[Federal Register Volume 60, Number 123 (Tuesday, June 27, 1995)]
[Notices]
[Pages 33217-33219]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-15659]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[ATSDR-95]
Proposed Procedures for Combined Analyses of Epidemiologic
Studies as Part of the Great Lakes Human Health Effects Research
Program
AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR),
Public Health Service (PHS), Department of Health and Human Services
(HHS).
ACTION: This notice announces the procedures ATSDR will use for
conducting combined research analyses as part of the ATSDR Great Lakes
Human Health Effects Research Program.
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SUMMARY: This notice describes the proposed procedures, meta- analyses
and pooled data analyses, to be used by ATSDR to conduct combined
analyses of epidemiologic studies supported by the ATSDR Great Lakes
Human Health Effects Research Program. ATSDR may choose to utilize one
or both procedures, depending on the data and the results of the future
feasibility studies. The procedures will be used for both new and
existing research investigations. Comments on this notice are
requested. The procedures outlined herein will be used on an interim
basis, subject to change based on comments received and experience
gained during implementation of these procedures.
DATES: Public comments concerning this Federal Register notice must be
received on or before December 26, 1995.
ADDRESSES: Comments on this notice should bear the docket control
number ATSDR-95 and should be submitted to: Division of Toxicology,
Research Implementation Branch, Agency for Toxic Substances and Disease
Registry, Mailstop E-29, 1600 Clifton Road, NE, Atlanta, Georgia 30333.
Comments on this notice will be available for public inspection at
the Agency for Toxic Substances and Disease Registry, Building 4, Suite
2400, Executive Park Drive, Atlanta, Georgia (not a mailing address),
from 8 a.m. until 4:30 p.m., Monday through Friday, except for Federal
legal holidays.
FOR FURTHER INFORMATION CONTACT: Dr. William Cibulas, Research
Implementation Branch, Division of Toxicology, Agency for Toxic
Substances and Disease Registry, Mailstop E-29, 1600 Clifton Road NE.,
Atlanta, Georgia 30333, telephone (404) 639-6306.
SUPPLEMENTARY INFORMATION:
Background
The ATSDR Great Lakes Human Health Effects Research Program is
[[Page 33218]] authorized in sections 104(I)(5)(A) and (15) of the
Comprehensive Environmental Response, Compensation, and Liability Act
of 1980 (CERCLA) as amended by the Superfund Amendments and
Reauthorization Act of 1986 (SARA) [42 U.S.C. 9604(I)(5)(A) and (15)];
and section 106, subsection 118(e) of the Great Lakes Critical Programs
Act of 1990 [33 U.S.C. 1268(e)]. This research program is designed to
investigate and characterize the association between the consumption of
contaminated Great Lakes fish and associated short- and long-term
harmful health effects. The research objectives of the program are to
(1) build upon and amplify the results from past and ongoing research
in the Great Lakes basin; (2) develop information databases and
research methodology that will provide long-term benefit to human
health effects research in the Great Lakes basin; (3) provide direction
for future health effects research; (4) provide health information to
State and local health officials, and to the concerned public and their
medical health care professionals; and (5) in concert with State and
local officials, increase the public awareness regarding the potential
health implications of toxic pollution in the Great Lakes basin; and
(6) coordinate as necessary with relevant Public Health Service (PHS)
research programs and activities, including those of the Food and Drug
Administration (FDA), Centers for Disease Control and Prevention (CDC),
National Institutes of Health (NIH), and the Indian Health Service
(IHS), as well as the Environmental Protection Agency (EPA), and State
and local health departments, to ameliorate adverse public health
impacts of persistent toxic substances in the Great Lakes basin.
Toward this end, ATSDR has developed a Great Lakes Health Effects
Research Strategy. The goals of this strategy are to identify human
populations residing in the Great Lakes basin that may be at greater
risk of exposure to chemical contaminants present in one or more of the
Great Lakes, and to ameliorate or prevent any adverse health effects.
This strategy is built upon the five traditional elements of disease
prevention: identification, evaluation, control, dissemination, and
infrastructure. This strategy has been endorsed by the Council of Great
Lakes Research Managers and has been adopted by the International Joint
Commission as a framework for the study of human health and other
ecosystem effects in the Great Lakes basin.
In fiscal year 1992, ATSDR funded nine research grants to study the
potential adverse human health effects of consuming contaminated fish.
These studies include eight epidemiologic investigations in presumed
susceptible populations, that is, Native Americans, sport anglers, the
urban poor, pregnant women, fetuses and nursing infants of mothers who
consume contaminated Great Lakes fish, infants and children, and the
elderly. The ninth study focuses on developing more sensitive methods
to detect persistent Great Lakes contaminants, such as polychlorinated
biphenyls, dioxins, alkylated lead, mirex, and methylmercury, in human
biologic tissues and fluids. In fiscal year 1993 ATSDR funded ten
grants which included nine continuation awards for investigations
funded in 1992 and one new award that established an interlaboratory-
based, quality assurance/control program for the ATSDR research
program. In fiscal year 1994, ATSDR funded continuation awards for all
10 research grants.
The impact of this research program will be felt most directly by
the communities within the Great Lakes basin. Collectively, these 10
research projects will (1) build upon and extend six existing human
health studies in the Great Lakes basin that include high-risk
populations; (2) establish two new subpopulations that include African-
American women, and men and women of reproductive age between 18 and
34; (3) improve analytical methodology for detecting low levels of
Great Lakes contaminants in human biologic tissues and fluids and in
environmental media; (4) characterize exposure to all 11 critical Great
Lakes contaminants identified by the International Joint Commission, as
well as other pollutants; (5) determine profiles and levels (body
burden) of Great Lakes contaminants in high-risk populations; (6)
identify sensitive human health end points from exposure to Great Lakes
pollutants, i.e., behavioral, developmental, reproductive, neurologic,
endocrinologic, and immunologic effects; (7) investigate paternal and
maternal exposure to Great Lakes pollutants and assess the potential
for related health effects in their children (transgenerational
effects); (8) increase collaboration, cooperation, and communication
between the researchers in the Great Lakes basin; and (9) provide
public health information to the study populations, health care
providers, and State and local health departments concerning human
health effects that may result from exposure to Great Lakes pollutants
by fish consumption.
Additionally, the research conducted by this program will help
delineate the relationships among contaminant levels in the
environment, exposure pathways, tissue levels, and potential human
health effects; allow for evaluation and interpretation of data across
human health studies to facilitate a basin-wide analysis of the
pollution problem in the Great Lakes; and provide a ``model'' for other
ecosystem-level studies intended to determine human health impacts of
hazardous waste.
Rationale for Combined Analyses of ATSDR Research Investigations
Combined analyses of the research studies of the ATSDR Great Lakes
Human Health Effects Research Program will provide qualitative and
quantitative research synthesis of the ATSDR- supported investigations.
It is expected that combined analyses of the studies will improve the
science base for investigations of consumption of fish contaminated
with persistent toxic compounds from the Great Lakes, strengthen the
scientific foundation for informed decision-making regarding public
policy, and improve coordination and linkages between research
activities and public health practices.
Procedures for Combined Analyses of ATSDR Research Studies
The combined analyses (research synthesis) of epidemiologic
investigations may be accomplished by meta-analysis of published
results or pooled analysis of primary data. Both methods use explicit
criteria, can be replicated, and provide a quantitative result. The
following procedures will address key methodologic issues that are
relevant to both methods of research synthesis, as well as their
advantages and limitations.
Meta-analyses attempt to analyze and combine the results of
previous independent studies of a given scientific issue. Meta-
analyses can be used to increase the power of statistical tests for
important end points and subgroups, to resolve uncertainty when studies
have conflicting conclusions, and to improve estimates of effect size.
Meta-analyses rely on the published reports of previous studies and are
relatively easy and inexpensive to perform. However, they are also
susceptible to many sources of bias and are influenced by statistical
methods. Six major areas have been identified as critical elements of
scientifically valid meta-analyses. Proposed meta-analyses of ATSDR
studies will be conducted according to a predetermined protocol which
will address the six major areas as follows: (1) study design,
including protocol and [[Page 33219]] literature search; (2)
combinability of results of separate studies; (3) control and
measurement of potential bias; (4) statistical analysis including
significance tests and point and interval estimation; (5) sensitivity
analysis to confirm final results; and (6) application of results which
provides perspective of pooled results.
Pooled data analyses attempt to analyze and combine the results of
individual subject level data across studies. Pooled data analyses can
facilitate the study of rare exposures as well as confounding and
interactions between established and suspected risk factors. Common
definitions, coding, cutpoints for variables, and adjustment for the
same confounders can be accomplished in pooled data analyses.
Consistency of findings and previously unrecognized errors,
inconsistencies, and associations may also be examined. However, pooled
data analyses are more difficult to conduct because they are labor- and
time-intensive. In addition, important methodologic issues remain
regarding the influence of study populations and methods on the results
of the pooled data analyses, and the integration of qualitative
assessments of research studies with quantitative estimates of the
results. Guidelines for a systematic methodology for the pooled
analysis of subject level data from previously conducted epidemiologic
studies focus on eight critical areas. Proposed pooled data analyses
for ATSDR studies will be conducted according to a predetermined
protocol which will address the eight critical areas as follows: (1)
location of all studies conducted on the topic of interest; (2)
selection of the studies for the pooling project; (3) obtaining the
primary data from original investigators and preparing the data for the
pooled analysis; (4) estimation of study-specific effects; (5)
examination of heterogeneity of these study-specific effects and how
they should be pooled; (6) estimation of the pooled effects with the
appropriate statistical model; (7) examination of heterogeneity between
studies if this exists; and (8) conduct of a sensitivity analysis.
Dated: June 20, 1995.
Claire V. Broome,
Deputy Administrator, Agency for Toxic Substances and Disease Registry.
[FR Doc. 95-15659 Filed 6-26-95; 8:45 am]
BILLING CODE 4163-70-P