ATSDR's Final Criteria for Determining the Appropriateness of a Medical Monitoring Program Under CERCLA

[[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.

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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

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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