[Federal Register Volume 60, Number 145 (Friday, July 28, 1995)]
[Notices]
[Pages 38839-38844]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-18578]
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[[Page 38840]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Agency for Toxic Substances and Disease Registry
[ATSDR-96]
ATSDR's Final Criteria for Determining the Appropriateness of a
Medical Monitoring Program Under CERCLA
AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR),
Public Health Service (PHS), Department of Health and Human Services
(HHS).
ACTION: Notice.
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SUMMARY: This notice announces the criteria for determining the
appropriateness of a medical monitoring program under the Comprehensive
Environmental Response, Compensation, and Liability Act (CERCLA). Draft
criteria were published for public comment on September 9, 1994 (59 FR
46648). The public comment period ended October 24, 1994. Comments were
received from 15 individuals representing States, industry, activist
groups, and environmental medicine clinics. This document reflects
those comments received on the draft criteria.
ADDRESSES: Division of Health Studies, Agency for Toxic Substances and
Disease Registry, 1600 Clifton Road, NE., Mailstop E-31, Atlanta,
Georgia 30333, telephone (404) 639-6200.
FOR FURTHER INFORMATION CONTACT: Dr. Wendy E. Kaye, Chief, Epidemiology
and Surveillance Branch, Division of Health Studies, ATSDR, telephone
(404) 639-6203.
SUPPLEMENTARY INFORMATION: Section 104(i)(9) of the Comprehensive
Environmental Response, Compensation, and Liability Act (CERCLA), as
amended [42 U.S.C. 9604(i)(9)], provides for the Administrator of the
Agency for Toxic Substances and Disease Registry (ATSDR) to initiate a
health surveillance program for populations at significantly increased
risk of adverse health effects as a result of exposure to hazardous
substances released from a facility. A program included under health
surveillance is referred to as ``Medical Monitoring or Screening'' by
ATSDR and is defined in the legislation as ``the periodic medical
testing to screen people at significant increased risk for disease.''
ATSDR has established criteria to determine when medical monitoring is
an appropriate health activity and the requirements for establishing a
medical monitoring program at a site. The legislation also states that
a mechanism to refer people for treatment should be included in the
program. Statutory language only allows ATSDR to provide medical care
or treatment in cases of public health emergencies as declared by the
President.
Background
ATSDR is responsible for the public health-related activities of
CERCLA. ATSDR's primary initial response at a hazardous waste site is
the public health assessment, which is required for every site on the
National Priorities List (NPL). A public health assessment can also be
conducted in response to a petition from the public. Other important
components of ATSDR's initial response at sites include health
consultations and public health advisories. During the process of
developing the public health assessments and health advisories, ATSDR
invites the participation of communities through a variety of avenues
such as public meetings, public availability sessions, and Community
Assistance Panels (CAPs). The documents produced by ATSDR during the
process are placed in a public repository to allow the public access to
the documents. The public health assessments, health consultations, and
public health advisories undergo review by ATSDR to determine if
follow-up health-related activities are needed for populations at risk
in the affected community.
The types of follow-up health activities recommended for a site
will depend on the amount of information on the possible exposures and
their suspected pathways. In any case in which an association has not
been established between an exposure and a specific adverse health
outcome, several research and health education activities may be
considered. Those activities could include health outcome studies, an
exposure assessment at the site, epidemiologic studies, or professional
education.
ATSDR's Division of Health Assessment and Consultation has
established a program for the investigation of exposures in communities
which enables a more timely response to questions on whether
individuals in a community are being exposed. The program incorporates
a variety of industrial hygiene techniques for measuring chemicals in
the environment, as well as selected biological markers of exposure.
The Division of Health Education provides a wide variety of
services to educate health care professionals and communities on the
effects of exposures to hazardous substances. Activities in a community
around a hazardous waste site may include conducting grand rounds for
health care providers on the effects of a specific chemical, providing
fact sheets on chemicals, conducting workshops on clues to
environmental disease, and producing case studies in environmental
medicine.
The Division of Health Studies is responsible for conducting
epidemiologic research, including several types of studies (cluster
investigations, disease and symptom prevalence studies, analytic
epidemiologic studies), surveillance programs, and exposure registries.
Cluster investigations and disease and symptom prevalence studies
investigate the occurrence of disease in populations. Analytic
epidemiology studies are conducted to evaluate the causal nature of
associations between exposure to hazardous substances and disease
outcomes. The surveillance program focuses on exposures to substances
at hazardous waste sites and includes systems that follow populations
exposed to hazardous wastes because of where they live or their
occupation. It also includes surveillance of emergency events in which
hazardous substances are released into the environment. The National
Exposure Registry maintains a listing of people exposed to hazardous
substances. The Registry is composed of chemical specific
subregistries. The chemicals are selected from the ATSDR/EPA priority
list of hazardous substances.
Medical monitoring is considered one of several follow-up health
activity options under the site-specific work conducted by ATSDR. A
medical monitoring program for the community around a site will be
considered with other health follow-up activities when the information
from ATSDR's initial response at the site is reviewed. In cases in
which there is no known association between the exposure and specific
adverse health effects (which could include health outcomes, illnesses,
or markers of effect), medical monitoring is not an appropriate public
health activity. In cases in which there is limited information on a
specific health effect's relationship to an exposure, then options such
as epidemiologic surveillance, a disease and symptom prevalence study,
or an epidemiologic study are more appropriate. When adequate
information exists that links exposure to a chemical with a specific
adverse health effect, further consideration will be given to the
appropriateness of medical monitoring in that population.
[[Page 38841]]
Medical monitoring should be directed toward a target community
identified as being at ``significant increased risk for disease'' on
the basis of its exposure. Significant increased risk will vary for
particular sites depending upon such factors as the underlying risk of
the selected outcome, the risk attributable to the exposure, and the
presence of sensitive subpopulations. These factors will be considered
when evaluating the appropriateness of medical monitoring in a
community. The CERCLA legislation also provides for a mechanism for
referral for treatment of those who are screened positive for the
selected health outcomes; therefore, a mechanism to refer people for
diagnosis, interventions, or treatment should be in place prior to the
initiation of a medical monitoring program.
The primary purpose of a medical monitoring program is not
considered to be a research activity that further investigates the
cause-effect relationship between exposure and outcome. The purpose of
a medical monitoring program is case-finding in order to refer
individuals for further evaluation and, as appropriate, treatment.
Within this framework, medical monitoring includes both testing for
early biological effect and an assessment of exposure using biological
specimens (for example, blood or urine), when appropriate. This is
provided as a service to individuals in communities where there is
believed to be an increased risk of disease from exposure to hazardous
substances released into the environment.
Criteria for Considering Medical Monitoring
The criteria outlined below will be used to determine the
appropriateness of conducting medical monitoring in a community and
will be applied in a phased approach. Phase I, conducted by ATSDR,
consists of an evaluation of the exposure and outcome criteria. Phase
II consists of an evaluation of the system criteria. Phase II will be
conducted with the input of a panel consisting of community, State and
local health officials, and ATSDR. At the end of Phase II, a detailed
medical monitoring plan will be written at sites where a monitoring
program is established. All of the criteria must be met at a site in
order for a medical monitoring program to be established at that site.
In addition, resources must be available to initiate and sustain the
program.
Phase I
Exposure Criteria
A. There should be evidence of contaminant levels in environmental
media that would suggest the high likelihood of environmental exposure
to a hazardous substance and subsequent adverse health outcomes.
The National Research Council (NRC) defines exposure as ``an event
that occurs when there is contact at a boundary between a human and the
environment at a specific contaminant concentration for a specified
period of time; the units to express exposure are concentration
multiplied by time'' (NRC, 1991). The specific contaminant
concentration and period of time will vary for different chemicals and
different media. The exposure must be to a hazardous substance as
defined under CERCLA, and the result of a release from a CERCLA-covered
facility. A release from a CERCLA-covered facility includes those
events that establish an open pathway of exposure (i.e., an unfenced
area with high soil contamination could be considered a ``release'') or
allows contaminants to go off-site via air, surface water, ground
water, or other pathway. The primary criteria for medical monitoring
should be documented evidence of exposure of a population to a
hazardous substance in the environment. An exposure will be considered
to be at a sufficient level if there is documentation of an increased
opportunity for exposure to a level that meets or exceeds some health-
based comparison value (such as Minimum Risk Levels (MRLs) or Reference
Doses (RfDs)) or that meets or exceeds a level reported in the peer-
reviewed literature to result in some adverse health effect.
Documentation is considered sufficient if it is from an exposure
assessment, environmental exposure modeling, or sampling from a general
area (for example, water samples from an aquifer or a town water
supply). Documentation of individual levels of exposure is not
required. In cases in which exposures are unknown or undocumented,
environmental monitoring is a more appropriate initial activity.
B. There should be a well-defined, identifiable target population
of concern in which exposure to a hazardous substance at a sufficient
level has occurred.
Initially, the target population of concern will be defined
geographically on the basis of exposure. In addition, all populations
considered will be assessed for the presence of any sub-population at
increased risk of the adverse health effects associated with the
exposures. An example of a subpopulation at increased risk would be
preschool children in an area with known lead exposures. The size of
the target population of concern is not a factor in the decision for
monitoring. In areas where biological markers of exposure have not been
collected, environmental sampling can be used to estimate exposure
levels. The target population of concern is the population in which
there is documented exposure at a sufficient level to place the
individuals in that population at significant increased risk for
developing some specific adverse health effect.
Outcome Criteria
A. There should be documented human health research that
demonstrates a scientific basis for a reasonable association between an
exposure to a hazardous substance and a specific adverse health effect
(such as an illness or change in a biological marker of effect).
Previous studies on human populations must demonstrate a reasonable
association between a particular exposure and an adverse health effect.
In order to make that inference, consideration should be given to the
strength, specificity, and consistency of the association among the
identified studies. The period of exposure (including the timing and
duration of the exposure) and its relationship to the latency period
for the disease or illness should also be examined if information is
available. Consideration should be given to whether the association has
demonstrated a dose-response relationship and whether the association
is consistent with the existing body of knowledge. This information
could include a variety of occupational, epidemiological, or other
studies involving human populations.
B. The monitoring should be directed at detecting adverse health
effects that are consistent with the existing body of knowledge and
amenable to prevention or intervention measures.
The monitoring should be established for specific adverse health
effects. The specific adverse health effect being monitored should be a
result of the possible exposure consistent with the existing body of
knowledge. An adverse health effect is consistent with the existing
body of knowledge if it has been described in the literature as caused
by that agent or by similar agents, taking into account structure-
activity relations.
In addition, the adverse health effects (disease process, illness,
or biomarkers of effect) should be such that early detection and
treatment or intervention
[[Page 38842]]
interrupts the progress to symptomatic disease, improves the prognosis
of the disease, improves the quality of life of the individual, or is
amenable to primary prevention. If the adverse health effects that are
of concern in an individual or in a community are not easily detectable
and not medically treatable, then medical monitoring would not be
beneficial and would not be an appropriate public health activity. An
easily detectable effect is one that can be found on clinical
examination, or through the use of simple, diagnostic tests in an
outpatient setting. Also, the test procedures must be acceptable to the
patient and the community. The diagnostic tests must be
nonexperimental, relatively noninvasive (such as the drawing of a tube
of blood for laboratory tests), and simple to administer.
Monitoring for Evidence of Continuing Exposure
At sites with exposure in the community, the monitoring program
might include biological markers of continuing exposure. For example,
the Bunker Hill Superfund site has had lead screening of children for
many years. Those sites would be ones in which the exposure is known to
have a variety of adverse health effects, but for which no tests are
available to detect those effects at a time when intervention could
affect the course of the disease process. In those instances, the
primary intervention is to remove the individual from the exposure.
This allows the medical monitoring system to recommend referral for
intervention prior to the onset of detectable adverse health effects. A
monitoring system that includes biomarkers of continuing exposure is
similar to medical surveillance of hazardous waste workers where
changes indicative of increasing or continued exposures occur
sufficiently early that the exposure can be curtailed and the risk for
disease reduced (Gochfeld 1990).
Phase II
General Information
Phase II of the program is carried out by ATSDR with assistance
from the community. When ATSDR has determined that exposure from a site
has met the exposure and outcome criteria, a site panel will be formed
based on recommendations from the community and the State and/or local
health departments to review the system criteria and to assist in the
development of a site-specific medical monitoring plan. The site panel
will include representatives from ATSDR, the community, State or local
health departments, local medical societies, and subject experts as
necessary. The site panel will function in much the same manner as the
Community Assistance Panels (CAPs) that are established at some sites
during the public health assessment process. The site panel will follow
the established procedures for those CAPs. The site panel will be
responsible for assessing the available community health resources and
determining the feasibility and extent of the screening program for the
community. If the panel determines that a screening program is feasible
in the community and ATSDR concurs with that decision, ATSDR will
develop a site-specific monitoring plan. That plan will be presented to
the site panel for review and concurrence. After the plan has been
developed and has undergone peer review, it will be presented to the
community at large for their input prior to establishing the program.
System Criteria
A. The general requirements for a medical screening program should
be satisfied.
The monitoring aspect of a health surveillance program consists of
the periodic medical testing to screen individuals who are at increased
risk of disease. Monitoring serves to identify those individuals with
an unrecognized adverse health effect. This is consistent with the
definition of screening as ``the presumptive identification of
unrecognized disease or defect by the application of tests,
examinations, or other procedures which can be applied rapidly.
Screening tests sort out apparently well persons who probably have a
disease from those who probably do not. A screening test is not
intended to be diagnostic. Persons with positive or suspicious findings
must be referred to their physicians for diagnosis and necessary
treatment.'' (Commission on Chronic Illness, 1957) In general, the
ability to predict the presence or absence of disease from test results
depends on the sensitivity and specificity of the test and the
prevalence of the disease in the population being tested. The higher
the prevalence, the more likely a positive test indicates disease
(Mausner & Kramer, 1985). In order for a screening program to be of
public health benefit, the population being screened should be at a
significantly high risk for the undiagnosed disease (i.e., the disease
should have a sufficiently high prevalence in the population).
Given that definition, there are certain requirements for screening
programs that should be considered when evaluating a possible medical
monitoring program for a site (adopted from Mausner & Kramer, 1985).
Those requirements are:
The natural history of the disease process should be
understood sufficiently for screening.
The early detection through screening should be known to
have an impact on the natural history of that disease process. For
example, the detection of breast cancer while it is localized has been
shown to increase the ten-year survival rate. For that reason, several
groups have made recommendations for the early detection of breast
cancer in asymptomatic women. Those recommendations include breast
self-examination, breast physical examination, and mammography (Mettlin
& Dodd, 1991; Kelsey & Gammon, 1991).
There should be an accepted screening test that meets the
requirements for validity, reliability, estimates of yield,
sensitivity, specificity, and acceptable cost. The purpose of ATSDR-
sponsored medical monitoring is not to develop new screening tests. The
medical monitoring program will use tests that have been recommended
and used for screening in other settings.
The U.S. Preventive Services Task Force has established criteria
for determining the effectiveness of preventive strategies including
screening tests. The criteria for effectiveness of a screening test
include the efficacy of the screening test and the effectiveness of
early detection. The Task Force used efficacy to mean accuracy and
reliability. The accuracy is measured using four indices: sensitivity,
specificity, positive predictive value, and negative predictive value
(see table below for definitions). A test with poor sensitivity will
result in a large proportion of persons with disease being told they
are free of disease (false-negatives). A test with poor specificity
will result in healthy persons being told they have the disease (false-
positives). There may be serious consequences in the use of screening
tests with poor sensitivity and/or specificity. Persons with false
negative results may have delays in diagnosis and treatment. False
positive results can result in follow-up testing that is uncomfortable,
expensive and potentially harmful. The evaluation and selection of a
screening test must include a determination of the likelihood of
producing false positive results (the positive predictive value (PPV)).
The PPV changes in accordance with the prevalence of the condition in
the screened population. PPV is unlike
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sensitivity and specificity in that it is not a constant characteristic
of a screening test. If the condition is sufficiently rare in the
screened population, even tests with excellent sensitivity and
specificity can have low PPV, having more false positive results than
true positive results.
Another important aspect in determining the efficacy of a screening
test is the reliability of the test. The reliability (reproducibility)
is the ability of the test to give the same result when it is repeated.
An accurate test with poor reliability can produce results that vary
widely from the correct value, even though the average of the results
approximates the true value. Poor reliability may be due to either
interobserver variation or intraobserver variation (U.S. Preventive
Services Task Force, 1989).
Definition of Terms
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Term Definition Formula*
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Sensitivity............ Proportion of persons a
with the condition who a + c
test positive.
Specificity............ Proportion of persons d
without the condition b + d
who test negative.
Positive Predictive Proportion of persons a
Value. with positive test who a + b
have condition.
Negative Predictive Proportion of persons d
Value. with negative test who c + d
do not have the
condition.
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*Explanation of Symbols
Condition absent Condition present
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Positive Test.......... a b
Negative Test.......... c d
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Legend: a=true +; b=false +; c=false -; d=true -.
The screening program should be one that is feasible and
acceptable to individuals and the community. Therefore, plans and
possible screening tests for a medical monitoring program will be
presented to the community for input prior to the initiation of any
recommended program.
B. An accepted treatment, intervention, or both, for the condition
(outcome or marker of exposure) must exist and a referral system should
be in place prior to the initiation of a medical monitoring program.
There should be established criteria for determining who should
receive referral for intervention or treatment. These criteria will be
based on the selected effect being screened for and the screening test
being used. Results will be evaluated by ATSDR longitudinally and
cross-sectionally to identify changes in the system or screening tools
that require follow-up (Gochfeld 1990). A referral mechanism should
exist so that those who are eligible for the intervention can be
referred to a qualified health care provider for further diagnosis,
treatment, or intervention. The referral must be for treatment or
intervention that is standard practice and not experimental in nature.
The medical monitoring (screening) program is not responsible for the
cost of the referral, the intervention, or the treatment of individuals
participating in the program.
C. The logistics of the system must be resolved before the program
can be initiated.
After medical monitoring has been determined to be appropriate for
a site, the specifics of the monitoring system will be detailed in a
site-specific medical monitoring plan. The site panel consisting of the
community members, appropriate health officials, and subject experts as
necessary will work with ATSDR to develop and review the site-specific
medical monitoring plan. The specifics of the medical monitoring system
recommended can vary for each site. The monitoring plan is the protocol
for the specific program to be proposed in a community. The plan will
outline the target community, the types of outcomes to be screened for,
the participants in the referral system, and the program reports. The
plan will include a review of the latency period for the outcomes being
monitored and the duration of the exposure to define the period of time
that the program will operate in a specific site population. The target
population; the completeness with which the exposed population can be
identified, contacted, and followed; the screening tests; and the
selected health outcomes will all influence the specifics of the
system. Existing medical facilities and personnel will be used when
possible.
The monitoring plan will be submitted for peer review prior to its
implementation at a site. The plan for a site might require additional
review by an expert panel (ethicists, NRC) to evaluate the screening
tests recommended. ATSDR's Division of Health Studies will work closely
with the Division of Health Education to provide professional health
education when needed to enhance the medical monitoring program.
Medical monitoring is one of ATSDR's service activities and is not
considered to be a research tool. The monitoring activity at each site
will be routinely evaluated for the effectiveness of the screening
tests in place and the types of effects being detected. Due to
confidentiality issues in dealing with small groups of people, the
reporting from the system will consist of annual reports noting the
number of individuals screened, the number of referrals made, and the
number of conditions diagnosed in the referral system. ATSDR will
develop a list that includes information on the types of exposures seen
in the communities and the types of screening tests that were included
in the monitoring. ATSDR can provide this information as available to
the site panels to assist them in deciding on the types of screening
tools based on what has been used in other areas.
The referral system will consist of the review of the screening
results and the referral to appropriate health care providers or
referral physicians. The specific mechanisms for determining who needs
referral and for selecting the health care providers in the referral
pool must be in place prior to the initiation of the medical
monitoring. Once the participant has been referred to the
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referral providers, those providers will be responsible for any
subsequent diagnosis, treatment, or intervention.
Summary of Medical Monitoring
Medical monitoring will be considered along with the other health
follow-up activities to be recommended for populations around specific
sites. The Division of Health Studies will make a determination on
whether a site meets the exposure and outcome criteria for medical
monitoring. If a site meets the previously discussed criteria and is
selected for further consideration of a medical monitoring program,
ATSDR will work with the community and other appropriate entities in
designing the specific monitoring and referral system for that site's
target population. ATSDR will notify, and where appropriate, work with
the state health department to establish the program. The Division of
Health Studies will monitor the program and be responsible for the
oversight on the annual reports.
References
Commission on Chronic Illness. Chronic Illness in the United States,
Vol. 1. Commonwealth Fund, Harvard University Press, Cambridge,
1957, page 45.
Gochfeld M. Medical surveillance of hazardous waste workers. In
Principles and Problems in Occupational Medicine State of the Art
Reviews: Hazardous Waste Workers. Gochfeld M and EA Favata, editors.
Philadelphia: Hanley & Belfus, Inc., 1990; 5(1):1-8.
Kelsey JL and MD Gammon. The epidemiology of breast cancer. CA-A
Cancer Journal for Clinicians 1991; 41(3):146-165.
Mausner JS and S Kramer. Epidemiology--an introductory text.
Philadelphia: W.B. Saunders, 1985, pages 220-230.
Mettlin C and GD Dodd. The American Cancer Society guidelines for
the cancer-related checkup: An update. CA-A Cancer Journal for
Clinicians 1991; 41(5):279-282.
NRC (National Research Council). Human Exposure Assessment for
Airborne Pollutants: Advances and Opportunities. Washington, D.C.:
National Academy Press, 1991, pages 17-37.
U.S. Preventive Services Task Force. Guide to Clinical Preventive
Services: An Assessment of the Effectiveness of 169 Interventions.
Baltimore: Williams & Wilkins, 1989, pages xxix-xxxvii.
Dated: July 24, 1995.
Claire V. Broome,
Deputy Administrator, Agency for Toxic Substances and Disease Registry.
[FR Doc. 95-18578 Filed 7-27-95; 8:45 am]
BILLING CODE 4163-70-P
