STATEMENT RELATING TO THE STUDY
"TREATMENT OF LEAD EXPOSED CHILDREN CLINICAL TRIAL" (TLC)

 TLC was a trial designed to determine whether a new medication called succimer, which removes lead from the body, by a process called chelation, could prevent lead-induced changes in growth, development and behavior. Older drugs used for the same purpose required intramuscular injection and were reserved for children with blood lead levels over 45 micrograms per deciliter. However, succimer could be given by mouth and was thought to have less side effects.

The sponsor of this research study was the National Institute of Environmental Health Sciences. The research was supported by the Office of Research on Minority Health of the National Institutes of Health. The institutions in the four cities participating in the study were CHOP (the Childrens' Hospital of Philadelphia), Columbus Childrens' Hospital, the University of Medicine and Dentistry of New Jersey and the Kennedy Krieger Institute. Each of these institutions, in turn, formed a network of participating institutions in their respective city. The Harvard School of Public Health served a the data coordinator and the Center for Disease Control served as the central laboratory for the study.

The study employed a classic and well respected research method using two research groups, that is, one group who would receive the medication and one group who would not. The use of a placebo_treated control group was justified because the standard of medical practice at the time did not recommend the use of drugs like succimer (chelators) for lead levels below 45 micrograms per deciliter.

But even if the research method was classic and appropriate, the sponsor and the institutional review boards (IRBs) approving the study at each institution had to assure that any potential risks were balanced against potential benefits of the study. Although some scientific evidence suggested that succimer might offer benefit, it was not convincing. On the other hand, the drug might also have unwanted side effects. Despite this lack of definitive evidence, some physicians were prescribing this new drug for children with moderate lead elevations. Children in the control group were treated in the same way they would have been treated under the Centers for Disease Control guidelines.

Several questions were and are pertinent to this inquiry.

Q.    Who were the subjects?

A.     The subjects were children between 12 and 33 months of age at treatment who had been exposed to lead and diagnosed with lead poisoning prior to being entered into the study. They had blood lead levels between 20 and 44 micrograms/ deciliter, in the moderate range of blood lead elevation according the Centers for Disease Control Guidelines. The subject population was known to be at greatest risk due to lead exposure, that is, low income, urban and principally African American.

Q.     Is the blood lead level range for the subjects above the normal level?

A. The level in the general population (1992) was then determined to be approximately 15 micrograms/deciliter. These children had lead levels in a range that was cause for concern, but not at a high enough level under the Centers for Disease Control guidelines to require administration of medications or removal from the home.

Q.     What was the standard of care for children in this moderately elevated group (20-44 micrograms/deciliter)?

A. Upon recognition of a lead level in this range, the standard of care was to activate the public health system (Baltimore City Health Department) to provide inspection of the house for lead hazards so that violations could be reported for remediation. Families were also counseled about housekeeping and cleaning measures to reduce exposure of the child to lead dust. Children were also evaluated for iron deficiency and treated if necessary.

Q.    What were the interventions above the standard of care that the subjects in the study (treated patients and placebos) received?

A.    The design of the study required that all children in the study (treated patients and placebos) would receive more frequent blood lead monitoring, vitamin and mineral administration, professional house inspection and house cleaning.

Q.     Are you saying then, that the children recruited for this study (treated patients and placebos) would have surveillance of their lead blood levels and some treatment benefits for slightly elevated lead blood levels not considered standard of care for that group of children?

A.    Yes. Also, the homes they lived in would be inspected and cleaned.

Q.     You say getting the blood tests was somehow an advantage. Why?

A.      If the blood tests showed lead levels in the 45+ micrograms/deciliter range, the family was notified to bring the child in for another blood test, and the standard of care for children in that range was instituted. In addition, these children were monitored more closely than those in the slightly elevated group. If the range was 60+ micrograms/deciliter, the standard of care for children in that range was instituted and participation in the TLC study was terminated.

Q.     What were the risks to the control group in not receiving the medication?

A.     This medication had not been proven to reduce lead_induced changes in children. That was the very purpose of the study, that is, to see if the medication could do that. So no known treatment was being withheld from the control group. The Food and Drug Administration had approved the use of this drug in experimental research in children of this age. This approval in no way suggested that this drug was effective for reducing lead blood levels in children.

Q.     What were the risks of the medication for those in the non-control group?

A.     The parents were advised that there could be short term side effects such as nausea, vomiting, diarrhea, skin rash or mild to moderate neutropenia (low white blood cell counts which could lead to infection).

Q.     Taking all of these factors together, was the study appropriately designed to protect all the subjects (treated patients and placebos) to the maximum extent possible while allowing this important inquiry to proceed?

A.     Yes. Both the non-control and control groups received information on their blood levels and vitamin/mineral treatment they would not otherwise have received. Their homes were inspected and cleaned. Their participation allowed the efficacy of the medication to be tested.

The results of the research study showed that the succimer did not have a long term positive impact on preventing lead-induced changes in growth, development and behavior. Although some might say this result proved that the research was a failure, just the opposite is true. The research was a success in that this form of treatment was not proven to be effective. Only by performing this type of controlled research study were the researchers able to make this important finding. If one did not have this type of controlled study, this medication may have been given to thousands of children — exposing them to the known side effects on the hope it might help — with no study to prove its effect, one way or the other.