Protections
for Subjects in Human Research. Proposed Rule. US EPA.
This
proposal, the first of several possible Agency actions,
focuses on third-party intentional dosing human studies
for pesticides, but invites public comment on alternative
approaches with broader scope.
... This proposal, however, focuses on the most pressing
of issues: defining appropriate ethical standards for investigator
conduct and for Agency use of third-party intentional dosing
human studies for pesticides.
B. Proposal
EPA proposes to extend the requirements of EPA's Common
Rule (40
CFR 26.101 through 26.124) to third-party research conducted
after the
effective date of the rule, which involves intentional exposure
of
human subjects, if the researcher intended to submit the
resulting
information to EPA, or to hold the information for later
inspection by
EPA, under FIFRA or the FFDCA.
...
In the United States, the National Commission for the Protection
of
Human Subjects of Biomedical and Behavioral Research issued
in 1978 The Belmont Report: Ethical
Principles and Guidelines for the Protection of Human Subjects
of Research. This document can be found in the docket
for this proposed rule and on the web at http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm.
For many U. S. federal departments and agencies, the principles
of the Belmont Report are
implemented through the Federal Policy for the Protection
of Human Subjects (the Common Rule). The Common Rule, promulgated
by 15 federal departments and agencies, including the EPA,
on June 18, 1991 (56 FR 28003), applies to all research
involving human subjects conducted, supported or otherwise
subject to regulation by any federal department or agency
that has adopted the Common Rule and has taken appropriate
administrative action to make it applicable to such research.
The Common Rule as promulgated by EPA (40 CFR part 26) has
applied to human subjects research conducted or supported
by EPA since it was put into place in 1991.
The
World Medical Association, a voluntary federation of national
medical associations, has developed and maintains ethical
standards documented in the Declaration
of Helsinki, first issued in 1964 and revised several
times since then. The latest version of the Declaration
is available at: http://www.wma.net/e/policy/b3.htm.
These
standards apply internationally to research on the diagnosis
and treatment of human disease, or that adds to understanding
of the causes and development of disease.
Under
the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) (7 U.S.C. 136-136y), EPA requires pesticide companies
to conduct studies needed to evaluate the safety of their
products. While some studies involving human subjects are
required, EPA has never required intentional dosing human
toxicity studies with pesticides. EPA has, however, required
studies to measure potential exposure to pesticides of users
or of workers and others who re-enter areas legally treated
with pesticides. Other required tests have evaluated the
effectiveness of pesticide products intended to repel insects
and other pests from human skin. In addition, EPA has required
studies to define pesticide metabolism and metabolic products
in humans, as a guide to interpretation of biomonitoring
studies of agricultural workers and others to protect them
from exposure to potentially dangerous levels of pesticide
residues.
...
Submission of these studies following FQPA elicited a strong
expression of public concern. In response, EPA convened
an advisory committee under the joint auspices of the EPA
Science Advisory Board (SAB) and the FIFRA Scientific Advisory
Panel (SAP) to address issues of the scientific and ethical
acceptability of such research. This
advisory committee, known as the Data
from Testing of Human Subjects Subcommittee (DTHSS),
met in December 1998 and November 1999, and completed its
report in September 2000. Their report is available in the
docket for this proposed rulemaking, and on the web at:
http://www.epa.gov/science1/pdf/ec0017.pdf.
Comments
on the use of data from the testing of human subjects.
A report by the Science Advisory Board and the FIFRA Scientific
Advisory Panel. US EPA. Report No. EA-SAB-EC-00-017. September
2000. 67 pages
C. Topics
for Public Comment
The Agency has considered a number of alternatives to the
positions described and invites public comment on whether
EPA should adopt any of these alternatives for the final
rule:
1. Should
EPA continue the case-by-case approach articulated in the
February 8, 2005, Federal Register Notice, not adopting
by rule ethical standards to guide decision-making with
respect to completed, ethically problematic human studies?
2. Should
a final rule establish the standard that EPA would rely
on all scientifically sound data from covered intentional
exposure human studies relevant to EPA decision-making,
without regard to any ethical deficiencies in the studies?
3. Should
a final rule establish a different criterion for acceptance
of research conducted before the effective date of the rule
than the criterion proposed in Sec. 26.601 of the regulatory
text? Should a final rule identify specific factors to be
considered or criteria to be applied in determining whether
research was
``fundamentally unethical'' or ``significantly deficient
with respect to prevailing standards''?
4. Should
a final rule establish the standard that, in making decisions
under FIFRA and FFDCA, EPA would never rely on data from
a study involving intentional exposure of any human subject
to a pesticide when a purpose of the study was to identify
or measure toxic effects?
5. Should
a final rule establish the standard that EPA would not rely
on an intentional exposure human study covered under proposed
subpart F if the study did not comply with the Common Rule,
without regard to when the research was conducted?
6. Should
a final rule establish the standard in NAS Recommendation
5-7 for all three categories of completed research covered
by proposed subpart F of the regulatory text--i.e., (1)
Research conducted before the rule becomes effective; (2)
research conducted after the rule becomes effective and
required to comply with EPA's Common Rule; and
(3) research conducted after the rule becomes effective
but not required to comply with EPA's Common Rule?
7. Should
a final rule apply a different standard to research conducted
after the effective date of the final rule, depending on
whether the research was subject to the requirements of
EPA's proposed subparts A through D?
8. Should
a final rule apply proposed subpart F to a different range
of third-party human research, including any of the categories
discussed in Unit IV., or apply different ethical standards
to research in different categories within an altered scope?
9. Should
a final rule apply a standard other than ``substantial''
compliance with the requirements in EPA's proposed subparts
A through D, perhaps requiring ``full'' or ``complete''
compliance with those requirements? How should minor, administrative
deficiencies be treated under an alternative standard?
10.
Should a final rule permit use of the exception procedure
in proposed Sec. 26.603 when research falling within the
prohibitions of proposed Sec. 26.221 or Sec. 26.421--i.e.,
research involving intentional exposure of pregnant women
or children--is deemed crucial to the protection of public
health?
11.
Should a final rule identify additional factors EPA will
consider in deciding whether to rely on a completed human
study that does not meet the appropriate standard in proposed
Sec. 26.601 or Sec. 26.602 of the regulatory text? |
