National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, DHHS.
Notice of proposed rulemaking.
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.
The Department invites written comments on this Notice of Proposed Rulemaking from interested parties. Comments must be received by June 20, 2011.
You may submit comments, identified by “RIN 0920–AA39,” by any of the following methods:
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Stuart Hinnefeld, Director, Division of Compensation Analysis and Support,
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:
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
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.
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).
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.
Cardis E, Gilbert ES, Carpenter L,
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.
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.”
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 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.”
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.
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.
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.
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.
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.”
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.”
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.”
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.
These reviews
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.
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
Boice JD.
National Cancer Institute.
Harris NL, Jaffe ES, Diebold J,
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.
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.
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
NIOSH also evaluated epidemiology study data potentially bearing on the issue of latency of CLL,
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.
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.
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 § 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.
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.
The proposed rule would remove § 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
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.
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 § 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.
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.
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.
The Regulatory Flexibility Act (RFA), 5 U.S.C. 601
The Paperwork Reduction Act (PRA), 44 U.S.C. 3501
As required by Congress under the Small Business Regulatory Enforcement Fairness Act of 1996 (5 U.S.C. 801
Title II of the Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531
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.
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.”
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.
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.
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.
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:
1. The authority citation for part 81 continues to read as follows:
42 U.S.C. 7384n; E.O. 13179, 65 FR 77487, 3 CFR, 2000 Comp., p. 321.
2. Remove § 81.30.
The following appendix will not appear in the Code of Federal Regulations.