UC-Davis doctors banned from research.

July 24, 2012 4:38 PM

2 UC Davis neurosurgeons accused of experimental surgery are banned from human research. Bacterial infection after surgery to remove glioblastoma is thought (anectodally by neurosurgeons) to confer survival advantage to patients, despite limited and contradicting information from previous studies (abstract 1, abstract 2). Drs. J. Paul Muizelaar and Rudolph J. Schrot, with patient consent, introduced Enterobacter aerogenes into open wounds of 3 terminally ill patients in an effort to prolong life. Two patients later died due to sepsis. Upon learning that Muizelaar and Schrot had given patients the bacteria, UC-Davis notified (pdf) the Food and Drug Administration of the serious non-compliance issue. Currently, both Muizelaar and Schrot remain employed at UC-Davis, and Muizelaar remains chairman of the Nuerological surgery department.
posted by nasayre (49 comments total)

Mod note: It's easy to Godwin the thread. Don't.
posted by jessamyn (staff) at 4:49 PM on July 24, 2012 [10 favorites]

Why would an IRB not have permitted this with the proper preparations?
posted by Matt Oneiros at 4:49 PM on July 24, 2012 [1 favorite]

The patients consented. The problem, as far as I can see, is that the surgeons hadn't made an adequate case to the FDA and to their Institutional Review Board (IRB) that their departure from the usual standard of treatment did not constitute human research or investigation of a novel biologic intervention. Surgery has been slower than medicine to embrace the idea that experimental approaches that deviate from the standard of care need substantial justification and evidence.
posted by gingerest at 4:55 PM on July 24, 2012 [1 favorite]

No, Muizelaar isn't Mengele, but his actions not only circumvented regulations, they were indeed evil. Terminally ill patients are a vulnerable class of people whose families often feel they have "no choice" but to consent to any "treatment" offered, even one that is going to subject them to horrible pain and suffering for no established benefit. Two of the three patients died of sepsis as Muizelaar proceeded with his belief in "laudable pus," yet he was pushing forward with five more, against FDA and IRB orders. Taking advantage of the desperate doth not a medical hero make.
posted by DrMew at 4:58 PM on July 24, 2012 [8 favorites]

I don't think the issue is that they couldn't have got permission if they'd asked for it, but rather that they didn't ask for it in the first place. Or rather, they had permission to do something more limited and then expanded their scope without asking. This is something that Does Not Amuse IRBs.

I mean, yes. Nobody was really "hurt". The patients consented, and they were terminally ill anyway. But researchers have to ask permission for that kind of thing, and not just of the patients. Institutional Review Boards exist for very good reason and we can't just say "oh, we'll let it slide because we totally would've given permission." Medical research, especially on human subjects, is an area that needs to be closely monitored and governed because the potential for abuse is astronomical. There's no room for selective enforcement.
posted by Scientist at 5:00 PM on July 24, 2012 [2 favorites]

Also, yeah, I should qualify that I don't actually believe nobody was hurt. Sepsis is not a great way to die, it's a pretty nasty thing. It is possible that the patients who were treated with the bacteria did not give fully-informed consent, that they were not given all the information. Part of the mission of IRBs is to make sure that people are given the full set of facts in cases like this.
posted by Scientist at 5:02 PM on July 24, 2012 [2 favorites]

They got permission for a one time use, but continued to perform the procedure.
posted by nestor_makhno at 5:07 PM on July 24, 2012

Scientist: "Institutional Review Boards exist for very good reason and we can't just say "oh, we'll let it slide because we totally would've given permission.""

I learned that the hard way when I took candy from my dad's supply just assuming he would give permission (as he always did before).. Seriously, don't just assume you have permission. ASK! Especially when it's, you know, potentially life threatening. What kind of shit researchers are these?
posted by symbioid at 5:12 PM on July 24, 2012 [4 favorites]

Something tells me they'll be all right.
posted by anarch at 5:13 PM on July 24, 2012 [3 favorites]

Oh! And sorry to serial-post, but good on UC Davis for not trying to cover this up. This guy (Dr. Muizelaar) is a very prominent person there, and all too often such people are protected by their institutions when they are found to be engaging in questionable behavior. I hope the school doesn't lose funding, it really sounds from the article like these guys were acting pretty much on their own and that as soon as the school got wind of it they reported the actions to the proper authorities.
posted by Scientist at 5:14 PM on July 24, 2012 [5 favorites]

The UC Davis IRB is broken and has been for a while. Last year or two, a new E.D. came in and things started improving remarkably. He left for another institution, though, and now things are as bad as they were. It takes FOREVER to get even simple proposals approved. (Some of my coworkers' grants have been threatnend because of IRB holdups.)

Those docs should not have done what they did, but they also might have been trying to find a workaround for a really frustrating institutional problem

Irony is, now there's fear that IRB approvals will take even longer.
posted by mudpuppie at 5:21 PM on July 24, 2012 [4 favorites]

When conducting experiments on human subjects, it's pretty much always better to ask for permission than beg forgiveness.
posted by rtha at 5:21 PM on July 24, 2012 [2 favorites]

It is extremely odd that it came to this. For those of you that don't bother to read articles, here's kind of the heart of it:

At Muizelaar's direction, the letter states, Schrot got IRB permission to move forward on Patient No. 1 with a "one-time procedure" that was "not associated with any research aim," the letter states.

University documents show that the physicians believed they had been given the go-ahead for all three surgeries, but officials later determined that they had been misinformed or were misunderstood by the doctors.

With the amount that the FDA screws up approvals, performs surveillance on whistle-blowers, fires and prevents placement of whistle-blowers, and approves trials that were blatant frauds such as the Duke case, I can't believe that the FDA would consider this a huge misconduct. Misunderstanding one vs. three is a very big deal, but it's a single instance of negligence and is not behavior motivated by unethical behavior or moral turpitude, the latter of which is apparently A-OK within the FDA.
posted by Llama-Lime at 5:21 PM on July 24, 2012 [2 favorites]

Medical research is very particular about procedures and permissions. But even an IRB isn't a guarantee of ethical behavior. Even with the full approval of an IRB, Jesse Gelsinger passed away from gene therapy trials that should not have been performed on him. And then you have the anti-vaccine loonies forming their own bogus IRB to pass off their own research as legitimate.
posted by Blazecock Pileon at 5:23 PM on July 24, 2012 [1 favorite]

"When I first told them of my experimental procedure, the fools laughed at me and dared to call me MAD! But now that two of my three patients are dead thanks to my incompetence, who's laughing NOW?!?"
posted by wolfdreams01 at 5:24 PM on July 24, 2012 [4 favorites]

To be clear, I'm not defending the surgeons, just trying to pick the facts from the outraged commentary in the Bee article. That said: if the case can be made (and of course it actually has to be made, with evidence, to the IRB and to FDA) that a treatment is more beneficial to these patients than standard care, and the patients in question have a very short lifespan in which to be treated, then delays in IRB review may pose a greater risk of harm to the patients than proceeding without review. That is, if institutional sluggishness prevents people from participating in novel, life-saving treatment, it may, in fact, occasionally be better to seek forgiveness than permission.
I certainly am not equipped to say that's the case here. Many IRBs have an expedited review process that addresses cases where the review needed is minimal (for minor protocol changes and for minimal-risk protocols) and cases where the need to implement the protocol is very urgent.
posted by gingerest at 5:31 PM on July 24, 2012

I should probably also be clear that I'm not endorsing proceeding without review, ever - I'm saying that the institution can (rarely) be more at fault for failing timely review than anyone else in the process.

By the way, since glioblastoma has a median survival time of 3 months without treatment and 14 months with aggressive chemo and radiation therapy, every new intervention in this disease is essentially experimentation with terminally ill patients.

(Bartek J. 2012. Key concepts in glioblastoma therapy. J neurology, neurosurgery and psychiatry 83(7):753 -60)
posted by gingerest at 5:53 PM on July 24, 2012 [1 favorite]

That said: if the case can be made (and of course it actually has to be made, with evidence, to the IRB and to FDA) that a treatment is more beneficial to these patients than standard care, and the patients in question have a very short lifespan in which to be treated, then delays in IRB review may pose a greater risk of harm to the patients than proceeding without review.

It is obviously an urgent matter to get approval for an experiment on a terminal patient. He might die before you get to experiment on him. You might not get another chance, since terminal patients appear so rarely in hospitals.
posted by charlie don't surf at 5:55 PM on July 24, 2012 [1 favorite]

My first thought was that this was the best situation for the worst of medical offenses, someone who is already on death's door.

Terminally ill patients are a vulnerable class of people whose families often feel they have "no choice" but to consent to any "treatment" offered, even one that is going to subject them to horrible pain and suffering for no established benefit.

Then I read that. Yeah, you would really need to restrict (if not abolish) this kind of thing. The initial discovery phase stuff to people who are rather emotionally stable (and on death's door) and capable of giving informed consent and not just, you know, consent.
posted by Slackermagee at 6:05 PM on July 24, 2012 [1 favorite]

Terminally ill patients are a vulnerable class of people whose families often feel they have "no choice" but to consent to any "treatment" offered . . . . Taking advantage of the desperate doth not a medical hero make.

I take exception to this and to the similar sweeping blanket generalizations about the cognitive abilities of patients and their families made by a bioethicist in the Bee article. Don't get me wrong: I'm not advocating that patients should receive any treatment they demand/prefer or that their wishes should supersede IRB findings or empirical evidence. And I'm not on any "side" in this particular case.

But.

If you're going to dismiss wholesale an entire "class" of patients (or patients in general since even non-terminal situations can be very stressful and upsetting) as too "vulnerable" or "desperate" to "think straight," then why even bother getting consent at all? Why not just subject patients to whatever the doctor and IRB decide is permitted? The article mentions the example of terminal patients going to Mexico for laetrile or what have you, but this might be a person who, in the bloom of health, also believed in dog psychics or Jesus or the designated hitter or something equally absurd. People routinely think and do wacky stuff while compos mentis, and many non-MDs are actually capable of being in intensely pressurized high-stakes freaky-ass situations without losing their ability to reason.

I have a big curiosity about medical stuff, and when I'm ill (or one of my critters is), I'm often fascinated by all the details and procedures. It's a learning opportunity. I like watching my own surgery videos and do it perfectly dispassionately. Similarly, many people, even when they're afraid and suffering, manage to confront their imminent deaths without coming unglued; what would make me come unglued is someone infantilizing me and trying to negate my sense of agency. This is maybe the last thing some of these people (or their loved ones) get to have any say in before the ultimate loss of control. Unless they demonstrate clear signs of being out of touch with reality or utterly unable to make a decision themselves, then why shouldn't we assume that, if they're receiving the necessary info, they're making the choices they think best and respect that?
posted by FelliniBlank at 6:24 PM on July 24, 2012 [4 favorites]

Many IRBs have an expedited review process that addresses cases where the review needed is minimal (for minor protocol changes and for minimal-risk protocols) and cases where the need to implement the protocol is very urgent.

And UC Davis is one of those institutions. Problem is, everyone tries to submit an expedited review because there's such a huge backlog, which leads to a backlog of expedited reviews as well.

My perspective on this might be slightly skewed. The kind of research my department performs on human subjects is more of the asking-questions sort than the hand-me-the-scalpel kind, so maybe we get pushed to the bottom of the pile. But I know from our contracts & grants analysts that there is campus-wide frustration with IRB's sluggishness, much of which can probably be contributed to understaffing. (I don't know if they actively reduced staff back during the layoff period 18 months ago, or if they're just not re-filling positions, but I do know they're understaffed.)

It's just one example of administrative sloth at UCD. (Not bloat. It's not really that bloated any more. Just slothful.)
posted by mudpuppie at 6:25 PM on July 24, 2012 [1 favorite]

You can't backdoor a research protocol by going to the IRB Director every time a prospective subject turns up and telling her that it's an emergency "innovative care" treatment. The FDA told them that they couldn't do this without specific evidence in animal models, but they ignored that suggestion and went right to experimenting on patients. The IRB was right to come down on them.
posted by demiurge at 6:27 PM on July 24, 2012 [2 favorites]

Yeah, I've got to say, as much as it slows medicine down, having someone else look over research on humans seems like a good idea, given what has been done in the past.

The specific example I am thinking of isn't listed, but it occurred in Montreal as I recall. Basically, they injected terminally ill patients with radioisotopes to see what the effect would be. Turns out, some of those patients illness were not nearly as terminal as expected, and the injections did a lot of harm.
posted by Canageek at 6:28 PM on July 24, 2012

It is obviously an urgent matter to get approval for an experiment on a terminal patient. He might die before you get to experiment on him.

If you were kin to someone dying of this horrible aggressive cancer, you would probably be kind of angry if you heard that there might be new treatment options but the person you loved was going to die before the approval to try them came through.

Maybe you're not old enough to remember, but there was a revolution in the NIH funding process and the IRB and FDA approval processes in the late 1980s because the clinical trials process was so slow, and people with AIDS were dying because the drugs available were ineffective but the experimental drugs were hung up in the approval process.

Even a fast-tracked drug takes seven months to come to market. You do the math for a median survival time of 14 months.
posted by gingerest at 6:29 PM on July 24, 2012 [3 favorites]

I don't think this was a case of the IRB moving too slowly to get paperwork completed, which is an administrative issue. This was a case of the IRB and FDA denying a protocol outright and the attempts to implement the research anyway, skirting around the IRB.
posted by demiurge at 6:31 PM on July 24, 2012

Terminally ill patients are a vulnerable class of people whose families often feel they have "no choice" but to consent to any "treatment" offered, even one that is going to subject them to horrible pain and suffering for no established benefit.

Again, if you take this as granted, there is absolutely no reason to ask the patient. Your choices are now 1) Never, ever use experimental therapies on this class of patients or 2) Use them without asking.

Is either case always correct?

Anybody thinking this case is simple hasn't even begin to think it through. Yes, there was contradictory evidence based on limited patient trials. How do you resolve this? More testing, of course.

Yes, sepsis is a nasty way to die, but it's a nasty and short way to die. GBM is a nasty, long way to die, as your brain -- and your memory, and your sole, is slowly eaten away, and you get the following choice -- repeated seizures, or repeated side effects from anticonvulsants.

There is one worse brain cancer -- a brainstem giloma. But otherwise, GBM is a nasty, painful, tortuous way to die. I've seen three people I know go from it, and not only did I see them suffer, I saw who else suffered.

I'll be honest. Killing these people by sepsis is arguably a kindness.

Now, you have two doctors who had a single-patient trial, but, for whatever reason, tried it on three patients. It is possible they thought they had a single *round* trial permission. It is possible they ignored the fact that they did not.

The issues with UCD's IRB are well documented. How many could have been saved, or enjoyed a better last year of life, if UCD's IRB acted in a timely fashion?

But, on the other side -- they explicitly killed two patients with an experimental treatment they did not have permission to perform. Human Research is a situation where it is trivial to act unethically -- even if the end result helps thousands.

The Nazis threw countless people into ice cold water and documented how quickly they died and why. Many, many people were killed by this. Did we burn the results of this horrible research?

No. We used it to develop hypothermia protocols, and protective gear, that has saved thousands of lives.

Ethically easy? This isn't even ethically hard. There are compelling ethical reasons against ever using this data -- and for using this data.

One more case. The process for human experimentation used to be much more complex and approval was much more difficult to obtain. This changed in the late 1980s. Why?

AIDS. AIDS activists demanded that potential treatments be fast tracked, because, well, once you went into full blown AIDS -- CD4 counts below 200/μl -- you died, horribly, within months.

Thanks to that, now, AIDS in developed nations is actually fairly rare. There a number of HIV+ patients, but the various regimes developed -- by trying on, and in some cases killing people -- have enabled many HIV+ patients to keep a functional immune system.

And now, this fast track process is under question.

This isn't easy. This isn't even hard. This is incredibly complex.

Do I condemn them? I don't know. I don't have all the facts. It may well be that, in the end, even though it rapidly kills 2/3rds of the patients, it grants a much longer survival time to those who survive.

In this case? Would I give this treatment -- knowing that the outcome was 66% fatal within two weeks, and 33% large extension of quality life?

I don't know. It's so far beyond hard that I don't even know how to start to answer the question.

I'm not even sure I know how to phrase it.
posted by eriko at 6:47 PM on July 24, 2012 [8 favorites]

Your choices are now 1) Never, ever use experimental therapies on this class of patients or 2) Use them without asking.

Couldn't your choice be "Have very stringent review board standards about what you can present to people with terminal illnesses and how you have to phrase it"? You don't HAVE to provide experimental treatment without asking, you just have to make sure that there are extra safeguards and people without a direct emotional investment (e.g. the review board) giving informed consent and ensuring that the patients and their families have the best information possible as they give (or don't give) their consent.
posted by Mrs. Pterodactyl at 6:53 PM on July 24, 2012 [1 favorite]

Jonathan Eisen, prominent open science practitioner and a professor at UC Davis, has an extensive blog post collecting relevant information and links.

In that post, there's a news article from 2008 about a lawsuit from a surgeon alleging wrongful termination for criticizing Dr. Muizelaar and speaking on "Dr. Muizelaar's unlicensed, illegal medical practices and documented medical incompetence," amongst other allegations. So perhaps there is a pattern here beyond a single case. Now, it may be that lawsuits like this happen somewhat regularly even without wrongdoing, but it may also be that Dr. Muizelaar, sixth highest paid person in the UC system, was reckless but kept around because he brought in enough money to pay his salary and more. If so, it would seem to make this particular negligence in following the IRB's directions.
posted by Llama-Lime at 6:55 PM on July 24, 2012 [1 favorite]

... that much worse and more inexcusable.
posted by Llama-Lime at 6:56 PM on July 24, 2012

Is there a possibility these guys could lose their medical license? Or are research neurosurgeons not answerable to their state medical board?
posted by muddgirl at 7:17 PM on July 24, 2012

Is there a possibility these guys could lose their medical license? Or are research neurosurgeons not answerable to their state medical board?

According to this, Muizellar, trained in the Netherlands, is not licensed in California, but has a "medical board permit" to practice at his medical center and affiliates.
posted by Brian B. at 7:42 PM on July 24, 2012

Yeah, but if you can't experiment on the helpless and infirm, who CAN you experiment on?
posted by blue_beetle at 7:49 PM on July 24, 2012

Yeah, but if you can't experiment on the helpless and infirm, who CAN you experiment on?

If I had given my permission to experiment with my health, one of of my reasons would be for scientific advancement, and the other two reasons would possibly be for free medical care and the possibility of actually surviving. They are all valid reasons. If the state rejected this proposal, I would view it as a violation of my civil rights.
posted by Brian B. at 7:57 PM on July 24, 2012 [1 favorite]

But, as a patient and possible lay-man, how can you be sure that the experimental treatment they offer you has actual science behind it, and is not a surgeon working on hunches? How do you know that the procedures they use to test the treatment will lead to conclusions, that the necessary controls are in place? How do you know that every care has been taken to inform you of the possible good AND bad that can come after the treatment?
IRB.
This is their job, to check those things so that you, as a vulnerable patient, can trust that the doctor offering you a possible miracle is basing it on something more than hope.
If the state or IRB rejected the proposal, there is a reason given for it, and it is done in the name of protecting your civil rights and of good science.
posted by nasayre at 8:07 PM on July 24, 2012 [1 favorite]

The bureaucratic slowness of IRBs is pretty legendary stuff. What could be done to speed up this very important job, without compromising the quality of their work and letting more dubious studies slip through the cracks? Can anyone with direct experience dealing with IRBs offer some suggestions?
posted by Scientist at 8:13 PM on July 24, 2012

Why the assumption that panic or fear would have to have anything to do with a terminal person's choice?

I'm not suffering from any terminal condition at all. Yet I can, pretty easily, while utterly free from panic or vulnerability, already judge that if I were terminal, I'd prefer a wildly experimental long shot. Why is a judgement that I would have nothing to lose so foreign to some people? I mean, clearly, I wouldn't want to pursue such a long shot if it were going to pauperize my family, or if the standard treatment held out much hope of a real recovery.

Truthfully, I can think of many terminal conditions where I'd much prefer a self administered treatment of a shotgun to the head than to die a lengthy dehumanizing and agonizing death. A willingness to try some sort of novel experiment -- even if it's someone's wild hunch -- instead is, if anything, less extreme.

I understand that running medical programs that way leads to a sort of wild west, so I don't say these doctors did the right thing. But find them problematic on that basis -- that there have to be either standards or chaos -- and don't base that on the idea that the terminally ill will always grasp at straws that they'd reject if they were more coldly rational about it.


If the state or IRB rejected the proposal, there is a reason given for it, and it is done in the name of protecting your civil rights and of good science.

Or the desire to cover the institution's butt. Or to satisfy internal politics.
posted by tyllwin at 8:15 PM on July 24, 2012 [3 favorites]

But, as a patient and possible lay-man...

I would determine for myself that my doctors were positively ambitious, and wished to be successful well beyond conventional treatment. I would also assume that conventional treatment would probably mean less incentive and genius from my doctors involved, and perhaps a routine, matter-of-fact, low expectations from them. However, my first reason of medical advancement trumps my game theory anyway.
posted by Brian B. at 8:22 PM on July 24, 2012

Yet I can, pretty easily, while utterly free from panic or vulnerability, already judge that if I were terminal, I'd prefer a wildly experimental long shot.

It's easy to say this when you're not terminally ill, and not looking at a specific experimental protocol. I see people all the time who are given the choice between (A) you will likely die within 6 months, but we will be able to manage your pain and other symptoms so you can comfortably spend time with your loved ones at home, vs. (B) this drug might give you a few more years, or it might kill you within the month, and you're going to have to spend that month in the hospital, probably puking and tired and too miserable to talk to your loved ones.

If the biggest failure of a long-shot experimental trial was to not change your outcome, everybody would go for it. Duh. But most of them have the strong possibility of killing you more quickly and/or making you more miserable on your way to death. It is not an obvious choice, to go with the wildly experimental long shot.
posted by vytae at 8:26 PM on July 24, 2012 [1 favorite]

But most of them have the strong possibility of killing you more quickly and/or making you more miserable on your way to death. It is not an obvious choice

That point is well-taken. But while the details may make quite a difference, I don't think that the immediacy of the situation is going to make much of one.
posted by tyllwin at 8:33 PM on July 24, 2012

Medical advancement is an important goal. But you are implicitly accepting the idea that what is being offered actually has the possibility of helping, because the doctors should know something you don't. But a patient is not well equipped to judge if a particular treatment will advance knowledge of medicine. What if you accepted an experimental treatment, but the trial was so poorly designed that proper conclusions could not be drawn from it? There would not be medical advancement in this situation. How do you know that the doctors aren't just trying crazy things? For example, these doctors could have tested their ideas in an animal model first, before trying it in humans. As far as I can tell, they didn't. This is often a pre-requisite before a trial is allowed in humans.
posted by nasayre at 8:34 PM on July 24, 2012

Nasayre, if it was a child, we could be more cautious and fret the objective pros and cons of pain and suffering. But adults have their own instincts to rely on and there is no wrong decision to make here, only a more timid one versus a more daring one. At some point in life we should all be ready to set aside our anxieties about living and be willing to take one for the team.
posted by Brian B. at 8:54 PM on July 24, 2012

Demiurge: You can't backdoor a research protocol by going to the IRB Director every time a prospective subject turns up and telling her that it's an emergency "innovative care" treatment.

The "research" part is actually quite important here, as that first patient Drs. Muizelaar and Schrot treated actually feel outside of the IRB's purview. This gets into a complicated grey area of the federal regs, but since I am a Certified IRB Professional, let me see if I can break this down.

Reading over the SNC letter to the FDA, it seems that the physicians first approached the FDA to get permission to use the bacteria as a "single patient treatment IND," which is a recognized part of the FDA's Expanded Access program to allow the use of non-approved treatments. Someone mentioned HIV drugs up-thread and they are the most cited example of when a Treatment IND may be issued to help speed the research and approval process. This was more of a "compassionate use" issue though; basically recognizing that the patients were near death anyway, and asking permission for a Hail Mary treatment. This still would have required FDA approval for each use of this treatment though.

All of this was made moot when the FDA rejected the request, rightly noting that the bench work and non-human research just wasn't available to justify it. As such, the Docs got started on doing that pre-clinical work. It was during this time that an eligible patient came along, the Docs re-approached the IRB, and things got all pear-shaped.

See, "innovative care" is actually a real thing. When a physician uses a drug off-label, that's "innovative care." If a surgeon got your consent to graft you with octopus tentacles to help with your carpal tunnel, that's (very) "innovative care." There are institutional rules put in place to provide safeguards on this (and the Docs did follow them for pt #1), but this isn't considered research and doesn't require IRB or FDA approval so long as the treatment is limited to a small number of individually considered patients, and the physicians don't plan on using the procedure to collect data for an IND application. This article discusses innovative care in a radiology context, but the same ideas apply generally.

The IRB will often be consulted in these cases, but it's not required. My own IRB had a case a few months ago of a polio researcher who wanted to pretty much infect himself with polio, as his bench work had suggested it might help fight his terminal cancer. Our cancer center leadership were ready to go ahead with it, the virus was coming from his own lab iirc (so there wasn't the additional legal hurdle like the UCD folks had), and they weren't planning on pursuing an IND, so my IRB wished him godspeed and good luck. It wasn't research, it was treatment, and the IRB doesn't get to tell doctors how to treat their patients, only their subjects.

That first patient at UCD then, was operated on and infected with bacteria in a perfectly legit way. It was only when the Docs asked the IRB to do a second patient, and were told by the UCD IRB that it was time to re-apply to the FDA before doing any more procedures, that things went awry. It'd be easy to start seeing malfeasance on the part of Muizelaar and Schrot (the ad hoc ethics committee seems particularly fishy), but I think it's much more that physicians -- even ones that do research regularly -- are often quite ignorant of the regulations governing their work. They're focused on the treatment aspect of the procedures they are developing, and the more opaque and byzantine regulations they need to be following can fade into the background.

This confusion is also why these bozos won't be losing their licenses. The FDA letter takes great pains to stress that Muizelaar and Schrot were acting in good faith, which is par for the course. Everyone knows the rules are complicated and everyone knows that physicians see the rules as secondary to their "actual" work. Also, it's a rare rare case when a doctor doing unapproved research can really be found to have been blatantly and maliciously ignoring disapprovals from the IRB or the Feds. The CAPA plan for these two is pretty typical: they'll step down from any research projects they're on, the junior partner will attend a training seminar, and the university will tinker with their policies and education efforts. After a while, both docs will be deemed rehabilitated and go back to working on human subjects research, probably on this very idea.



One last thing on IRB slowness before I wrap up this too long comment. This is inside baseball griping, so feel free to skip.

The nature and scope of what IRBs cover has transformed tremendously over the past decade or so. The major shift came with the Gelsinger case that was noted up-thread, which really kicked the research community out of a torpor and made requirements for getting approval for human subjects research much more stringent (not even at the IRB level, but throughout the process, particularly for Conflict of Interest oversight). What passed for an IRB application back in the late 90s/early 00s would get laughed out of the office now. The passage of HIPAA and the establishment of IRBs as privacy boards also added more to the workload, and research in general has been a metastasizing field with an attendant increase in volume of submissions. Yet, offices that handle research oversight and review (like the IRB), are rarely high on institutions' list of concerns. My own office is fortunate enough to have a director that kicks ass and has seriously transformed the quality, culture, and speed of my IRB, but my institution also bought a shiny new hospital, and apparently didn't even consider how to integrate their investigators or IRB into our own system. Don't get me wrong, I've met colleagues who I would describe as "incompetent chucklefucks," but I've also met a lot more who simply don't have the staff or infrastructure to deal with what's being asked of them, or the funding to improve either.
posted by Panjandrum at 3:05 AM on July 25, 2012 [17 favorites]

Correction: Muizelaar and Schrot got cited for serious AND continuing non-compliance, which is all the non-compliances you can have. Still, barring additional admonition in the form of an FDA audit or a congressional hearing, that doesn't change much.
posted by Panjandrum at 3:11 AM on July 25, 2012

Oh holy crap. There are articles in these blog aggregations that accuse Muizelaar of practicing medicine without a license! He isn't even licensed to practice medicine in California, he has an SFP, a Special Faculty Permit. This permits him to "practice at other hospitals that are formally affiliated in an educational or instructional manner as a part of the medical school's instructional program, since the SFP is purely an academic appointment and not intended for the holder to practice medicine at large.."

But here is the kicker:

"The other interesting fact about the SFP is that a hospital is not required to report adverse malpractice actions against such a holder because in fact, the SFP holder does NOT have a medical license, thus the general rules of reporting do not apply to the SFP holder the way they apply to a holder of a valid, unrestricted California medical license."

Mulezaar has beeb head of neurosurgery for yers, and had plenty of time to get a full CA certification. I can only assume that he did not because it confers immunity from public disclosure of malpractice accusations. And one of his peers accused Malezaar of having significant problems with disproportionally high mortality and malpractice actions, and those accusations go back to 2008.

It seems to me, this guy should have been kicked out of the medical profession years ago.
posted by charlie don't surf at 4:07 AM on July 25, 2012

From the Medical Board of California website:

Special Faculty Permit under Section 2168 of the Business and Professions Code:
An internationally trained physician, who is sponsored by the dean of a California medical school and has been recognized as academically eminent in their field of specialty by the Medical Board of California, may be issued a Special Faculty Permit under Section 2168 of the Business and Professions Code. This permit authorizes the physician to practice, with all the rights and privileges of a California medical license, only in the sponsoring medical school and its formally affiliated hospitals.

It's a real medical license, limited to work in the sponsoring hospital system. It takes a lot of time and money to get a California MD if you did your education and training overseas. Some people have to go through residency again, which can be up to 7 years for surgery, plus 2-3 years of fellowship to specialize in neurosurgery. There are a lot of reasons other than "immunity from public disclosure of malpractice accusations" to get an SFP instead.

I don't mean to be an apologist for these guys, but the high emotional pitch around this case is obscuring some of the facts around the conduct and expectations of medical research in general and in this field in particular.
posted by gingerest at 7:40 PM on July 25, 2012 [1 favorite]

Yeah, it's pretty common not to get another medical license in a different state/country. That's why I asked if they could lose the license granted by "their state", not the state of California.
posted by muddgirl at 7:50 PM on July 25, 2012

Guessing: Prof. Muizelaar could be subject to administrative enforcement and penalty against his SFP, but I think complaints in California probably fall outside the scope of his Dutch license (unless there's a code of professional conduct that covers extrajurisdictional misbehavior.)

(By the way, looking into his research record, he's a very big deal in his field and I'm not surprised if arrogance is what landed him in this mess.)
posted by gingerest at 9:13 PM on July 25, 2012

Then I read that. Yeah, you would really need to restrict (if not abolish) this kind of thing. The initial discovery phase stuff to people who are rather emotionally stable (and on death's door) and capable of giving informed consent and not just, you know, consent.

There are plenty of cases of 'crazy' stuff being tried on terminally ill patents where the end result was their no longer being terminally ill. One case I can think of was someone who had both AIDS and Lukimea being cured of both by a bone marrow transplant from someone with immunity to AIDS. There are lots of stories of terminally ill cancer patients having their lives extended by experimental drugs that hadn't been tested before.

The logic to this seems pretty warped

1) People who are about to die from something with no well-tested cure have no choice but to try untested cures.
2) Because they have no choice, they cannot consent
3) Without consent, things cannot be done to them
4) Therefore, they can not be allowed to have untested cures, and must die instead.

Also, how do you think cures become tested in the first place?
posted by delmoi at 11:53 PM on July 25, 2012

Also, how do you think cures become tested in the first place?

Usually, on animals.
posted by muddgirl at 6:50 AM on July 26, 2012