[Federal Register Volume 76, Number 54 (Monday, March 21, 2011)]
[Proposed Rules]
[Pages 15268-15275]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-6329]
[[Page 15268]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
42 CFR Part 81
[Docket Number NIOSH-209]
RIN 0920-AA39
Guidelines for Determining Probability of Causation Under the
Energy Employees Occupational Illness Compensation Program Act of 2000;
Revision of Guidelines on Non-Radiogenic Cancers
AGENCY: National Institute for Occupational Safety and Health, Centers
for Disease Control and Prevention, DHHS.
ACTION: Notice of proposed rulemaking.
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SUMMARY: The Department of Health and Human Services (HHS) is proposing
to treat chronic lymphocytic leukemia (CLL) as a radiogenic cancer
under the Energy Employees Occupational Illness Compensation Program
Act of 2000 (EEOICPA). Under current guidelines HHS promulgated as
regulations in 2002, all types of cancers except for CLL are treated as
being potentially caused by radiation and hence as potentially
compensable under EEOICPA. HHS proposes to reverse its decision to
exclude CLL from such treatment.
DATES: The Department invites written comments on this Notice of
Proposed Rulemaking from interested parties. Comments must be received
by June 20, 2011.
ADDRESSES: You may submit comments, identified by ``RIN 0920-AA39,'' by
any of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
E-mail: NIOSH Docket Officer, [email protected]. Include
``RIN 0920-AA39'' and ``42 CFR 81.30'' in the subject line of the
message.
Mail: NIOSH Docket Office, Robert A. Taft Laboratories,
MS-C34, 4676 Columbia Parkway, Cincinnati, OH 45226.
Instructions: All submissions received must include the agency name
and docket number or Regulatory Information Number (RIN) for this
rulemaking. All comments will be posted without change to http://www.regulations.gov and http://www.cdc.gov/niosh/docket/archive/docket209.html, including any personal information provided. For
detailed instructions on submitting comments and additional information
on the rulemaking process, see the ``Public Participation'' heading of
the SUPPLEMENTARY INFORMATION section of this document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.regulations.gov or http://www.cdc.gov/niosh/docket/archive/docket209.html.
FOR FURTHER INFORMATION CONTACT: Stuart Hinnefeld, Director, Division
of Compensation Analysis and Support,\1\ National Institute for
Occupational Safety and Health (NIOSH), 4676 Columbia Parkway, MS-C46,
Cincinnati, OH 45226, Telephone 513-533-6800 (this is not a toll-free
number). Information requests can also be submitted by e-mail to
[email protected].
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\1\ The name of the NIOSH Office of Compensation Analysis and
Support (OCAS) was changed to the Division of Compensation Analysis
and Support (DCAS) in March 2010.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Public Participation
II. Background
A. Introduction
B. NIOSH Reconsideration of CLL Basis for Reconsideration Risk
Model
C. Purpose of the Rule
D. Technical Review by the Advisory Board on Radiation and
Worker Health
III. Summary of Proposed Rule
IV. Regulatory Assessment Requirements
A. Executive Order 12866
B. Regulatory Flexibility Act
C. Paperwork Reduction Act
D. Small Business Regulatory Enforcement Fairness Act
E. Unfunded Mandates Reform Act of 1995
F. Executive Order 12988 (Civil Justice)
G. Executive Order 13132 (Federalism)
H. Executive Order 13045 (Protection of Children From
Environmental, Health Risks and Safety Risks)
I. Executive Order 13211 (Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution, or Use)
J. Plain Writing Act of 2010
I. Public Participation
Interested persons or organizations are invited to participate in
this rulemaking by submitting written views, arguments,
recommendations, and data. Comments are invited on any topic related to
this proposal. In addition, HHS invites comments specifically on the
following questions related to this rulemaking:
(1) Does epidemiological and other scientific research support
finding that CLL is caused by radiation, and what are the major
limitations of the determination (whether affirmative or negative)?
(2) If CLL were to be covered under EEOICPA, does the risk model
proposed by the National Institute for Occupational Safety and Health
(NIOSH) use the best available science and methodological approaches to
express the dose-response relationship between radiation exposure and
CLL? Does the approach NIOSH is taking in this package appropriately
account for the uncertainty associated with the limited evidence of
radiogenicity? In this context, did NIOSH make use of appropriate
biological and epidemiological information in the development of its
proposed model? If not, please cite specific research studies that
NIOSH should have considered as well as alternative modeling approaches
that could also be considered.
Comments submitted by e-mail or mail should be addressed to the
NIOSH Docket Officer, titled ``NIOSH Docket 209,'' and should
identify the author(s), return address, and a phone number, in case
clarification is needed. Comments can be submitted by e-mail to:
[email protected]. E-mail comments may be provided as e-mail text or
as a file attachment. Printed comments can be sent to the NIOSH Docket
Office at the address above. All communications received on or before
the closing date for comments will be fully considered by HHS.
All comments submitted will be available for examination in the
rule docket (a publicly available repository of the documents
associated with the rulemaking) both before and after the closing date
for comments. A complete electronic docket containing all comments
submitted will be available at http://www.cdc.gov/niosh/docket/archive/docket209.html and http://www.regulations.gov, or comments will be
available in hard-copy by request. NIOSH includes all comments received
without change in the docket, including any personal information
provided.
II. Background
A. Introduction
The Energy Employees Occupational Illness Compensation Program Act
of 2000 (EEOICPA), 42 U.S.C. 7384-7385, established a compensation
program to provide a lump-sum payment of $150,000 and prospective
medical benefits as compensation to covered employees suffering from
designated illnesses incurred as a result of their exposure to
radiation, beryllium, or silica while in the performance of duty for
the Department of Energy (DOE) and certain of its vendors, contractors,
and subcontractors. This legislation also provided for lump-sum
payments for certain survivors of these covered employees.
[[Page 15269]]
Under Executive Order 13179 (``Providing Compensation to America's
Nuclear Weapons Workers''), the Department of Labor (DOL) has primary
responsibility for administering the compensation program. HHS performs
several technical and policymaking roles in support of the DOL program.
One of these is to develop guidelines, by regulation, to be used by DOL
to assess the likelihood that an employee with cancer developed that
cancer as a result of exposure to radiation in performing his or her
duty at a DOE facility or an atomic weapons employer facility. HHS
published a final rule establishing these ``probability of causation''
guidelines on May 2, 2002 (67 FR 22296) under 42 CFR part 81.
The HHS probability of causation guidelines comprise a set of
policies and procedures by which DOL determines whether it is ``at
least as likely as not'' that the cancer of a nuclear weapons employee
was caused by radiation doses the employee incurred while employed at a
facility both involved in the production of nuclear weapons and covered
under EEOICPA. These procedures direct DOL to use one or more
appropriate quantitative risk assessment models to calculate the
probability that a cancer was caused by the relevant radiation doses.
The risk models, originally developed by the National Cancer Institute
(NCI) and again revised by an expert work group, chaired by NCI, in
2002 for use under EEOICPA, are contained within a computer program
called the NIOSH Interactive RadioEpidemiological Program (NIOSH-
IREP).\2\ NIOSH-IREP contains a risk model for every type of cancer
covered by an EEOICPA claim, except for CLL. The guidelines designate
CLL as non-radiogenic, and hence require DOL to assign a probability of
causation value of ``zero.''
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\2\ An interactive version of NIOSH-IREP is available on the
Internet at: https://www.niosh[dash]irep.com/irep--niosh/.
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There were two related scientific reasons for designating CLL as
non-radiogenic at the time the HHS guidelines were promulgated in 2002.
The first was that the epidemiological studies did not demonstrate
radiation as the cause of CLL, a conclusion reached by a number of
expert scientific committees, as well as by NIOSH.\3\ This evidence
included studies of a variety of designs on populations with a variety
of high radiation exposures, including British ankylosing spondylitis
patients treated with x-rays; \4\ U.S., Canadian, and European women
exposed to radiation during treatment for uterine cancer; \5\ nuclear
workers in the United Kingdom and internationally; \6\ and Japanese
atomic bomb survivors from World War II.\7\ No major epidemiological
study as of that date had found a statistically significant increase in
the risk of CLL associated with radiation exposure, let alone a dose-
response relationship.\8\
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\3\ 67 FR 22296, 22302 (May 2, 2002) (codified at 42 CFR part
81).
\4\ Darby SC, Doll R, Gill SK, et al. Long-term mortality after
a single treatment course with X-rays in patients treated for
ankylosing spondylitis. Br. J. Cancer. 1987;55:179-190.
\5\ Curtis RE, Boice JD, Stovall M, et al. Relationship of
leukemia risk to radiation dose following cancer of the uterine
corpus. J. Natl. Cancer Inst. 1994;86:1315-1324.
\6\ Muirhead CR, Goodill AA, Haylock RGE, et al. Occupational
radiation exposure and mortality: second analysis of the National
Registry for Radiation Workers. J. Radiol. Prot. 1999;19:3-26.
Cardis E, Gilbert ES, Carpenter L, et al. Effects of low doses
and low dose rates of external ionizing radiation: cancer mortality
among nuclear industry workers in three countries. Radiat. Res.
1995;142:117-132.
\7\ Preston DL, Kusumi S, Tomonaga M, et al. Cancer incidence in
atomic bomb survivors. Part III: Leukemia, lymphoma and multiple
myeloma, 1950-1987. Radiat. Res. 1994;137:S68-S97.
\8\ A dose-response relationship between radiation and CLL would
be a finding that the incidence of CLL among populations increases
with increases in the amount of radiation dose. With such a
relationship, populations with a moderate amount of radiation dose
would be found to have a moderate frequency of CLL, populations with
a high amount of radiation dose would be found to have a high
frequency of CLL, and populations with a very high amount of
radiation dose would be found to have a very high frequency of CLL.
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The second reason was that, even if NIOSH had determined that CLL
should be treated as radiogenic, NIOSH scientists judged it would not
have been feasible to develop a quantitative risk model, specifying a
dose-response relationship between radiation and CLL, given the
existing scientific evidence at that time. Hence, it was not feasible
to include CLL as a radiogenic cancer under the guidelines.
B. NIOSH Reconsideration of CLL
Basis for Reconsideration
In the original technical documentation for NIOSH-IREP, the
discussion of the rationale for excluding CLL from consideration under
EEOICPA stated that this decision would be revisited as new scientific
information became available. Although HHS received little comment on
the designation of CLL as non-radiogenic during the rulemaking that
established the probability of causation guidelines under EEOICPA,
NIOSH has steadily since heard concerns about this policy decision from
EEOICPA claimants, their representatives, and others.
In response to stakeholder input, the Congressional appropriations
language for fiscal year 2004 directed NIOSH to conduct epidemiological
research and other activities to ``establish the scientific link
between radiation exposure and the occurrence of chronic lymphocytic
leukemia.'' \9\ To this end, a focus on the radiogenicity of CLL was
added to existing research conducted under the NIOSH Occupational
Energy Research Program (OERP). On July 21, 2004, OERP convened a
public meeting, during which a panel of six experts in epidemiologic
and molecular CLL research, unaffiliated with NIOSH, met to: (1)
Discuss available research strategies for investigating the potential
relationship between the incidence of CLL and worker exposures to
ionizing radiation; and (2) identify gaps in current research.\10\ The
consensus among the panelists was that the current scientific evidence
was inconclusive with respect to CLL's association with ionizing
radiation and additional research was required to definitively answer
this question.
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\9\ NIOSH publication 2006-100. Report of the public meeting to
seek input on gaps in chronic lymphocytic leukemia (CLL)
radiogenicity research, held July 21, 2004.
\10\ A summary of the proceedings of this meeting can be found
in: NIOSH Publication 2006-100. Report of the public meeting to seek
input on gaps in chronic lymphocytic leukemia (CLL) radiogenicity
research, held July 21, 2004.
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Subsequent to the July meeting, five additional subject matter
experts unaffiliated with NIOSH were asked by NIOSH's Division of
Compensation Analysis and Support to provide their individual judgments
as to whether
the evidence of an association, or lack thereof, between radiation
exposure and the risk of developing CLL [is] sufficient to continue
to regard CLL as a non-radiogenic cancer and to continue to exclude
it, a priori, from eligibility for compensation under EEOICPA.\11\
\11\ NIOSH, Office of Compensation Analysis and Support (OCAS).
Chronic lymphocytic leukemia (CLL): reconsideration of exclusion
from eligibility for compensation under EEOICPA. 2005. This document
is included in the docket for this rulemaking.
This second round of review was undertaken because the purpose of the
July 2004 expert panel convened by OERP was focused on how to
definitively address the question of radiogenicity, rather than on the
narrower context of the continued exclusion of CLL from consideration
under the unique conditions prescribed under EEOICPA. That is, EEOICPA
requires that consideration be given to the uncertainty associated with
risk models and, in fact, requires that probability of causation (and
hence, the compensation decision) be evaluated at the upper 99th
percentile of the credibility level of the distribution of
[[Page 15270]]
possible outcomes. Because of this, the IREP program was designed to
include cancers whose central estimate of the risk coefficient, while
not statistically significant, may be significantly greater than 1 at
the upper uncertainty limit and thus produce a probability of causation
greater than or equal to 50 percent (i.e., be compensable).
The experts chosen for this review were selected by NIOSH based on
their past experience in the area of radiation epidemiology, with the
goal of obtaining a diverse range of perspectives on the matter. Each
of the five experts consulted posited a scientific opinion about the
weight of the evidence. The full text of these opinions is available in
the docket for this rulemaking.
One reviewer concluded that ``the available evidence is
insufficient to rule out an association between ionizing radiation and
CLL.'' \12\
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\12\ Crowther, MA. Letter to Centers for Disease Control and
Prevention. Report submitted to NIOSH, November 17, 2004. A copy of
this report is available in the docket for this rulemaking.
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A second reviewer found no evidence on epidemiologic grounds to
support the contention that CLL is induced by radiation, stating that:
From the scientific point of view, this evidence could be
interpreted as the absence of a convincing association between
radiation exposure and subsequent CLL. If risks are present, but,
are not identified in epidemiological studies, then they are
certainly much smaller than the risks estimated for other types of
leukemia.\13\
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\13\ Zablotska, L. Comments on the arguments for covering
chronic lymphocytic leukemia under the Energy Employees Occupational
Illness Compensation Program Act of 2000 (EEOICPA) advanced by its
stakeholders in ``Chronic Lymphocytic Leukemia: Reconsideration of
Exclusion from Eligibility for Compensation under EEOICPA.'' Report
submitted to NIOSH, December 16, 2004. A copy of this report is
available in the docket for this rulemaking.
The reviewer did comment, however, that CLL remains one of the most
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controversial issues in radiation epidemiology:
Though in the past it was thought to be definitely non-
radiogenic, recent discoveries, particularly from genetic and
molecular studies, provide evidence that lymphatic cancers may
differ to a great degree from other types of leukemia. If risks are
present, they are probably so small as to render them virtually
undetectable in individual studies under currently available
scientific epidemiological methods.\14\
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\14\ Id.
This reviewer refrained from offering an opinion on whether CLL should
be included in the list of cancers that are potentially compensable
under EEOICPA and concluded ``from an epidemiological point of view it
is not possible to prove that there is no risk of CLL due to
occupational radiation exposure. It is only possible to say that
currently we do not have solid scientific evidence to say that CLL is
radiogenic.'' \15\
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\15\ Id.
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A third reviewer concluded that
In fact, the scientific evidence pertaining to the molecular
mechanisms of CLL induction weighs heavily towards the conclusion
that CLL is similar to other hematological malignancies whose
etiology involves structural changes on the chromosomal level that
cause mutational changes on the molecular level, altering important
cellular functions, and, ultimately, leading to malignant
transformation of a cell. The weight of this scientific evidence is
in support of the conclusion that the somatic mutations that
contribute to the genesis of CLL can be produced by ionizing
radiation exposure.\16\
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\16\ Richardson DB. Chronic lymphocytic leukemia:
Reconsideration of exclusion from eligibility for compensation under
EEOICPA. Report submitted to NIOSH, November 2004. A copy of this
report is available in the docket for this rulemaking.
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He concluded by stating:
Available scientific evidence suggests that CLL incidence will
be increased by exposure to ionizing radiation. Scientific evidence
does not provide a sufficient basis for regarding CLL as non-
radiogenic.\17\
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\17\ Id.
A fourth reviewer concluded his review by stating ``my expert
opinion supports including CLL as a radiogenic cancer and against the
continuing, and it seems to me, arbitrary practice of exclusion.'' \18\
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\18\ Ozonoff, D. Letter to Russell Henshaw, NIOSH, regarding
Reconsideration of CLL. Report submitted to NIOSH, December 1, 2004.
A copy of this report is available in the docket for this
rulemaking.
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A fifth reviewer found that ``[t]he body of scientific evidence
indicates that chronic lymphocytic leukemia (CLL) is not caused by
exposure to ionizing radiation at any level of dose.'' \19\ He
concluded that,
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\19\ Boice, JD. Reconsideration of chronic lymphocytic leukemia
for purposes of compensation. Report submitted to NIOSH, January 7,
2005. A copy of this report is available in the docket for this
rulemaking.
based on epidemiologic studies of radiation finding no evidence for
an association with CLL, coupled with the etiologic and clinical
differences between CLL and the other forms of leukemia that are
caused by radiation, CLL should not be considered a radiation-
inducible cancer.\20\
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\20\ Id.
This reviewer also provided a counterargument to Reviewer 3's
position that the type of genetic damage that may be involved in the
carcinogenesis of CLL, namely deletions of chromosomal material, can be
caused by radiation, which is a known clastogen (an agent that breaks
chromosomes). According to Reviewer 5, other carcinogenic
clastogens besides radiation (e.g., benzene and tobacco smoke) found by
epidemiological studies to cause myeloid leukemia, have also been found
not to cause CLL, and hence proposes that another, unspecified
carcinogenic mechanism must operate for CLL.\21\
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\21\ Id.
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In sum, of the five reviewers, three offered their support for the
consideration of CLL as radiogenic for the purposes of potential
compensation. Three reviewers, Reviewer 1, Reviewer
2, and Reviewer 3, offered the opinion that, while
the evidence presented by the epidemiology studies reviewed in 2002
might not have provided conclusive proof that CLL is caused by ionizing
radiation, genetic studies offer a perspective much different from that
demonstrated by epidemiology studies and should be considered. The only
stated opposition to including CLL came from Reviewer 5, who
recognized that the conclusions reached by NIOSH with regard to other
cancers deemed potentially compensable were based on NIOSH's stated
policy to ``err on the side of the claimant when the state of
scientific knowledge is lacking.'' \22\
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\22\ NIOSH. Charge to reviewers: Chronic lymphocytic leukemia:
reconsideration of exclusion from eligibility for compensation under
EEOICPA. Undated. This document is available in the docket for this
rulemaking.
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Finally, NIOSH asked four subject matter experts to review a 2009
draft report of the CLL risk model. Of those reviewers, two also
provided reviews in 2004 (Reviewers 2 and 3). The
2009 reviewers were not charged specifically with reviewing the
evidence of radiogenicity and were asked to evaluate the proposed risk
model (discussed below) based on the premise that CLL has a probability
of causation greater than zero. According to the NIOSH summary of the
2009 reviews,
[t]he reviewers did not disagree with our basic conclusion,
namely that CLL could be radiogenic, and that, from an
epidemiological perspective, we can only conclude that we currently
do not have solid scientific evidence of a well-defined dose-
response from the LSS [Life Span Study of Japanese atomic bomb
survivors] data, but not that there is no risk of CLL due to
occupational radiation exposure.\23\
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\23\ NIOSH, Office of Compensation Analysis and Support (OCAS).
Response to review comments on draft report: development of a CLL
risk model for NIOSH-IREP. December 1, 2009. This document is
available in the docket for this rulemaking.
Of these reviewers, only one premised his opinion about CLL
radiogenicity on the compensation program's inclusion of other cancers
with similarly weak
[[Page 15271]]
evidence of radiogenicity; the other 2009 reviewers addressed only the
science. One of those individuals, Reviewer 2 in the 2004
review, reversed her prior opinion that epidemiological evidence in
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support of CLL's radiogenicity is lacking and stated that
new evidence that came into light in the year since the report has
been issued, provides evidence for the hypothesis advocated by [the
report's authors] that CLL may be radiogenic and that its risk
profile may be similar to that previously observed for other types
of leukemia and/or [non-Hodgkin's lymphoma]. These studies are of
particular importance because they provide evidence from the low-
dose studies, a dose range of primary interest for occupationally
exposed workers in the U.S.\24\
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\24\ Zablotska LB. Evaluation of a prototype CLL risk model for
potential inclusion in the computer program NIOS-IREP. Report
submitted to NIOSH, September 2009. A copy of this report is
available in the docket for this rulemaking.
These reviews \25\ have led NIOSH to better appreciate some of the
possible limitations of the epidemiological evidence, and particularly
the substantial reliance on mortality studies for a disease that may
not always be recorded as the primary cause of death, being principally
a slowly developing cancer of old age. An examination of the long
latency period between initial radiation exposure and CLL diagnosis has
led some researchers to conclude that many epidemiology studies fail to
``appropriately account for a protracted induction latency, and
morbidity period between radiation exposure and CLL mortality.'' \26\
Another limitation stems from the low incidence of CLL, resulting in
studies limited by low statistical power.\27\ NIOSH's review of both
epidemiological and biological research has demonstrated that evidence
for the radiogenicity of CLL is growing, and that ``[i]rradiation may
have been given a clean bill of health with respect to CLL with less
than adequate evidence.'' \28\
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\25\ A timeline of the various reviews initiated by NIOSH is
available in Appendix A.
\26\ Richardson DB, Wing S, Schroeder J, et al. Ionizing
radiation and chronic lymphocytic leukemia. Environ. Health Persp.
113:1-5. 2005.
\27\ Id.
\28\ Hamblin TJ. Have we been wrong about ionizing radiation and
chronic lymphocytic leukemia? Leuk. Res. 2008;32:523-525.
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Under EEOICPA, NIOSH is required to develop guidelines using the
1985 radioepidemiological tables (or its successor) in computing
probability of causation. The Act further requires that the probability
of causation decision be made at the upper 99 percent credibility
level.\29\ When the original 1985 radioepidemiological tables were
revised in 2002, the expert working group (chaired by NCI) included
additional cancers that did not have statistically significant excess
relative risk coefficients. The logic for doing so is based on the fact
that, if one accounts for uncertainty, it is possible for the upper
limit for the risk coefficient to be greater than 1, even if the
central estimate of risk is not statistically significant. The
technical basis behind the revised radioepidemiological tables,\30\
including the provision for including cancers with non-statistically
significant central estimates of risk, was documented in a report
reviewed by the National Academy of Sciences (NAS). NAS supported the
inclusion of cancers without demonstrated radiogenicity, but proposed
an approach for calculating the Assigned Share for those cancers that
differed from the approach used for cancers with demonstrated
radiogenicity in the 1990 draft report of the working group to revise
the radioepidemiological tables. NIOSH-IREP includes models and
calculates probability of causation for all cancers except CLL. It does
so by considering the uncertainty associated with the excess relative
risk (ERR) values and using the 99th percentile of that probability
distribution in the probability of causation calculation. Given that
the law requires the use of the upper 99 percent credibility level in
making compensation decisions, \31\ the inclusion of CLL despite the
limited evidence of radiogenicity, is considered appropriate by NIOSH.
In short, the NIOSH-IREP risk models for those cancers lacking
statistically significant central estimates of risk account for the
uncertainty inherent in epidemiological studies of the association
between ionizing radiation exposure and cancer.
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\29\ 42 U.S.C. 7348n(c)(3)(A).
\30\ National Academy of Sciences. A Review of the Draft Report
of the NCI-CDC Working Group to Revise the 1985 Radioepidemiological
Tables. National Academies Press. 2000.
\31\ 42 U.S.C. 7348n(c)(3)(A).
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NIOSH also considered the classification of CLL in relation to
other lymphomas (although CLL is designated a leukemia, clinically and
etiologically it appears to be a lymphoma \32\) of primary importance
to this effort. CLL is now classified as a form of non-Hodgkin's
lymphoma (NHL) by both NCI and the World Health Organization.\33\ Under
contemporary classification schemes, NHL comprises CLL and small
lymphocytic lymphoma (SLL); SLL and NHL are both compensable under
EEOICPA.
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\32\ Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-
Hermelink HK, Vardiman J, Lister TA, and Bloomfield CD. World Health
Organization classification of neoplastic diseases of the
hematopoietic and lymphoid tissues: Report of the clinical advisory
committee meeting--Airlie House, Virginia, November 1997. J. Clin.
Oncol. 17:3835-3849.
Boice JD. Reconsideration of chronic lymphocytic leukemia for
purposes of compensation. January 7, 2005.
National Cancer Institute. Adult non-Hodgkin lymphoma treatment
(PDQ[supreg]): health professional version. Modified July 8, 2010.
http://www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/healthprofessional/allpages. Accessed July 15, 2010.
\33\ National Cancer Institute. Adult non-Hodgkin lymphoma
treatment (PDQ [supreg]): health professional version. Modified July
8, 2010. http://www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/healthprofessional/allpages. Accessed July 15, 2010.
Harris NL, Jaffe ES, Diebold J, et al. World Health Organization
classification of neoplastic diseases of the hematopoietic and
lymphoid tissues: Report of the clinical advisory committee
meeting--Airlie House, Virginia, November 1997. J. Clin. Oncol.
1999;17:3835-3849.
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Finally, in the Agency's judgment, including CLL as a potentially
compensable cancer would be in keeping with already-established Federal
policy. The U.S. Department of Veterans Affairs (VA) recognizes CLL as
a form of non-Hodgkin's lymphoma, and thus a radiogenic cancer, for the
purpose of compensation under the Nuclear Test Personnel Review
Program.\34\
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\34\ Kocher DC and Apostoaei JA. Screening doses for induction
of cancers calculated with the Interactive RadioEpidemiologic
Program (IREP). Fort Belvoir, VA: U.S. Department of Defense,
Defense Threat Reduction Agency, March 2007. Technical Report DTRA-
TR-07-4.
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With respect to the radiogenicity of CLL, the Agency finds the
evidence of radiogenicity offered by epidemiology studies to be non-
determinative, but no longer believes that it is possible to state that
the probability of causation equals zero. NIOSH has weighed the non-
determinative epidemiology evidence, the mechanistic argument for CLL
causation, similarities between CLL and other compensated cancers, the
classification of CLL, and the treatment of CLL as a potentially-
compensable radiogenic cancer by the VA, and finds sufficient evidence
to include CLL as a compensable cancer under EEOICPA, and thus allow
claimants with CLL to be eligible for dose reconstruction. The
remaining issue NIOSH had to address to pursue such a policy was the
practical matter of developing a model with a quantitative dose-
response relationship for CLL.
Risk Model
The NIOSH efforts to develop a quantitative radiation risk model
for CLL began with a review of key papers on the epidemiological,
molecular, and clinical bases of CLL, including but not limited to
those cited by Richardson et
[[Page 15272]]
al.\35\ and by Boice; \36\ the NIOSH Annotated Bibliography for CLL;
\37\ the CLL special issue of the British Journal of Haematology; \38\
and the Biological Effects of Ionizing Radiation (BEIR) VII
committee.\39\ NIOSH also compiled information pertinent to developing
the new model: Sex and age-specific background incidence rates for CLL
from the NCI's Surveillance, Epidemiology, and End Results (SEER)
registry for the U.S. population \40\ and from the International Agency
for Research on Cancer (IARC) databases for the Japanese
population.\41\
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\35\ Richardson DB, Wing S, Schroeder, J, et al. Ionizing
radiation and chronic lymphocytic leukemia. Environ. Health Persp.
2005;113:1-5.
\36\ Boice, JD. Reconsideration of chronic lymphocytic leukemia
for purposes of compensation. Report submitted to NIOSH, January 7,
2005.
\37\ Silver SR, Hiratzka SL, Schubauer-Berigan MK, Daniels RD.
Chronic lymphocytic leukemia: A systematic review. Cancer Causes
Control. 2007;18:1077-1093.
\38\ CLL special issue of British Journal of Haematology.
December 2007;135:629-848.
\39\ National Research Council, Board on Radiation Effects
Research. Health risks from exposure to low levels of ionizing
radiation: BEIR VII Phase 2. The National Academies Press,
Washington, DC, 2006.
\40\ National Cancer Institute. Surveillance Epidemiology and
End Results (SEER) Program. http://seer.cancer.gov. Accessed July
15, 2010.
\41\ Parkin DM, Whelan SL, Ferlay J, Raymond L, Young J (eds.).
Cancer incidence in five continents, Volume VII. Lyon, France: World
Health Organization, International Agency for Research on Cancer,
1997. IARC Scientific Publication No. 143.
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NIOSH also evaluated epidemiology study data potentially bearing on
the issue of latency of CLL,\42\ and created a risk model for CLL by
modifying the existing NIOSH-IREP risk model for lymphoma and multiple
myeloma \43\ to include an extended latency period. Use of the lymphoma
and multiple myeloma risk models as a starting point was considered
appropriate, given the classification of CLL as a form of non-Hodgkin's
lymphoma.
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\42\ See Appendix C, Assessment of potential latency for
incidence of CLL, lymphomas, and multiple myeloma, in Development of
a risk model for chronic lymphocytic leukemia for NIOSH-IREP.
January 5, 2010. A copy of this report is available in the docket
for this rulemaking.
\43\ Land CE, Gilbert ES, Smith JM, et al. Report of the NCI-CDC
Working Group to revise the 1985 NIH radioepidemiological tables.
Bethesda, MD: U.S. Department of Health and Human Services, National
Institutes of Health, National Cancer Institute, 2003. NIH
Publication No. 03-5387.
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The extended latency period for CLL was examined in some detail.
After reviewing a number of studies, the midpoint of the latency period
for CLL within the draft risk model was set at 15 years, with an
uncertainty band of 5 years. As with other cancers in the
NIOSH-IREP model, the risk of developing CLL is considered to be very
low for short times after exposure with the magnitude of the risk
increasing by an adjustment factor that confers the maximum risk value
at 20 years post-exposure.
A draft report entitled ``Development of a Risk Model for Chronic
Lymphocytic Leukemia,'' which includes NIOSH's analysis of the
literature along with the justification for the proposed model, was
provided to four subject matter experts for review in 2009.\44\ Two of
the four individuals previously were asked to provide their judgment
regarding the evidence of radiogenicity of CLL in 2004. NIOSH received
comments on many substantive issues with regard to CLL, including the
potential radiogenicity of CLL; implications of reclassification as an
NHL; the appropriateness of using the NIOSH-IREP lymphoma and multiple
myeloma model for CLL; the appropriateness of extended latency for CLL;
and a number of additional issues pertinent to this rulemaking. NIOSH
addressed these comments in a report available in the regulatory docket
for this rulemaking. The comments resulted in one major modification to
the proposed risk model: The shortening of the midpoint of the latency
period for CLL from 15 to 10 years, while maintaining the uncertainty
in the midpoint at 5 years.\45\
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\44\ The names of experts whose opinions were solicited, the
request, and the responses from these experts are included in the
NIOSH Docket for this rulemaking.
\45\ NIOSH, Office of Compensation Analysis and Support (OCAS).
Response to review comments on draft report: Development of a CLL
risk model for NIOSH-IREP. December 1, 2009.
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The CLL risk model was quantitatively tested by calculating
probability of causation results for males between 20 and 40 years of
age hypothetically exposed to 1 Sievert (Sv) of high-energy gamma
radiation. Although the evaluations were restricted to exposures to
males, the results for women are very similar, because the same risk
coefficient is used and the age-specific incidence patterns in Japanese
women and U.S. women are similar. The results of these evaluations
indicate that the probability of causation exceeds 50 percent only at
the 99th percentile, and then only for times since exposure greater
than 15 years for men initially exposed at age 20. Doses higher than 1
Sv will be required to produce 99th percentile values of probability of
causation that equal or exceed a value of 50 percent for older ages at
time of exposure or at time of diagnosis.
CLL is considered a disease that originates from a population of
antigen-selected, mature B lymphocytes. As such, these cells could
potentially undergo transformation to CLL clones anywhere within the
hematopoietic or lymphatic system, thus complicating the reconstruction
of the radiation dose to the target organ. This is particularly
problematic for reconstructing doses due to internally deposited
radionuclides, because the radiation dose in this case is most often
not homogeneously distributed within the body. To resolve this issue,
NIOSH proposes to use a probabilistic approach to dose reconstruction
where the radiation dose to the B lymphocytes is a weighted average,
based on the dose to a given site and the probability that a B cell
precursor for CLL will occupy that site. A document that provides the
scientific basis for this approach to reconstruction of dose has been
prepared by NIOSH and is included in the NIOSH Docket for this
rulemaking.
C. Purpose of the Rule
The purpose of this rule is to provide for coverage of CLL under
part B of EEOICPA. Presently, the probability of causation guidelines
at 42 CFR part 81 designate CLL as non-radiogenic and require DOL to
assign a probability of causation to CLL of zero, when presented in a
claim for compensation under part B of EEOICPA. This proposed revision
would remove the designation of CLL under Sec. 81.30 of the
guidelines. In concert with this change, NIOSH would add a CLL risk
model to NIOSH-IREP and DOL would refer CLL claims under part B of
EEOICPA to NIOSH for dose reconstructions, to be followed by
determinations of probability of causation by DOL under these revised
guidelines.
D. Technical Review by the Advisory Board on Radiation and Worker
Health
EEOICPA required that HHS obtain a technical review by the Advisory
Board on Radiation and Worker Health (the Board) prior to establishing
the probability of causation guidelines to be amended through this
rulemaking.\46\ HHS interprets this requirement also to apply to any
revisions HHS would make to these guidelines. Hence, HHS will obtain a
technical review by the Board and consider the findings of this review
in promulgating the final regulation.
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\46\ 42 U.S.C. 7384n(c).
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III. Summary of Proposed Rule
The proposed rule would remove Sec. 81.30 of 42 CFR part 81 thus
rescind the designation of CLL as a non-radiogenic cancer under this
part. The effect of this rescission would be that a qualified claim for
CLL under part B of EEOICPA would be referred by DOL to
[[Page 15273]]
NIOSH for radiation dose reconstruction and, upon completion of the
dose reconstruction, DOL would determine the probability of causation
and complete the adjudication of the claim on that basis. Presently,
such claims are not referred to NIOSH for dose reconstruction, since
under the current language of Sec. 81.30(a), DOL is required to assign
a probability of zero to CLL.
Upon promulgation of the final regulation, DOL would identify open
and closed cases (NIOSH estimates the number of closed cases to be
about 363) under part B of EEOICPA involving CLL claims and attempt to
notify the claimants of the new provision. In addition, NIOSH would
assist DOL in identifying active and closed cases involving multiple
primary cancers including CLL, to identify those whose outcome might be
affected by the new provision. For all cases involving CLL, NIOSH would
revise the dose reconstruction to take into account radiation doses
relevant to CLL, and DOL would recalculate the probability of causation
accordingly.
IV. Regulatory Assessment Requirements
A. Executive Order 12866 and Executive Order 13563
Executive Orders 13563 and 12866 direct agencies to assess all
costs and benefits of available regulatory alternatives and, if
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety effects, distributive impacts, and equity). Executive
Order 13563 emphasizes the importance of quantifying both costs and
benefits, of reducing costs, of harmonizing rules, and of promoting
flexibility. This rule has been designated a ``significant regulatory
action'' although not economically significant, under section 3(f) of
Executive Order 12866. Accordingly, the rule has been reviewed by the
Office of Management and Budget.
The rule is consistent with the requirements of 42 U.S.C. 7384n(c).
The rule does not interfere with State, local, or Tribal governments in
the exercise of their governmental functions.
The rule is not considered economically significant, as defined in
Sec. 3(f)(1) of E.O. 12866. CLL is a rare cancer, with a lifetime risk
of 0.48 percent; according to data provided by NCI, an estimated 1.1
percent of all cancers will be CLL.\47\ This low risk among the U.S.
population, coupled with the weak evidence for CLL's radiogenicity,
indicates DOL is unlikely to receive a substantial volume of claims for
CLL, thus limiting the administrative expenses associated with such
claims and the potential compensation costs. Since 2001, NIOSH has
received approximately 33,000 cases \48\ that included all cancers
currently covered under EEOICPA; given that an estimated 1.1 percent of
all cancers occurring among adults are CLL, NIOSH estimates that
approximately 363 of those cases would have sought compensation for
CLL. NIOSH also receives an average of 200 new cases per month from
DOL, and therefore estimates an expected total of 12,000 cases over the
next 5 years; based on the 1.1 percent incidence rate, NIOSH estimates
that approximately 132 of those cases will seek compensation for CLL.
The Agency expects to review the 363 reopened cases plus 132 new CLL
cases in the first 5 years after promulgation of this rule--a total of
approximately 99 CLL cases per year for the first 5 years. The
estimated cost to NIOSH of conducting dose reconstructions is $12,000
per reconstructed case ($1,188,000 per year); DOL estimates its direct
cost per adjudicated case to be about $8,000 ($792,000 per year); and
DOE estimates its cost per case to be $198 per each DOL request for
employment verification, and $372 for responding to each NIOSH request
for exposure data ($56,430 per year). In sum, NIOSH estimates the
administrative costs to the three Federal agencies associated with CLL
cases to be $2,036,430 per year.
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\47\ National Cancer Institute. SEER Cancer Statistics Review
1975-2007; Table 1.14. Lifetime risk (percent) of being diagnosed
with cancer by site and race/ethnicity: both sexes, 17 SEER areas,
2005-2007.
\48\ This figure represents the number of individual cases
requiring dose reconstruction that have been forwarded to NIOSH by
DOL.
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Based on our knowledge of the exposure potential for the claimant
population and the probability of causation guidelines discussed above,
NIOSH expects that approximately 30 percent of CLL cases--30 cases per
year--will result in compensation. Compensated claimants receive
$150,000 plus medical expenses, which are estimated to cost about
$20,000 per year (costs tend to be higher in the first year of
treatment, but benefits are payable only from the date of filing a
claim, and most claimants have already begun treatment by that time).
The financial award granted to successful claimants comes directly from
the U.S. Treasury's Energy Employees Occupational Illness Compensation
Fund (42 U.S.C. 7384f); NIOSH estimates that annual compensation will
amount to $5,100,000. In total, this rule is estimated to cost the
Federal government (the three Federal agencies plus the U.S. Treasury)
$7,136,430 per year, or just over 7 percent of the established $100
million annual threshold for economic significance.\49\
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\49\ NIOSH further estimates the upper bounds of potential costs
associated with CLL compensation. To address any potential
uncertainty in the incidence estimate, multiplying by a factor of 2
will increase the CLL incidence rate from 1.1 percent to 2.2
percent. Doing so will result in a total of 990 cases, or 198 CLL
cases per year for the first 5 years. Reconstructing 198 cases per
year will likely cost NIOSH $2,376,000 per year, DOL $1,584,000 per
year, and DOE $112,860 per year for an estimated total cost to the 3
Federal agencies of $4,072,860. With an incidence rate of 2.2
percent, NIOSH predicts that 30 percent, or 60 cases, will be
compensated. Given an award of $150,000 per case plus medical
expenses, NIOSH estimates that the rule will result in compensation
of $10,200,000. In total, NIOSH estimates that this rulemaking will
cost the Federal government no more than $14,272,860 annually.
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There are no feasible alternatives to this regulatory action. OMB
has reviewed this probability of causation rule for consistency with
the President's priorities and the principles set forth in E.O. 12866
and E.O. 13563.
B. Regulatory Flexibility Act
The Regulatory Flexibility Act (RFA), 5 U.S.C. 601 et seq.,
requires each agency to consider the potential impact of its
regulations on small entities including small businesses, small
governmental units, and small not-for-profit organizations. We certify
that this rule will not have a significant economic impact on a
substantial number of small entities within the meaning of the RFA. The
rule affects only DOL, DOE, HHS, and certain individuals covered by
EEOICPA. Therefore, a regulatory flexibility analysis as provided for
under RFA is not required.
C. Paperwork Reduction Act
The Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., requires
an agency to invite public comment on and to obtain OMB approval of any
regulation that requires 10 or more people to report information to the
agency or to keep certain records. This rule does not contain any
information collection requirements. It provides guidelines only to DOL
for adjudicating compensation claims and thus requires no reporting or
record keeping. Information required by DOL to apply these guidelines
is being provided by HHS and by individual claimants to DOL under DOL
regulations at 20 CFR part 30. Thus, HHS has determined that the PRA
does not apply to this rule.
[[Page 15274]]
D. Small Business Regulatory Enforcement Fairness Act
As required by Congress under the Small Business Regulatory
Enforcement Fairness Act of 1996 (5 U.S.C. 801 et seq.), the Department
will report the promulgation of this rule to Congress prior to its
effective date. The report will state that the Department has concluded
that this rule is not a ``major rule'' because it is not likely to
result in an annual effect on the economy of $100 million or more.
E. Unfunded Mandates Reform Act of 1995
Title II of the Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531
et seq.) directs agencies to assess the effects of Federal regulatory
actions on State, local, and Tribal governments, and the private sector
``other than to the extent that such regulations incorporate
requirements specifically set forth in law.'' For purposes of the
Unfunded Mandates Reform Act, this rule does not include any Federal
mandate that may result in increased annual expenditures in excess of
$100 million by State, local or Tribal governments in the aggregate, or
by the private sector, adjusted annually for inflation. For 2010, the
inflation adjusted threshold is $135 million.
F. Executive Order 12988 (Civil Justice)
This rule has been drafted and reviewed in accordance with
Executive Order 12988, ``Civil Justice Reform,'' and will not unduly
burden the Federal court system. Probability of causation may be an
element in reviews of DOL adverse decisions in the United States
District Courts pursuant to the Administrative Procedure Act. However,
DOL has attempted to minimize that burden by providing claimants an
opportunity to seek administrative review of adverse decisions,
including those involving probability of causation. HHS has provided a
clear legal standard for DOL to apply regarding probability of
causation. This rule has been reviewed carefully to eliminate drafting
errors and ambiguities.
G. Executive Order 13132 (Federalism)
The Department has reviewed this rule in accordance with Executive
Order 13132 regarding federalism, and has determined that it does not
have ``federalism implications.'' The rule does not ``have substantial
direct effects on the States, on the relationship between the national
government and the States, or on the distribution of power and
responsibilities among the various levels of government.''
H. Executive Order 13045 (Protection of Children From Environmental,
Health Risks and Safety Risks)
In accordance with Executive Order 13045, HHS has evaluated the
environmental health and safety effects of this rule on children. HHS
has determined that the rule would have no effect on children.
I. Executive Order 13211 (Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution, or Use)
In accordance with Executive Order 13211, HHS has evaluated the
effects of this rule on energy supply, distribution or use, and has
determined that the rule will not have a significant adverse effect.
J. Plain Writing Act of 2010
Under Public Law 111-274 (October 13, 2010), executive Departments
and Agencies are required to use plain language in documents that
explain to the public how to comply with a requirement the Federal
Government administers or enforces. HHS has attempted to use plain
language in promulgating the proposed rule consistent with the Federal
Plain Writing Act guidelines.
List of Subjects in 42 CFR Part 81
Cancer, Government employees, Occupational safety and health,
Nuclear materials, Radiation protection, Radioactive materials,
Workers' compensation.
For the reasons discussed in the preamble, the Department of Health
and Human Services proposes to amend 42 CFR part 81 as follows:
PART 81--GUIDELINES FOR DETERMINING THE PROBABILITY OF CAUSATION
UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION
PROGRAM ACT OF 2000
Subpart E--Guidelines To Estimate Probability of Causation
1. The authority citation for part 81 continues to read as follows:
Authority: 42 U.S.C. 7384n; E.O. 13179, 65 FR 77487, 3 CFR, 2000
Comp., p. 321.
Sec. 81.30 [Removed]
2. Remove Sec. 81.30.
Dated: December 9, 2010.
Kathleen Sebelius,
Secretary, Department of Health and Human Services.
Note: The following appendix will not appear in the Code of
Federal Regulations.
Appendix A
Chronology of CLL-Related Activities Initiated by NIOSH
------------------------------------------------------------------------
Date Description
------------------------------------------------------------------------
May 2002..................... NIOSH publishes Probability of Causation
Rule (42 CFR part 81), excluding CLL for
eligibility under EEOICPA. CLL is the
only type of cancer granted an a priori
probability of causation of 0%.
July 2004.................... Based on direction from the U.S.
Congress, the NIOSH Occupational Energy
Research Program convenes a public
meeting in Washington, DC to: (1)
discuss available research strategies
for investigating the potential
relationship between the incidence of
CLL and worker exposures to ionizing
radiation and (2) identify gaps in the
current research.
September-October 2004....... The NIOSH Office of Compensation Analysis
and Support (now the Division of
Compensation Analysis and Support
(DCAS)) recruits five outside experts,
not affiliated with NIOSH, to evaluate
if:
the evidence of an association, or
lack thereof, between radiation
exposure and the risk of developing
CLL [is] sufficient to continue to
regard CLL as a non-radiogenic cancer
and to continue to exclude it, a
priori, from eligibility for
compensation under EEOICPA.
November 2004-January 2005... NIOSH receives opinions on the
radiogenicity of CLL from outside
experts regarding and prepares
summaries.
July 2005.................... Because the opinion of a majority of
subject experts is that CLL should not
continue to be excluded from eligibility
of compensation under EEOICPA, NIOSH
begins the development of a model
capable of quantifying the risk of
developing CLL as a consequence of
exposure to ionizing radiation.
[[Page 15275]]
August 2005-June 2009........ NIOSH conducts research into an
appropriate risk model for CLL,
including selection of the appropriate
target organ and methodology for
reconstructing dose.
July 2009.................... NIOSH completes draft report that
describes the CLL risk model (and the
scientific rationale behind it) and
recruits four subject matter experts to
review the draft model.
September-August 2009........ NIOSH receives subject matter expert
comments on the draft CLL risk model.
January 2010................. NIOSH addresses subject matter expert
comments on the CLL risk model and
finalizes the risk model.
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[FR Doc. 2011-6329 Filed 3-18-11; 8:45 am]
BILLING CODE 4163-18-P