This story sounds familiar, but I can't remember where I've heard about this earlier. IF I were a betting man, I'd wager this won't be the last such scandal to be discovered.

What the --?! We've known about the dangers of lead paint and lead poisoning since the 1970s, haven't we?

At the risk of bringing up one of those phrases, this sort of high-handed and hurtful 'research' sounds very much like some of the 'research' that was being done in parts of europe in the early 1940s ...

Why does this story make me want to find the researchers and kick them in a sensitive place?

Fragano @ 4: Because you're being very, very generous to them.

John A. Arkansawyer #4: I have to go through an internal review process that's pretty stringent if I receive any grant support for research. I have to ensure that any of my students who carry out research go through that process. All they do -- all I do at the most -- is interview people. These researchers exposed children to known toxins. Causing them massive trauma doesn't seem generous to me.

Fragano @6 - I think John meant your massive-trauma inclination is generous because the (ahem) researchers in question deserve nastier. (Something slow-acting, perhaps, and cumulative.)

And it was a Johns Hopkins-affiliated project. Supposedly Hopkins had no real knowledge of the details. But it was Johns Hopkins that was involved in Tuskegee, and it was Johns Hopkins that was involved in HeLa, and now it's Hopkins again.

You'd think they'd be keeping a closer eye on research being conducted under their umbrella.

Unpardonable.

Oh, my God. I wouldn't have thought such a thing would be done so recently.

There was an older disgrace which came out recently-- experimental done on mental patients(?) in Latin America. Anyone remember what that might be?

Nancy Lebovitz at #10: Guatemala? http://www.msnbc.msn.com/id/39456324/ns/health-sexual_health/t/us-apologizes-guatemala-std-experiments/

Not kick them. If this is as bad as it sounds, the folks running the research need to spend the remainder of their days in high-security Federal housing, with free room, board, and medical care.

john-- thanks, that's probably it. At this point, I'm paranoid enough that I won't swear there couldn't be two different news stories along those lines.

Dear God. How do people managing such a "study" sleep at night? What stories do they tell themselves which allow them to ignore their own lies?

Researchers have found that exposure to lead participation in authoritarianism reduces IQ and causes poor impulse control.

I hope the investigators find everybody involved and notify the victims and the perpetrators, in case the perps have any assets left to sue for. It won't begin to be close to enough, but it's a part of justice that often gets left out.

Arkansawyer @5:

Note that Fragano didn't specify how hard he wanted to kick them, or in what sensitive place. Assuming (as I think reasonable) that the people responsible for the Study are male, my suspicion is that they would at least be removed from the Gene Pool.

OTOH, I don't think he'd actually act on his feeling while we're still in the "Presuming Guilt by Accusation" phase.

Before the pile on continues, everyone needs to STOP.

First, as Fragano alluded to, ALL research involving human subjects must be approved by an IRB, an Institutional Review Board.

Second, we already know how toxic lead is to the developing brain. There is not one IRB in the US that will allow a toxicity study of lead in humans.

Third, this was a lead ABATEMENT study. They were trying to find out which kind of treatments were best at protecting children in the Baltimore public housing system. There was a control group of children in more modern housing, where lead paint had never been used, but there was NO placebo group. All children in exposure situations were getting one type or another of the abatement measures. The court ruling disagreed with the IRB definition of the "control" group, but that's a legalistic disagreement; the IRB felt that children in homes with no lead paint would not be at risk from lead exposure inside, but could still be exposed in other situations.

Someone didn't understand the study, and the reporter failed to make this clear. This was a study of children who were at risk of exposure to lead, and how abatement measures inside their housing could potentially reduce their risk. Children were not being deliberately exposed to lead; that was not the aim of this study.

The PDF of the ethical aspects, and a brief summary of the jurisprudence can be found here.

Ginger, your link is behind a pay wall.

Everything you said is consistent with the parents not being told about lead levels in their homes.

It's at least possible that they weren't told so they wouldn't interfere with the experiment by moving or extra cleaning.

Nancy @ 19: I didn't realize that -- thanks! I'll excerpt here:

"First, the project was one of the first primary prevention studies to perform lead-safety measures
before children were exposed to lead paint. Most attempts to control lead hazards in Baltimore
and other cities in 1993 were in response to already poisoned children. Second, all the homes had some degree of lead abatement, and therefore all families benefited, even if the children in homes with more extensive repairs were expected to have less lead exposure. Third, while the research provided for a control group
(children living in modern housing that was built without lead paint), there was no placebo arm. Thus, no child enrolled in the research lived in a residence with untreated lead hazards.’ Fourth, the consent forms clearly explained that living in housing that had undergone renovation for lead abatement may not fully protect one’s child from lead exposure: “The repairs are not intended, or expected, to completely remove exposure to lead.””

"Many of the facts in the case are not yet known because
the case has not proceeded beyond summary judgment, which
the lower court granted in favor of the researchers. The trial
court held that, even assuming all disputed facts in favor of
the plaintiffs, the researchers did not have a legal duty to the
parents to abate or e l i n a t e hazards the researchers did not
create. In a 96-page opinion that went far beyond this ques-
tion, the Court of Appeals (Maryland’s highest court) reversed,
arguing that research can create “special relationships,” and
remanded the case back t o the lower court for trial.’l The
court’s opinion, which calls the research unethical and com-
pares it to the U.S. Public Health Service experiments at
Tuskegee, is the basis for much of the negative publicity sur-
rounding the case.I3 Judge Raker, who concurred with the
ruling only, stated that he thought the court might be acting
unfairly by choosing to publish such a scathing opinion be-
fore all the evidence had been p r e v e n t e d . ’

Previous comment held in moderation...

I'm not sure what the PDF says, cause I don't want to buy it, but the problem is not that there were some children with lead poisoning (or rather, that is a societal problem, not the researchers problem). The problem is that the researchers knew that some children were exposed to lead poisoning, and did not inform their parents.

Ginger 20: So this is really just another "journalist" doing an "OMG THINK OF THE CHILLLLDRENNNN!!!!11(sin²Θ+cos²Θ)!!" story?

Mepf. Comment held in moderation. I suspect my use of Greek letters may be the culprit.

All non-spam comments released from moderation.

Multiple exclamation points are what did it in your case, Xopher.

#1 Martin Wisse: This story sounds familiar, but I can't remember where I've heard about this earlier.

Could have been any time in the last ten years.

From the linked story: "Litigation surrounding the research has gone on for more than a decade, and in 2001 the Maryland Court of Appeals compared the study to the Tuskegee syphilis experiment, which withheld medical treatment for African-American men with syphilis."

Emphasis mine.

Ah, that makes sense, James. I'll keep that in mind in the future.

Ginger is correct that we are talking about allegations made in the complaint in a lawsuit. That doesn't mean this is a hoax or overblown, but it does mean that this is pretty early in the allegations and we don't yet know what the evidence is. The NYT article has a link to the complaint here:

https://www.documentcloud.org/documents/249648-armstrong-vs-kennedy-krieger-class-action.html

However, what Ginger is referring to is an article written by a medical ethicist in response to a 2001 court decision - not to the current lawsuit. It appears, from the abstract, to be addressing the issue of IRBs and of the parents' ability to give medical consent on behalf of their children. It isn't a factual rebuttal to the complaint in this case. Link to the abstract here:

http://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2002.tb00719.x/abstract

What the complaint appears to be saying is that the children were moved into 'abated' apartments that were nonetheless still dangerous. So no, they were not a control or placebo group in the sense that the researchers did not say "Hey, let's move some kids into an apartment and let 'em eat lead paint chips!" But the allegations are that the apartments were still dangerous, and that the parents did not give informed consent.

Sorry, got called away to a patient.

The legal review is of the original suit, which was sent back down for retrial, which is why the case has a date of 2001.

The intention of the suit seems to be that at least one family felt their consent was not fully informed, and that is a potential valid suit. However, the newspaper article makes it sound like the investigators deliberately withheld information from the families, which is not the case. Those children were already living in at-risk housing that was being treated for lead abatement. The researchers did not increase the risk of the children. That is the critical part. ALL of the children were potentially exposed to lead, based on where they lived and on their blood work being positive for lead. The family that sued is claiming that their child's lead levels increased despite the abatement, and that this is directly related to the abatement investigation -- however, the Hopkins researchers never entered the apartments. They were monitoring the children during the abatement procedures to find out which method was best.

Fragano @ 6, Fox @ 7 has it right: This case sounds* to me more like crimes against humanity than ordinary iniquity.

*Sounds before considering Ginger's counterarguments, which don't fully convince me but which do make me realize there may be more to this than it sounds at first blush. But I wonder--is this looking for an effective method or a cost-effective method?

Ginger @30: While I agree that the newspaper article is a little unclear, you're mixing up a lot of issues in your comment.

Whether the children were already living in lead-infested housing has nothing to do with whether the researchers moved them into dangerous housing, or whether the parents understood what was going on and gave informed consent (which is sufficient to bind their children) to accept those risks. Nor is it important whether the researchers themselves actually went into the apartment buildings.

The lawsuit, as I understand it, appears to be claiming that the children were moved into "less lead" apartments that still had too much lead, thus were unsafe for the children to live in, and that the parents were unaware of this but the researchers were.

Here is a link to the Maryland appellate opinion in the 2001 case, which has some rather harsh things to say about the researchers' actions (and yes, it mentions the IRB). There are suggestions that the IRB massaged the description of the study to get around federal rules about 'nontherapeutic' research on children.

By the way, the issues on appeal from the lower court were whether the research institute (KKI) had a legal duty to warn of the potential hazards of the abated apartments.

http://www.law.uh.edu/healthlaw/law/StateMaterials/Marylandcases/grimesvkennedykreiger.pdf

Ginger #18 et seq

Even with all this information, I'm still very concerned about the ethics of this research.

Okay, I agree that my comment was premature, based on the suggestion that the researchers withheld information about unsafe conditions. The salient questions appears to be, 1) Did the researchers house people in apartments which, while they were safer than the original housing, nevertheless still left the children exposed to lead, and 2) Were the parents of the children fully informed of the conditions, and did they give "informed consent."

Maybe the answer to #1 is, in fact, No, and to #2, Yes. Nevertheless, I share Fragano's discomfort...

If you described it as a study where you compared lead levels that result from different types of lead abatement (and no child was living in a place without abatement) it sounds a whole lot less sinister, doesn't it?

Connie, #35: Actually, no, it doesn't. Because that description makes it clear that you are in fact using children as lab animals to test the effectiveness of various abatement methods.

As a physician, it sounds like a lot of studies I've seen along the lines of: Gee, if we make a half-hearted* effort to help young black children** with a major problem that could affect the rest of the lives, is it good enough?

*you may insert any body structure you like here.

**you may insert any undervalued, underprivileged section of humanity here that you like.

I once participated very loosely in a study to see how many alcoholics we killed (they were, I will admit, already dying) with a surgery called a hepatorenal shunt. (Answer--all but one died more quickly than if we left them alone.) The sole survivor did very, very well, however.

If the informed consent did not specify that the lead abatement might be subtotal, Ginger may be giving them too much credit.

Lee @ 36: "children as lab animals to test the effectiveness of various abatement methods." -- this is not illegal nor even unethical -- as long as all families understand the implications. This is the crucial part.

mythago @ 32: "Here is a link to the Maryland appellate opinion in the 2001 case, which has some rather harsh things to say about the researchers' actions (and yes, it mentions the IRB). There are suggestions that the IRB massaged the description of the study to get around federal rules about 'nontherapeutic' research on children." -- yes, I know that the Appellate Court was harsh; this is covered in that ethical review which is unfortunately behind a paywall. I had to cut and paste into Word, correct formatting errors, and deal with other issues as well, so please pardon the delay.

Here is the next summary of the review:

CONSENTING TO NON-THERAPEUTIC RESEARCH
The court’s first holding is quite broad in its prohibition of
non-therapeutic research that poses any degree of risk:

We hold that in Maryland, a parent, appropriate relative, or other applicable surrogate, cannot con-
sent to the participation of a child or other person under legal disability in nontherapeutic research
or studies in which there is any risk of injury or damage to the health of the subject.”

Two distinct challenges can be made to this ruling. First,
with respect to the specific case: Was the lead abatement
research non-therapeutic? Or did it pose greater than mini-
mal risk? Second, and more generally, do guardians have the
moral and legal authority to consent on behalf of a child or
other legally incompetent person to participate in non-thera-
peutic research that poses any risk of injury? The Kennedy
Krieger Institute and its amici curiae focused on the second
question in their motion for reconsideration filed last Sep-
tember. The amici were concerned by the potential
“immediate and long term consequences of the Court’s
broadly worded decision. ”

The amici argued:
A rule prohibiting “nontherapeutic research or studies in which there is any risk of injury” would prohibit virtually all medical and public health research involving children and other persons under a legal disability.” The amici pointed out that this ruling is not consistent with the federal regulations pertaining to the participation of children in research. The regulations permit children to participate in non-therapeutic research (or, in the language of the regulations, research that does not offer the prospect of direct benefit) provided that it involves only minimal risk.’”

Non-therapeutic research that poses greater than minimal risk is permitted if the risk is only a minor increase over minimal risk and the research offers the potential for generalizable knowledge of vital importance about the subjects’ disorder or condition . ‘ If the non-therapeutic research poses
more than a minor increase over minimal risk, it is permitted if the research presents an opportunity to prevent or alleviate serious health problems and it is reviewed and approved by a national panel of experts. In all cases, parental consent is required.

"If the research is therapeutic for those whose homes were abated, is this the case for the control group? The control group consisted of healthy children living in modern urban housing. Their houses were not treated because they were assumed to be lead-free. The children, then, did not appear to receive any potential medical benefit as they were not expected to have high lead exposures. However, the Johns Hopkins University’s IRB was concerned with calling this arm of the study the control group because federal regulations were, in its words, ‘‘really quite specific” about using children as controls when there is no potential benefit; therefore, it suggested claiming that the control group was not merely a control, but was “being studied to determine what exposure outside the home may play in total lead exposure; thereby, indicating that these control individuals are gaining some benefit.. . .”

Although many therapeutic clinical trials use the randomized double-blind control methodology to ensure that any improvement in the treatment group is due to the therapy or prevention strategy being tested, this does not prove that the methodology is ethical. Rather, in recent years, there has been some criticism regarding the use of placebos, particularly the use of placebo-controlled research trials when a known treatment exists. In this trial, however, the researchers did not choose to create a placebo arm of children who lived in houses with suspected lead hazards whose homes would be randomized to receive no lead abatement. All of the homes that were suspected of having lead hazards were given some degree of lead abatement or had received a full lead abatement treatment previously. Instead, the researchers chose an observational control group of children whose homes were not at risk for lead hazards, and exposed these children to the minimal risk of five phlebotomies. Thus, the IRB failed to appreciate the ethical design of this study It was a therapeutic trial that included an ethically appropriate (minimal risk) control arm."

Lee @36: It looks like there are rat models for lead abatement.

Less snarkily: We know that lead poisoning can be very effectively prevented by spending large amounts of money. It's easy. Build new housing. Therefore any study on the effectiveness of lead abatement is not about whether we can do it effectively, it's about whether we can do it sort of okay for less. Ethically that is problematic. It's really a general social problem, and the researchers in this study just happen to be located at the sharp point where general indifference transforms into specific misery. They may have meant well. But if they thought about it, they would not have positioned themselves at that sharp point.

TomB @ 40: It's probably not that simple. How do we know those methods actually work to protect our children?

From a review in 1998:

"These analyses further demonstrate that a strong relationship between interior dust lead loading and children's blood lead levels persists at dust lead levels considerably below the U.S. Department of Housing and Urban Development's current postabatement standards and the Environmental Protection Agency's guidance levels. Finally, these analyses demonstrate that a child's age, race, mouthing behaviors, and study-site specific factors influence the predicted blood lead level at a given level of exposure. These data can be used to estimate the potential health impact of alternative health-based lead standards for residential sources of lead exposure."

From a Hopkins study in 2010:

"Of the 769 healthy children and teens in the study, ages 12 to 20, more than 99 percent had lead levels below 10, with an average level of 1.5 micrograms per deciliter. Those with lead levels in the upper quarter of the normal range appeared to have worse kidney function than children with lower lead levels. Kidney function is defined by the speed with which the kidneys filter the blood. Those with lead levels above 2.9 had a kidney filtration rate 6.6 units (milliliters of blood filtered per minute and adjusted for body size) lower than children whose lead levels were below 1 microgram per deciliter. Researchers also found that for each twofold increase in the amount of lead in the blood, the kidney’s filtration capacity dropped by 2.3 units in males and by 3.3 in females. The link between higher lead levels and worse kidney function persisted even after investigators eliminated high blood pressure — less than 5 percent of those in the study had it — as a possible factor affecting kidney status.

In the current study, the investigators measured kidney function by estimating the kidneys’ filtering capacity, called glomerular filtration rate (GFR), using two tests: a standard creatinine test, which measures the speed with which the kidneys filter out creatinine from the blood, and a newer test that measures how fast the kidneys filter out the protein cystatin C. Cystatin C is believed to be a more accurate gauge because, unlike creatinine, which can fluctuate depending on muscle mass and other factors, its levels are more stable. Indeed, the differences in kidney function were far more pronounced when the researchers looked at cystatin C and not as significant when they applied the standard creatinine test. The investigators say this could mean that past studies that have used creatinine tests may have underestimated the true effect of lead on kidney function.

Lead exposure is a well-established risk factor for neurological damage and developmental delays in children, while chronic exposure to high lead levels is a well-known cause of chronic kidney disease in adults. Despite the elimination of lead from gasoline and paint, most Americans still have detectable lead levels in the blood. The mean blood lead levels in the 12-to-19-year-olds were 1.5 micrograms per deciliter in 1991 to 1994 and 1.1 micrograms per deciliter from 1999 to 2000, researchers say.

Current exposure sources include lead paint, folk remedies, glazed pottery, soil and drinking water in some urban areas with older housing."

Again, this is a study of healthy children who should not be exposed to high levels of lead and yet who seem to have enough to possibly cause problems. This is not unethical research; this is prospective research looking to see if we've missed anything. Despite Federal standards which were tightened in 1991, our children are still getting some lead from somewhere, and it could affect their health even at these supposedly low-enough levels.

There's another crucial issue here. Many assume that lead-free living spaces were available. They were not. Tell the parents, who will definitely increase the risk if they try to scrape off and remove that paint themselves? You're damned either way.

Many agencies were rushing to figure out and fund what types of lead abatement were effective, much less cost-effective. If you can't get everybody out immediately, at least you should gather as much info as fast as possible on what works.

Also, the legislation to inform people moving into these places (or already living there) wasn't in place yet. The people doing lead abatement knew these kids were at terrible risk but whistle-blowing meant landlords' associations might have hauled them to court and bleed the funds they were using to solve the problem.

I can't tell what was happening here. Reading about this makes my stomach hurt. Turning that into a fury about dreadful people deliberately hurting children is a knee jerk response we're better off not making.

It's the kind of emotional stampeding that gets us into things like the war with Iraq.

Ginger, thanks for digging into the details of this. I appreciate the clarification.

I ran across the controversy about this study when the EPA-sponsored CHEERS study came under fire. If I recall correctly, the Maryland court decision about informed consent was taking the norms that form the background to the Common Rule and giving them teeth that extend beyond federally funded studies. The Common Rule is the regulatory basis for needing IRBs, and it sets out what is - and is not - ethical human research.

50 years after nuremburg you would think all of this would be thrashed out.The uproar over the CHEERS study -- and
attempts to use human studies in the pesticide reviewprocess -- resulted in new regulations that narrowed what can be considered informed consent. So uproar and outrage makes things better, but there is still slot of discussion about how to properly design NON-therapeutic studies that are trying to quantify and document and respond to potential environmental harms.

Martin Wisse @1: This story sounds familiar, but I can't remember where I've heard about this earlier.

I immediately thought of the Law & Order: SVU episode "Loophole." The Wikipedia synopsis reads:

An anonymous letter leads to an apparent child-pornography case and the testing of pesticides on unwitting apartment tenants. Olivia is also exposed to the pesticide and develops medical symptoms similar to those exhibited by the victim and his mother. The latter part of the episode explains a controversial United States Environmental Protection Agency rule that allows intentional dosing of human beings in pesticide experiments.

Here are some links with background and "whoops, we shoulda done it better" analysis:

http://irb.duhs.duke.edu/wysiwyg/downloads/OHPRconf06/C1_EthicalIssuesInResearchOnHomeHealthHazards.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805023/

Both are by the same guy, but provide an easy to read summary of the problems trying to be studied and the lessons learned in the research community.

And reading them will make you blood boil a little, so while there is always more work to be done it does help to remember that some changes have already been made.

It sounds like there were some ethical problems with this study, but what really outrages me (and what the papers don't even touch on) is the larger problem of lead-contaminated housing in the US.

According to HUD, about 75% of housing built before 1978 has at least some lead paint in it. But the general attitude seems to be one of willful blindness. Most states don't require landlords to test for lead paint. Most states do require home sellers to disclose any known lead hazards, but these "disclosures" are easily wiggled out of: unless there's an actual record of lead paint, sellers can just claim ignorance - and most buyers will take an "I don't know of any lead paint" statement to mean "there probably isn't any", because they don't know how common this problem is. Kids are supposed to be screened for elevated lead levels, but a lot aren't, especially low-income kids.

It's tremendously unfair that being poor means having a greatly increased chance of being exposed to neurotoxins that can lead to lifetime cognitive deficits. But no one wants to shoulder the expense of fixing the problem, so they're hiding it (or at least, allowing it to be hidden) instead.

Lizzy L. @34: The researchers had nothing at all to do with the housing of the families. They only collected blood samples (phlebotomies) from the children living in houses that had already undergone lead abatement or houses that were getting abatement, or from children in houses that did not ever have lead paint.

The abatement methods could vary -- did the walls simply get painted over? Was older (leaded) paint removed first, thus creating hazardous dust? After painting, did they need one coat? Two? Sealant? Is one type of paint better than another? These are all valid questions, and to paint epidemiologic research as "half-assed" is enraging. There is nothing I can say to you, Dr. Throwmearope, that would be even half-polite. I am a veterinarian involved in bench-to-bedside research, and all research that has passed IRB and HSRRB review is worthy of consideration. I know how stringent the regulations are; I sit on the IACUC for review of animal research proposals.

This was a media report based on a lawsuit, not on investigative reporting. That is the half-assed part. Disagree with the published paper from that research, fine; slam the researchers because a reporter used a malpractice lawyer's twisted words to impugn the researcher's motives -- no, not acceptable.

Ginger, the Times article pretty much states that the housing was provided by the researchers. You say this was an assertion of the lawsuit, and not factual. Bad reporting, then.

Ginger @49: The appellate opinion is not a 'media report'. According to that opinion, federal funding is not available to studies on children when the goal of the study is purely to use the children as test subjects, rather than to offer a benefit to the children, and the review board suggested that the study's documentation be re-worded to make it look like the former rather than the latter.

We absolutely should not make knee-jerk decisions about the facts. But that cuts both ways. "Oh, they had an IRB so it must have been ethical" is a knee-jerk reaction. So is "But the apartments were abated and better than where they were living, so they were actually being helped."

The problem with this study, according to the appellate opinion (and the later case), are that

- the 'abated' apartments were not lead-free, nor were they necessarily abated to the degree that the children living there were protected from undue exposure to lead.

- there was no direct benefit to the children; the point of the study was to use them essentially as collection units. This was not like a drug study where a mentally ill child uses an experimental drug with the hope that the drug will both alleviate the child's problems and will result in good data.

- the IRB knew that they were not going to meet guidelines for federal funding by saying 'we are using the kids as collection vessels' and so suggested, bluntly, stretching the truth.

- and there is a question as to whether the parents understood exactly what was going on and what the risks were.

I mean, look, if you want to study the effects of alligator bites on children, it is not ethical to take children living in a five-alligator apartment, move them to an apartment you tell the parents has been de-alligatored but which actually has a single alligator in the bathtub, and to do so not for the purpose of saving children from alligators but to see if reducing the alligator level from five to one still results in kids getting bit. It is not ethical to deceive the federal government about the real purpose of the alligator study. Nor is it a defense to say "But at least there were four fewer alligators in the apartment!"

Now, if what you are saying is that the parents were in fact fully aware of the risks and were told that they were only being moved into less leady-y apartments, that the appellate court was wrong about the facts, and so on, then that's one thing, but those are different arguments than the ones you've been making.

Thanks for the shout-out, abi, but to give credit where credit is due, I picked up the link from @EllenDatlow -- I should have just hit the vanilla "retweet" button, but I wanted to add something to the content of the tweet, because the date of when this happened effin' blew my mind. (In the 1990s! I cannot get over this!) And then, 140 characters being what they are, there was no room for the "via" part. Damn and blast.

Regardless. Thank you so much for blogging this. This kind of crap needs more attention. We need bright lights to make the roaches scuttle and take aim with our shoes and Raid cans.

Also - you're also knee-jerking very vigorously when you get angry about "a malpractice lawyer's twisted words." Is the appellate court's opinion a "malpractice lawyer's twisted words"? Do you believe that all lawsuits involving medical research are medical-malpractice suits?

The emotional belief that all lawsuits involving doctors are outrageous and unfair attacks on innocent doctors, who always care deeply about their research subjects because the IRB is the guardian at the gate, is very much an emotional, knee-jerk reaction that tells us nothing about the underlying facts.

Dr. Ginger @ 49

First off I did not use the term that you used, because I no longer speak like that.

Secondly, I am not (thank God) a researcher. But I have sat on an IRB for a few years. Some of the proposals were met with appalled silence while we looked for wiggle room to deny the application in a professional way.

I recall one app that we passed (all 30 of us, after prolonged discussion, debate, reviewing all of the available data, etc, etc). Turned out to be a very bad idea and quite a few people suffered irrevocable damage before the trial was stopped. Yet even in hindsight, it still looks like a good idea. I've even heard the idea floated again as something we could tweak to achieve better results. I am thankful I no longer have to decide these kinds of things.

My husband is a veterinarian, and sometimes it seems to me you guys do a better job of protecting your clientele than we do.

My issue was informed consent. If the family was told an abatement was done, but the researchers were not sure how effective it was; then depending on how it was phrased, it could be valid informed consent. If the family even understood the informed consent. These are all issues we doctors have addressed over the years ad nauseam without much resolution I'm afraid.

Just because you are a conscientious researcher, does not mean that everyone shares your ethos.

I mentioned the hepatorenal shunt study. My involvement was to get informed consent from the participants. I particularly remember the longterm survivor, because he was pretty far gone mentally from the ammonia build up in his brain.

I told him that he was dying slowly and the surgery would likely kill him quickly. So he said, "Okay, do the surgery." I doubled his Lactulose, made sure his ammonia level was down and asked him again.

He said, "I want the surgery because I will die quicker than I am dying now." Believe me the debate about whether that constituted informed consent was heated. In the end, we operated. When I left that state eight years later, he was still alive and doing well.

But because of him, some surgeons are still doing hepatorenal shunts despite the documented 90% plus mortality.

Maybe this case was a noble cause, but would they have tried it in a white neighborhood? I have my doubts.

And of course, Mythago did a much better job of explaining the pitfalls than I did and beat me to it. Sorry for the pile on.

Catherine @ 48: Yes. And there's part of my emotional range, varying from disappointment to disgust, with Obama.

There are literally hundreds of public works projects such as lead removal which badly need done and which would put people to work, none of which have been advocated by the president at a time when work is badly needed.

I did not vote for bringing an eleven-dimensional chess set to a gun fight.

Not even to a knife fight.

And damn John Edwards, anyway, while I'm at it.

Catherine @48: Well said.

Ginger -- thanks for bringing a more detailed discussion of the facts than my "read this" approach. Have you sat on IRBs that do in fact look at studies of environmental exposures involving humans? I'm not a doctor, and I know that there are really tough cases like the one talked about by Throwmearope, but I have focused on studies that try to look at toxic exposures in the households. Ginger -- isn't an observational study involving animals by definition less ethically fraught than an observational study involving humans?

Here is my take:

America is really, really bad at keeping people safe in their homes. We regulate outdoor air, but we don't regulate indoor air. The fragrances and air fresheners that get sold? The only thing that protects you is general consumer protection laws, nothing that actually requires an evaluation of whether spraying that stuff inside your house makes asthma or allergies worse.

Catherine is completely spot-on on the problem with our lead laws. The same problem exists for PCBs and asbestos in private homes.

Pesticides for use in the home are regulated, and that is exactly where the CHEERS study came in. The directions for use are supposed to keep children safe...but that raises the question of whether anyone is actually using a particular pesticide as directed. I had a student in class last semester who confidently told me that no one on his farm read the pesticide labels before using the pesticides. We would all like to hope that parents would be more careful, but are they? How do we build a record to show in a scientific way that the directions for use are not protective unless we do the observational studies that can then be fed back into the regulatory machinery and used to make protections better for kids?

EXCEPT: Full informed consent about any pesticide study should (in my opinion) involve educating the parents about the dangers of the pesticides. And what fully educated parent would then proceed to use the pesticides? Well, parents with limited options living in roach infested housing...but even so, they would minimize use and be careful after a full disclosure education by researchers. Researchers who know about the dangers cannot just sit back and allow ignorance to expose children under their observation to danger - in my opinion. The Maryland court agreed -- and made great legal precedent (yes, comments like that make lawyers look like vultures but that court decision will cause a lot of other researchers to think more carefully about their research design).

After you fully inform parents of the danger, you change the behavior. That is the dilemma that researchers grapple with. Some researchers emphasize that they are only observing and not changing behavior or inducing behavior but FAILING to change behavior can (in my opinion) be an ethical problem. Researchers are stuck with trying to do good science -- science that we desperately need done in order to pass the laws and regulations that we say need scientific support -- so my focus isn't on the individual researchers but on the system we have set up to regulate things like pesticides.

Oh, and in changing the system well articulated outrage like Catherine at 48 is GREAT.

Throwmearope @54: No, I don't think I said what you said; you're a doctor, and you're offering a very different perspective, even if in the end we agree.

If I may get on my soapbox for a moment, part of the reason we don't regulate things in the household is that companies making money off selling those things don't want us to. (See, e.g., Canada's ongoing defense of exporting asbestos to developing nations.) So they fight regulation, and when regulation is inevitable, they want it to be as weak as possible so that it doesn't actually require them to change what they're doing. This is very handy if somebody who was hurt by the product then tries to hold them accountable, because they will claim 1) there was no regulation requiring them to put warnings on their stuff, take the dangerous goo out of the product, not sell it, whatever, and 2) when the regulations DID pass their product fell well underneath the Government Will Getcha level and therefore must be perfectly safe.

Mea @ 57 mentions pesticides.

The idea that people using pesticides on farms don't read the label scares me. I was a farmer, I used pesticides, I took the training course. I read the labels (I'm not in the USA, part of this is government regulation).

Did I read every little detail? Probably not. If you're working with pesticides and aren't reading the label enough to put the right dose on the crop, at a time when it will work, you're wasting money. Some of the stories I have heard from the USA, things like a film of chemistry on surface water, sound like that sort of wasteful incompetence.

Some accounts I've read of farming in the USA (quite a few years ago now), comparing it with what was been done in Europe, suggested that the farming wasn't paying as much attention to detail in the USA, but there was a tendency to compare the figures for the best in Europe with the averages for the USA.

Anyway, farming is dominated by big business, not because they own the land or run the farms, but because they control the market. And that's so divorced from the actual production that they don't care about that iridescent film on the water in the drainage ditch. I used to sell grain to Cargill, and they didn't care whether it was possible to grow it at the price they paid.

Mea @ 47 those links are definitely useful for background information. According to the first one at the time of the study 95% of the low income housing in the City of Baltimore had lead paint. In that context I can buy the argument that as a practical matter the study did not put the children at any additional risk.

Does anyone know what the final outcome of the case was? Every discussion of the case I've found focuses on the appellate decision with no mention of what happened afterwards. I'd like to know what the trier of fact ended up deciding.

It just struck me why the new lawsuit is only just now being filed. The 2001 appellate decision ruled that in Maryland parents can not give consent on behalf of their children for non-therapeutic studies that carried any risk. Since the study was started in 1993 that means the kids are now turning 18, and thus can now bring their own lawsuits.

Looks like the plaintiffs in the original lawsuit involving lead housing won their case against the non-profit housing corporation -- their landlord -- but dropped the claim against the researchers:

http://articles.baltimoresun.com/2009-11-04/news/0911040012_1_city-homes-paint-lead

Don't know if the researchers made a separate settlement or if the plaintiff's lawyers just made a reasoned judgement that it would be hard to ultimately win against the researchers.

Regarding pesticide use - in the United States properly registered pesticides have a statement "It is a violation of federal law to use a pesticide in a manner inconsistent with its labeling" and the label instructions are supposed to prevent things like over-application that results in a sheen on non-target water. But the law also has really strong protections for farmers applying on their own land, so enforcement results in basically a warning the first time and then low fines for subsequent violations. There isn't any distinction in the federal law for a family farmer or a big agricultural mega-corporation.

Ginger, Throwmearope, Mythago, and everyone else: Thanks for bringing more details and discussion. This is much more interesting as a real conversation (even a heated one) than as yet another outrage fest.

Tom B: Unless there are infinite resources available, you do indeed want low-cost alternatives. The cost of remediating old housing with lead paint in it is pretty high, as I understand it. It's important to know what does and doesn't work, and it's important to know what price each alternative carries.

Mia @ 61
I just found the Maryland courts website and found the answers to my question. In the Grimes case Kennedy Krieger got a stipulation of dismissal. If there was a settlement agreement it looks like it wasn't filed with the court. The Higgins case was removed to federal court. I could go on PACER and get the pleadings, but that would cost money.

The lead case in the Baltimore Sun story was a separate but related case. in that one Kennedy Krieger again got a stipulation of dismissal with no settlement agreement filed.

Nicole @52, that's not the only attribution-related error you made.

(Not the first time that's happened, either. Do people just see the A and stop reading?)

Heckblazer at 63 - thanks for the discombobulation of the cases. Shows the downside of quick googling over systematic research!

Mea @ 57: I don't do human studies; when I did tox research, it was on rats. The IACUC is the relevant oversight committee for animal research.

All human subject research must follow stringent regulations (as Fragano knows all too well), even if the research entails nothing more than a questionnaire. The NIH Office of Extramural Research index has a list of topics, including research involving children; if you look at the Kennedy Krieger Institute website, you will find that they not only treat children with a variety of medical issues, they do a lot of research on children as well. They are heavily funded by NIH, so they are required to abide by all the PHS regulations in order to maintain their funding. It's the same for animal-based research; if you get NIH funding, you must adhere to PHS Policy, etc.

Doing toxicity research is very different in animals, because this is one of the major reasons for using animals: to protect humans. We still address the health and welfare issues, identifying humane endpoints, for example, but we don't have the legal issues like informed consent.

I think the Appellate Decision that disagreed with the KKI IRB was overly harsh; although the IRB may have misidentified the control group, there was no proof that they did so in order to avoid Federal regulations. In fact, the IRB was only one of three committees tasked with reviewing all research proposals; they have a specific committee for reviewing protocols for risk/safety issues as well as one for scientific merit. Focusing on the IRB as "the bad guys" is simplistic, and overlooks the input of the other two committees (and all three are required; I checked).

Kennedy Krieger Institute specializes in childhood diseases (ranging from genetic to traumatic), so they had very good reason to look at the effects of lead abatement methods on blood lead levels. There's nothing unethical about finding ways to check the methods used to protect children from known toxins. Since children are the susceptible population, it makes sense to draw blood from them and not from the adults in the same houses. Even though it looks like the actual blood lead levels were below the Federally-mandated values, the fact that some levels seemed to rise over time means that someone somewhere was being exposed to lead. Whether it was caused by the abatement method, or lack of abatement due to landlord negligence, or high lead levels from local pollution, we don't know. I do know that drawing blood from patients doesn't elevate blood lead levels.

I had read about this in my biomedical ethics class. As others have commented here, it was a lot less clear-cut than "let's stick children in houses with lead in them." Which, actually, doesn't mean there wasn't a violation of medical ethics. But it's a weird gray area.

See, there's this thing. As everyday citizens, do we have an obligation to get children out of houses with lead in them? Yes, in the general sense (to work toward a world with less toxic houses.) This study takes on the general-sense obligation and does a reasonable job of trying some things to get there, because we can't get there instantaneously.

But the obligations of a medical professional are different, and that's where the ethics become dubious. A medical professional doing research has the obligation not only do avoid worsening people's conditions, but the obligation also to alleviate them if it's possible. And it becomes very, very difficult to settle on an ethical course of action if the immediate situation is fixable (a child is living in a lead-filled house? Get them out!) and the situation that it's a part of is not (a zillion kids are living in a zillion lead-filled houses; we don't have enough lead-free houses...)

In situ observation poses a problem. If the researchers don't interfere with sucky ground conditions or urge patients away from them, they're tacitly condoning harm; if they do interfere, they're losing valuable information on things that would be happening anyway... Or so runs the justification, which was the same justification for the Tuskeegee syphilis study.

The long and short of it is, once we've opened the box, we can't really know what "would be happening anyway", and the health care professional's obligation to make things better means that trying to set up "happening anyway" as if the professional weren't there is an error of thinking, in conflict with the principle of beneficence. Because the professional is there.

You wind up very quickly at the heavy-handed utilitarian problem of 'is it OK to sacrifice one child's health for the health of the next generation?' and the answer is, 'no, of course not' but it's also, 'aww, geez. So what else can we do for the health of the next generation...?'

And, at the very bottom of it, limited access to health care sucks deeply, and the administrators who made the economic decisions that led to it within the past few generations have caused huge amounts of death and suffering through neglect: because when there is a shortage of doctors, any individual doctor can only do so much, and only intervene on behalf of so many patients. But that is the Bigger Problem, of course.

albatross @62: Unless there are infinite resources available, you do indeed want low-cost alternatives.

There is a finite number of lead contaminated homes. The cost for replacing each one is also finite. I'm willing to consider less expensive lead abatement techniques, as long as they are proven effective without experimentation on children.

I do understand that if the "you" is an individual who cannot remedy the greater problem, then it is a triage situation. You do what you can. But if "you" is society, there is so much more we can do.

John A Arkansawyer @56: There are literally hundreds of public works projects such as lead removal which badly need done and which would put people to work, none of which have been advocated by the president at a time when work is badly needed.

That is so true, and it would be cost-effective too.

TomB @68: "I'm willing to consider less expensive lead abatement techniques, as long as they are proven effective without experimentation on children."

How do you propose to test the effectiveness of the lead abatement methods without testing the children to see if they're being exposed? Would you prefer to have the families leave the apartments while lab animals are housed in those locations? How do you think the families will tolerate this disruption of their lives? Where will the families go, and who will pay for this?

I'm serious. What are your acceptable alternatives for this kind of assessment? What would you think a reasonable researcher would offer? Or should offer?

Also, will you be testing the lab animals to ensure that they do show lead levels upon exposure? Validating them ahead of time? How many will be enough to get valid results from all the houses? How long should the animals be housed in those homes? How will you prevent allergens from the rats/mice/other species from contaminating the homes? How will you assure the families that these animals won't make their homes a mess? Who will be responsible for feeding, watering, testing, and monitoring all the animals? What precautions will they take to prevent accidentally contaminating the home with other sources of lead? Should the home be sealed up during this time?

What happens if a rat or mouse suddenly dies in that home? Is it because the home is really toxic?

How will you write the Informed Consent form for using animals in peoples' homes? What happens if people don't consent to the use of animals? What kind of compensation must be offered in case a researcher or animal destroys something valuable in the home? Who will do the pre- and post-study inventory of the homes? How do you know they won't lie?

I could go on. This is the kind of questioning that is done in committee review, no matter whether this is an animal or human study proposal. For human studies, it's even more intense because of the ethics of "using" humans as subjects.

The reviews of the Appellate Decision center on several legal difficulties, one of which is Informed Consent (the basis of the Grimes lawsuit, IIRC); another is the ethics of "using" children as subjects, particularly in situations where the children might be exposed to a hazard.

Here, the lower court found that there seemed to be no basis for trial and dismissed the case; the plaintiffs appealed -- as is their right -- and the Appellate court found an issue with the IRB approach. It doesn't mean this was unethical research on the part of KKI, although the Appellate judges certainly had some words to say about the review process. PHS policy on children in research is clear, and the reviews I excerpted above should explain this well enough.

The bottom line is, KKI researchers attempted to validate a hazard abatement method by the least invasive methods possible, by simply drawing blood from subjects. They were not the abatement contractors, nor the landlords. The original NYTimes article made it seem like evil researchers were once again using innocent children as subjects for their evil research, when the truth is far more complex and less evil.

Ginger @66/69: No, the bottom line is that the researchers were using children as collection units for the benefit of their own research, not for the benefit of the children.

I disagree very strongly with your reading of the appellate decision. Was it harsh? Yes. Was it inaccurate? No. As the quoted language shows, the reviewers plainly suggested that the description of the study be massaged because it did not benefit the research subjects, and therefore would not have been eligible for federal funding; so it was rewritten to (falsely) suggest that the children themselves were also directly benefiting from the study.

"What else could we do?" is an argument that the ends justify the means, and it's very dangerous one because it allows a well-meaning researcher to avoid tough moral questions about consent and harm; it's OK for me to use an unconscious patient as a test dummy or perform research on children that subjects them to lead exposure, because what I learn will help others, QED.

"What else could we do?" is not a counterargument; "I can't think of a better way" is not the same as "therefore, it is ethical and appropriate to proceed with what I'm doing."

From a legal perspective, despite the language in the complaint, the lawsuits really aren't about calling the researchers bad human beings or locking them up. (This is a civil suit, not a criminal case.) It's about who should bear the costs of those choices. Someone who chooses actions that cause harm to others ought to bear the costs of that harm.

@#70 Mythago

Having had a pelvic exam done by a med student without anesthesia, I'd vote for the anesthesia.

This was not a common practice in my medical school. We had a saint of a nurse who put up with 14 of us examining her one after the other, after the other. . .

As I recall the poor dear was conscious the whole time.

Another way to approach lead abatement studies would be to do so only with adults. We absorb lead but our brains are more resistant (already too damaged for it to matter much, whatever) to lead. Of course, the drawback would be most adults don't eat paint flakes off the floor.

As the quoted language shows, the reviewers plainly suggested that the description of the study be massaged because it did not benefit the research subjects... it's OK to ... perform research on children that subjects them to lead exposure, because what I learn will help others

But that's not at all what's happening here.

The "no benefit" population is the children living in housing WITHOUT lead paint. There's an ethical issue, but it's not exposing them to lead--it's doing blood draws to check whether there are lead exposures outside of the household exposures. (Both soil contamination and water contamination are possible sources of lead exposure.)

I would caution against reading too much into the appellate decision. By overturning the summary judgement all the court did was find that Krieger Kennedy had a duty to warn the parents about lead exposure. That does not mean that Krieger Kennedy failed to carry out that duty.

Throwmearope @71, the point isn't that an unskilled pelvic exam is probably more comfortable under anesthesia than not; the point is that the anesthetized patients had no prior knowledge that students would be performing pelvic exams not medically necessary for their own condtions, upon them while they were out, and were not given the chance to consent or to deny consent. That makes me feel incredibly icky, for what should be obvious reasons.

The nurse, whatever discomfort she endured, had consented to the activity ahead of time. Makes all the difference.

@Rikibeth #74

In the US, I don't believe the custom of training med students to do pelvics by using hapless patients who are anesthetized and completely unaware is very common, if it happens at all.

Informed consent is one of my particular bugaboos, so I agree with you. Unconscionable.

But training med students to do Paps is a real tough issue every year, probably in every med school. I was grateful that the RN was willing to put up with us.

Throwmearope @75

This article from 2010 claims "90% of medical students at four Philadelphia-area medical schools," so it would not surprise me to learn that the practice is more common in the US than you believe. Ick, ick, ick.

Ginger @69: How do you propose to test the effectiveness of the lead abatement methods without testing the children to see if they're being exposed?

I wrote without experimentation on children. By all means test and observe the children. But as soon as there is indication they may be at risk, get them and their families out. Leaving them in a harmful situation to see how bad it gets is experimenting on them.

Good questions about animal studies. Of course it is a serious responsibility and it's real work to do it right. Even more so if it's humans. But my original comment was based on the idea (snarkily) that it might not be hard to find rats and mice who had already been living there. Informed Consent forms are probably not be required for removing rodents from a home.

Sorry, Avram. *blush*

I think it wasn't just the "A" - I think it's also because I'm used to communicating with abi on Twitter, so the combination of things lit up that contextual association in my brain.

Again, apologies.

*crawls back under rock*

Tom @77: This was a controlled, randomized, clinical trial of abatement methods within a larger controlled, randomized, and fully blinded clinical trial testing an at-the-time new oral medication for removing lead from children's blood streams.

So far as I am aware, all clinical trials, particularly those with such high import, employ stopping rules. At several intervals along the way, the timing of which depends on statistical considerations of when is a result reliable, the two arms of treatment are compared to see if there is a difference. If there is, the trial is stopped immediately and the preferred course of action is instituted.

And, as is also the case in clinical trials, there was an independent body called the Data & Safety Monitoring Committee attached to the trial. This committee were sent periodic data reports and held yearly meetings. They were actively involved in reviewing interim results to see whether the trial should be stopped.

In the sub-study, where methods of abatement were being studied, I don't know if stopping rules were employed or whether the larger DSMC the oversaw the sub-study, whether the sub-study had a separate DSMC, or whether they had a DSMC at all.

Even if all of this was in place, and the interim analyses showed clear preference for completely abated housing, the irony is that there was at the time very little inner city housing stock that was lead-free; Baltimore was somewhat unusual as the city had just begun to implement more stringent requirements about lead-free public housing; but most of the public housing stock was not lead-free.

In addition, the pre-existing lead levels of these children at entry to the larger study were required to be below the CDC standard for treating lead poisoing. In the context of the larger clinical trial, if at any time a child's lead level went about the CDC standard (at that time I think it was 45 mg/dL blood), they were to receive immediate treatment, which was usually initiated within something like 48 hours of knowing the lab result. This requirement would have applied to all the children in the abatement sub-study. In all the cities participating, such a child would be moved to the cleanest housing available, but would still likely be exposed to lead in their home environment - because that was a question of the availability of lead-free housing stock, usually public housing for these children, and as I've said, such housing stock was not readily available.

Cases of early childhood lead poisoning virtually disappeared in the 1970s, when gasoline was de-leaded and leaded paint was banned. However, the problem continued to flourish in the inner city, among our most vulnerable children, because of the housing stock. But this showed barely a blip in public statistics about lead - and there was very little enthusiasm among policy makers for abatement once this new drug came out. It seemed a much easier solution. That was the true experiment, and unethical - but that's the way our society functions. The poorest, the most vulnerable continue to be exposed to toxins the rest of us have the resources to avoid.

There is one caveat to my understanding: I cannot say with certainty that all of the children in the abatement study were also enrolled in the larger clinical trial. But that has been my understanding of the situation.

Another interesting side-light is that oral chelating agent did not signficantly alter the children's cognitive outcomes; in fact, the children receiving the drug did slightly worse and suffered statistically significant adverse events. We all knew that the drug would lower blood lead levels over the short term; what we did not know was whether that short term drop would be enough to prevent the cognitive delays associated with higher lead levels (the CDC standard of 45+). People in the lead field argued back and forth about the ethics of the trial: one side said that remediation, even short of full abatement which at that time was an unrealistic goal, was the only ethical response. The other side said, we know the drug works and to withhold at these lower levels was unethical. It turned out that, I will reiterate, that the drug dropped lead levels but did not prevent cognitive delay and had some harmful side effects to boot leaving us with full abatement as the clear winner - scientifically and policy-wise.

Policies that cost society money will never be put into place without research like this. And I am not sure myself whether the sub-study was ethically performed - it seems that despite the signed "informed consent" forms, which will help & probably ultimately win the case for the researchers involved, the actual process of making sure that the parent completely understood what was going on was very poorly done in the abatement study. And requirements by IRB boards around gaining truly informed consent - and not just a signature on a piece of paper - have tightened up considerably, not just because of this one case but many many others out there during that time period, before the HIPA act when our medical records were routinely used for research without our knowledge or consent.