August 18, 2003
Public Information and Records Integrity Branch (PIRIB)
7502C
Office of Pesticide Programs (OPP)
U.S. Environmental Protection Agency
1200 Pennsylvania Ave., NW.
Washington, DC 20460-0001
RE: Docket ID number OPP-2003-0132
The Children’s Environmental Health Network strongly
supports the establishment of criteria and standards for
the U.S. Environmental Protection Agency (EPA) to apply
in deciding the extent to which it will consider or rely
on various types of research with human subjects to
support its actions. We appreciate the opportunity to
submit comments as part of this rulemaking process.
The Network is a national multi-disciplinary non-profit
organization dedicated to protecting the fetus and child
from environmental toxicants and to promoting a healthy
environment. The Children’s Environmental Health
Network was created to promote the incorporation of these
basic pediatric principles in policy and practice:
Children
are growing. Pound for pound, children eat more
food, drink more water and breathe more air than
adults. Thus, they are likely to be more exposed
to substances in their environment than are
adults. Children have higher metabolic rates than
adults and are different from adults in how their
bodies absorb, detoxify and excrete toxicants.
Children’s
systems, including their nervous, reproductive,
digestive, respiratory and immune systems, are
developing. This process of development creates
periods of vulnerability. Exposure to toxicants
at such times may result in irreversible damage
when the same exposure to a mature system may
result in little or no damage.
Children
behave differently than adults, leading to a
different pattern of exposures to the world
around them. For example, they exhibit
hand-to-mouth behavior, ingesting whatever
substances may be on their hands, toys, household
items, and floors. Children play and live in a
different space than do adults. For example, very
young children spend hours close to the ground
where there may be more exposure to toxicants in
dust, soil, and carpets as well as low-lying
vapors such as radon or pesticides.
Children
have a longer life expectancy than adults; thus
they have more time to develop diseases with long
latency periods that may be triggered by early
environmental exposures, such as cancer or
Parkinson's disease.
Children do
not have control over their environment and are not able
to remove themselves from harmful situations. They must
rely on adults to assure they are in a healthy
environment.
Though the
process of child growth and development does not change,
the world in which today’s children live has changed
tremendously from that of previous generations. One of
these changes is the phenomenal increase in substances to
which children are exposed. Synthetic chemicals are
ubiquitous in our environment worldwide, and traces of
these compounds are found in all humans and animals. For
the majority of the thousands of new chemicals introduced
into children’s environments since World War II,
little is known about the health effects on children.
The Network has closely followed the issue of EPA’s
handling of third-party research involving human subjects
for several years and has submitted numerous comments to
the Agency on this topic. It is our sense that the EPA
has had great difficulty in understanding that it has an
obligation to protect human rights while responsibly
implementing the laws of the nation with respect to
pesticide regulation. An extraordinary variety of
organizations share our concerns, such as the American
Public Health Association, the Association of Women's
Health, Obstetric and Neonatal Nurses, the National
Medical Association, the Farmworker Justice Fund, the
National Council of La Raza, and religious denominations
including the United Methodist Church, the Evangelical
Lutheran Church, the Catholic Church and the Presbyterian
Church. In 1999, more than 45 organizations wrote to the
Administrator expressing their concerns about tests that
intentionally dose humans with substances designed to be
toxic, with no conceivable benefit to the subject, solely
for eliminating or lessening regulatory safety margins.
Clearly, these organizations agree with us that the issue
now before the Agency is of the highest import. Yet, to
this date, there has been a failure to act.
This issue is of course vital to any individuals who may
participate directly in such studies as subjects; their
welfare must be assiduously protected. But the decision
on whether and how to conduct tests to be submitted to
the Agency and how the Agency will assure compliance with
ethical standards also has implications for a variety of
different populations, from all children, to children
with disabilities, to children in minority and/or
farmworker communities, to farmworkers and others. For
example, deciding that it would be acceptable to use
“data” from a “study” where a dozen
healthy adult men drank a pesticide cocktail to eliminate
one of the core safety factors used in regulating
pesticides would directly affect children. Such a
decision would allow children to be exposed to that
pesticide at ten times the level previously considered
acceptable. Thus the Agency must consider, as directed by
Executive Order 10345 and EPA policy, the impact its
policies, standards and guidance in this matter will have
on children.
Just as the EPA is responsible for protection of health
and the environment, also it is responsible for assuring
the protection of human rights. The U.S., along with most
other nations of the world, have made strong commitments
to the protection of human rights in research. Neither
the EPA nor the pesticide manufacturers have been
exempted from these agreements. When we fail to provide
adequate protection from exposure to toxicants in the
environment, there are groups who will be more affected;
most often these are low income or minority communities.
These same communities are the ones that most likely
would be tempted by large incentives to participate in
human studies that are of no benefit to them personally
or to their communities. This is a critical issue that
must also be addressed.
For these reasons and others, the Network strongly
supports the adherence to the highest ethical and
scientific standards in conducting scientific inquiry and
in setting policies, guidelines and standards. Direction
and policy from the EPA on this matter is long overdue
and the Network commends the Agency for proceeding with
rulemaking on this topic.
Correcting the Record
The Network strongly urges the EPA to correct troubling
and inaccurate statements included in the Federal
Register notice of this request for comments regarding
the findings of the joint SAB/SAP Data from Testing of
Human Subjects Subcommittee (DTHSS) advisory committee,
created in 1998 to examine some of these issues. Whether
this is a matter of poor recall or a deliberate effort to
erase the work of its advisory process, it is important
to set the record straight. The EPA and the public will
be ill-served if the Agency builds its standards on the
foundation of such faulty history as presented in the
Register. The Federal Register notice mischaracterizes
(at best) a main conclusion of the committee:
“No clear consensus emerged from the advisory
committee process on the acceptability of NOAEL or NOEL
[respectively, No Observed Adverse Effect Level or No
Observed Effect Level] studies of systemic toxicity of
pesticides to human subjects, and significant differences
of opinion remain on both their scientific merit and
ethical acceptability.”
It is true that the panel did not reach a complete
consensus on every single issue. However, as the numerous
citations below attest, there was a full consensus on the
specific issue of the acceptability of human studies to
assess systemic toxicity of pesticides and thereby
develop NOAEL/NOEL’s. Below are direct quotes from
the committee report that clearly demonstrate that this
indeed was their consensus. From the committee’s
report, page 11:
“the Subcommittee, in general, would not support
human experimentation primarily to determine a No
Observed Adverse Effects Level (NOAEL).
(emphasis in the original)
and page 12:
[other types of studies would result in ]“fewer of
the ethical quandaries that arise when they are used
simply to establish a NOAEL that lacks cogent scientific
value and whose purpose can be interpreted as simply an
argument for higher permissible exposure levels.”
(emphasis in the original)
and page 16:
“Considering the other problems associated with the
use of NOAEL/LOAEL’s (e.g. design dependency, not an
estimated value but the result of a test), the
Subcommittee does not believe human studies should be
used to directly estimate these quantities.”
and page 17:
“It agreed that, generally, human dosing experiments
are not appropriate if the primary intent of the study is
to determine or revise a NOEL or NOAEL so as to eliminate
the interspecies uncertainty factor.”
and page 26:
“But research that yields benefits to the population
at the expense of risk to the subjects of research is
ripe for exploitation, and may arguably be inherently
exploitative. In this vein, the Subcommittee would not
support human dosing that intended bring (sic) about
increased allowable residue levels.”
Relating to differences of opinion on these tests, the
report makes repeated statements, such as:
“If it can be justified at all to expose human
subjects intentionally to toxic substances, the threshold
of justification for such action should be very
high.”
The Network calls on the Agency to discard the faulty
interpretation published in Federal Register notice and
urges the Agency to protect against the use of this
defective analysis in further developing these standards
and criteria. The Agency’s reluctance to
straightforwardly acknowledge recommendations by its own
advisory panel that it apparently is balking at accepting
(by, for example, not acting on the recommendations for
several years now) does not bode well for the ability of
EPA to uphold its responsibility to protect human rights
even while it serves as a responsible steward of the
nation’s pesticide registration process.
General Comments
The Network provides brief answers to the questions
raised in the Federal Register notice after our general
comments on this issue.
The genesis of this current effort evolved from concerns
raised by one specific type of test conducted by
pesticide registrants or similar “third
parties”: human studies conducted by manufacturers
after the passage of the Food Quality Protection Act
(FQPA) in 1996. These studies involved dosing people
orally with organophosphate pesticides to determine acute
“no effect” levels (herein called HOPT, or
human oral pesticide toxicity studies). The joint SAB/SAP
panel whose recommendation was misrepresented in the
Federal Register, as described above, focused on this
category of “study.”
As the Federal Register notice states, “EPA is now
interested in addressing these issues more broadly, and
in all Agency programs.” The Network commends EPA
for seeking Agency-wide guidance. Protection of human
subjects and support of ethically- and
scientifically-conducted studies should be an Agency-wide
goal and standard and the Network strongly supports the
adoption of rigorous standards regarding tests involving
human subjects.
The Agency considers many types of studies, including
some studies required as part of the “Occupational
and Residential Exposure” pesticide test guidelines.
These contain requirements for biological monitoring of
pesticide exposures to workers exposed as applicators and
in post-application work situations. These studies as
well as epidemiology studies that might be considered by
the Agency are in a different category than the HOPT
studies, in that they were assessing exposures and health
impacts among people who already were exposed in order to
determine the need for additional protections. While a
strong agreement exists that no regulatory testing of
pesticides should ever be conducted on children (unlike
pharmaceuticals), children might well be subjects of
epidemiological investigations to monitor exposures and
effects of pesticides. All of these studies are
scientifically and ethically different than the HOPT
studies.
Though the Agency is developing standards for all
programs, the critical issue at this time remains the
HOPT study. The Network believes that, whether under
either a general Agency-wide standard that considers all
types of studies or under criteria focused solely on this
single category of study, no genuinely ethical or
scientific yardstick would allow such studies to be
submitted and considered by the Agency. No matter the
lens through which these HOPT studies are scrutinized,
every facet of review would lead to the same conclusion:
they are scientifically invalid, they are unneeded and
thus, they are a priori unethical.
Specifically regarding the HOPT-type studies, two
categories of “acute” hazard are at issue. One
is the issue of acute systemic toxicity, such as occurs
when there is a sufficient level of inhibition of the
enzyme acetyl cholinesterase (ACHE). In defining what
level of such inhibition is an “effect” versus
an “adverse effect,” the Network believes these
effects, if measurable, should be presumed to be adverse,
at least to those in the population who are most
susceptible. Even for assessment of this type of acute
toxicity -- toxicity to adults -- the HOPT studies are
inappropriate. They have been typically conducted on a
small group of 10-50 healthy adult male volunteers and
are not superior to similar data generated from animal
testing. In fact, one could easily imagine a strong
participation bias acting here by which men who are
healthier and who are less susceptible to the ACHE
inhibition effect volunteer repeatedly for these tests
whereas those who have more adverse effects do not.
The second category of acute hazard is disruption of
normal developmental processes in utero and in early
stages of life. These effects are acute effects because
typically they can occur only during relatively brief
“windows of vulnerability” that occur during
unique developmental processes. History is replete with
examples of errors that have occurred when we have
attempted to treat children as if they were merely small
adults. Indeed, it is likely that the presence in the
brain of a developing fetus of a xenobiotic substance
such as an organophosphate insecticide would confer a
unique set of hazards. Laboratory researchers have found
that certain organophosphate pesticides are associated
with changes in DNA expression in the brains of rodents
in utero, and other profound biological changes, even at
levels below those that result in measurable changes in
the activity of acetyl cholinesterase. Thus, the
mechanisms of action for developmental toxicity may be
unrelated to those causing toxicity in adults. This is a
basic fallacy of relying on HOPT studies to better
address risks to humans. Such tests will not generate
developmental neurotoxicity data. If the Agency is most
interested in the developmental toxicity to the fetus,
and we would argue that is indeed the case, then the
highest quality data are from animal studies. As the
National Academy of Science noted in its 1993 report,
Pesticides in the Diets of Infants and Children, data
derived from experiments conducted on human adults can
not be assumed to be valid indicators of a
chemical’s toxicity to the fetus, infant or young
child. Since human oral pesticide toxicity tests cannot
provide information on developmental toxicity to the
fetus, they are unnecessary.
The Network has concluded that HOPT testing does not
conform to the Declaration of Helsinki principles. First,
according to the Declaration:
“The primary purpose of medical research involving
human subjects is to improve prophylactic, diagnostic and
therapeutic procedures and the understanding of the
aetiology and pathogenesis of disease.”
Obviously, testing ACHE inhibiting pesticides to
determine LOEL/LOAELs does not fall under that statement
of purpose. Second, the Declaration states:
“Medical research involving human subjects should
only be conducted if the importance of the objective
outweighs the inherent risks and burdens to the subject.
This is especially important when the human subjects are
healthy volunteers.”
This criterion also is not met by HOPT testing, given the
marginal to zero benefit of the information in terms of
its ability to predict risks to children. Thus, these
HOPT tests are clearly unacceptable under any ethical
framework adopted by the EPA.
Additionally, of the Agency’s 49 test guidelines for
pesticides on human health, not a single test standard
includes oral challenge to determine acute toxicity
thresholds. Nor has the Agency ever initiated a process
to develop such guidelines. While the Agency has
requested that companies go beyond the routine testing to
generate additional data in many, many instances, we are
unaware of a single instance when EPA requested that a
registrant do such a HOPT test, to fill an information
gap in the EPA’s risk assessment process. No nation
requires such testing as part of its pesticide
registration process. Clearly, no requirement human oral
pesticide toxicity studies has been identified by
experts. As a result, the testing that has been conducted
has been a hodgepodge of study designs and the companies
have been allowed to define “adverse effect”
among their test subjects in any way they have pleased.
The result has been “negative” studies in which
subjects were terminated because of symptoms or ACHE
depression, in which there was prolonged ACHE depression,
and so forth. By failing to regulate these studies out of
existence, the EPA has invited a situation where there is
a not only a breach of human rights but also an
opportunity for companies to use these ill-gotten gains
as a means of misleading farmers and the public about
pesticide risks.
Our views in this regards are supported by a clear
consensus by the SAB/SAP panel that was convened to
advise the EPA on this issue. In addition to the comments
from the panel report that we have cited above, the panel
stated that:
“Any policy adopted by the Agency must reflect a
special concern for the interests of vulnerable
populations, such as fetuses, children, adolescents,
pregnant women, . . .”
“. . . we believe that they (pregnant women) should
be excluded from clinical studies with pesticides, as
should all other sensitive subpopulations such as the
elderly, those with already compromised health, children,
and adolescents.”
“The most serious problem of those identified above
is that of generating data applicable to the developing
child (or fetus). There seems little probability that
high quality data relevant to children can be derived
from studies on adults at this time, or in the
foreseeable future. The Subcommittee rules out the only
alternative, the testing of children and adolescents, as
being ethically unacceptable. There are too many unknown
dangers to justify the effort, even under the most
extraordinary circumstances.
“Though the Subcommittee opposes the use of children
and adolescents as experimental subjects particularly in
relation to intentional exposure to toxic agents, it also
supports the concept that the relevance of studies to
assessing the risk to children should be specifically
addressed. Special concerns were expressed that risks to
developing organ systems might be less reversible than to
mature systems and that the risk to children is
unacceptable. This concern also would affect the
potential ability to generalize from adult subjects to
children.”
Yet the Network believes that even these statements fall
short. The Network agrees with the panel’s minority
report that the report does not go far enough to protect
children, including:
“The applicability of adult studies to
children’s safety is nowhere mentioned in the draft.
The Draft acknowledges the enhanced vulnerability of
children as a reason to exclude them from dosing. If
children are different, then what information can adult
dosing provide that is of use to set FQPA standards for
protecting children?
“. . .children will be placed at higher risk of
exposure to neurotoxic pesticides if this is allowed to
become part of EPA’s pesticide policy.”
Given that Executive Order 13045, “Protection of
Children from Environmental Health Risks and Safety
Risks,” and other policies require the Agency to
specifically consider environmental health or safety
effects on children, clearly any Agency policy on this
topic must be even more protective of children than that
recommended in the SAB/SAP report.
In summary, for a solid framework for the Agency’s
standards and criteria, the Network urges the Agency to
follow these broad principles:
Children
should not be subjects of studies involving
intentional dosing.
Conducting
HOPT-type studies in adult volunteers provides
limited or no information that protects children.
The Agency cannot assume that such tests are
going to prove protective of children.
HOPT
studies are not ethical in that they serve no
purpose in improving our ability to diagnose,
treat, or understand the etiology of disease nor
do they provide information sufficient to
overcome the risks to individual subjects.
Any
policy adopted by the Agency should reflect the
highest standards of respect for human subjects
and should prohibit research protocols that
override the interests of subjects in order to
obtain useful data.
Any
policy adopted by the Agency must reflect a
special concern for the interests of vulnerable
populations, such as fetuses, children,
adolescents, pregnant women, the elderly, and
those with fragile health due to compromised
respiratory function or other reasons.
In
no case should developing humans (i.e., the
fetus, infant, young children, or adolescents) be
exposed to toxic chemicals. There are currently
too many unknown dangers to justify such studies,
even under the most extraordinary circumstances.
Bad
science is always unethical; research protocols
that are fundamentally flawed, such as those with
sample sizes inadequate to support reasonable
inferences about the matter in question, are
unjustifiable.
The
EPA should take whatever administrative action is
necessary to extend the protections of 40 CFR
Part 26 to all human research activities whose
results will be submitted to the Agency.
If
it can be justified at all to expose human
subjects intentionally to toxic substances, the
threshold of justification for such action should
be very high. Pesticide exposure to human
subjects must be approached with the greatest
degree of caution. If studies are to be accepted
by the Agency, the Agency has the obligation to
assure that the studies have been conducted with
the very highest of scientific and ethical
standards. If the EPA scientists feel certain
studies are needed for risk assessment, then EPA
should provide guidance for how they are done. If
they are not needed for risk assessment, then, a
priori, they are not justified.
In
considering research protocols, it is not enough
to determine a risk/benefit ratio; it is
important also to consider the distribution of
risks and of benefits, and to ensure that risks
are not imposed on one population for the sake of
benefits to be enjoyed by another. It is also
important to be sensitive to the difference
between a reversible risk and one that may be
irreversible, such as possible interference with
normal neurological development.
The Network
urges the Agency to adopt and expand Food and Drug
Administration’s (FDA) policy with respect to use of
human data for regulatory purposes. We believe the FDA
policy provides a number of safeguards and the experience
of the FDA is instructive. In 1980, 1981, and in 1996 the
FDA issued regulations in this area (21 CFR Part 50)
which provide clear and enforceable requirements for
informed consent of human subjects in any studies that
are submitted to the FDA for regulatory approval of
products. Likewise, in 1981 and in 1991, the FDA issued
regulations related to requirements for Institutional
Review Boards for such studies (21 CFR Part 56). The FDA
also has issued regulations on the use of foreign
clinical studies. These regulations require that the
studies conform to whichever of the following provides
greater protection of the human subjects: the Declaration
of Helsinki or the laws and regulations of the country.
Additionally and critically, a mechanism for the
administration and enforcement of these standards must be
established. The Agency must be held to the highest
standards in meeting its responsibilities under these
standards. For studies that are submitted to EPA for
regulatory or risk assessment purposes, the Agency should
establish a stronger locus of control for this issue,
such as within its Office of General Counsel, and staffed
by fulltime individuals whose duties address exclusively
compliance oversight. EPA’s science staff,
enforcement office, and possibly the international
office, need to be involved as well, given the complexity
of assuring that any regulations in this area are
followed (especially when studies are conducted in other
countries). EPA needs to budget for the inspection of
laboratories that conduct human research for the purpose
of product registration, to assure the complete integrity
of the process. (Pesticide testing laboratories have been
caught in acts of wholesale falsification of test data
submitted for pesticide registrations. ) If the Agency
determines it will accept third-party studies conducted
outside of the U.S., it must be prepared to grapple with
the challenges of overseas studies. The Network is deeply
concerned that such tests may be performed in other
nations precisely because research oversight and human
protections can be lax and financial inducements to
potential subjects that may be minimal in the U.S. can be
far more coercive. The Network does not believe the
Agency currently has the ability to oversee such studies,
creating an inherent danger by using data obtained out of
the country, particularly in developing countries.
The Agency needs also to sever this issue from the issue
of the management of the protection of human subjects in
its own research and in the research carried out in its
own laboratories or funded by its extramural research
program. It needs to strengthen its own internal
processes of informed consent and Institutional Review,
establish a strong central office within its Office of
Research and Development to enforce this process, and
invest in individual training of all of its research
program staff (including staff within program offices who
fund research) to elevate and strengthen the protections
it provides. At the EPA, as elsewhere, no one should be
allowed to be involved with funding or conduct of human
research unless they have completed a course in research
ethics. To our knowledge, this is not a requirement at
the EPA at this time.
Comments on Specific EPA Questions
1. Applicability of existing standards—a. Is it
appropriate to use a standard intended to guide the
conduct of research (e.g., the Common Rule, Declaration
of Helsinki, or the Nuremberg Code) to assess the
acceptability for review of completed research?
Yes. Obviously the Agency should not be using data from
unethically conducted studies. Utilizing data from past
experiments that don’t meet today’s ethical
standards would require a thorough ethics review and
quite possibly such data would not be usable, which would
most appropriate. In the late 1980s, 22 of EPA’s own
scientists filed a petition to request that then-EPA
Administrator Lee Thomas not utilize an experiment
conducted in a Nazi concentration camp as a basis for the
regulation of phosgene as a toxic air contaminant
(Science Magazine, April 1, 1988). At that time, EPA
withdrew the assessment on the basis of ethical
considerations.
The 1998 SAB/SAP ethics review identified that at a
minimum studies need to meet U.S. ethical standards of
their time, regardless of where they are conducted. The
EPA needs to write a regulation that clarifies how it
will assure (and enforce) that the studies it uses meet
ethical standards.
b. Is it appropriate to use a standard intended to guide
the conduct of therapeutic or diagnostic medical research
or to clarify causes of disease, such as the Declaration
of Helsinki, to assess the acceptability for review of
other kinds of research without diagnostic or therapeutic
intent, conducted with healthy subjects?
This question demonstrates the extent to which the EPA is
confused about this issue. The Declaration of Helsinki
clearly states that such research is either for the
purpose of improvement of diagnosis and treatment or for
broadening the understanding of health and disease.
Studies such as the HOPT or similarly ill-conceived
studies should not be submitted under the Declaration of
Helsinki, not only because they are performed solely for
the purpose of meeting a narrow commercial interest (that
is completely unrelated to human health and wellbeing)
but also because they do not meet even the basic
requirements that a study be scientifically valid and
have adequate statistical power.
c. Should the Agency apply the same standard of
acceptability independent of the type of substance tested
(e.g., pharmaceutical, pesticide, pathogen, or
environmental contaminant)? If not, how might differing
standards be applied when a single substance has multiple
uses, e.g., as both a pesticide and a drug?
These are four very different circumstances and it is
critical that the EPA disentangle them. There is a wide
gap between pharmaceutical testing, where the substance
tested is reasonably expected to provide a human health
benefit, and where the FDA requires Phase I clinical
trials, versus a pesticide, where there is no health
benefit and EPA has no such requirement. It is
unconscionable and unethical to dose humans with
substances designed to be toxic with no conceivable
benefit to the subject for the purpose of being able to
expand the market for such a substance by attempting to
eliminate or lessen regulatory safety margins.
As for testing of pathogens and environmental
contaminants, like any study these would need to pass
muster of individual Institutional Review Boards. We
would not ban them across the board because quite
possibly such studies could expand knowledge about the
diagnosis or treatment of diseases or causes of diseases
or ill health.
d. Does it matter who maintains a standard, or by what
process it is maintained? For example, would it be
appropriate for EPA to accept and apply a standard
maintained by a private, non-governmental organization,
as is the Declaration of Helsinki?
It is surprising that the EPA is asking this question.
The Declaration of Helsinki has been adopted by the World
Medical Association; the U.S. member of this association
is the American Medical Association. Thus, medical
practitioners are ethically bound this document just as
attorneys must follow the ethical guidelines of the
American Bar Association. The Common Rule incorporates
the Declaration of Helsinki in consideration of ethics of
research conducted outside of the U.S. Moreover, the FDA
has elected to explicitly incorporate the principles of
the Declaration of Helsinki into its regulations in Sec.
312.120(c)(4), which it utilizes as follows:
TITLE 21. CHAPTER I. PART 312. --INVESTIGATIONAL NEW DRUG
APPLICATION Subpart F--Miscellaneous
Sec. 312.120 (c) Conformance with ethical principles.
(1) Foreign clinical research is required to have been
conducted in accordance with the ethical principles
stated in the “Declaration of Helsinki” (see
paragraph (c)(4) of this section) or the laws and
regulations of the country in which the research was
conducted, whichever represents the greater protection of
the individual.
(2) For each foreign clinical study submitted under this
section, the sponsor shall explain how the research
conformed to the ethical principles contained in the
“Declaration of Helsinki” or the foreign
country’s standards, whichever were used. If the
foreign country’s standards were used, the sponsor
shall explain in detail how those standards differ from
the “Declaration of Helsinki” and how they
offer greater protection
The primary questions for the Agency are: why would it be
appropriate for the EPA to be less protective with
respect to human studies on pesticides than the FDA is
for studies regarding drugs and therapeutic devices?
Should physicians disregard the ethical standards of
their profession when it comes to the conduct of human
studies for pesticides? Would it be appropriate for
anyone other than a physician to conduct such
investigations? Also, the EPA should ask itself, what
makes sense, in the context of regulating multinational
companies? The Declaration of Helsinki applies to nearly
every medical professional body in the world and thus
represents a harmonized set of ethical guidelines for
medical professionals that they themselves developed.
It only makes sense that the EPA (like FDA) would utilize
these as a framework for assuring that pesticide human
studies conducted outside the U.S. (and therefore outside
of U.S. laws) meet high ethical standards. Moreover, such
researchers often already are making efforts to comply
with FDA guidelines, since many of the same laboratories
handle both pesticides and pharmaceuticals. Ultimately,
the EPA should be asking which standards are most
protective of test subjects and most appropriate for the
Agency, rather than expecting that the medical profession
will adopt a lower standard for pesticides. EPA’s
considerations of which standard to apply should consider
first the protections offered test subjects and second
EPA’s ability to administer the application of the
standard in a manner that is fair and equitable.
e. Should the Agency extend the requirements of the
Common Rule to the conduct of third-party research with
human subjects intended for submission to EPA?
Yes. We agree strongly with the recommendation made in
1998 by the EPA’s own SAB/SAP advisory panel which
the Agency has not yet adopted: “The EPA should take
whatever administrative action is necessary to extend the
protections of 40 CFR Part 26 [the Common Rule] to all
human research activities whose results will be submitted
to the Agency.” (p. 3 and p. 39 of the report). We
point to the precedent in the FDA for formally doing so,
including research conducted in other countries.
What are the advantages and disadvantages of conducting a
rulemaking or undertaking other Agency action for this
purpose alone?
We see only clear advantages in fulfilling the
Agency’s responsibility to the protection of human
rights by making clear to all parties how it will extend
these protections to human test subjects. The
disadvantage in undertaking rulemaking is the time that
would be required to finalize such a rule. In the
interim, the EPA will need to rely on its policy-making
apparatus to achieve this goal. When it comes to
pesticides, this could be done via a PR (Pesticide
Registration) notice that would be replaced when a final
rule is put in place.
2. Should the standard of acceptability vary depending on
the research design?—
This question is oddly phrased, such that it doesn’t
have a “yes” or “no” answer. Do
standards of acceptability vary? No. The standards of
acceptability for studies do not “vary depending on
the research design.” The problem facing the EPA is
not that it is difficult to identify what these standards
are, or should be, but the woeful failure of the EPA to
identify these standards, communicate them clearly,
implement them, and enforce them. Is research design
among the standards of acceptability? Yes. It is a
fundamental ethical principle in all standards that have
been developed that no research should be conducted on
humans if it is of questionable scientific value. We have
suggested that there is one category of study, human
dosing with ACHE pesticides to determine NOEL/NOAELs,
that is unacceptable as a category, because it is of
limited scientific value and provides no information
relevant to diagnosis and treatment of disease, or
improvement of human health.
a. Should the Agency apply the same standard of
acceptability independent of whether the research design
involves intentional exposure? For example, should the
same standard apply to research involving intentional
exposures to human subjects, to research designed to
follow-up accidental exposure, and to studies of
individuals occupationally or incidentally exposed?
Once again the EPA is asking the wrong question.
Intentionality of exposure is not the issue. The issue is
the intent of the research. Is it intended to improve our
ability to diagnose or treat disease? Will it illuminate
issues regarding causes of disease or improvement of
health? Within the category of studies that would provide
real human health benefits, some might utilize
intentional exposures, others might not. For such
studies, the Institutional Review Board would need to
take a very careful look at the risks to such subjects to
assure that the benefits outweigh the risk, that subjects
are very carefully monitored, and so forth. In other
words, such a study would need to receive a very careful
review yet might be the only way to gain valuable
information for public health. As the SAB/SAP panel
recommended: “Unintended exposures provide valuable
opportunities for research; it is an error not to take
full advantage of such opportunities to gain major
information through careful incident follow-up.”
b. Should the Agency apply the same standard of
acceptability independent of the level of exposure of the
human subjects? For example, does it matter if the level
of exposure to a chemical is below the Reference Dose or
other established health standard designed to protect the
general public? Should the same standard apply if
intentional exposure to an environmental pollutant occurs
at ambient levels, or at elevated levels? If research
involves intentional exposure to a pesticide, does it
matter if exposure results from use of the pesticide in
conformity with approved label directions?
Certainly, any study that is conducted with the intention
of poisoning subjects, or otherwise making them ill,
should be viewed differently than a study conducted at
levels that are well below such levels. However, the
Agency needs to be very cautious about using the
substance’s Reference Dose or other established
health standard as an automatic assurance that lower
exposures would be of no concern. As the Agency well
knows, the Reference Dose derived from animal tests may
or may not be protective of all humans in the population
and certainly is not protective when we have less than
perfect knowledge of the toxicology of a substance. In
other words, such studies must be approached with great
caution and only under the strictest regulatory
supervision. This is especially the case if such studies
were to involve children, pregnant women, poor minority
groups, prisoners, the elderly, or other vulnerable
populations.
c. Should the Agency apply the same standard of
acceptability independent of the pathway of exposure? For
example, should the same standard apply when exposure is
oral, or dermal, or by inhalation?
Yes. It is difficult to understand why the Agency would
even consider this as a question. The route of entry of
the substance into the body is not the point.
d. Should the Agency apply the same standard of
acceptability independent of the effects being evaluated?
For example, should the same standard apply to a study
measuring transitory changes in blood chemistry or levels
of a substance in urine that applies to studies measuring
longer-lasting changes? Should the same standard apply to
a study of localized skin irritation that applies to a
study of systemic dermal toxicity? Should the same
standard apply to studies measuring organoleptic effects,
such as taste or smell, that applies to studies of toxic
effects? Should the same standard apply to measurements
of toxic effects and to measurements through genomic or
proteomic assessments?
Again, we have stated that a certain category of studies,
the HOPT studies should be banned. The reason for our
concern does have to do with the fact that this is
deliberate dosing to elicit systemic neurotoxicity. In
terms of other studies, we certainly think that a common
set of ethical standards should apply. It would be up to
the Institutional Review Board to grapple with the issues
such as the nature of the effects, whether the effect is
reversible or irreversible, and how the effect is
measured. Most daunting is that often we do not yet have
enough information to know if an effect is reversible
until studies are conducted! This means that in addition
to refusing to accept the HOPT studies, we would
recommend that the EPA take a very cautious approach to
requiring or accepting any human dosing studies.
e. Should conduct of research in compliance with the
provisions of the Common Rule or another standard for the
protection of human subjects be accepted as evidence of
its ethical acceptability?
As discussed elsewhere, the Agency has the responsibility
to assure compliance with whatever standard it adopts.
Requiring compliance with the provisions of the Common
Rule is an important first step but is only relevant to
research conducted in the U.S., since researchers in
other countries are not covered by the Common Rule. In
the U.S., allowing the testing entity to self-report
compliance with the Common Rule would not be adequate
assurance of acceptability. The Agency will have to
establish and implement a system for independently
assuring that its standards have been followed. For other
countries, the U.S. needs to require compliance with the
Declaration of Helsinki as well as the domestic laws of
that country. It needs to have a system in place to
assure such compliance, as well.
f. Should the Agency consider whether research has been
performed consistent with an EPA guideline for data
development in determining its acceptability? For
example, EPA has published guidelines for certain kinds
of human studies required for pesticide registration;
should conduct of a required study in compliance with an
EPA guideline be accepted as evidence of its
acceptability?
No. Tests that are developed under EPA Guidelines involve
a public process and extensive review by EPA’s FIFRA
Scientific Advisory Panel. Tests that are required by the
EPA presumably have a key role in EPA’s safety
determinations. But this alone is not a guarantee or
presumption that a test has been conducted ethically or
scientifically. The EPA must have the capability of doing
surveillance and enforcement to assure that the
guidelines have actually been followed, and should not
rely on a paper trail for such assurance.
g. Should the Agency apply the same standard of
acceptability independent of a study's statistical power?
Again, the EPA is asking the wrong question. It should
ask whether statistical power is among the considerations
of whether a study meets scientific criteria for ethical
acceptability. The answer is “yes.” No matter
what the risks to subjects, it is unethical per se to
conduct a study that a priori has inadequate statistical
power or is otherwise a priori not expected to be able to
answer the question under study. As mentioned above, we
believe that the HOPT studies do not address questions
about acute toxicity, nor do they have adequate
statistical power. A study without adequate statistical
power is unacceptable under any standard of research
ethics.
h. Should the Agency apply the same standard of
acceptability whether or not a human study design is able
to measure the same endpoints in humans that have been
observed in animal testing of the same substance? For
example, if the most sensitive adverse effects shown in
animal studies have been detected through
histopathological evaluation of brain tissue, is
subsequent research involving intentional exposure of
human subjects acceptable?
Not necessarily. This consideration would not trump
ethical principles of human research.
i. Should the Agency apply the same standard of
acceptability to intentional dosing studies independent
of whether there are alternative methods of obtaining
data of comparable scientific merit that would not
require deliberate exposure of humans?
This is always a question in considering the ethics of a
human study. As mentioned above, deliberate dosing of
human subjects should be considered to be a last resort
(unless people are already being dosed at such levels on
a regular basis, as explained elsewhere.) Even when a
substance has an anticipated therapeutic benefit, human
dosing should be done only after careful consideration
and a determination that there are no alternative means
to obtain the information that is required. Embedded in
this is the concept of the importance of the information.
Dosing of human subjects with pesticides is not warranted
merely to make small improvements in the level of
precision of a lower effect level, for example. Other
types of studies would require case by case consideration
by Institutional Review Boards to answer this question.
If not, to what extent, if any, should the cost of the
alternate method be a factor?
“Cost savings” cannot make an unethical study
ethical.
j. What special considerations, if any, should the Agency
apply in judging the acceptability of studies when some
or all of the subjects are from populations likely to be
vulnerable to coercion or undue influence, such as
children, prisoners, pregnant women, mentally disabled
persons, or economically or educationally disadvantaged
persons?
All ethical guidelines for research make it clear that
such populations should be avoided whenever possible and
require special protections. As mentioned earlier:
“In no case should developing humans (i.e., the
fetus, infant, young children, or adolescents) be exposed
to toxic chemicals.”
Before any tests on such populations are undertaken,
special care must be taken, especially to involve
ethicists and those who can speak for those populations
and any Institutional Review Board should want to take
special care in the review process.
3. Should the standard of acceptability vary depending on
the provenance of the research?—a. Should the Agency
apply the same standard of acceptability without regard
to who or what organization sponsors or supports the
research? Since 1991, human research conducted or
supported by the U.S. government has been subject to the
Common Rule. Should the same standard apply to research
conducted or supported by others? Should a single
standard apply independent of whether the sponsor is a
commercial enterprise, a non-profit organization, another
government in the United States (such as state, tribal,
or local), or the government in another country? Should
the same standard apply without regard to the test
sponsor's interest in a regulatory matter that could be
affected by EPA's consideration of the data?
The critical issue is whether the research will provide
any benefit in terms of diagnosis, treatment, or health
protection. Generally, as a regulatory agency, EPA must
of course be mindful at all times of the test
sponsors’ interests in performing tests and of
course of the almost overwhelming economic incentives
that companies have to find ways to market more of their
products. However, like all government entities, the EPA
must always assure the protection of human rights as it
fulfills its mission as a regulatory agency protecting
human health and the environment, considering, when
appropriate, economic concerns. This would mean that the
EPA must be very cognizant of who conducted and/or
supported the research and must be prepared to apply
greater scrutiny to tests conducted and/or supported by
those with an economic interest in the results. That is
because there are enormous financial incentives to
economic interests to cut ethical corners (here as well
as in many other areas).
b. Should the Agency apply the same standard of
acceptability independent of who or what organization
conducts the research? For example, a research
organization--public or private--holding a
“Federal-Wide Assurance” from the Department of
Health and Human Services' Office of Human Research
Protections usually promises to comply with the Common
Rule in all its human research.
See above.
Should third-party work conducted by a research
organization holding a Federal-Wide Assurance be assessed
by the same standard that applies to other third-party
human research?
Yes.
c. Should the Agency apply the same standard of
acceptability without regard to where the research was
conducted? For example, does it matter whether research
is conducted entirely in the United States or partially
in the United States? If it is conducted outside the
United States, does it matter in what country it is
conducted? What are the advantages and disadvantages of
judging the acceptability of human studies based on a
single uniform standard versus prevailing local standards
(e.g., in different countries)?
Generally, the same high standards must apply to domestic
as well as internationally-conducted tests. As mentioned
earlier, tests conducted outside of the U.S. place
special challenges on the Agency. Such research will be
very difficult to audit and the EPA needs to budget
adequate resources for inspection to assure that it is
done ethically and properly. As mentioned above, the
Declaration of Helsinki is more applicable than the
Common Rule in international situations.
d. Should the Agency apply the same standard of
acceptability without regard to the reasons the research
was conducted? If not, how might the Agency determine
intent?
The impact of and motivation for tests is not related to
the standards that are applied. However, this issue must
be considered when it comes to the issue of how EPA will
assure that the highest ethical standards have been
applied. As indicated by the HOPT tests that have forced
the EPA to address these concerns, the pressure for
acceptance of these tests comes in large part because of
their presumed regulatory impact. The primary motive of
industry will be to find ways to make regulations more
permissive, so that they can sell more products. This is
as it should be but it is the job of the EPA to assure
that there are strict and clear ethical boundaries that
cannot be breached. This is because the profit motive of
companies is not a benefit that can justify risks to
human volunteers, absent some overriding interest such as
to improve the ability to diagnose or treat disease or to
improve health.
e. Should the Agency apply the same standard of
acceptability to submitted research without regard to who
submitted it? For example, should the same standard apply
to submissions from regulated industry, from public
interest groups, from the public, or from other
governments? Should the Agency apply the same standard of
acceptability independent of whether the study was
submitted voluntarily, or in response to a particular
regulatory requirement of EPA?
All research, submitted voluntarily or as a result of a
requirement, regardless of the submitter, should be
subject to the same strong standard.
f. Should the Agency apply the same standard of
acceptability to human research which is not submitted,
but which the Agency obtains at its own initiative from
the scientific literature or other sources, independent
of how or where EPA obtains it?
Yes, the EPA should also apply a strong ethical standard
to human research obtained at its own initiative.
4. Should the standard of acceptability vary depending on
EPA's potential use of the data?
No. The same standard should apply regardless of how EPA
intends to utilize the data in its regulatory activity.
--a. Should the Agency apply the same standard of
acceptability independent of whether the results of the
study would support a more or less stringent regulatory
position? For example, should the same standard apply
whether the data indicate that the substance tested is
more risky or less risky than is indicated by other
available data?
The same standard applies whether the data indicates the
substance is more or less risky to humans.
b. Should the Agency apply the same standard of
acceptability without regard to how EPA intends to use
the results, e.g., to reduce or remove the traditional
tenfold interspecies uncertainty factor, to provide an
endpoint for use in calculating a Reference Dose or
Reference Concentration for the test substance, to
provide a dose-response function for use in quantitative
risk assessment, or for some other purpose?
The same standard applies whether the Agency is using
data to establish an endpoint, an uncertainty factor, or
for any other regulatory purpose. As mentioned above, we
believe that certain types of tests, such as oral dosing
with ACHE inhibitor pesticides for the purpose of
establishing a NOAEL or a NOEL are unethical and that EPA
should ban their use in regulatory decisions. In
addition, EPA should consider banning any human study
whose object is the reduction of the interspecies
uncertainty factor, for the same reasons that we feel
that the ACHE inhibition studies do not have scientific
merit. For other studies, we believe that Institutional
Review Boards would have to take a careful look at any
proposed design that involves intentional human dosing
with any compound for the purpose of eliminating the
interspecies uncertainty factor, identifying an endpoint
for a reference dose in humans, or to describe a human
dose response function. Any such study is likely to have
unanticipated adverse consequences and, unless there is
some overriding concern having to do with improving our
ability to diagnose or treat disease or to improve
health, these studies may be difficult to justify.
5. Should the standard of acceptability vary depending on
EPA's assessment of the risks and benefits of the
research to the subjects or to society?—
Yes. However, EPA needs to consider not only its point of
view, but also the viewpoints of others. Such others
might include representatives of the general public and
people with specific expertise in areas such as ethics,
medicine, child health, human rights, human research, and
environmental justice. Some of the factors that EPA needs
to consider are: What kinds of incentives are offered to
subjects in these studies? Do they understand that they
are being tested with pesticides or are they told that
the material might be a pharmaceutical? In terms of
benefits to society, these need to be drawn narrowly to
include only research that is likely to improve our
ability to diagnose, prevent, or treat disease, or to
improve health. It is difficult to posit societal
benefits that outweigh the risks of deliberately dosing
human subjects with pesticides at toxic levels.
a. Should the Agency apply a standard of acceptability
based on a comparison of the anticipated benefits of the
research in relation to the risks to human subjects,
provided the risks are minimized and informed consent is
obtained?
A principle of medical ethics is that this weighing of
risks and benefits needs to occur at the level of the
individual, and not at an aggregate, societal level. To
take an extreme example that makes the point, the
possible societal benefits of the Tuskegee experiment did
not justify the pain and suffering to the individuals who
were subjects in that experiment. Thus, the SAB/SAP panel
recommended: “In considering research protocols, it
is not enough to determine a risk/benefit ratio; it is
important also to consider the distribution of risks and
of benefits, and to ensure that risks are not imposed on
one population for the sake of benefits to be enjoyed by
another.”
The SAB/SAP committee also commented: “If the use of
human subjects in pesticide testing can be justified,
that justification cannot be to facilitate the interests
of industry or of agriculture, but only to better
safeguard the public health.” We would agree and
would further assert that there would be very few
instances in which the dosing of a human subject with a
toxicant or potential toxicant would be justified.
b. Should the Agency independently assess the risks of
the research to the subjects and the benefits of the
research to the research subjects or to society, or
should it defer to the judgment of Institutional Review
Boards or similar oversight panels?
The Agency cannot assume that IRBs or other oversight
panels will do their job correctly all of the time. EPA
must hold companies who develop and present such research
accountable for assuring that the IRBs have actually
applied the standard it establishes and that submitted
research meets this standard. It cannot delegate this
responsibility to others or assume that, because there is
a paper trail, all is well. That being said, EPA should
not attempt to recreate the effort of the IRBs, nor
should the EPA run all of the research through its own
IRB. Rather, EPA needs to find an approach that will set
high standards and hold others accountable to those
standards.
c. If EPA were to assess independently the risks and
benefits of human research, on what range of information
should it base its assessment? How might EPA obtain
information relevant to such an assessment?
As noted above, we are not advocating for EPA running all
of the research through its own IRB. Rather, EPA needs a
process to enforce whatever regulations it puts into
place. What we would recommend is that following the
development of regulations (or perhaps initially
Pesticide Registration Notices), EPA would put forth
guidelines to industry clearly outlining its expectations
for compliance with ethical guidelines. It would then
develop enforcement policies and a trained staff of
investigators who can assure that the guidelines have
been followed. At a minimum, such a procedure needs to
assure that the only benefits considered had to do with
human health and not company return on investment. It
needs to assure that the full array of risks were
assessed and further that there was integrity of the
informed consent process and implementation of any IRB
recommendations.
6. How should the Agency implement standards of
acceptability?
The Network believes that the FDA’s regulations and
regulatory guidance in this regard should be the starting
point for considering how EPA can address this question.
The FDA standards should be viewed as a starting point,
since it makes sense to have stronger standards for
pesticides and industrial chemicals than for drugs and
medical devices (which a priori involve possible
therapeutic improvements for illnesses.) One possible
weakness of the FDA regime may be its capacity to
actually enforce its regulations, particularly in
international labs. This means that the EPA must draft
regulations and must fund inspection and enforcement
activities; otherwise it has no basis on which to enforce
the compliance with such standards. These standards and
procedures should include transparency to the public and
reviews independent of the Agency.
If the Agency is unable or unwilling to dedicate the
resources necessary to assure compliance with appropriate
standards for a class of tests, the Agency should
promptly and visibly declare that to be the case. In that
case, the Agency should have a moratorium on the
acceptance of human studies, to remove the incentive for
third parties to conduct and submit such tests, in the
absence of protections for the wellbeing of the subjects
of such experiments. If the Agency and Congress feel that
there is a public interest that warrants the time and
effort of EPA staff to consider such data, then it needs
to appropriate funds to assure protection of human
subjects as well.
a. To what extent and how should the submitter of
research with human subjects to EPA be required to
document or otherwise demonstrate compliance with
appropriate standards for the protection of human
research subjects, e.g., fully informed and fully
voluntary participation, and independent oversight of
research design and conduct by an Institutional Review
Board or comparable entity?
See above. EPA needs to issue guidelines to third parties
laying out the required documentation. EPA needs to use
its inspection and enforcement authority to make sure
that the documentation is accurate.
b. How should the Agency determine compliance with an
appropriate standard for human research data which is not
submitted, but which it obtains from the scientific
literature or other sources?
If such information is not described in research
articles, EPA should contact investigators and research
institutions to assure that indeed appropriate efforts
were made to protect human subjects. EPA will need to
develop guidelines and procedures to assure that it can
carry this out in an efficient manner. It also will need
to create an independent, adequately funded office within
its Office of General Counsel whose job it is to assure
that programs implement these procedures properly.
c. To what extent should new standards be applied to
research which has already been conducted, or is
underway? Should a different standard be applied to such
research? Does fairness require a period of transition to
any new rule or standards of acceptability, or do other
considerations override that factor?
What is relevant is the prevalent ethical standards at
the time of conduct of the study, not when the EPA issues
a policy. The reason EPA needs to make a clear statement
of policy is so that everyone understands what behaviors
are expected and to assure that companies will uphold the
same standards of ethics for human studies, regardless of
where in the world they are conducted.
EPA should not accept any such data until the Agency has
established clear policy to assure ethical conduct and it
should advise industry that any studies that are
conducted prior to issuance of such a policy are likely
to be rejected. EPA should not take a “case by
case” approach which could result in arbitrary and
inconsistent decisions in these matters.
In certain extreme cases, for example, the concentration
camp experiments conducted by Nazi scientists, or, closer
to home, radiation experiments by the U.S. government
several decades ago, it has been recognized that there is
a category of research that may have been believed
ethical years ago, but is so abhorrent that the use of
the data today is very controversial. The EPA needs to be
sensitive to these issues and, if and when it is ever
confronted with such data, may need to assemble a special
ethics panel to advise it on whether the data are
appropriate for any use today.
d. Should the Agency apply the same standard of
acceptability to research already submitted to or
obtained by EPA and to research newly submitted to or
obtained by EPA? Does it matter if the submitted research
was conducted for the specific regulatory purpose at hand
or for other purposes (even though the study was
conducted after EPA issued a policy on human testing)?
Does fairness require a period of transition to any new
rule or standards of acceptability, or do other
considerations override that factor?
The Agency should apply the same standard of
acceptability to research already submitted as to
research newly submitted. It is not relevant ethically
whether the research was conducted for the regulatory
purpose or another purpose. Fairness to human subjects
requires that there would be no transition and that EPA
would as quickly as possible take steps to protect their
welfare.
Conclusion
This is an issue of great import that calls for prompt
and protective Agency action. We share the general
concerns that were raised repeatedly at the joint SAB/SAP
December 1998 meeting about the ethical, moral and
scientific implications of the human testing of
pesticides. The EPA should not have allowed the situation
where on one hand it has no policies or oversight system
to protect human subjects in tests (theoretically
discouraging such tests on humans), while on the other
hand accepting such experimental studies when submitted
in the course of pesticide regulation.
We are disappointed that so little has been done by the
EPA since 1998 to address the situation.
However, we were heartened by the Agency’s
moratorium on the acceptance of such experimental tests
and by its intention to establish standards and
guidelines on tests involving human subjects. This at
least has delivered the message that the EPA is taking
the issue seriously.
The adoption of standards which do not adequately assure
ethically and scientifically valid tests and which do not
protect human health would not be an improvement of this
sad situation.
Thus, in brief:
EPA
needs to adopt strong and enforceable standards
with regards to all regulatory data submissions
for human testing of pesticides and other
chemicals. It should follow FDA’s lead and
promulgate enforceable regulations for third
parties that clearly articulate policies and
expectations. These comments have highlighted
some key principles that should form the
foundation of these standards, as well as
provided direction on some specific Agency
questions.
The
Agency needs to delegate the responsibility for
this task to one strong central authority, such
as the Office of General Counsel, and provide
adequate resources and training for this effort.
This includes cleaning its house with regards to
its own internally conducted and funded research
to train its scientists and to assure that the
highest ethical standards are followed there as
well.
These
efforts must move forward with alacrity.
In addition,
the EPA must, immediately, issue a supplemental notice to
correct the record regarding its misrepresentation of the
conclusions of the SAB/SAP Data from Testing of Human
Subjects Subcommittee (DTHSS) advisory committee. Such
false and misleading statements at best create confusion
among those who would seek to contribute to EPA’s
rulemaking process, and at worst convey the impression
that the EPA has already concluded that it will ignore
the input of its own scientific advisors.
The Network thanks you for your consideration of these
vital issues.
Sincerely,
Lynn Goldman, MD, MPH, Chair, Board of Directors
Daniel Swartz, Executive Director
Cc: Marianne Lamont Horinko, Acting EPA Administrator
Joanne Rodman, Associate Director, OCHP
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