AMCHP 2005 ANNUAL CONFERENCE
DELIVERING RESULTS, IMPROVING PREGNANCY & BIRTH
February 19-23, 2005
SUSAN PANNY: I was asked to talk about our program in Maryland , with specific reference to informed consent, informational materials, linkage to services and the challenges of working with commercial laboratories.
The goal of newborn screening is to eliminate through early identification and treatment disorders that we can screen for as a cause of morbidity and mortality and to improve the quality of life for affected individuals. In short, newborn screening finds babies with rare genetic disorders so they may be treated.
As you heard, newborn screening is not just a laboratory service, it's a system of care, including not only testing but also follow‑up, definitive diagnosis, treatment, long‑term management, education and program evaluation.
And as you heard, all of this was set out in the Journal of Pediatrics by the U.S. Newborn Screening System Guidelines No. 2, which came out of a federally funded consortium, the Council of Regional Networks for Genetic Services. The goal for newborn screening follow‑up is to ensure that each affected infant receives the full benefit of early detection and optimal long‑term treatment and management.
I'm basically a follow‑up person, although I did have a long wet bench lab life. And I find it very aggravating, to be honest, that when people talk about newborn screening, they focus almost entirely on the laboratory. And yet I think that the follow‑up component is at least, and probably more vital, to making the system work and assuring that every child really gets the full benefit of newborn screening than anything else.
Follow‑up includes both short‑term follow‑up, where we assure that a definitive diagnostic workup is done, once the child has a positive newborn screening test result, and that we can be sure at the end of that definitive diagnostic workup that the infant really either has the disorder or does not, and that if the infant has the disorder, the infant is then started on the appropriate treatment.
Long‑term follow‑up is that we try and ensure that the infant continues over the entire lifecycle to receive appropriate treatment and we try and monitor the long‑term outcome.
Long‑term tracking of affected children is absolutely essential. It provides the data for outcome evaluation, for program evaluation, and for determining the clinical utility of screening. So why is follow‑up important? It assures the benefit to the family and the infant. It collects the data needed for program evaluation, and it's the glue that holds all of the other program components together.
What do you need to run a follow‑up system? Well, you need trained personnel in follow‑up unit. You need a database, so that you can follow each child and what happens to each child, whether the results are normal or abnormal, although, of course, the kids with the abnormal results have big long files and the kids with normal results have real short files.
We need to have appropriate administrative secretarial and computer support. There needs to be, in my opinion, medical direction of the follow‑up unit. We need to have good protocols for the follow‑up of each individual abnormal result. We need to have cooperation from our birthing facilities, our hospitals and our birthing centers. We need to have informed families. And we need to have also informed primary care providers, and we would prefer for our patients to all receive their care in the setting of the medical home so that we really have a primary care provider with whom we can interact to be sure that every child gets what they need.
We need to have, and these are very important, our specialty consultants and our specialty providers and our specialty centers. These are the people who do the definitive diagnosis and who help the PCP, the primary care provider, to manage the children in the long‑term.
We need to have our screening labs and our diagnostic laboratories, and then we need effective communication between all of these components.
So you can tell that I'm Tony Holtsman's student. The role of the state in newborn screening is to assure that all infants are offered screening without regard to the family's ability to pay, to assure that all infants with results that are not normal are followed up to resolution, and to assure that all affected infants receive appropriate treatment in the necessary time frame without, again, regard to the family's ability to pay, and to assure that all affected infants receive appropriate long‑term care.
Let me tell you a little bit about the history of our program in Maryland . I obviously think that all the things that I had on the previous slide can best be done by the public health apparatus in a state.
So what has our state done? Well, in Maryland , actually both health professionals and families advocated for screening back in the early '60s. And in 1963 our laboratory and state public health laboratory began to perfect the Guthrie technique. In 1965, legislation was passed, and mandatory PKU screening began. In 1973, a statute was passed setting up a commission on hereditary disorders. And this commission was set up to provide the guidelines, ethical and practical, under which all genetics programs, not just newborn screening, but all genetics programs were to operate in the state of Maryland. And shortly after it was established, the commission decided that all genetic testing, including newborn screening in our state would be voluntary and would require informed consent.
They also looked at what we were screening for and what the technology made it possible to screen for, and they did all of the debate and looked individually at three additional disorders. Maple syrup urine disease, homocystenuria and tyrasurenemia and recommended to the department that they, these disorders should be added to our screening panel.
And that's the way decisions are made in Maryland about what is in our screening panel. The advisory council looks at the issues and makes recommendations to the department of health and it's the department of health then that decides whether or not to implement, which is usually a financial and resource decision. In 1975, it takes about two years in Maryland to prom mull gate regs, new regulations were passed and they required informed consent for newborn screening. Our 1965 mandatory PKU screening legislation was repealed.
In 1978 hypothyroidism was added to our screening panel. In 1988 galactecemia was added, although galacecemia screening, I will say, didn't work very well until we changed the methodology in 1987. In 1984, biotinidase deficiency was added. In 1985 sickle cell disease was added to the screening panel. In 2000, hearing screening was added. And this is an exception, because this was not the Advisory Council on Hereditary Disorders that made this recommendation. This was separate legislation. But infant hearing screening is part of our newborn screening program, and in fact the second half of our informational booklet has to do with infant hearing screening.
In 2001, congenital adrenal hyperplasia was added; and in 2003 tandem masspectrometry was added. In 2003 we also had a commercial laboratory, Pediatrics, which was licensed in Maryland , and sometime this year cystic fibrosis will be added to our screening panel.
Each of the disorders that were added, with the exception of the disorders that are detected by tandem masspectrometry, which were not detected by the older methodology, for each of those disorders the disorders were considered by the advisory council on a individual basis, disorder by disorder. Tandem masspectrometry was not done that way; and I'll talk a little bit about that later.
Our usual features of our program in Maryland . Well, for one thing we had short‑term follow‑up established right at the outset and there was a special unit established in the state health department to conduct short‑term follow‑up and also long‑term follow‑up. And the state hired two expert metabolic nutritionists to provide free of charge through the health department from the outset the dietary management of those disorders which are managed by special diets.
From the outset, we have always linked parents and patients to services. Newborn screening is part of our genetics and children's special healthcare needs unit, and one of the earliest, we were one of the earliest states to have an advisory commission. Our advisory commission is consumer dominated, but it includes medical experts and it also includes members of the Legislature, which is very nice if you want to explain something to the Legislature if you can get another legislator who understands the issue in depth to explain it.
They have credibility with each other that no medical person will have.
And then it's unusual that we have voluntary screening with informed consent and that we have a routine second specimen. So we know a lot about how many false negatives we have on our first screen, which not too many other states know. Only those states that really have a second specimen that screens for the entire panel.
We also have state designated metabolic disease centers, and they receive state subsidies. And they started to do that in 1981. And then of course we support the other expert centers as well. Hematology and endocrine follow‑up as well. But the first centers that we supported were the metabolic centers.
I guess I have inadvertently deleted the slide that says what kinds of services we're talking about when we talk about linking patients to services.
Well, perhaps of first importance is that we have the state designated metabolic centers because those are the folks that need to do the definitive diagnosis and who need to work with the child's pediatrician to provide the long‑term care.
Then we also have our nutritionists who provide the dietary management. Since we are all in the same unit, basically, we will be the people who will refer this child to medical assistance or children's medical services, which is our fee for service program in the children's special healthcare needs unit, should they be eligible and need assistance to afford the care that they need.
We also support parents support groups. We have a series of centers and outreach clinics so that if you don't absolutely have to go to the center, this is an interim visit: You can be seen very close to home by one of our genetic outreach clinics, and there are 16 of them. We're not a big state, so nobody lives too far from one of those centers. And we did provide the dietary management but not the formula, unless the ‑‑ and the low protein modified food products that are needed for the treatment of those disorders. If in fact the family needed that kind of assistance, we tried to see if we couldn't make them legal eligible for medical assistance or for children's medical services. We also had in 1995 passed a law requiring insurers to cover these products. And we find that also approximately 70% of the self‑insured and otherwise ERISA waivered insurance programs actually follow the lead of the perhaps which are actually regulated by the state of Maryland and also cover both the formulas and the low preteen modified food products. For those families who somehow or other just can't access those formulas and those food products, we have a formula co‑operative in which we buy things up front and the families reimburse us as they can.
So nobody in Maryland goes without the appropriate formula. Even though it's a hodgepodge and a patchwork quilt of ways we fund it.
So how did we add disorders? As we said, there are classical criteria for selecting disorders to screen for. And our advisory council looked at most of the time each disorder one by one and looked at its incidence, whether there was treatment available, whether we had a good screening test and whether it was low enough in cost to add that so that the entire program would be cost‑effective.
And in fact there are specific criteria for what is a good screening test. It has to be accurate reproducible, inexpensive, noninvasive, sensitive, specific and a positive test has to have a high positive predictive value.
Well, everything changed when we looked at tandem masspectrometry. As we said, one test identifies multiple disorders. And so we didn't look at the disorders individually. Although we certainly felt that AMCAD, (inaudible) dehydrogenase deficiency did meet our criteria. But once you were going to screen for that, you needed MSMS to do it and we did not feel that we could not share all the other information that came out of that screen. We had to share it. We didn't feel that we could not share it with the child's physician and the child's family.
So we looked at what the advantages of identifying a whole cohort of kids who were affected by some of these rare and not very well understood disorders. And we found that there were many advantages. We could determine the clinical spectrum, how many cases are classical, how many are variant cases. We could learn about the epidemiology, the birth prevalence and the gene frequencies. We could look at the genetics, the inheritance pattern, what mutations occur. We could look at the natural history and pathophysiology of these disorders. We could look at the development and evaluation of treatment, also genetic counseling and prenatal diagnosis would be available to the families who would then have more reproductive and family planning options, and we were looking forward to the refinement of diagnosis and screening.
So that even though it wasn't the classical set of disorders, these advantages were noted. And one thing about it is that many of these disorders are rare, and if you identify kids in newborn screening you're going to get the biggest possible cohort, the most inclusive cohort, and of course it's easier to study a disorder when you have a few more patients rather than this center has one patient and that center has one patient and then the next state has another patient. If you get them all together, and then are able to compare notes, you're going to be able to learn a lot more about some of these disorders.
So there was strong advocacy by parent groups, and they involved the legislators and the metabolic geneticists were very excited about the opportunities for research and for their refinement of treatment and the development of new treatments. The discussion, however, was almost entirely laboratory focused. And the advisory council decided to exceed to the requests of speed of implementation and very little attention was paid to the adequacy of resources for public and professional education follow‑up protocols or manpower, database and funding for the increased workload of the metabolic centers. The metabolic geneticists were excited but they expected somehow or another to find the money to cover their increased workload.
I wanted to talk a little bit about informed consent for newborn screening in Maryland . Long ago we decided that we had to go with a simple goodwill informed consent. And we feel that the informed consent is most effective when obtained by a health professional. We don't always get that these days with personnel so overextended in the hospitals.
We feel it's analogous to other medical testing in babies and children. If you want to do a test you need to tell the parents what test you want to do, why you think it's a good idea and you get at least their implicit consent.
We however use an informational booklet. It's very long and very detailed. That was a direction in which programs were going at one time. And the actual permission form is actually in the back of the informational brochure. So families are supposed to have this information before they sign this. And I should say that this booklet is a legal document, according to our attorney general. And it must be approved by the Attorney General's office, and I fight constantly between the medical educators who want everything very simple and the AG's office who wants everything very legalistic. It's a very long detailed informational booklet. We've provided them to the child birth educational groups, hospitals, birthing centers, OB , pediatric and family practice offices.
Well, when we started with tandem masspectrometry we had to re‑examine what we were doing with informed consent. And we had to remind ourselves that newborn screening is a population‑based program and populations are very diverse: Demographically, culturally and educationally. We know because we have an informed consent program that not all parents want their babies screened. There are five to ten families out of our 70,000 births a year in Maryland where the family refuses screening. And also we had a genetic counseling student who did her master's thesis on what parents wanted to know if there was no effective treatment. And approximately a third of the parents that she interviewed said that they did not want to know about the disorder unless there was effective treatment.
So how can you explain a very large number of disorders, more than 30, complex, rare metabolic disorders, without common names, and with varying degrees of treatability to the general population in this kind of formula? And our conclusion is you can't.
And it's not just the parents. Professional education is also an issue. So in 2004, in collaboration with Dr. Terry Davis at LSU and sponsored by MCHB, genetics branch we undertook some focus groups to find out what parents and health professionals thought we ought to do.
And we were, we have done a lot of very interesting things, most parents did not feel the need for very detailed information, initially. Most parents did not read our long brochure. However, if the baby had a positive test result, and we interviewed a special group of parents like that, they found that when they were called they ran to find this booklet. They remembered they got it and they pulled it out and they did find that it answered most of their questions.
Well, if we have a long booklet and they don't really read it, they want something much shorter and simpler, how are we going to get this to people in the right time frame? We're talking about, you know, day five of life or something like that. So right now, and not everybody is on the Internet. So we are at this point wondering if we can do both booklets to each family at once in the hospital, and if they don't need this they won't look at it.
And the other thing that we found that was fascinating to me is that parents had absolutely zero idea, most of them, that the state was in any way shape or form involved in newborn screening.
The last thing I was going to talk about briefly is the challenge of working with a commercial newborn screening laboratory. In Maryland , as Kay told you, our commercial laboratory competes with the state public health lab on a hospital‑by‑hospital basis. And most of the problems that we've encountered stem from having more than one lab. And I should say that to be able to work in a collegial and honest way with two laboratories, both of whom wish the other ones were out of business, is a trick and a half. There were some issues that we were very concerned about. Those are the ones that are in black, that didn't turn out to be so important.
Families who couldn't pay the fee, we weren't so concerned about that because it turned out that the pediatrics was also willing to just do the whole hospital and not charge individual families who couldn't pay.
We did indeed continue to get the volume of samples in our state lab needed for QA and QC, so far we're still financially viable. And we use our lab slip in newborn screening to collect a whole lot of other data, infant hearing screening data and hepatitis B screenings and so forth.
So that has not been an issue either because pediatrics has adopted more or less our form. But the issues that are a problem are the ones that are in purple. It's really difficult to compare test results, especially since we have two specimens. So if the first specimen goes to pediatrics and the second specimen goes to the state health department laboratory, you can't really compare it very well, because different laboratories have different cut offs and different techniques. This is a real problem.
Also, the problem of trying to integrate our database and the commercial database, without any new resources for database, this is still an ongoing formidable problem. They don't have any reason specifically to want to make their database particularly friendly to us. They're willing to help us download the data from their database, but, you know, we're one state. And they're trying to do business with individuals all across not only the U.S. but the world. So they're not going to change their database for us. Also, there have been some concerns on the part of the commercial laboratory, especially with some of the changes in leadership there, about reporting to the state follow‑up unit. And so we have different interpretations now of what should be reported. So we don't get reports all the time if the baby is not born in one of their contract hospitals. If a baby is not born in a hospital, it's a home birth. We don't get reports if a baby is born in a military facility. Because it's federal turf it's not really yours. We've addressed each one of those kinds of issues but they still keep occurring. And that's probably for me, the most concerning thing. Because remember I want to assure that all infants are offered screening without regard to the ability to pay. And if I don't know who was screened where, I can't tell that everybody was screened.
And I hate to assure that all infants with abnormal results are followed up. But I can't do that if I don't know about all of them. We certainly can assure that all the affected infants receive the appropriate treatment in the necessary time frame if we know about them. But not if we don't know about them.
And the same thing is true with the long‑term care. But one thing we really can't do is evaluate program performance the same way we used to. We really can't evaluate false negative rates, false positive rates. We can't really evaluate the time frames very well, because we don't have that data from our commercial laboratory.
So right now 15 to 20% of our samples are being done in the commercial laboratory and that is eroding our ability to evaluate our program's performance, and I'm very uncomfortable we might miss a kid somewhere because they've thought we've screened them and we think they've screened them. So those are the challenges we've been trying to meet in working with a commercial partner as well as the state health department laboratory.
Questions, comments and complaints will be addressed at the end, right?
KAY JOHNSON: I'm just going to apologize, Theresa and I did this, but I, she sent emails ‑‑ emailed her presentation to me and I put it on the wrong computer. So bear with me while I get it off of removable drive.