THURSDAY, December 8, 2005

Session 1: Bioethics and American Children

Norman Fost, M.D., M.P.H., Professor of Pediatrics and Director of the Program in Medical Ethics, University of Wisconsin Hospital

In today's discussion, we enter a new field of inquiry for the Council — the ethical and bioethical issues involved in the care of infants, children, and young adults.  They are, as has so often been said, the future of our nation and the world.  They will confront the problems and the promise of biotechnology and social change.

We can scarcely imagine today what the nature of those problems and challenges and potentialities will be.  Certainly, they will involve such things as the uses of psychotrophic agents in children, questions of human experimentation and clinical trials, issues of consent, assent, and surrogate decisionmaking, as well as end-of-life decisions, attitudes and values toward the disabled and the handicapped, the questions of priority and the allocation of resources on the basis of age and development, decisions of the utmost significance during intrauterine and neonatal life, epidemic obesity, universal vaccination, genetic testing.  The list goes far beyond anything we can fully envision at this time.

We have invited speakers whose expertise includes many of the areas that I've mentioned, and many others they will bring to our attention.  We have asked them to be free to look at the issues as individuals, from their own point of view, from their expertise, and from their experience.

The second item, which we will discuss tomorrow, is a staff paper on the subject of human dignity, a concept which is much used and much abused in the bioethics literature today.  It has been used repeatedly by the Council itself, and we thought it wise perhaps to reflect on some of the dimensions of this concept.

Before we begin, let me ask if you will express your appreciation to Dr. Kass.  He happily will be with us as a member of the Council, and we will have continued access to his wisdom and his intelligence.

Leon, thank you very, very much.

(Applause.)

Our first speaker this morning will be Dr. Norman Fost, who hardly needs any introduction in the field of pediatric ethics.  You have a summarization of his career and curriculum vitae, and I will ask him to address us — Norm, there you are.  And I have asked him very clearly to tell us what he thinks over the many, many years of his cogitations on this subject we should be addressing and the nation should be addressing.

Norm?

DR.FOST:  Thanks very much, Ed, for inviting me to this distinguished group. 

Dr. Pellegrino's invitation reminded me of the famous exam question, "Discuss the universe and give two examples."  I've decided instead to give three examples to be unduly ambitious, and to talk about the three issues of the many that we could talk about that seem to me most pressing.

Through the lens of someone who has been engaged in these issues for 40 years — not as long as Dr. Pellegrino but I'm gaining on you — as a pediatrician, as an investigator, as a human subject, as Chair of an IRB for 28 years, Chair of the Hospital Ethics Committee, someone who has written and taught about these issues and had the opportunity to be involved in federal policy.

And let me say that I think ethics does matter, that Councils and Commissions like this have had a — that there's been a dramatic change.  I'm going to try to make the point that there have been dramatic changes in the well being of children as a result of committees and councils and commissions like this, and I think there is the opportunity to have more influence.

I'm going to talk about three issues, two of which will seemingly overlap with other speakers, namely end-of-life decisions, research issues, and issues about genetic screening.  But I've talked with all of them, and I think there will be minimal overlap and what they say will sort of pick up where I leave off.

But before I do that, I want to just say a few words about two overriding issues that seem to me to dwarf traditional bioethics concerns with regard to children. 

First is the continuing problem of 40-plus million Americans without insurance, a third of them children, somewhere between eight and ten million children without third party coverage, not eligible for Medicaid, who die at a higher rate than others, who suffer, who come into life with burdens, who leave the starting gate with a 200-pound gorilla on their back, whether due to prematurity or single mothers on drugs or lack of access to care.

And this is always mentioned as the most important problem involving children and Americans, but not enough is done about it.  It's a big issue, and I'm not going to say any more about it, because it is so complicated.  But I hope the Council will take some cognizance of it in a larger context.

Second, I want to just say a few words about child abuse, which is a special interest of mine.  I've been director of a child protection team for 35 years, and, here again, it's a problem that affects millions of children. 

I mean, there are over a million reports of child abuse in the United States, and we know that that is the tip of the iceberg.  Underreporting is somewhere in the five to ten to one range.  That is only five to — only 10 to 20 percent of cases get reported.

And in the area of physical abuse alone, we have known for 30 years how to prevent this.  Dr. Henry Kempe did a landmark study 35 years ago, showed that we can predict 80 percent of cases of physical child abuse in the delivery room.  We know before they go home who these children are.

And in a randomized, controlled study, showed that the simple intervention of lay home visitors, lay people asked to spend an average of five hours a week with these usually single mothers, had dramatic effects in reducing the incidence of physical abuse, permanent disability, and, in some cases, even death.

We are the only country in the world that I know of, certainly one of the few, that does not have routine home visitors.  It's considered bizarre in other countries that we allow these children to be born and go home, and nobody checks in, nobody offers to help.  It is extraordinary.

But Dr. Kempe's studies have been repeated many times, the effectiveness of home visitors, professional or lay visitors, has been shown in — when done correctly, to have very dramatic effects.  In fact, I would say the most important professional thing I've ever done is to have the chance to be involved in starting a nonprofit agency in Madison whose sole purpose is to recruit lay volunteers for home visitors.  It has been copied elsewhere around the country, and it has been immensely gratifying.

So, again, it's a huge issue.  It affects, logarithmically, more children than the issues that we're going to be talking about.  And I hope the Council at some point can take that up.  I'd be happy to talk more about it when the occasion arises.

But I will concentrate on the three traditional issues.  From a historical perspective, what I'd like to do is say something about how it was when I started out in this field, how it is now, and, in my view, how it should be, because I think things were terrible.  I think there have been dramatic changes.  But I think there is still work to be done, and I'll suggest what that might be.

So first some comments about withholding and withdrawing life-sustaining treatment, end-of-life decisions in children who are ill and handicapped and in need of medical care.  My entre into bioethics was facilitated by a single patient, a child who has come to be known as the Hopkins Mongol case, in the language of the day, a newborn with Down's Syndrome and duodenal atresia, intestinal obstruction of a kind that's very easily fixed in a simple operation that has virtually 100 percent success rate.

This was in 1971 when I was in my second year as Chief Resident at Hopkins.  The parents typically did not want surgery done.  It was withheld, an NPO signed, "Nothing by Mouth" was put on the child's crib, and he was put into a room by himself and allowed to die of dehydration over a 15-day period.

With the help of the Kennedy Foundation, we made a movie of that case.  That has been seen by more than a million people, and became the centerpiece of a symposium at the Kennedy Center in Washington.  That was one of the first cases to bring bioethics into the public sphere.  It was one of the first widely-publicized cases that attracted, appropriately, public scrutiny and discussion.

I went to the record room at Hopkins at the time and found six other cases of the identical situation — that is, children with Down's Syndrome and duodenal atresia who had been allowed to die.  In fact, a case just about three years before that had been taken to court by Dr. Robert E. Cooke, the Chair of Pediatrics, to try to get court intervention, without success.  The court said that the parents had the right to make that decision.

Shortly after that case and the publicity surrounding it, a national survey was done of pediatricians and pediatric surgeons, and 70 percent of them agreed with what was done in that case.  That is, 70 percent of American pediatricians polled said that, if confronted with the same case, they would defer to the parents' wishes.  They would not go to court.  They would not seek to override the parents.

A similar survey was done in Massachusetts and produced the identical result; 70 percent of pediatricians in Massachusetts said they thought it was — what the parents had asked for was okay, and they would go along with it.

An article was published in The New England Journal by one of my teachers at Yale, Dr. Raymond Duff, reporting that one in five deaths at the Yale New Haven nursery over a two-year period was due to withholding of standard medical treatment.  This included children with Down's Syndrome and other relatively modest handicaps or disabilities, and children with profound disabilities who had little prospects for a long or meaningful life.

And in the last paragraph of that article Dr. Duff said, "If what we did is illegal, then that shows that the law needs to be changed."

The world 30 years later is dramatically different, I think in part as a result of the work of a prior Presidential Commission on Bioethics, work by the American Academy of Pediatrics, scholars in the field, and so on.  There has been a complete reversal of this situation.

The turning point came in the mid-1980s when President Reagan implemented so-called Baby Doe regulations that prohibited discrimination on the basis of handicap.  And to the best of my knowledge, since 1985, there has not been a single case of a child who has — with Down's Syndrome or spina bifida, the other common malformation, who has died due to withholding of standard care simply on the basis of having Down's Syndrome or spina bifida.

Needless to say, such children sometimes die, and sometimes due to withholding of treatment, but because of some profound, often untreatable, illness, not because they have Down's Syndrome.

So it has been a dramatic change.  The status of children with disabilities and the medical treatment that they receive is 180 degrees different from what it was 30 years ago, and even 20 years ago.  But this long history of undertreatment, of inappropriate, and I think what is now widely agreed to be inappropriate withholding of treatment in such children, has been replaced by what many of us consider overtreatment. 

That is, there was a rebound effect from the Baby Doe regulations.  Dr. Kopelman, one of the later speakers, has written eloquently about this, and what we have now is a country in which children receive treatment regardless of whether it serves any interest of theirs, children who have little or no prospects for a meaningful or long life, but suffer in intensive care units or in intensive care units in their homes, in part as a result of fear of legal repercussions, in part due to what I consider misinterpretation of the famous or infamous Baby Doe regulations.

Dr. Nelson I know will be saying a lot more about this subject, but I think work is needed, and I hope the Council will contribute to this discussion about finding a middle ground.  One of the causes of the transformation in this area is not just the Baby Doe regulations, but the growth of hospital ethics committees, infant care review committees as they were called at the time, which introduced for the first time almost obligatory multidisciplinary/multidimensional discussions in end-of-life decisions, not just for children but for all hospital patients.

As you know, these committees are now required by the Joint Commission on Accreditation of Hospitals, and it's my view there has been a dramatic change in just the process by which these end-of-life decisions are made.  So the debate is over a much narrower ground of cases, a much narrower band of cases. 

But in my view, there still is undue overtreatment, and it is now very difficult in many parts of our country for a child to die when there's widespread agreement that that would be in that child's interest.  Dr. Nelson will be saying much more about that.

Second, I'd like to say something about research, and start again with personal experience.  In the 1960s, a local reporter at WABC in New York, WABC TV in New York named Gerald Rivers lurched into national prominence with a sensational series of reports of alleged abuses of profoundly retarded children at the Willowbrook Hospital in Long Island, a state institution for the profoundly retarded.

Newly-admitted children to Willowbrook, he discovered, were deliberately infected with the Hepatitis virus using fecal extracts from other children in the institution.  The reporter soon acquired a new name to better fit his celebrity status.  Gerald Rivers became Geraldo Rivera, which is perhaps the most serious legacy of Willowbrook.

(Laughter.)

It's beside the point that Willowbrook, in my view, has been badly and consistently misreported over the decades, and was framed by Geraldo Rivera and everybody since as a non-therapeutic research study to learn about the epidemiology of Hepatitis.  It was, in fact, intended as an early vaccine study.  That is, Dr. Krugman thought what he was doing was trying to prevent the infection of Hepatitis in these children, where it was endemic.

Dr. Krugman was vilified for what were called coercive recruitment techniques and disregard for minimum standards of informed consent.  My own view is that the consent procedures used by Dr. Krugman exceeded any in any study I've known since, and this, mind you, was before IRBs existed, before there was any — there were any requirements for research involving human subjects.

One last point in the category of personal disclosures.  My senior thesis at Yale involved a study of chromosome breaks in children who had had viral infections, and my source of my patient material were the children at Willowbrook.  That is, I found a nurse there who would call me when there was a new outbreak of some viral disease — measles, rubella, or hepatitis. 

I would drive down with my little bag, go into the main ward there.  The nurse would find an appropriate patient, yank his or her arm through the crib rails, I would draw blood and go back to New Haven and do my studies.  No committees, no parents, no consent, no review, no nothing.

Well, I'm not here today to discuss the pros and cons of the Willowbrook studies, Dr. Krugman's or mine.  The point is that it was typical of the day — that is, research involving children and most everyone else — was a free for all with no regulations, no oversight, no committees, no review, and usually no standards for consent from everybody — from anybody.

This was standard practice.  One of my heroes at Yale, Dr. Robert Cooke, elucidated with his mentor, Daniel Darrow, most of what we know about the role of potassium in the body, in part by taking infants out of orphanages in New Haven, bringing them into a clinical research unit where they were exposed to heat stress. 

Meticulous balance studies were done.  These studies resulted in what ultimately became WHO electrolyte solution, and Dr. Cooke conservatively estimates he saved several billion lives through this research on a very small number of children, but is just astonished at what he did, looks back with sort of horror that he was able to do that, and has said many times, "If there was just some committee that I had — just any group of people that I had to check this out with, it never would have happened.  I could have done the studies on sick patients with very minimal risk."

When I was an intern at Hopkins, one of my fellow interns did a landmark study on hernias in children by taking infants who had been admitted to the hospital for an elective herniorrhaphy the next day.  He was interested in the question of whether children with a hernia at one side were at risk for a hernia on the other. 

So at midnight when he was done with his regular intern duties, he would pick these children out of their cribs, take them down to the emergency department, inject their abdomens with high opaque, radio-opaque dye, jiggle them around, put on a lead apron on himself, sweet talk an emergency room X-ray tech to take a flat plate of the abdomen, including the gonads, and published a landmark study showing a high incidence of inguinal hernia.

To this day, those parents have no idea who their — that their children had their gonads irradiated with very primitive X-ray machines.

And, finally, these examples are by the dozens.  But just to make the point, Dr. Gross at the Boston Children's Hospital, the Chief of Cardiovascular Surgery there in the 1970s, was interested in the role of the thymus — an immunology poorly understood at the time — and took children who were brought to the OR from elective surgery for congenital heart disease, took out the thymus on some and not others, and did heterologous skin transplants to see what the role of the thymus was in rejection.

The children would come back to the ward with these funny patches on their arms.  The nurses didn't know what it was, couldn't answer the parents' questions.  Again, no permission from anybody.  So we've come a long way.

Three weeks ago Dr. Nelson and I spent a day and a half discussing whether an investigator at the University of Chicago could admit children to a hospital overnight to give them a single injection of a probably harmless drug, and collect a few blood samples.  It took one year for this investigator to get permission from his local institution and still required the permission of the Secretary of Health and Human Services.  And Dr. Nelson and I were part of a committee to advise the Secretary on that.

So the kinds of egregiously unethical research involving children and everybody else that was done in the 1960s, like starving mongols to death, is ancient history.  But just as the undertreatment of handicapped infants has been replaced by overtreatment, in my view the underregulation of research has been replaced by overregulation and disregulation, with severe sanctions against institutions for failure to document compliance with rules, many of which have little or no relationship to protection of human subjects.

Let me just give one example, again, of dozens in the discussion.  We could expand on this if you like.

As you all know, Duke University some years ago was shut down by the Office of Human Research Protections for alleged violations in protection of human subjects.  There were 25 different categories cited by the Office of Human Research Protection.  I'm just going to mention one.

One was the failure to document a quorum in the conduct of the IRB's business.  The Chair of the IRB, whom I know well, showed that they had documented a quorum at the beginning of the meetings and used Roberts Rules, which state that a quorum is presumed to exist unless it's challenged by somebody during the meeting.

The leader of the site visit from OHRP said, "No, sir, the common rule — the federal regulations require that all business conducted at the meeting must be approved by a quorum of those of the committee.  You had over 100 action items at each committee, and you did not document a quorum, we know that there's a lot of Brownian motion at these committee meetings, people leave to take pages, to go to the bathroom, and what not, and so we have suspended all 2,200 protocols because you have no documentation that a quorum existed.

As a result of that suspension, Duke, and now everybody else, documents a quorum 100 times during a meeting.  The minutes from — I'm Chair of our IRB.  The minutes of our meetings are 150 single-spaced pages for a three-hour meeting.  This is — the quorum rule, of course, is only one of the many things we have to document.

One last anecdote about the quorum rule.  OHRP went on to shut down eight consecutive academic medical centers.  The University of Wisconsin was ninth on the list.  We fully assumed that we would be shut down because we were guilty of all the transgressions, virtually all, that have happened at Duke. 

And while we had taken steps to correct them to be in compliance, we knew that if our records were examined that they could show that our 2,000 active protocols also had been approved without documentation of a quorum and many other things for each one.

Miraculously, we were not shut down.  We received a commendation letter.  And as a result of this, when accreditation of IRBs started, one of the new accreditation agencies asked us to become their beta site, their testing site, since we were held in such high esteem by the federal agency.

We were glad to do this.  It gave us a chance at essentially a free look at accreditation.  It was literally cost-free.  If we flunked, it would be confidential.  If we passed, we would be accredited, so it seemed like a no-brainer.

The accreditation manual had 270 items.  We had six months to prepare.  There was a four-day site visit.  We flunked 70 percent of those items, 70 percent of 270 items.  This was an IRB that had received a commendation from the federal authorities.

Let me just mention the quorum rule as an anecdote.  We, of course, as a result of the Duke experience had learned to document a quorum 100 times at each meeting for each action item.  But the site visitor said, "You haven't documented whether a non-scientific member of the IRB was in the room.  The federal rules require that each IRB must have a non-scientific member, somebody whose major expertise is in non-scientific areas."

Well, we had several such members, and so we were quite confident that there always was at least one such person in the room.  But the site visitor said, "You haven't documented it.  All you've said is that you have a quorum, but how do we know if the quorum included a non-scientific member?"

Well, virtually all our votes are unanimous or unanimous minus one.  We just keep talking until we reach consensus.  And I asked, "Has there ever in the history of the world been a study which involved humans, a research study, in which the vote was tipped due to the vote of the non-scientific member?  Do you know of any such instances?"

Well, of course, nobody knew of such an instance, but that was beside the point.  A rule is a rule.  As a result of that requirement by that agency, Hopkins, I was told, in one of their IRBs began passing a clipboard around at their IRB meetings where all 24 members signed the clipboard for each of 100 items at the committee — 2,400 signatures at one meeting — to make sure that the non-scientific member and other IRB requirements were met.

This is silly, of course, but if it were just the only example I wouldn't bother you with it.  In my view, there are a dozen similar kinds of rules, and the problem is that research which used to be too easy is now too hard.   That it is now very difficult to get senior faculty to participate in IRBs. 

We had a very valued member storm out of a meeting and quit permanently because of discussions like this, saying, "This is not what I'm here for.  I'm happy to donate 150 hours a year of my time at no reimbursement to protect human subjects, but not for this kind of nonsense."

It is harder for investigators, of course.  Clinical research is dying in my view, as a field of inquiry.  That is, there is a dramatic decline in the number of young American physicians going into this area.  If you look at the lead author of New England Journal articles over the last decade, less than 50 percent are now American authors.

If you look at the number of M.D. principal investigators of NIH funding, it is also in almost a straight line decline.  Children are the most serious victims of this decline in clinical research.  That is, children, unlike adults, are almost always treated with what is euphemistically called innovative therapy.

My colleague Paul Lietman at Hopkins says innovative therapy means if you don't want to learn any — if you promise not to learn anything from what you're doing, you don't have to go through an IRB.  Eighty percent of all drugs prescribed for children in America have never been approved or tested for safety or efficacy in children. 

And as we know, children are not little adults.  History is littered with examples of large numbers of children who have died or suffered because of treatments that were quite okay in adults, but turned out to be toxic and even lethal in children — chlorenphenicol, sulfonamides, oxygen given indiscriminately to children for 80 years before anyone asked the question whether there might be a dose-response curve.

Even simple bicarbonate, used as a buffer for patients with acidosis, shown by Dr. Michael Simmons to cause death and profound brain damage in infants with hyaline membrane disease.  And on and on.

That is, children need research more than adults.  The problem is not that there's too much research in children, or too much unregulated research as went on 30 years ago, but not enough.  The problem is that children are now "experimented on" but without — and no systematic way and without any collection of data.

That said, the regulations for research need some refining.  Sara Goldkind will say more about this.  I just want to mention briefly a couple of elements of the regulations that seem to be problematic and possibly an example of persistent underregulation.  Dr. Goldkind will say much more about this.

In my view, the justification for non-therapeutic research on children has never been made.  The brilliant work of the National Commission for the Protection of Human Subjects never really, in my view, made the case for allowing non-therapeutic intrusions into children without children who were incapable of consent.

The argument that was made was a utilitarian one, namely that it's good for children as a class.  We wouldn't want to live in a world in which no non-therapeutic research is done on children.  And it's good for them to have such studies done with restrictions.

One of the restrictions was it's okay as long as the research is of minimal risk.  Realize, of course, that there is no such exception for adults.   That is, the utilitarian argument is equally true.  We could — knowledge could advance much more efficiently with adults, if it weren't for this pesky consent problem. 

If we could do more non-therapeutic research on adults without their consent, we could learn a lot more a lot faster, but this is absolutely taboo and appropriately so, but yet the argument is allowed for children.

The minimal risk rule, defined in the federal rules as the probability and severity of harm, comparable to what would happen on a routine visit to the doctor, is interpreted widely — in a widely and wildly variable way.  Published studies have shown that IRB chairs and IRB members interpret this to include everything from venapunctures to non-therapeutic bronchoscopies and small bowel biopsies.

Investigators make the claim either that this is minimal risk in my hands or this is what happens on a routine visit to my office.  I do a bronchoscopy on everybody I see.  And the variation in IRB acceptance of this kind of argument is quite remarkable.

So more work is needed in this area.  Dr. Goldkind may say some more about it, but I think we do not have enough conceptual work or even practical, pragmatic definitions of the minimal risk rule.

The other area that, in my view, needs much more work is the notion of assent.  Legally valid informed consent is not possible with young children, and so this term "assent" was invented as a surrogate — the requirement that children at least be told in language that's meaningful to them what is proposed, and essentially that they don't need to do it if they don't want to.

I don't think this is taken seriously.  I think if it were, it's hard to imagine why any seven-year-old would let himself or herself be stuck with a needle if it had no relationship to his or her health care, and they didn't want to do it.  Moreover, there has never been an adequate discussion as to why the age of seven is used as a boundary for this requirement. 

Three-year-olds know perfectly well what a needle stick is all about.  They know perfectly well that they don't want it, for the same reason that adults don't want it, because it's annoying, because it hurts, and they would just rather not do it.  But there is no respect for three-year-olds or infants for such invasions.

Well, I don't want to have non-therapeutic research on children stopped, but I think, as I say, conceptual work is needed, and this Council is very qualified to either do that work or facilitate it.

Finally, let me just say a few words about genetic testing, which Dr. Pellegrino referred to, which in my view is the most serious of these three areas that is affecting the most number of children.  And, again, I'd like to start with a historical example and a personal experience, and then express my concern about where we are today, and then I'll close.

In 1960, PKU, Phenylketonuria, was known to be an admittedly rare, but a well understood, cause of profound mental retardation.  It affects approximately 1 in 10,000 live-born children.  The biochemistry of it was fairly well understood.  It's due to inability to metabolize an amino acid named phenylalanine, which is ubiquitous in proteins.

It was known that if you could diagnose this early enough and get a child started on a restricted diet that you could ameliorate, and in some cases prevent completely, the profound brain damage that uniformly occurs. 

But the test that was available at the time, a urine test, was inconvenient to get.  It was obtained at the first well baby visit after the child had been on a normal diet for a while and the horse was out of the barn.  That is, by the time children were diagnosed, brain damage had already occurred.

The diet was expensive and unpalatable.  Parents had an awful time getting children to cooperate with it.

There were three breakthroughs in 1960 — the discovery by Dr. Robert Guthrie of a simple test, making it cheap and efficient to diagnose this condition on all newborns on a single drop of blood; second, the development by Mead Johnson of Lofenalac, a low phenylalanine milk that was reasonably affordable and palatable; and, three, the election of John Kennedy.

President Kennedy, because of his profound interest in mental retardation, his family's interest, with Dr. Guthrie formed a so-called PKU lobby and arranged for laws to be passed in all states requiring PKU testing, realizing correctly that doctors in offices would be unlikely to adopt a test for a disease that affected 1 in 10,000 children — something that a pediatrician might never see in his or her entire career.  So mandatory newborn screening for PKU became the national policy.

In 1973, I was invited by Dr. Barton Childs to be part of a commission — a committee at the Institute of Medicine to look into the PKU story.  This was my first exposure to national policy.

The problem was, it turned out, that the PKU test was the worst test in the history of the world.  It had a sensitivity and specificity that have not been matched to the best of my knowledge.  That is, the test had a five percent true positive rate.  It had a 95 percent false positive rate.  That is, a child with a positive test, confirmed by a whole blood assay, had a 20 to 1 chance of being normal.

This was not appreciated for many years.  So many normal children, we now know, were started on a restricted diet, and it turned out that a phenylalanine-restricted diet was as harmful, or more harmful, as a diet with excess of phenylalanine.  That is, this essential amino acid, when withheld from normal children, resulted in brain damage due to starving of brain cells, and every other cell in the body, because phenylalanine is a part of so many proteins.

So many children — we don't know how many — were made retarded by this program.  Some were killed.  In fact, kwashiorkor developed in America in the PKU program in children who had profound protein malnutrition because of the restricted diet.

Well, if that happened to a child with PKU, you might say nothing ventured, nothing gained, these children had little to lose.  They were — had terrible prognoses anyway.  But when this happened in a normal child, it's obviously a major tragedy.

In 1965, the American Academy of Pediatrics sent a letter to the Secretary of DHHS urging that the mandatory PKU screening programs be stopped, because we didn't understand the significance of the test, and we didn't know how to regulate the diet.

This letter was suppressed.  People were called Luddites who were against newborn screening.  The PKU lobbying was very powerful, and testing went on until 1971 when a political scientist named Joseph Cooper uncovered this story through the Freedom of Information Act and led to the appointment of the IOM Committee, whose report was published in 1975 articulating principles for ethically responsible newborn screening, particularly genetic screening or screening for genetic disorders.

These guidelines published by the Institute of Medicine in 1975 have been essentially photocopied by a dozen committees, commissions, councils, professional groups, lay groups.  There is virtual unanimity on the principles of responsible genetic screening, and newborn screening in particular. 

It is not a controversy, and it represents another marvelous example of the good work of ethics, of thoughtful people and ethics, law, public policy, patients, parents, and so on, agreeing on guidelines.  The only problem is that the guidelines are systematically ignored.  That is, newborn screening has expanded like topsy, with the same mistakes that beleaguered the PKU program happening over and over again.

That is, numerous screening and treatment programs have been implemented without testing, evaluation of the tests, without any systematic study of the sensitivity, specificity, or predictive value of the test, or of the interventions.

This happens in part because genetic testing and treatment falls outside of the regulations of the FDA.  That is, there is no toll gate through which an investigator or an innovator has to go to get these kinds of programs approved.  He or she only needs to persuade existing committees and state health departments to simply add another test onto the drop of blood or the drops of blood that now exist for virtually every newborn in America.

I won't take time to rehearse for you other examples of newborn screening gone awry, and the large number of children in my view who have been killed, normal children in some cases, by screening and treatment programs that have never been adequately evaluated.  Not enough research.

The new technologies, such as tandem mass spectrometry, now make it possible to test for hundreds of conditions on this single drop of blood.  And, indeed, a committee of the American College of Medical Genetics has persuaded the Secretary's Advisory Committee on Genetic Testing to recommend to the Secretary national implementation of a uniform standard for testing of newborns using tandem mass spectrometry.

These recommendations include over 50 conditions, half of which have no known association with human disease.   That is, approximately half of the tests on the committee's recommended list are abnormalities that have been observed whose relationship to clinical manifestations are unknown or uncertain, and the other half roughly involve serious diseases but diseases for which the sensitivity and specificity and predictive value of the test is unknown, and in which the interventions have never been systematically tested.

It is telling, in my view, that the UK equivalent of the FDA has recommended implementation of only one of these 50 conditions.  Even worse, multi-array DNA testing — that is, the ability to test for a thousand genetic variations using recombinant DNA techniques on a single drop of blood is also now upon us, and work is proceeding rapidly to add multi-array genetic testing to the newborn PKU spots.

So we now already have many states, including Wisconsin, that does routine testing without consent, without prior research, for dozens of conditions using tandem mass spectrometry.  And I predict, unless there is some dramatic change in the way we think about these things, the way we do these things, that multi-array DNA testing will occur within the next few years, as soon as the cost comes down to make it efficient to do it.

This, to me, is a calamity involving every child in America, the amount of mischief.  The amount of harm, psychosocial harm that will occur to families and children, not to mention medical harm, is, in my view, going to be quite extensive. 

And, worse, 20 years from now we won't know what harm has been done, because in the absence of systematic studies we won't know which children were helped and which were harmed, because we won't know whether like — in the PKU program, we won't know if a positive test meant that that was a child who was destined to become brain damaged or dead, or whether it was a false positive test that had poor predictive value.

In summary, where have we been?  Where are we?  Where are we going?  In the area of end-of-life decisions, there has been a transformation from egregiously unethical undertreatment, withholding of simple treatment from children with excellent prospects for long, happy lives, to serious overtreatment.

A thoughtful kind of undertreatment has been replaced, in my view, by a thoughtless kind of overtreatment.  In the area of research, egregiously unethical research with no oversight or regulation has been replaced by too little research, with excessive and inappropriate regulation.  The result has been an expansion of innovative therapy, a decline in physician investigators or funds to support them.

And, finally, in the area of genetic screening, the mistakes of the PKU program has resulted in guidelines about which there is little dispute, but practices which have not changed at all and which arguably may become much worse due to the advent of multi-array testing.

I could tell many other stories in all these categories, and there are, of course, other issues that we haven't talked about.  But these seem to me worthy of Council's attention.

Thank you for the opportunity to present to you.

CHAIRMAN PELLEGRINO:  Thank you very much, Dr. Fost.  Dr. Fost is going on 35 years in bioethics.  Bioethics itself was invented or baptized in 1972, according to some people. You were there at the beginning.  And thank you very, very much for your reflections on pediatrics and pediatric ethics since then.

I'd like to open to Dr. Fost's paper. The members of the Council put on their red light, indicating that they'd like to talk, to save me from being a traffic cop.

Leon?

DR. KASS:  Thank you very much for a really lucid and illuminating paper.  I have I guess — and I appreciate and feel the force of each of these issues.  But if I could draw you out on sort of the — some of the tacit ethical suggestions that you made along the way. 

First, the second point on the research issues, you begin by saying the case for non-therapeutic research on children hasn't been made.  You concluded by saying you don't want this to be shut down, and, therefore, I assume you think the case can be made.  And I wonder — on non-utilitarian grounds, I assume, and I wonder if you would — if you have any sort of beginning inklings as to how you could do this.

Our mutual friend Paul Ramsey thought it was impossible to make such a case, and I'm not sure I agree with you that the case hasn't been made.  But if you think that there is a way to make it, I would be interested to hear at least the outline.

And, second, I wonder whether, if we follow your suggestion that there is egregious — well, you didn't say egregious overtreatment, but that there has been an excess — that there has been a turn in the direction of excess treatment, and I'm not exactly sure how you describe what constitutes the excess.

At one point, you talked about cases in which it would be in the child's interest to die, and I wonder whether we might, 10 or 15 years from now, if such a formulation were made the standard of care, whether we would say the case — we regret the way in which that case was made.  In other words, could — are you able to articulate, for yourself at least, and suggest how we might articulate the principles for deciding that this kind of treatment is really excessive.

The Council has dealt with this with respect to end-of-life issues in the adults, and we've, in a way, affirmed the old standards where the treatment is excessively burdensome or where it's useless.

I take it you might think that there are some treatments that would be efficacious and not excessively burdensome, but that might still be excessive under the present circumstances.  I don't know that you mean that, but if you could say a little bit more on the ethical side of what you think constitutes too much, or how we would recognize it.

DR.FOST:  Thanks, Leon.  First, I'm glad you mentioned Paul Ramsey, who was maybe more than anyone else responsible for my entering this field as an undergraduate at Princeton.  He was immensely influential in getting me interested in these issues and stimulating me to get involved, and an important mentor to me throughout my life, a really wonderful man.

Paul Ramsey did not quite say "impossible."  In his famous debates with Richard McCormick, he said for a number of years it was impossible to find an ethically coherent justification for non-therapeutic research in children.  But I'm sure, as you remember, Leon, near the end he said that perhaps we had to sin bravely, as he put it.  That is, we have to do this kind of research.  We have to admit that it's wrong, but we have to do it.

What's the ethical rationale for that?  In my view, a better rationale than the simple utilitarian one would be what some have called a constructive consent.  That is, to have a reasonable inquiry as to what a child in that circumstance would do if he or she understood all the ramifications. 

That is, if an infant had a moment of lucidity and could understand everything that we understood, might he or she agree to allow a mere venipuncture in the interest of the class to which he belongs, the class of children or children with a certain disease, and so on.

That seems to me at least a more plausible basis.  I think the bottom line is that, like Paul Ramsey, I don't want to see this — to see a shutdown, a prohibition of non-therapeutic research.  I think that the minimal risk rules and the assent rules are useful boundaries, but need to be, in the case of minimal risk, better defined. 

I think that it has gotten way out of control.  I was part of the National Commission deliberations, not as a member but as a consultant.  And I know that what was meant by that rule was things that happen on a visit to a general pediatrician for a routine well baby visit, and that has gotten way out of hand.  So I think that needs to be reined in, and I think if it were reined in I'd be comfortable with it.

And I just think assent needs to be taken more seriously.  That is, children really — somebody really needs to say to them, and we need to have more monitoring of it, "Junior, let me make something clear.  We want to stick a needle and get some blood from you.  You don't have to do this if you don't want to."

Now, would everybody say no?  I don't think so.  As Will Gaylin famously said, "A parent has a right to decide that their children are not going to grow up to be a selfish little bastard."  So that is some parents, and many parents in fact, would persuade their children that they want them to volunteer for this kind of research, because they think it's good for them to be a volunteer, and it's important to be altruistic.

That does happen, and I think it's appropriate.  I don't think it's abusive.  Parents do more serious things in the name of altruism for their children.

So it's a long-winded way of saying I think the common rule is adequate to protect children in this regard, if minimal risk were defined more rigorously and if assent were taken more seriously.  That would still leave the problem of infants and children who can't speak at all a little bit out there, but I invite you and the others on this Council to help us.  I think with some more work we might be able to come up with an appropriate rationale.

With regard to your second question, I think if — the problem is that even for children who meet the parameters that you describe for adults, that it's treatment that is excessively burdensome.  And without compensating benefit, it is difficult in many settings to allow these children to die a dignified death.

The Schiavo case is an adult case, of course, but there are many children similar to Terri Schiavo, or not quite in a persistent vegetative state which is harder to diagnose in infants and children, but with profound brain damage in which there is unanimity among the medical people that this child has little prospect for any kind of social interaction, any opportunity to experience any of the pleasures of life, even those of a profoundly retarded person, and in which hospital attorneys or neonatologists, fearing legal consequences, or the kind of public maelstrom that surrounded the Schiavo case, even the involvement of the United States Senate, are reluctant to pull the plug or to stop treatment. 

Skip Nelson will be saying much more about this later, and I don't want to intrude on his territory and where he has a lot of clinical experience.  But I think it is very difficult to let children die in many settings, because of a very defensive attitude by lawyers, by physicians.

In fact, Loretta Kopelman is the co-author of a famous study in The New England Journal with her husband Arthur, a neonatologist, showing that after the Baby Doe regulations large numbers of neonatologists in America stopped using their judgment about what was in the interests of their patients — that is, shifted towards overtreatment, which was defined as treating children who they thought had no interest in being children, as a result of the Baby Doe regulations, as a result of, in my view, a false fear that the Baby Doe regulations prohibited them from acting in the interests of their children.

So, in summary, again, a complicated area and a long-winded answer, but I think the sorts of guidelines that apply to adults are applicable to children.  We can't even — it has become increasingly difficult to even apply those.  I think the use of ethics committees provides a really reasonable procedural safeguard against the kind of egregiously unethical withholding and withdrawing that occurred 30 years ago.

I think it's hard to find cases of really what we would call egregiously unethical withholding of treatment that has been processed through an appropriately-constituted ethics committee.  And, as always, the courts are, and should be, available to people who disagree with ethics committees or with decisions that are being made in that way.

I hope that's responsive.

CHAIRMAN PELLEGRINO:  Any other questions?  Gil, and then Dr. Lawler.

PROF. MEILAENDER:  Yes.  I want to raise several questions, several areas.  I'm going to pass on the end-of-life questions for the moment, not because I think they're unimportant, but just to try to get at a few deeper issues in some of the other areas.

First, with respect to the research, just as an aside, there is probably no way we could settle this without getting out the text, but I don't think Ramsey changed his mind, by the way.  The sin boldly stuff was, at least on my recollection, what Ramsey loved to do.  That is, play with possible justifications that one might come up with for various things. 

It was not, I think, his preferred proposal on the matter, but we'd have to get the text to decide that one.  But on the research, I want to sort of get at a couple of what seem to me to be deeper questions, and then also on the genetic testing.

The examples you gave were wonderful in a certain way of the requirements, the hoops that you are forced to jump through, and which do seem ridiculous to probably almost anybody sitting there listening.  Raise a deeper question, though, exactly what — what's the larger concern here?  The larger concern is, whom shall we trust?  And how do we structure circumstances in such a way that we think, you know, trustworthy people are making decisions that are wise.

And we find ourselves in a circumstance, not just here but in many areas of our life, where the only way we can seem to find to do it is regulation/overregulation to the point of absurdity.  But one of the reasons we find ourselves in that circumstance has to do precisely with the history you recounted, in a way.

So I'd be interested if you could say just a little more about that kind of question about exactly how we satisfy ourselves if there are people whom we can trust. 

And then, one — second question on the research.  This follows up on Leon's question.  On the one hand, you don't want to shut down non-therapeutic research on children.  On the other hand, you don't think a moral justification for it, up until now, that's satisfactory has been provided.

Would you be willing to say that to take up the question in a non-frivolous manner would require leaving open the possibility, as one possible answer, that it should stop?  That is to say, your answer to Leon was simply you're confident that an appropriate rationale can be found if we work on it.

Well, and that may be true, but wouldn't — if we're really serious and not frivolous in taking up the question, wouldn't we, from the start, have to have at least as one possibility the idea that maybe there wasn't any justification, and we just couldn't say that?

And then, on the genetic testing, if I can just put one more question before you, there must be deeper impulses or urges at work that lead us to want to know, with respect to these newborns, not just about PKU but about a couple hundred or a thousand possible abnormalities, even if, as in many cases you've said, not for now at least directly connected to any known disease.

What's going on there?  In other words, is there some larger cultural power or impulse at work about what we want from a baby or our need to know something if we can know it.  In other words, are we going to solve these problems just by a recommendation, or are there some sort of deeper issues at work that push us in certain directions?  And that may be very much harder to get a hand on than just a regulation. 

I'd be interested if you could say something about that.

DR.FOST:  Thanks.  Those are all great questions.

First, with regard to who to trust in the research area, it's my view that IRBs have worked extraordinary well.  That is, that's — that's the main thing that has changed since the '60s and the '70s, the common rule and local IRBs to implement them.

It's very difficult to find, in the last 20 years — and there have been several studies to support this — an example of the kind of egregiously unethical research that was common and ubiquitous in the '70s.  There is a lot of conceptual basis for IRBs.  I myself am very enamored of what's called ideal observer theory.  Put in simple language — many heads are better than one.

And I think it's so hard to find an example of, really, the kind of research that was common back then that whenever something happens that's controversial it becomes a cause celebre.  So the death of Ellen Roche at Hopkins, the death of Jesse Gelsinger, stay with us for years and years and years, probably decades, and in my view don't even themselves constitute egregiously unethical research.

That is, I think it's very difficult.  I think there is a case to be made, both sides of those cases, and yet they've acquired — they've become poster children as research gone wild.

Research has not gone wild.  The Roche case and the Gelsinger case are remarkable, because they are exceptionally uncommon, and even those cases I think have been — there has been demagoguery about them, and they've been overstated.  So in my view IRBs have done an amazing job.

Have they produced a zero-risk situation, a situation in which no human subject ever gets mistreated?  No, of course not.  Nothing can.  But it's remarkably rare for — to have unanticipated complications of those sort, but, more importantly, to have research that would attract widespread condemnation.

So can you trust them?  No, I wouldn't trust investigators.  I think investigators, left to their own devices, will run through the stop signs for all the reasons that they did 30 years ago, not because they are evil or mercenary, but because they — their eye is on curing cancer in our lifetime and advancing science and advancing knowledge.

So, no, you need committees.  I don't think we need the kind of micromanagement at the federal level.  I think the local IRBs have generally done a good job.  I think the sanctions are way too punitive, and for all the wrong reasons.  So that's my response to that.

With regard to non-therapeutic research, is it possible that a serious inquiry will lead to the conclusion that there's no justification for it?  Sure.  Where would that lead?  Would that lead to — lead me to recommend the policy of no more non-therapeutic research involving children?  No, I'd come out somewhere where Paul Ramsey came at, and we — I'd be happy to dig out the text with you.

By the way, it was sin bravely, I think, not sin boldly.

But, obviously, national policy should not hinge on what Paul Ramsey thought.  It should hinge on what a consensus of people in America think today.

So it may be that there is no — it may be one of these unresolvable issues in which there is no real compelling moral argument for it, but there is not a horrendous argument against it either, if we keep it — if we keep the noise level down and keep it to truly minimal risk/research.

And your last issue, what drives this mania for testing?  I had notes on that, and I'm glad you gave me a chance to expand.  I didn't want to use up too much of the air time.

There are several factors that are quite common in these — in this repetition compulsion.  One is that the PKU lobby has been duplicated over and over again.  That is, there almost always is a very zealous lobby that forms, consisting of parents of children who have died or have become profoundly — you know, if your child died of a rare disease, you understandably don't want to see this happen again to anybody ever. 

And so — but you're not a scientist, and so you say it's just unimaginable to me that every child in America isn't tested for this very rare disorder, and so that something can be done about it.  So parents are very much out in front of this.

Second, they are put out in front by the testers, some of whom have, frankly, commercial interests, so there is serious financial conflicts of interest in some cases.  That wasn't the case in PKU, and it's not the case in all screening programs. 

But there are commercial testing laboratories who would love to have this happen, and are funding publicity campaigns, as happens in other areas of medicine.  So there is just frank commercial conflicts of interest.

Third, there are empires that don't make people rich, but that make people more powerful or influential.  Let me tell you a personal story there.  I've been interested in newborn screening for cystic fibrosis.  I was co-investigator of what is I think the largest clinical trial ever done.  Dr. Farrell at University of Wisconsin randomized over 600,000 infants over a 10-year period, to see if early diagnosis and treatment for cystic fibrosis was helpful.

Fifteen years ago, before that trial was even done, was even started, I was invited by WHO to attend a technical assistance conference to help other countries begin cystic fibrosis newborn screening.  There were 25 countries there — Bahrain, the Soviet Union, Argentina.  They all wanted to start newborn CF screening, and my thought was, why?  I don't know of any evidence that it's helpful. 

I know of lots of reasons why it might be harmful.  Our study explicated and documented many of these harms, medical as well as psychosocial.  You have far more serious problems in your country than cystic fibrosis.  You don't even know what the incidence of cystic fibrosis is in your countries.

My sense of what was going on is that the people at the meeting were the equivalent of state lab directors who, you know, it was another machine.  It was another couple of people on their staff whose expanded budget — it was getting more information, possibly some research interest.  I don't think they were getting rich off of it, but they — technicians like to do things.  Doctors like to do things.  Testers like to test.  So that's part of it also.

And part of it is very poorly thought out moral claims of justice and unfairness.  If Wisconsin is screening for 30 conditions, it's unfair that a child in Iowa — and this has been the argument used driving the Secretary's Advisory Committee as far as I can tell.  We need a uniform policy.

Well, if it's a bad policy, there's no virtue in it being uniform.  There is no unfairness in not distributing something that has no known value or whose harms may exceed the benefits. 

So those are some of the factors that have driven this, and they have been repetitive.

CHAIRMAN PELLEGRINO:  Dr. Lawler?

PROF. LAWLER:  Yes.  Thanks for the great presentation.  Just one point of clarification.  The Baby Doe regulations were a great advance in terms of protection of the rights of people with Down's Syndrome.   And that protection is more urgent than ever as there are fewer and fewer people with Down's Syndrome around.

Now, you said that has led to a regime of overregulation, over — of overtreatment — overtreatment, right.  Now, the only thing I didn't understand fully is whether that overtreatment is based upon a misinterpretation of — a fearful misinterpretation of the existing regulations, or if the regulations, as now exist, need to be mended in some way, need to be changed in some way.  What's the bottom line on that?

DR.FOST:  Thank you, again.  I mean, it's as if I've planted these questions.  First, I agree with you completely that the Baby Doe regulations were absolutely essential, or something like them.  That is, I hope I've conveyed my personal view that it — I think I used the word "egregiously unethical" withholding of treatment from children with Down's Syndrome, spina bifida, and many other children, with excellent prospects for meaningful, happy lives.

The overreaction, in my view — and Dr. Kopelman and Dr. Nelson may disagree with this — my view is that overtreatment that's based on Baby Doe regulations is based on a false understanding of them.  That is, I think the Baby Doe regulations have been widely misinterpreted and misapplied.

For example, to whom do the regulations apply?  Any regulation has to say who it applies to.  It applies to state health departments.  It's a regulation requiring state health departments to respond in a certain way if there's a report of medical neglect, of refusal to provide medically necessary treatment.

Absent a report, the state has no duties.  And, in fact, the Inspector General under President Reagan found all 50 states to be in compliance, even though thousands of babies were still being allowed to die in seeming violation of the substance of the rules.

The rules do not apply to doctors, hospitals, or parents.  So they don't, in my view, impose a single requirement on physicians, families, and hospitals making local decisions.  They're as free as they ever were at — I mean, they are subject to tort law and criminal law and all of the other laws that always did exist, but in my view the Baby Doe regulations have actually no legal implications for treatment decisions.

So the overtreatment that has been predicated on them is misstated and is a misinterpretation of them.  Is that responsive to your question?

PROF. LAWLER:  Exactly.

DR.FOST:  Yes.

DR. ROWLEY:  Thank you very much, Norman, and it's nice to see you again.

I have a different question, because you really raised three issues, of which you dealt with only one.  Our Council meets every few months, and I think I've been a proponent of dealing with ethical issues related to children.  We have actually in the past had several people come and speak with us about children, particularly early childhood development and brain development in young infants and children, which were very helpful for me.

I think that, in fact, we are going to have to make a choice, because we can't deal with the three issues that you raised.  And you made a point that the issue you were actually going to discuss affected far fewer children than the two that you did not discuss.

And so from your perspective of the Council and where — I hate to use the term "where it could have most effect," because I'm all in favor of tilting at windmills if only — if that's the major thing we should be doing.  But I would appreciate your opinion as to whether — which of the issues that you raised, such as our dreadful neglect of children born into poverty, infants born into poverty, or child abuse, as compared with those that you spent the time discussing.

DR.FOST:  Janet, thank you for bringing  me back to what really matters, as you always do.  Yes.  I didn't talk at length about the problems of poverty or the solutions to it or the problem of the uninsured out of sheer diffidence.  I mean, because I don't have any particular expertise, certainly compared to other members of the panel or other experts who you could bring in.

I mean, I have an ordinary person's notion of what needs to be done.  But those are overwhelmingly the problems that oppress and afflict American children — being born into poverty, into situations in which access to health care are constrained. 

And child abuse I would put third on the list, because that only — but that only involves a few million children as compared with the tens of millions — I mean, these numbers are just absurd — who start off life with no fair opportunity to really succeed.

So those are the overwhelming problems.  And, yes, if this Council could have an influence on the President's policies or the country's policies on something that really affected children, I would much rather you spent all your time on doing something about problems of poverty and access to health care and child abuse than these other three angels on the head of a pin issue, which in the final analysis affect very few children.

So, and part of it, I talked about things.  There's a story Robert Morley, the great British comic actor, tells that — if you'll indulge me — he was explaining why he quit school at age 12, and he said it was an exam question.  The exam question was, "Describe and discuss the Cape of Good Hope."  "And I wrote in my exam booklet, "I don't have the foggiest idea where or what the Cape of Good Hope is, but I do know the 12 apostles." 

And he wrote the names of the 12 apostles and said something about each.  And he said, "They flunked me," and it showed me once and for all they weren't interested in what I did know but only in what I didn't know.

So I talked about what I do know, because it's comfortable, and it seemed to me overreaching to go into any more detail about things that I really am not very expert in.

DR. ROWLEY:  No.  But I — that was not the purpose.  The purpose was really to say if we as a group have to make a decision, which will be in a sense a group decision, what kind of advice can you, as a consultant, give us on that?  So that was the purpose of the question.

DR.FOST:  My advice would be that you spend what time and resources you have in making recommendations that affect children who were born into poverty and children who are born without reasonable access to health care.  If you can make some recommendations that might influence national policy in those areas, it would be time well spent.

PROF. DRESSER:  I have a related question, perhaps to push you in this area, because I think one of the reasons we haven't done as much as we should in bioethics on these issues is because we don't know how to approach it.  It seems so overwhelming.  And I know that some of us on the Council do want to get into these social justice questions.

So I guess one way I think about it is with limited resources, how would you allocate them differently from the way they are allocated now?  And I'd be interested in what thoughts you might have, not just about allocation of health care resources and how that might better affect children, but also research resources. 

So if you were thinking about taking the NIH budget and making it more child friendly, how would you spend your money?

DR.FOST:  You've caught me off guard, Rebecca, which is good.  So I don't have well thought out responses to that question.  So I'll think aloud.

First, let me just say with regard to resources in health care, I've gotten into big trouble with the American Academy of Pediatrics for suggesting that the way we deliver pediatric health care should be dismantled.  That is, having a pediatrician for every child is an extremely expensive way of providing mega hours of service that has no known relationship to health. 

Roughly half of a pediatrician's time is spent doing health supervision, which has no known relationship to the health of children.  And these are — everything that's done on those visits could be done far more cheaply and efficiently by a nurse or someone with even less training.  I mean, all of the immunizations, all of the weighing and the measuring and the eye checks, and all of that, you don't need a doctor to do that.  The doctor spends almost no time doing anything that you need a medical degree or training for.

So we could expand access of children if it were — if they didn't have to be funneled through pediatric offices, if we had more of a public health program with well baby stations as occurred 50 and 75 years ago, where immunizations were given and/or even acute illnesses were managed by a non-M.D.  So I would change that, if I could.

I would change the allocation of health resources away from acute illness towards more preventive services, of which child abuse is simply the most important example I know of.  That is, prevention through home visitor programs rather than the $5 million treatment of every kid who gets whacked in the head and then we take care of him or her the rest of their life.

With regard to research, I would greatly shift the emphasis away from biomedical research into more epidemiologic and public health research.  My M.P.H., my one year getting a master's in public health, showed me just how much more powerful epidemiologic approach is to health care, both in research and implementation.  I could give dozens of examples that are probably familiar to you of how — I'll just give one just to make — make the point.

My colleague Murray Katcher, a pediatrician in Madison, discovered that were 100,000 patients admitted to hospitals each year for severe scald burns, almost all infants and the elderly.  If the hot water heaters were set at 130 instead of 140 — at 140 it takes two seconds to get a third degree burn.  At 130, it takes 45 seconds.  So you would end burns forever if the heaters were set at 130.

He set out to do that.  And to make a long story short, he did it.   So there is an intervention that — all new water heaters in America now are set at 130.  You can't get people to turn the old ones down.  So it will be 40 years before they all expire.

There is a piece of research and implementation that cost zero, didn't cost one cent, that is going to prevent hundreds of thousands, millions of cases of suffering and death due to hot water burns, child-resistant containers — another virtually free intervention that has prevented tens of hundreds of thousands.

So I would shift the whole national research budget to more public health epidemiologic study and interventions of that sort.  And I myself would spend less on hard science, assuming fixed dollars.

CHAIRMAN PELLEGRINO:  Dr. Hurlbut?

PROF. HURLBUT:  You mentioned the massive experimentation that is being done through off-label use of drugs, and then you also said that clinical research is dying, and that we're looking at a whole new set of potential interventions that are quasi-therapeutic related to genetic screening.  And it seems by implication those could go backwards, too, into fetal development eventually.  In other words, you might end up administering drugs to pregnant women to — to deal with some things eventually.

Well, looking at it post-natally, is there a way we can enter into this difficult arena through the current therapeutically justified trials, research, therapeutically?  In other words, given the difficulty of defining and justifying non-therapeutic interventions, can we get a better handle on some of the research that needs to be done through the therapeutic trials?

DR.FOST:  Yes, definitely.  If the PKU program had been subject to a — even a randomized clinical trial, which is sometimes hard to justify for what you think is a uniformly horrendous disorder, some children with PKU would have been lost — that is, would fail to have been treated.  But many hundreds — we don't know the number — of normal children would have been saved.  That is, we would have found out in a year or two, instead of 10 or 15 years, what we were doing. 

So that's point number one is if these new technologies were studied systematically, I think in the long run we're less likely to harm and more likely to help.

Even for conditions in which it is hard to justify a randomized trial, even a simple registry — I mean, we presently don't have a requirement for states that are implementing all of these programs to maintain a registry, a state or a national registry.  That alone would at least allow for some observational collection of data, so that 10 years from now we know what the outcomes of all these children are.

So, in my view, that's urgently needed — a national registry for all children that are screened and treated as a result of these new technologies.

Third, I think having the laboratories of the states that — let me say that differently.  Having variation among the states I think is a good idea, not a bad idea.  That is, right now some states like Wisconsin are doing them.  Others are holding off. 

I hope it stays that way for a time, because it's not quite a prospective randomized trial, but it's a reasonably controlled trial.  So that 10 years from now we'll be able to look at children in Idaho and with — who have these conditions, and we can always diagnose the conditions, and we can always get a sample of blood and find out who has these chemical abnormalities and who doesn't.

So I think in the absence of better knowledge having some variation in the way states approach this is a healthy thing.  I worry a lot about a national standard being implemented.  I hope that's responsive.

CHAIRMAN PELLEGRINO:  Other comments?

DR. KASS:  Norm, I wonder — again, this may be to ask something outside of your area of expertise.  But none of the things that you have spoken about deal with the question of the mental health of children.  And I wonder if — I mean, child abuse is one area, and the consequences of poverty and deprivation imply that part of the cost is in terms of mental well being broadly conceived.

But do you have any suggestions along these lines?  And not just concerning, let's say, the health of the identifiable abused children, but more generally whether there are things for this Council to be thinking about in that area.

DR.FOST:  Yes.  In fact, I've written a couple of papers, which I'd be happy to provide to you, on essentially the perils of innovative therapy in emotional and behavioral disorders of children.  That is, the inadequate amount of prospective randomized, controlled trials, the difficulty in getting funding is a big part there, but also in getting investigators and some fighting off what I consider to be somewhat demagogic opposition or resistance to experimenting on children, or using them as research subjects, in treatment trials, in therapeutic trials.

So I think mental health is especially forlorn as an area for systematic research for interventions, pharmacologic, behavioral, and others.  And there's way too much innovative therapy that is, as you probably know and other members of the Council, millions — tens of millions of American children get SSRIs prescribed for everything from depression to behavior problems to anxiety to obsessive-compulsive disorder, with almost no data.  And we now know that these drugs have serious adverse effects, that suicidal ideation is now — and suicidal behavior has been unequivocally shown to be increased in children.

Well, that may be worth it if you're prescribing it for something that's a real problem and for something for which there's a real benefit, but we don't know that.  And I could cite more specific data, and I can send you the article that shows it.

So the general answer is there is a tremendous shortfall in the amount of research that should be done on children with mental, emotional, and behavioral disorders.  There is way too much innovative therapy going on, especially in that area.

DR. KASS:  May I?  This was welcomed, but let me — let me just put it a little harder.  I talked about mental health and well being.  The answer came back in terms of the medical treatment of disorders.  And this may be what Gil was hinting at when he was asking about the drive toward testing.

Should we be concerned about what in previous discussions — we've had a few discussions of this so-called problem of medicalization, of the — the revision of the understanding of child development and child-rearing in medical terms such that the turn is immediately for some kind of medical testing, medical intervention. 

Do we need — I mean, is this something that ought to concern us?  How one actually conceives normal child development, child-rearing practices, and to what extent the desire to see these increasingly either through neuropsychiatric terms or medical terms is itself something to be worried about, or is it — are we going in the right direction, but we just don't have enough of it?

DR.FOST:  Okay.  I think I understand your question better.  Well, let's take ADHD as an example.  That often arises in these discussions — attention deficit hyperactivity disorder.  Explosion in medical approach to that disorder, millions of prescriptions a year for children — for treatment of a disorder which has no gold standard test, for which diagnosis is uncertain, and criticism by many people who think that whatever problem a child has is something that would be better if it were understood as an environmental problem, behavioral problem, a parenting problem, a school problem, and so on.

I think there's truth on both sides of that debate.  That is, I think there's no reason to be phobic about medicalization of a problem, if medicine helps — if it's safe and effective, and if we're sure it's getting to the right children, and if we have systematic studies and have reasonable non-toxic drugs. 

So the fact that ten million children are getting a drug that may help them perform better in school, if it's a safe drug and if it does help them perform better in school and makes their lives better for that reason — I mean, hypothetically, if the drug had no side effects and were free, I don't see any reason, just because it's a drug, that we should be against it.  Nor would I see any reason to be against better schools with better teacher-child ratios or better parenting or environmental or behavioral approaches or nurturing that would produce the same result.

But the problem, as you know, is it's easier and cheaper to find a drug that will solve the problem than to figure out how to get the teacher-student ratio down from 30 to 1 to 10 to 1.  So I don't see any a priori reason to be for or against any of these things. 

Obviously, we should be doing research on all of these fronts, and we should be looking for the most effective, most efficient, safest, best way to help children.  I don't see any reason to be for or against drugs just because they're drugs.

CHAIRMAN PELLEGRINO:  Dr. Meilaender?

PROF. MEILAENDER:  This is a question that's related in a way, though coming from a very different angle.  And I can only come at it — I mean, I'm not a practitioner, so I just have to go on my own tiny little experience.

But it was interesting to me before, in an answer to an earlier question, when you said that — I think you were talking about allocation of resources or something and you said that — that pediatricians spend a great deal of their time doing things that you don't need medical training for.  I mean, you could have other people do them.

But that's connected to the medicalization question, because I would have said — again, now just off — just off my own personal experience, that pediatrics is the one area of medicine where there is still a good bit of talk that goes on between doctors and patients. 

Now, that's not something maybe that you need certain kinds of medical training for, but I wouldn't want to call it an unimportant part of medical care.  And, indeed, I think from the lay person's perspective one of the problems with — I mean, a lot of the jokes that people make about doctors — there's no talk that goes on.  You've got to kind of yank him back in the door sort of.

So it just — the question that interests me is sort of how we ought to try to think about these questions, and whether we need to think about them in — well, I was going to say larger, but that prejudges the question — just what the right frame of reference is to think about these.

You see, I would say that it's good that pediatricians spend a lot of time just talking, even if it doesn't require some sort of hyperspecialized training.  And I wonder if you could just think about that a little bit.

DR.FOST:  I think it would be good if pediatricians spent a lot of time talking, but they don't.  No, there are numerous studies that show —

PROF. MEILAENDER:  Mine do, but —

DR.FOST: Yes.  Well, it has been studied.  Maybe it's not the same everywhere.  I'm sure it's not the same everywhere.  But the studies that have been done show — first of all, I think what — the main thing that parents want out of that well baby visit is — is talk.

And to talk about the long list of concerns about child-rearing and child behavior and what to do about drugs and alcohol, and all of the other things that beset parents and children these days, the problem is empirically that the amount of time that a typical pediatrician spends talking about those things in a well child visit is about 90 seconds.  That's the average.

Second, those things could all be very well done, as good or better, by a qualified and trained nurse, nurse's aid, social worker, somebody who could be equally knowledgeable.  You don't need to go to medical school and take — in fact, there is very little in medical school or in residency training on those issues. 

Pediatricians get remarkable little training in all of that, in some programs better than others.  But the point is you don't need a pediatrician to do it. 

So if I just had access to the dollars that go into pediatric care in America, defined as care that children get in pediatrician's offices, I could get a much bigger bang for that buck, including much more talk — and I don't mean to belittle talk at all.  I agree with you, I could get much more talk by reallocating it to less expensive, equally qualified practitioners.

PROF. MEILAENDER:  Yes.  I don't really know exactly what got me to this, or how we come to it from where you started us.  But I don't think it's just the amount of talk.  It's a question of who you're talking to.  See, I mean, I want to — when I'm sick, there are certain people I want to talk to.

Get out of the medical realm entirely, the large congregation, of which I'm a member, sends all sorts of people to the hospital to talk to members of the congregation.  And as I once told my pastor a while back, "When I'm in there, you'd better be there to talk to me."

It's not just a question of amount of talk.  It's the question of to whom you're speaking.  And, once again, that's got something to do with the way we conceive of what's important in medicine.  I just — I don't want to lose that in the focus on specific specialized technical details.

DR.FOST:  You're referring or suggesting that the authority of the doctor may have some added value that would not accrue to a less prestigious person?

PROF. MEILAENDER:  Well, that may be true.  And it's — you know, I take — I spent a lot of time and money going to see this person, and I expect something other than just technical expertise.

DR.FOST:  Right.  I mean, I think when you're sick or when your child is sick there's a lot of truth to what you say, and validity to it.  But if your child is bed-wetting, I don't know that the kind of advice that you need, and the kind of remedies that are available, and where do I start, and what do I do about this, I don't know that there's much added value in having somebody with an M.D. after his or her name as compared with somebody who knows the field, knows what's available, knows what to do, can get you started on the right track in an empathic way.

CHAIRMAN PELLEGRINO:  Alfonso?

DR.GÓMEZ-LOBO:  This is just a brief reflection from someone looking at all of these things completely from the outside.  And I'm very much impressed by the — your reference to poverty and to the deprivation of access to health of young children, because of the social condition. 

And it seems to me that that seems to be sort of a grounding reality, and my reflection is simply this.  As a Council, we should consider that surely as part of bioethics, as part of social justice issues.  And I just hope that in the final report on issues relating to childhood we go into that as deeply as we can.

Now, I think that there's an intersection with politics and social policy that it's very hard for us to tackle.  But, still, it seems to me it — it seems to be so central, so deeply rooted in virtually everything that happens afterwards that we should really as a Council consider it, I think.

DR.FOST:  Yes.  Let me just give you one fact that ties some of this together, some of my comments together.  One-third of all abused children in America are ex-prematures.  One-third of all abused children in America are ex-premature children.

Prematurity accounts for about six percent of American births.  It accounts for about 33 percent of child abuse in America.  Who gets born — the reasons for that are multiple.  Prematures are born, many of them, to teenage mothers.  They are children who are notoriously difficult to take care of.  They have disabilities and handicaps.  There's a lack of bonding.  In the newborn period they're in an intensive care unit for weeks or months, and the parents take this stranger home, and so on.

Who has premature children?  Teenage mothers, poor mothers, mothers without prenatal care, mothers who have health and drug problems of their own.  That is, poverty, lack of prenatal care, prematurity, child abuse, if you could just reduce the incidence of premature — our problems of prematurity dwarf.  I mean, you know, it's one of those many areas of American health where we're near the bottom of the list of industrialized countries.

If something could be done to reduce that, there would be reduced child abuse.

CHAIRMAN PELLEGRINO:  Dr. McHugh?  We have time for one more question.

DR. McHUGH:  Just one question.  I enjoyed your presentation, Dr. Fost, and I particularly appreciated some of those old stories that I remember about how, really, the doctors lost the trust of families who had given their children into hospitals and discovered that — some of them discovered directly, others indirectly, that the doctors and even the nurses themselves had lost some interest in the loved one that they had submitted there.

And the loss of trust or the betrayed trust has produced what it always does — namely, this increase in regulation, the regulations that are completely out of control now and are interfering with our capacity to work it. 

But, you know, the blame does fall back upon us.  We did it, and now we are paying a terrible price.  And to win back the trust of the American people of this sort requires not only the presence of IRBs but the particular demonstrations, as you've demonstrated today, of the — of what we are losing.

Now, I'd just like you to look ahead now, since, you know, we have — this world we're in now and we ourselves aren't perfect — what kinds of things do you think we are going to think in 10 or 15 years from now represent egregious betrayals of trust in hospitals and places of that sort, to the families, that bring our children — their children to them?

I wonder whether, for example, you might think in terms of whether managed care in the great shortage of time now presented to — in-hospital to patients and families that might lead — mean longer time, or investments of more resources for the care of them, even with chronic illnesses like the AIDS epidemic in young children, and whether we are prepared to carry the concerns and services that those kids need.

And you have mentioned in this little discussion with Dr. Meilaender how little talk gets done.  And maybe little talk gets done by pediatricians and other M.D.'s because they don't know any psychology, and we don't teach psychology in most — to most medical students.  It's the only basic science they don't know anything about.

And, eventually, even empirical psychology would help them in this, and this neglect might be something that people will come to regret and ultimately find, once again, imposed upon them.  Do you have any predictions from what we're doing now?

DR.FOST:  Well, I'll accept your invitation to wax political for a moment.  If I — if you asked me to guess what will most embarrass us, or make us ashamed of ourselves 25 years from now, it would be the massive reallocation of funds from the lower and middle classes to the upper classes. 

That is, in a country that has these problems that we've been talking about, the continuing widening of the gap between the rich and the poor and the reallocation of funds in the — from those who are least well off to those who are best off.  That, to me, should be an embarrassment, and I think will be.  And the effect that that will have on our children will become clearer as time goes on.

Second —

DR. McHUGH:  Are we doctors contributing to that?  Are we — in the way we run our hospitals and insist on the lengths of stay and things?  Is that really — by the way, the care of the poor is certainly something we all agree on, and those of us who live and work in hospitals of — in the inner city see this all the time.

But the pressure is not simply in relationship to whether the government is going to take a concern for the poor, but whether the hospitals themselves are contributing to the abuse of the poor and the kind of regulations that they are prepared to enforce upon their young physicians.

In our hospital, the doctors are told that they have to have a certain short length of stay to be darn sure that they get the money from — and these are for the poor.

DR.FOST:  Well, you know, Justice Cardozo said laws aren't written until they're first broken.  So I think things like managed care and length of stay rules, and so on, were necessary.  That is, I think the waste in the American health care system was, and still is, prodigious, the inefficiency. 

And given the finitude of funds that are available, I think squeezing inefficiency out of that was unavoidable and necessary.  And doctors weren't doing it on their own, so payers had to hire managed care companies to do it for them. 

So I think that was unavoidable, necessary, and the studies that I read — not all that bad in the final analysis.  That is, there are efficient managed care systems, like Kaiser Permanente, where satisfaction rates are as high or higher in fee-for-service systems and where patients are actually quite pleased with the care they get, even though there has been a great squeezing down, and so on.

I think another thing that we at least should be embarrassed about 25 years from now — whether we will be or not, obviously, I don't know — is this constant ability to find new technologies to spend our money on when we — we just — we're just out of money when it comes to solving problems like the uninsured.

So it seems to me remarkable that the State of California has $3 billion to spend on stem cell research.  Forget the ethics of stem cell research, about which you've dealt in great depth.  But that the citizens of that state could decide that they have $3 billion for a technology that has as yet no known payoff, and even when it does the number of people who it's likely to help are going to be measured in a state that has prodigious problems with education, with access to health care, with poverty, and so on.

We always can come up with a billion here and a billion there for some new technical thing that is fun and fascinating.  But we're just out of money.  We just can't afford to have basic access to simple, ordinary, primary health care for 40 million people.

CHAIRMAN PELLEGRINO:  Thank you very much, Dr. Fost.  I'm afraid the schedule requires that we intervene at this point and have our break.  I'll take the Chairman's prerogative of extending it beyond the time in the agenda, which is supposed to be at 10:45.  And if you'll return at 10:50, we'll start promptly.

Thank you very much, Norman, for drawing on your extensive experience. 

And let me thank the Council members for their close questioning on a very important topic.

Thank you.

(Applause.)

(Whereupon, the proceedings in the foregoing matter went off the record at 10:39 a.m. and went back on the record at 10:59 a.m.)