Vulnerable to coercion or undue influence
August 5, 2014 5:11 AM   Subscribe

A two-part series on problems in the clinical trials industry, from Medium.com:
The Best-Selling, Billion-Dollar Pills Tested on Homeless People
How the destitute and the mentally ill are being used as human lab rats
and
Why Are Dope-Addicted, Disgraced Doctors Running Our Drug Trials?
posted by Joe in Australia (28 comments total) 15 users marked this as a favorite

 
that is absolutely messed up. Drugs should be for the public good, not for private profit, and therefore the tests should be done by public agencies, not behind closed doors.
posted by rebent at 6:10 AM on August 5, 2014 [2 favorites]


Why would we blame the doctors for this? Since when are doctors in charge?
posted by oceanjesse at 6:17 AM on August 5, 2014


I used to have plenty of friends in Philly who used to do these trials for money to go traveling with. You could make a few thousand dollars being in the hospital for a month. Some of the trials sounded terrible, such as an anti nausea drug that made a friend uncontrollably throw up, but others sounded relatively benign and they sat around and smoked cigarettes and watched movies all day (it was the 90's). I always meant to go do one myself but never got around to it.

Of course these were early 20's women and men who wanted money to go around the country and stay at different punkhouses. A far different situation than a 50 year old addict etc...
posted by josher71 at 6:39 AM on August 5, 2014 [1 favorite]


"Since 2000, just 45 doctors have been banned by the FDA from conducting clinical trials. Yet among them I found four, including Berger, who had also been disciplined by state medical boards for problems unrelated to their work on clinical trials."
This doesn't sound like the big systemic problem that the author is trying to make a case for it being.
posted by Blasdelb at 6:41 AM on August 5, 2014 [2 favorites]


I can think up a cynical reason for hiring doctors who are currently in a corner: they're now your doctors, if you offer a job to those that are most amenable and under the most pressure.

It feels like the above ought to be the plot of a John Grisham novel.
posted by Slackermagee at 6:53 AM on August 5, 2014 [2 favorites]


Why Are Dope-Addicted, Disgraced Doctors Running Our Drug Trials?

Why are we assuming that somebody using drugs is automatically incompetent?

Oh, yeah, America. Carry on.
posted by eriko at 6:56 AM on August 5, 2014 [12 favorites]


In general, depending on the context of a clinical trial and the context of what required discipline, clinical trials seems like an ideal place to put doctors in timeout - with their decades long education and invaluable knowledge and experience.
I did eventually find a couple of companies that would defend a decision to knowingly hire a disciplined doctor. One of these cases involved Maurice Buchbinder, a cardiologist who was sanctioned by the California medical board over a 2007 incident. Buchbinder was inserting a stent into a 68-year-old man with a failing coronary artery when the patient became agitated and had to be restrained. According to eyewitnesses, Buchbinder returned when the still-distressed patient was restrained on a gurney, and called him an “animal.” Then he twisted the patient’s nose, pinched him several times, and bent his wrist. (Buchbinder did not respond to multiple requests for comment, but during his medical board hearing he argued that he used only sufficient force to protect the patient from harm.)

The prestigious Scripps Memorial Hospital in La Jolla, California, suspended Buchbinder, but the event did not dissuade the French firm Stentys from hiring him to lead a 2013 trial of an advanced stent. René Spaargaren, the firm’s chief medical officer, told me that Stentys would never hire someone who had been disciplined for negligence or fraud. In this case, the company weighed Buchbinder’s disciplinary record against his other attributes, including his strong medical and communications skills. Spaargaren pointed out that Stentys wanted Buchbinder to present the results of the study, and serve as a spokesperson with the FDA. Regarding the incident with the man on the gurney, he noted: “Everybody understands that sometimes you can lose your temper.”
I’m failing to see what is actually wrong here. Where someone who clearly has no business being around patients, but is still a doctor with all the knowledge and skills involved, is being kept away from patients but still has his talents exploited. Just because he is clearly an asshole doesn’t mean he shouldn’t be employed in contexts appropriate to his assaholism.
posted by Blasdelb at 6:57 AM on August 5, 2014 [10 favorites]


Why are we assuming that somebody using drugs is automatically incompetent?

Oh, yeah, America. Carry on.


I get that it's an assumption that one ought to be careful with, but I think it's important to hold medical practitioners to the same sobriety standards when they're treating patients than we hold them to when they drive cars.
posted by entropone at 7:13 AM on August 5, 2014 [7 favorites]


Blasdelb: Then he twisted the patient’s nose, pinched him several times, and bent his wrist.

The board dutifully noted that Dr. Buchbinder observed the AMA's ban on purple nurples, swirlys, Indian burns, and noogies.
posted by dr_dank at 7:17 AM on August 5, 2014 [6 favorites]


The first article implies they used to not pay people for trials and I'm curious when that started. I too did medical trials in Philly for money when I was a student and I was paid back in the 80s. I only did harmless dermatology trials. There where always rumors flying around about how much money you could make if you were willing to test more serious stuff.
posted by interplanetjanet at 7:24 AM on August 5, 2014 [1 favorite]


Like I said above, I think this is an issue of too much privacy. I don't think it's the doctors at fault here, any more than any individual can be at fault. And I don't see evidence that pharma corps are preferentially recruiting disgraced doctors.

The problem is that there is room for malfeasance. There is the opportunity for it and there is no oversite to protect against it.
posted by rebent at 7:26 AM on August 5, 2014


Where someone who clearly has no business being around patients, but is still a doctor with all the knowledge and skills involved, is being kept away from patients but still has his talents exploited. Just because he is clearly an asshole doesn’t mean he shouldn’t be employed in contexts appropriate to his assaholism.

Ah, the joys of research!
posted by maryr at 7:59 AM on August 5, 2014 [1 favorite]


I find it weird that y'all are focusing on the doctors, and not the disadvantaged being used like lab rats.
posted by five fresh fish at 8:08 AM on August 5, 2014 [3 favorites]


There are two independent articles, one of them focuses on a story about doctors that seems to be written in search of a problem.
posted by Blasdelb at 8:10 AM on August 5, 2014 [2 favorites]


The problem is that if you introduce market forces, then of course the least-advantaged will end up participating in the trials, since they need the money the most.

The solution is to conscript all Americans into drug trials. It can be like jury duty: each of us takes a turn (say every five years) and then you're off duty. If a drug targets particular illnesses or conditions, then people with those conditions will be in a special pool of drug triers. All medical care during your drug trial will be covered, and the patent for the drug will belong to the American people as a collective at the end of the trial.
posted by anotherpanacea at 8:13 AM on August 5, 2014 [1 favorite]


eponybrilliant
posted by feckless fecal fear mongering at 8:38 AM on August 5, 2014 [1 favorite]


Re: the disadvantages being used as lab rats. In all seriousness, you are not going to find the advantaged (healthy, well and otherwise engaged) suitable for trials of antipsychotics ( perhaps phase I but otherwise no). Historically it was institutionalized patients. I would ask the question--where would one secure patients, in sufficient numbers, to conduct phase II and III trials. You are not going to take patients who are currently doing well on medication regimes, take them off their medications, and risk substantial decompensation. Nor are you likely to find patients who are off their meds, or not responding, to volunteer for long term trials. I am not proposing a solution but I do wonder what are the legitimate and ethical alternatives for large scale trials of medications such as these.
posted by rmhsinc at 8:51 AM on August 5, 2014 [2 favorites]


We shouldn't drug the homeless, I mean eventually they'll be our only source of food and we don't want to ruin that.
posted by blue_beetle at 8:59 AM on August 5, 2014 [1 favorite]


anotherpanacea--surely you jest. it is an interesting concept. Would participation be voluntary: even for potentially lethal drugs, do you get to choose whether you are to be in the placebo/control or experimental group, do you get excused for another five years if you are ill, on vacation, in jail, or you are an officer of the court, have a financial interest, know the researchers, etc I want to see the jury selection process in this. The bottom line on this is it would still be the retired, unemployed, poor and sick who become the primary jury pool.
posted by rmhsinc at 8:59 AM on August 5, 2014


The first article is all over the place that I really don't think it ever makes the point it wants to make. It runs through the terrible treatment our society affords to the homeless, and how mental illness can compound that fact, to set the scene. The author then crams in a scattershot of stories and commentary on everything from studies using approved drugs and their known adverse effects to clear clinical malpratice to the fact that the FDA is under-resourced. It's a mix of known issues with clinical trails and things that have nothing to do with clinical trials.

When the article actually does get around to the question of whether recruiting from homeless/impoverished populations is ethical, it completely fails to have any insight into the problem. It handwaves away the statement that outright excluding these individuals would be unethical by snidely noting that the ethicist making that statement later worked for a drug company. Yet, that statement is fully in line with decades of ethical thought and federal regulations and guidance on the topic. The Common Rule, for instance, specifically note that "economically disadvantaged" individuals may be recruited, stating:
When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects. (45 CFR 46.111(b), 21 CFR 56.111(b), among others)


Systematically excluding the homeless would absolutely be considered unethical as it would contradict the principle of Respect for Persons and their autonomy as laid out in the Belmont Report, the foundational document for ethics in modern medical research. You can no more exclude the homeless than you could exclude persons who do not speak English. The Belmont Report in fact specifically touches on the problem of involving persons who may not be in a position where their consent could be voluntarily given:
In most cases of research involving human subjects, respect for persons demands that subjects enter into the research voluntarily and with adequate information. In some situations, however, application of the principle is not obvious. The involvement of prisoners as subjects of research provides an instructive example. On the one hand, it would seem that the principle of respect for persons requires that prisoners not be deprived of the opportunity to volunteer for research. On the other hand, under prison conditions they may be subtly coerced or unduly influenced to engage in research activities for which they would not otherwise volunteer. Respect for persons would then dictate that prisoners be protected. Whether to allow prisoners to "volunteer" or to "protect" them presents a dilemma. Respecting persons, in most hard cases, is often a matter of balancing competing claims urged by the principle of respect itself.
It also deals with the concept of Justice in selection of subjects:
One special instance of injustice results from the involvement of vulnerable subjects. Certain groups, such as racial minorities, the economically disadvantaged, the very sick, and the institutionalized may continually be sought as research subjects, owing to their ready availability in settings where research is conducted. Given their dependent status and their frequently compromised capacity for free consent, they should be protected against the danger of being involved in research solely for administrative convenience, or because they are easy to manipulate as a result of their illness or socioeconomic condition.
Note that none of this recommends that the poor be cut out entirely from participating in clinical trials, but that their participation requires additional oversight. Hence the reason for guidance on minimizing coercion and undue influence (terms the author seems to think are too milquetoast), compensating subjects, and informed consent. There's a whole forest of writing on this topic outside of federal guidance as well, which the author seems to have not engaged with at all. The question of whether the impoverished can take part in research studies is a settled question.

The question of how they may take part is still open to interpretation, but the author doesn't seem to have much new or insightful to say on that topic. Saying "the ethical problem is whether it is acceptable to take advantage of their desperation," ignores the fact that this question was present from the very start of the modern era of ethical research, is written into the laws governing research, and is specifically something that IRBs are supposed to consider when reviewing research protocols.

There's a great expose to be written on the shady practices of for-profit research clinics -- IRB-shopping, unethical recruitment, poor clinical care, etc. -- but this is not it. I do get an incredibly skeevy vibe from the South Coast Clinical Trials mentioned in the article (and holy shit their blog makes my skin crawl). Throwing together a bunch of conflated issues about homelessness, mental health, clinical trials, and approved drug side effects, however, is not really addressing that problem. Nor is treating a literally decades old ethical debate like you're the first one to have ever considered it very helpful.
posted by Panjandrum at 9:11 AM on August 5, 2014 [8 favorites]


Isn't there a corollary to Betteridge's Law of Headlines that pertains to headlines that ask the question 'Why?'. If not, I shall create it here, using Betteridge's language, modified somewhat:

"Any headline which ends in a question mark and asks the question 'Why?' can be answered by the phrase: Because of money."
posted by eclectist at 9:18 AM on August 5, 2014 [4 favorites]


The problem is that there is room for malfeasance.

There is always room for malfeasance, no matter how many rules you have. Theoretically, you could demand an incredibly high standard, with multiple years of testing, etc., then what you get is no researchers at all.

And it *still* isn't a guarantee that you won't see malfeasance!

Back when mortgage issuance was rational, there was a rule for loan officers. If they had 0.5% or less of their loans going bad, they were doing something wrong. Lending to the 98% successful class makes a lot of money, despite the extra cost of handling the 2% that default, and those officers weren't making that money for the firm, and it was a huge chunk of money. But they didn't fire them, they showed them the number and said "lighten up a bit on the requirements. We're good with that." So, they either did, or *then* they were let go.

The real issue is *serial* malfeasance. People screw up, and people are actively evil. When they screw up, you punish them, let them know what the right thing to do is and let them go on. If they keep screwing up, they're either actively evil or deeply incompetent. Those people you eliminate entirely. If you managed to set standards so high that no person who would ever screw up and no person who's actively evil were able to get certified, you would also eliminate pretty much everybody else.

Now, when serial malfeasance keeps happening, then there's an issue -- but it's not that there's room for it. It's that the *last* step in the "evaluate, correct, monitor, eliminate on recurrence" isn't happening. Making the first step harder *won't* fix the last step, because if a malfeasor or incompetent gets through, they're going to keep screwing up.
posted by eriko at 9:40 AM on August 5, 2014 [3 favorites]


We've much more serious problems with clinical trials :

We need far more transparency in the trials so that people know what happens. In particular we need access so that other researchers can find learn how drug companies manipulated the experiment design to falsify results and obtain approval.

Ideally, drug patents should not exist, effectively making all drug companies into generics. In that scenario, we'd still develop new drugs just fine, since the government pays for that, but the actual clinical trials should be carried out by public interest organizations.

I'm not worried about a disgraced doctor running a trial if the results and data all become public afterwards and nobody is making a fortune off the drug via patents.
posted by jeffburdges at 10:25 AM on August 5, 2014


Panjandrum: I am curious about your take on this, as you stated some very interesting facts about ethics, at least as codified by the links you provided.

While it is great to say "we have followed the Ethics Guidelines", I am failing to see the "how" they have followed those guidelines. Especially with the second part in which you quoted, here:

One special instance of injustice results from the involvement of vulnerable subjects. Certain groups, such as racial minorities, the economically disadvantaged, the very sick, and the institutionalized may continually be sought as research subjects, owing to their ready availability in settings where research is conducted. Given their dependent status and their frequently compromised capacity for free consent, they should be protected against the danger of being involved in research solely for administrative convenience, or because they are easy to manipulate as a result of their illness or socioeconomic condition.


It's that last sentence there that bothers me. "Given their dependent status and their frequently compromised capacity for free consent... or because they are easy to manipulate as a result of their illness or socioeconomic condition."

Homeless people, and specifically mentally ill homeless people are very easily coerced. Coercion, by the standard definition, is :"the practice of forcing another party to act in an involuntary manner by use of intimidation or threats or some other form of pressure or force. It involves a set of various types of forceful actions that violate the free will of an individual to induce a desired response, usually having a strict choice or option against a person in such a way a victim cannot escape..."

Force does not always denote physical violence. Economic coercion is just as real as physical coercion. If you offer someone who is living on the streets money, and they have no other means to get money, you are performing an act of coercion, because the pressure of not having money outweighs the individuals ability to turn down the offer. Because our society requires you to have money to survive, and survival is kind of hardwired into our behavioral patterns, the use of money to elicit a behavior is economic and socially coercion. Of course, then we run into a whole other standard of ethics, but those are outside of the discussion of medical drug trials.

I will also note that you stated: "Throwing together a bunch of conflated issues about homelessness, mental health, clinical trials, and approved drug side effects, however, is not really addressing that problem."

Sorry, good journalism is not about offering policy. It is simply shining light upon a situation or circumstance. If you wanted an answer as how to change the reality, look elsewhere.

Frankly, I would prefer to see MORE stories about the effects of pushing clinical trials off onto the private sector. Frankly, I find that appalling, as the transparency, and the regulatory jurisdiction becomes even vaguer and harder to actually manage once you start hiding the actions of the "research" behind corporate trade secrets and contract agreements. Also, who is your 3rd party oversight in this situation? Are you relying on the researchers themselves to report abuses or misconduct? Really? You seem to have much more faith in individuals ability to sacrifice their livelyhood when they screw up or "lose their temper." Also, were a mentally ill homeless person to try and report some kind of ethical problem (to whom again?), who is more likely to be believed? The doctors and staff at the private testing lab, or the mentally ill homeless person? What private company is out there acting as a watchdog for these vulnerable people?


And then we get into the facts of off-label prescriptions of atypical antipsychtic drugs for "a dizzyingly broad range of conditions, including insomnia, depression, anxiety, bipolar disorder, agitation, autism, ADHD, and post-traumatic stress disorder." I mean, WHAT THE ACTUAL LIVING FUCK?

But, I guess it's all ok, because we settled that ethically, it's ok to use the most vulnerable populations of our society as "volunteers" for drug trials, so a private industry and make more money.
posted by daq at 11:29 AM on August 5, 2014


Frankly, I would prefer to see MORE stories about the effects of pushing clinical trials off onto the private sector. Frankly, I find that appalling, as the transparency, and the regulatory jurisdiction becomes even vaguer and harder to actually manage once you start hiding the actions of the "research" behind corporate trade secrets and contract agreements.

Gov't cuts funding, the private sector comes into fill the void. That's how it's happening at Johsn Hopkins right now.

Do IRB's handle complaints?
posted by josher71 at 11:50 AM on August 5, 2014


I'm not worried about a disgraced doctor running a trial if the results and data all become public afterwards and nobody is making a fortune off the drug via patents.

You will find very very few companies are going to be interested in making drugs if they can't make a fortune off of them. I'm not saying you shouldn't publicize the data, mind you, but unless the government (or, I don't know, HHMI) wants to take over the entire pharmaceudical industry, someone is going to need to make money.
posted by maryr at 2:54 PM on August 5, 2014


Homeless people, and specifically mentally ill homeless people are very easily coerced.

What we're really talking about here is "undue influence," not coercion or "economic coercion." The fact that the author felt the need to come up with a new, and more menacing sounding, term for a situation already defined in the Federal guidance is part of what made me feel like he doesn't actually have much to say on this subject. The first guidance link I provided discusses undue influence as occurring, " through an offer of an excessive or inappropriate reward or other overture in order to obtain compliance."

That perfectly fits with the phenomenon being discussed here. No need to come up with new terminology. That same guidance doc also defines coercion as occurring "when an overt or implicit threat of harm is intentionally presented by one person to another in order to obtain compliance."

So threatening to kick someone out of a homeless shelter unless they take an investigational drug is coercion. Offering to pay someone a great deal of money is undue influence. The problem is that coercion and undue influence are situational and their effects are not so easily defined. A person who is told that their child's neuroblastoma is not responding to conventional treatment is also (in the colloquial sense) easily coerced. So is someone in prison. So is someone who is so poor they are desperately trying to avoid becoming homeless.

So where do we draw the line? How poor is too poor to take part in a clinical trial? How upset is too upset to enroll your child in an investigational treatment? The ethical determination that was made, and that I agree with, is that you cannot turn someone away from a study because of their life situation. If they want to participate and they have no clinical conditions which might exclude them, they have the right to take part. This is doubly true for a population which might get some benefit from enrolling in a treatment study, such as the mentally ill with (already approved) anti-psychotics. Hence the reason the focus is on creating an consent process which strives to minimize coercion and undue influence.

who is your 3rd party oversight in this situation?

Every clinical trial is regulated by the FDA and must be approved by an IRB. Every IRB must be registered with the Office for Human Research Protections (part of DHHS). For industry funded drug studies, either the FDA or the reviewing IRB may, at any time and for any reason, audit a study to ensure compliance both with federal regulations and the study protocol reviewed and approved by the IRB. Subjects can also contact the reviewing IRB to complain or voice concerns, using that contact information that is required, by law, to be in their (again, legally required) consent form. Covering up or not reporting adverse events and/or protocol deviations can lead to sanctions including jail time. The second article proposes that these are entirely inadequate for oversight, even as it notes several instances where that oversight was effective. Both the FDA inspectors and IRBs in general could use more staff and better funding, but clinical research is not the anarchic Wild West of devious researchers the articles make it out to be. There are also definite concerns about the quality of the review provided by some commercial IRBs and the work done by CROs, but this is an issue of better, and better funded/staffed, regulation. Mandating that one class of people should not be able to be in clinical trials is not going to solve this problem.

good journalism is not about offering policy

This isn't even good journalism. In building its case that allowing the homeless and impoverished to enroll in drug trials, it routinely conflates research risk with clinical risk; it relies heavily on anecdotal evidence; and makes a poor distinction between Phase I studies and studies using already approved drugs. For instance, the article makes several mentions of interviewing people who are, or had been, in trials using Abilify, and notes the side effects of that drug. Yet, these people have, by their own admission, conditions for which Abilify -- FDA approved for over a decade -- would be prescribed to them in regular clinical care. When the article does finally address Phase I trials, which are what everyone thinks about when they think of clinical trials, it notes all the ways that risk was minimized for subjects. For the subject death it focuses on, the article quotes the expert witness for the family of the deceased as saying the problem was failure to follow standard of care.

The article makes no attempt to actually find out the prevalence of homeless individuals taking part in clinical trials, nor does it try to address how many of those are in treatment studies with approved drugs which may hold benefit to the subjects vs. the number enrolled in Phase I safety and efficacy trials. The author's approach to finding out how much taking part in this ill-defined mass of studies yields wildly variant results, probably because, again, he didn't bother to differentiate between the various types of studies or attendant risks. As with the terminology noted above, the author clearly failed to do his research on any of the regulations, guidance, or writings on the subject of research ethics which have come out in the past 40 years. The only thing this article is shining a light on is the fact the author has a problem with poor people taking part in research and decided to pound out a mish-mash of confusion about the nature of drug trials, the risk of approved vs. unapproved drugs, the side effects of psychiatric medicines, and some scaremongering about Big Pharma. The article contributes very little to the discussion about how problematic enrolling vulnerable populations into a study can be.
posted by Panjandrum at 3:13 PM on August 5, 2014 [3 favorites]


Do IRB's handle complaints?

Yes. One of the required elements of informed consent is that the subjects be given "An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject." In practice this means all consent forms will have contact information for the study team and for the reviewing IRB.
posted by Panjandrum at 3:19 PM on August 5, 2014 [1 favorite]


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