounced otherwise.

Yes. Either normal saline or a similar isotonic crystalloid solution is the standard of care of fluid therapy.

No.

I’m not sure what the literature has to say on saline fluid replacement. If it’s like anything else in EMS, there’s either little or no research available.

Saline has no oxygen carrying capacity whatsoever. It’s used only to increase the circulating fluid volume and blood pressure.

I disagree. As long as the patient or their guardian is able to revoke consent at any time during the 30 days, I have no problem with it. The study has been well publicized in the areas it has been taking place. The intended market for PolyHeme is in EMS and hospital emergency departments so that’s where the testing should take place.

St. Urho
Paramedic

7

ok, I haven’t read the studies so this is just general opinion. But sooner or later you’re always testing “unproven” treatments on pts, just as you’re always practicing new procedures on then. All the lab and clinical trials prove it’s real world success. I’m guessing that one of the advantages of polyheme is it skips the whole type and crossmatching bit. This would be most usefull in prehospital and er situations. We often transfuse blood in the er without a consent, although one is required for routine transfusion. As st urho said that’s where it has to work, so it’s not proven until it works there.

8

outlierrn- The other big advantage is that PolyHeme has a longer shelf-life than blood products and doesn’t require refrigeration. This makes it practical to stock PolyHeme on the ambulance.

9

Hmm…can PloyHeme be made from blood that has passed its “use by” date?

If so…

10

d’oh, that should have read all the lab and clinical trials DON’T prove it’s real world success, carry on.

11

As a 20+ year ER nurse, I think PolyHeme has a great deal of potential for saving lives. Based on the manufacturer’s discussion of how it is made, it appears that PolyHeme is essentially a Ringer’s Solution with the blood component hemoglobin added. All of the reaction-causing antigens, antibodies and other cellular components are removed so the risk of hemolytic reaction is absent. This can greatly accelerate patient stabilization. One of the scenerios in the cited literature was that 20 units can be infused in 20 minutes. It would take a minimum of 10 hours for whole blood or packed red cells of the same volume to be delivered, even if not delayed by crossmatching. It also appears that the hepatitis and HIV threat is absent in this product. The only issue I have is the continuation of treatment with PolyHeme after the pateint resumes the ability to give consent, although if the patient has the option to revoke consent, then it is a non-isssue. I would certainly want this product given to me if I was in shock and in need of large amounts of blood. Example: Young woman’s car is T-boned on her side of the auto but she appears to be okay. Within 15 minutes of arrival to community ER she begins to crash from occult liver laceration. She wonn’t make it to the OR because it’s 2 AM and the OR staff must be called in (no 24-hour OR). MedEvac takes 15 minutes to arrive for transport but she only has about 5 based on her BP. Give PolyHeme without permission/consent? Absolutely. Unfortunately, this patient did die - from circumstances more than anything else. She would have been retrievable in a different setting or with the option to have this type of product available.

Don’t be confused: In my initial post on this forum, I indicated I am a Licensed Battlefield Guide at Gettysburg and I am. I’m also a burned-out ER nurse (but no longer smoldering!).

12

I understand and appreciate what you’re all saying about the potential of Polyheme. I agree.

What I really was to discuss though, is whether this particular study methodology is necessessary or appropriate or ethically sound. Specifically about two elements. The first being “enrolling” patients is the study under condition practically guaranteed to preclude informed consent. The second being the continuation of the protocol past the point when whole blood or other necessary blood products are at hand, again without consent.

I just want to point out that to many people including me, the idea of informed consent is THE fundamental ethical underpinning of human medical research. It is not something to put aside lightly.

So maybe a better way to pose this issue is, is Polyheme SO promising and SO useful that we ae warranted in putting the usual ethical rules?

And do we really need to? Can we devise protocols that gather the needed information from a population who provide advance consent? It wouldn’r necessarily be fast or easy, but it seems possible.

13

Yes, yes it is that promising. Others have made the arguement more forcefully, but if it lives up to the hype, PolyHeme is superior in every way to available blood transfussions.

Also, let me ask you what the alternative to this clinical trial is. How else should research into emergency medicine take place?

Medicine, and emergency medicine in particular is filled with cock-up treatments that ended up doing more harm than good. Military Anti-Shock Trousers, aggressive rehydration therapy for people in shock, aggressive dehydration therapy for closed head injuries and on and on. All of these medical practices were instituted simply because they seemed like a good idea at the time, some doctor or inventor managed to market the device or technique, and then it was widely used and applied upon people incapable of giving informed consent. With the PolyHeme trial, medicine has advanced to simply saying that we’ll have a limited initial deployment and we’ll use real science to determine if it’s helpful or harmful.

The less invasive trials involving prior consent to demonstrate safety, etc. have already taken place. In the past, PolyHeme would have simply been universally adopted. Now, we’re double checking prior work to make sure that we have a really valid sample involving the type of acute hemodynamic shock that it would actually be used for.

The only real alternative if you wanted to even allow emergency medicine to advance would be to adopt PolyHeme into protocols and standards of care universally, but now you have an equally untested and potentially unsafe treatment being used upon people that cannot meaningfully consent for everyone instead of a smaller trial first.

This PolyHeme trial is the best way to go.

14

I know that The Dope has a general rule against Zombie-Threads, but it doesn’t seem like this thread has been down for too long so I thought I’d try to bring in a bit more perspective on what happened with the now-complete trial.

Basically, PolyHeme failed. It didn’t prove to reduce mortality when applied to EMS systems, and it likely will not be approved.

http://www.northfieldlabs.com/amb_trial.html

Was the trial still a mistake? I would argue that it was not. Again, if a mechanism for such clinical trials was not in place, there’s an excellent chance that PolyHeme would now be a part of the standard of care for pre-hospital hypovolemic shock, and even more people would have been hurt and have no meaningful way of giving consent to that treatment.