Title 42—Public Health--Volume 1
PART 81—GUIDELINES FOR DETERMINING PROBABILITY OF CAUSATION UNDER THE ENERGY EMPLOYEES OCCUPATIONAL ILLNESS COMPENSATION PROGRAM ACT OF 2000
§ 81.0   Background.
The Energy Employees Occupational Illness Compensation Program Act (EEOICPA), 42 U.S.C. 7384-7385 [1994, supp. 2001], provides for the payment of compensation benefits to covered employees and, where applicable, survivors of such employees, of the United States Department of Energy, its predecessor agencies and certain of its contractors and subcontractors. Among the types of illnesses for which compensation may be provided are cancers. There are two categories of covered employees with cancer under EEOICPA for whom compensation may be provided. The regulations that follow under this part apply only to the category of employees described under paragraph (a) of this section.
(a) One category is employees with cancer for whom probability of causation must be estimated or determined, as required under 20 CFR 30.115.
(b) The second category is members of the Special Exposure Cohort seeking compensation for a specified cancer, as defined under EEOICPA. The U.S. Department of Labor (DOL) which has primary authority for implementing EEOICPA, has promulgated regulations at 20 CFR 30.210 et seq. that identify current members of the Special Exposure Cohort and requirements for compensation. Pursuant to section 7384(q) of EEOICPA, the Secretary of HHS is authorized to add additional classes of employees to the Special Exposure Cohort.
§ 81.1   Purpose and Authority.
(a) The purpose of this regulation is to establish guidelines DOL will apply to adjudicate cancer claims for covered employees seeking compensation for cancer, other than as members of the Special Exposure Cohort seeking compensation for a specified cancer. To award a claim, DOL must first determine that it is at least as likely as not that the cancer of the employee was caused by radiation doses incurred by the employee in the performance of duty. These guidelines provide the procedures DOL must apply and identify the information DOL will use.
(b) Section 7384(n)(b) of EEOICPA requires the President to promulgate these guidelines. Executive Order 13179 assigned responsibility for promulgating these guidelines to the Secretary of HHS.
§ 81.2   Provisions of EEOICPA concerning this part.
EEOICPA imposes several general requirements concerning the development of these guidelines. It requires that the guidelines produce a determination as to whether it is at least as likely as not (a 50% or greater probability) that the cancer of the covered employee was related to radiation doses incurred by the employee in the performance of duty. It requires the guidelines be based on the radiation dose received by the employee, incorporating the methods of dose reconstruction to be established by HHS. It requires determinations be based on the upper 99 percent confidence interval (credibility limit) of the probability of causation in the RadioEpidemiological tables published under section 7(b) of the Orphan Drug Act (42 U.S.C. 241 note), as such tables may be updated. EEOICPA also requires HHS consider the type of cancer, past health-related activities, the risk of developing a radiation-related cancer from workplace exposure, and other relevant factors. Finally, it is important to note EEOICPA does not include a requirement limiting the types of cancers to be considered radiogenic for these guidelines.
§ 81.4   Definition of terms used in this part.
(a) Covered employee, for purposes of this part, means an individual who is or was an employee of DOE, a DOE contractor or subcontractor, or an atomic weapons employer, and for whom DOL has requested HHS to perform a dose reconstruction.
(b) Dose and dose rate effectiveness factor (DDREF) means a factor applied to a risk model to modify the dose-risk relationship estimated by the model to account for the level of the dose and the rate at which the dose is incurred. As used in IREP, a DDREF value of greater than one implies that chronic or low doses are less carcinogenic per unit of dose than acute or higher doses.
(c) Dose-response relationship means a mathematical expression of the way that the risk of a biological effect (for example, cancer) changes with increased exposure to a potential health hazard (for example, ionizing radiation).
(d) EEOICPA means the Energy Employees Occupational Illness Compensation Program Act of 2000, 42 U.S.C. §§ 7384-7385 [1994, supp. 2001].
(e) Equivalent dose means the absorbed dose in a tissue or organ multiplied by a radiation weighting factor to account for differences in the effectiveness of the radiation in inducing cancer.
(f) External dose means the portion of the equivalent dose that is received from radiation sources outside of the body.
(g) ICD-10-CM means the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification, https://www.cdc.gov/nchs/icd/icd10cm.htm.
(h) Interactive RadioEpidemiological Program (IREP) means a computer software program that uses information on the dose-response relationship, and specific factors such as a claimant's radiation exposure, gender, age at diagnosis, and age at exposure to calculate the probability of causation for a given pattern and level of radiation exposure.
(i) Internal dose means the portion of the equivalent dose that is received from radioactive materials taken into the body.
(j) Inverse dose rate effect means a phenomenon in which the protraction of an exposure to a potential health hazard leads to greater biological effect per unit of dose than the delivery of the same total amount in a single dose. An inverse dose rate effect implies that the dose and dose rate effectiveness factor (DDREF) is less than one for chronic or low doses.
(k) Linear energy transfer (LET) means the average amount of energy transferred to surrounding body tissues per unit of distance the radiation travels through body tissues (track length). Low LET radiation is typified by gamma and x rays, which have high penetrating capabilities through various tissues, but transfer a relatively small amount of energy to surrounding tissue per unit of track length. High LET radiation includes alpha particles and neutrons, which have weaker penetrating capability but transfer a larger amount of energy per unit of track length.
(l) NIOSH means the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, United States Department of Health and Human Services.
(m) Primary cancer means a cancer defined by the original body site at which the cancer was incurred, prior to any spread (metastasis) to other sites in the body.
(n) Probability of causation means the probability or likelihood that a cancer was caused by radiation exposure incurred by a covered employee in the performance of duty. In statistical terms, it is the cancer risk attributable to radiation exposure divided by the sum of the baseline cancer risk (the risk to the general population) plus the cancer risk attributable to the radiation exposure.
(o) RadioEpidemiological Tables means tables that allow computation of the probability of causation for various cancers associated with a defined exposure to radiation, after accounting for factors such as age at exposure, age at diagnosis, and time since exposure.
(p) Relative biological effectiveness (RBE) means a factor applied to a risk model to account for differences between the amount of cancer effect produced by different forms of radiation. For purposes of EEOICPA, the RBE is considered equivalent to the radiation weighting factor.
(q) Risk model means a mathematical model used under EEOICPA to estimate a specific probability of causation using information on radiation dose, cancer type, and personal data (e.g., gender, smoking history).
(r) Secondary site means a body site to which a primary cancer has spread (metastasized).
(s) Specified cancer is a term defined in § 7384(l)(17) of EEOICPA and 20 CFR 30.5(gg) that specifies types of cancer that, pursuant to 20 CFR part 30, may qualify a member of the Special Exposure Cohort for compensation. It includes leukemia (other than chronic lymphocytic leukemia), multiple myeloma, non-Hodgkin's lymphoma, renal cancers, and cancers of the lung (other than carcinoma in situ diagnosed at autopsy), thyroid, male breast, female breast, esophagus, stomach, pharynx, small intestine, pancreas, bile ducts, gall bladder, salivary gland, urinary bladder, brain, colon, ovary, liver (not associated with cirrhosis or hepatitis B), and bone.
(t) Uncertainty is a term used in this rule to describe the lack of precision of a given estimate, the extent of which depends upon the amount and quality of the evidence or data available.
(u) Uncertainty distribution is a statistical term meaning a range of discrete or continuous values arrayed around a central estimate, where each value is assigned a probability of being correct.
(v) Upper 99 percent confidence interval is a term used in EEOICPA to mean credibility limit, the probability of causation estimate determined at the 99th percentile of the range of uncertainty around the central estimate of probability of causation.
§ 81.5   Use of personal and medical information.
Determining probability of causation may require the use of the following personal and medical information provided to DOL by claimants under DOL regulations 20 CFR part 30:
(a) Year of birth.
(b) Cancer diagnosis (by ICD-10-CM code) for primary and secondary cancers.
(c) Date of cancer diagnosis.
(d) Gender.
(e) Race/ethnicity (if the claim is for skin cancer or a secondary cancer for which skin cancer is a likely primary cancer).
(f) Smoking history (if the claim is for lung cancer or a secondary cancer for which lung cancer is a likely primary cancer).
§ 81.6   Use of radiation dose information.
Determining probability of causation will require the use of radiation dose information provided to DOL by the National Institute for Occupational Safety and Health (NIOSH) under HHS regulations 42 CFR part 82. This information will include annual dose estimates for each year in which a dose was incurred, together with uncertainty distributions associated with each dose estimate. Dose estimates will be distinguished by type of radiation (low linear energy transfer (LET), protons, neutrons, alpha, low-energy x-ray) and by dose rate (acute or chronic) for external and internal radiation dose.
§ 81.10   Use of cancer risk assessment models in NIOSH IREP.
(a) The risk models used to estimate probability of causation for covered employees under EEOICPA will be based on risk models updated from the 1985 NIH Radioepidemiological Tables. These 1985 tables were developed from analyses of cancer mortality risk among the Japanese atomic bomb survivor cohort. The National Cancer Institute (NCI) and Centers for Disease Control and Prevention (CDC) are updating the tables, replacing them with a sophisticated analytic software program. This program, the Interactive RadioEpidemiological Program (IREP) 1 , models the dose-response relationship between ionizing radiation and 33 cancers using morbidity data from the same Japanese atomic bomb survivor cohort. In the case of thyroid cancer, radiation risk models are based on a pooled analysis of several international cohorts 1a .
1 NIOSH-IREP is available for public review on the NIOSH homepage at: www.cdc.gov/niosh/ocas/ocasirep/html.
1a Ron E, Lubin JH, Shore RE, et al. “Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies.” Radiat. Res. 141:259-277, 1995.
(b) NIOSH will change the risk models in IREP, as needed, to reflect the radiation exposure and disease experiences of employees covered under EEOICPA, which differ from the experiences of the Japanese atomic bomb survivor cohort. Changes will be incorporated in a version of IREP named NIOSH-IREP, specifically designed for adjudication of claims under EEOICPA. Possible changes in IREP risk models include the following:
(1) Addition of risk models to IREP, as needed, for claims under EEOICPA (e.g., malignant melanoma and other skin cancers)
(2) Modification of IREP risk models to incorporate radiation exposures unique to employees covered by EEOICPA (e.g., radon and low energy x rays from employer-required medical screening programs, adjustment of relative biological effectiveness distributions based on neutron energy).
(3) Modification of IREP risk models to incorporate new understanding of radiation-related cancer effects relevant to employees covered by EEOICPA (e.g., incorporation of inverse dose-rate relationship between high LET radiation exposures and cancer; adjustment of the low-dose effect reduction factor for acute exposures).
(4) Modification of IREP risk models to incorporate new understanding of the potential interaction between cancer risk associated with occupational exposures to chemical carcinogens and radiation-related cancer effects.
(5) Modification of IREP risk models to incorporate temporal, race and ethnicity-related differences in the frequency of certain cancers occurring generally among the U.S. population.
(6) Modifications of IREP to facilitate improved evaluation of the uncertainty distribution for the probability of causation for claims based on two or more primary cancers.
§ 81.11   Use of uncertainty analysis in NIOSH-IREP.
(a) EEOICPA requires use of the uncertainty associated with the probability of causation calculation, specifically requiring the use of the upper 99% confidence interval (credibility limit) estimate of the probability of causation estimate. As described in the NCI document, 2 uncertainty from several sources is incorporated into the probability of causation calculation performed by NIOSH-IREP. These sources include uncertainties in estimating: radiation dose incurred by the covered employee; the radiation dose-cancer relationship (statistical uncertainty in the specific cancer risk model); the extrapolation of risk (risk transfer) from the Japanese to the U.S. population; differences in the amount of cancer effect caused by different radiation types (relative biological effectiveness or RBE); the relationship between the rate at which a radiation dose is incurred and the level of cancer risk produced (dose and dose rate effectiveness factor or DDREF); and, the role of non-radiation risk factors (such as smoking history).
2 Draft Report of the NCI-CDC Working Group to Revise the 1985 NIH Radioepidemiological Tables, May 31, 2000, p. 17-18, p. 22-23.
(b) NIOSH-IREP will operate according to the same general protocol as IREP for the analysis of uncertainty. It will address the same possible sources of uncertainty affecting probability of causation estimates, and in most cases will apply the same assumptions incorporated in IREP risk models. Different procedures and assumptions will be incorporated into NIOSH-IREP as needed, according to the criteria outlined under § 81.10.
§ 81.12   Procedure to update NIOSH-IREP.
(a) NIOSH may periodically revise NIOSH-IREP to add, modify, or replace cancer risk models, improve the modeling of uncertainty, and improve the functionality and user-interface of NIOSH-IREP.
(b) Revisions to NIOSH-IREP may be recommended by the following sources:
(1) NIOSH,
(2) The Advisory Board on Radiation and Worker Health,
(3) Independent reviews of NIOSH-IREP or elements thereof by scientific organizations (e.g., National Academy of Sciences),
(4) DOL,
(5) Public comment.
(c) NIOSH will submit substantive changes to NIOSH-IREP (changes that would substantially affect estimates of probability of causation calculated using NIOSH-IREP, including the addition of new cancer risk models) to the Advisory Board on Radiation and Worker Health for review. NIOSH will obtain such review and address any recommendations of the review before completing and implementing the change.
(d) NIOSH will inform the public of proposed changes provided to the Advisory Board for review. HHS will provide instructions for obtaining relevant materials and providing public comment in the notice announcing the Advisory Board meeting, published in the Federal Register.
(e) NIOSH will publish periodically a notice in the Federal Register informing the public of proposed substantive changes to NIOSH-IREP currently under development, the status of the proposed changes, and the expected completion dates.
(f) NIOSH will notify DOL and publish a notice in the Federal Register notifying the public of the completion and implementation of substantive changes to NIOSH-IREP. In the notice, NIOSH will explain the effect of the change on estimates of probability of causation and will summarize and address relevant comments received by NIOSH.
(g) NIOSH may take into account other factors and employ other procedures than those specified in this section, if circumstances arise that require NIOSH to implement a change more immediately than the procedures in this section allow.
§ 81.20   Required use of NIOSH-IREP.
(a) NIOSH-IREP is an interactive software program for estimating probability of causation for covered employees seeking compensation for cancer under EEOICPA, other than as members of the Special Exposure Cohort seeking compensation for a specified cancer.
(b) DOL is required to use NIOSH-IREP to estimate probability of causation for all cancers, as identified under §§ 81.21 and 81.23.
§ 81.21   Cancers requiring the use of NIOSH-IREP.
(a) DOL will calculate probability of causation for all cancers using NIOSH-IREP.
(b) Carcinoma in situ (ICD-10-CM codes D00-D09), neoplasms of uncertain behavior (ICD-10-CM codes D37-D44 and D48), and neoplasms of unspecified nature (ICD-10-CM code D49) are assumed to be malignant, for purposes of estimating probability of causation.
(c) All secondary and unspecified cancers of the lymph node (ICD-10-CM codes C77 and C7B.01) shall be considered secondary cancers (cancers resulting from metastasis of cancer from a primary site). For claims identifying cancers of the lymph node, Table 1 in § 81.23(a) provides guidance for assigning a primary site and calculating probability of causation using NIOSH-IREP.
§ 81.22   General guidelines for use of NIOSH-IREP.
DOL will use procedures specified in the NIOSH-IREP Operating Guide to calculate probability of causation estimates under EEOICPA. The guide provides current, step-by-step instructions for the operation of IREP. The procedures include entering personal, diagnostic, and exposure data; setting/confirming appropriate values for variables used in calculations; conducting the calculation; and, obtaining, evaluating, and reporting results.
§ 81.23   Guidelines for cancers for which primary site is unknown.
(a) In claims for which the primary cancer site cannot be determined, but a site of metastasis is known, DOL will calculate probability of causation estimates for various likely primary sites. Table 1 of this paragraph (a) indicates the primary cancer site(s) DOL will use in NIOSH-IREP when the primary cancer site is unknown.
(b) DOL will select the site producing the highest estimate for probability of causation to adjudicate the claim.
§ 81.24   Guidelines for leukemia.
(a) For claims involving leukemia, DOL will calculate one or more probability of causation estimates from up to three of the four alternate leukemia risk models included in NIOSH-IREP, as specified in the NIOSH-IREP Operating Guide. These include: “Leukemia, all types” (ICD-10-CM codes C91-C95), “acute lymphocytic leukemia” (ICD-10-CM code C91.0), and “acute myelogenous leukemia” (ICD-10-CM codes C92.6 and C92.A).
(b) For leukemia claims in which DOL calculates multiple probability of causation estimates, as specified in the NIOSH-IREP Operating Guide, the probability of causation estimate DOL assigns to the claim will be based on the leukemia risk model producing the highest estimate for probability of causation.
§ 81.25   Guidelines for claims including two or more primary cancers.
For claims including two or more primary cancers, DOL will use NIOSH-IREP to calculate the estimated probability of causation for each cancer individually. Then DOL will perform the following calculation using the probability of causation estimates produced by NIOSH-IREP:
3 Evaluating Equation 1 based on the individual upper 99th percentiles of PC 1 , . . ., PC n approximates the upper 99th percentile of PC total whenever PC 1 , . . ., PC n are highly related, e.g., when a common dose-reconstruction is the only non-negligible source of uncertainty in the individual PC i 's. However, this approximation can overestimate it if other sources of uncertainty contribute independently to the PC 1 , . . ., PC n , whereas treating the joint distribution as fully independent could substantially underestimate the upper 99th percentile of PC total whenever the individual PC i 's are positively correlated.