Document X18pkxM5oeadVkMVZj7RMKkG

Jul 24 04 03:42a P 2 Center for Regulatory Effectiveness S u ite 7 0 0 11 D u p o n t C ircle, N.W. W ashington, D.C. 20036-1231 Tel: (202) 2 6 5 -2 3 8 3 Fax: (202) 9 3 9 -6 9 6 9 w w w .T h eC R E .co m March 3, 2004 Kerry Weems Principal Deputy Assistant Secretary for Budget, Technology and Finance U.S. Department o f Health and Human Services 200 Independence Ave., SW Hubert Humphrey Bldg., Rm. 514G Washington, DC 20201 Dear Mr. Weems: We are recommending that HHS and NIH add the Report on Carcinogens (RoC) program to the list o f programs in the FY 2007 NIH budget which will be evaluated by HHS/NIH and OMB with the Program Assessment Rating Tool (PART). The RoC program is administered by the National Institute o fEnvironmental Health Sciences (NIEHS) and the other federal agencies which participate in the NationalToxicology Program (NTP). The principal mission of NIH and the NTP is health research.1 The RoC program is not a research program, and it competes for resources for that principal mission; therefore issues concerning its justification should be given serious attention. The scientific community and RoC stakeholders, including government agencies withrelated programs, have raised serious and legitimate issues regarding the usefulness o f the RoC program and the manner in which it is administered. Those issues are discussed below in connection with specific PART questions. Although the RoC program is Congressionallymandated, it is still subject to PART evaluation and budget justification, as has been made clear by OMB.2 This should be particularly true when many o f the PART issues pertain substantially to whether the program is being conducted in accordance with Congressional intent. 1 Research is also a basic strategic goal of HHS. Goal 4 of the HHS Strategic Plan for FY 2004-09 is "Enhance the capacity and productivity of the nation's health research enterprise." The use of HHS funds for the RoC program impacts that goal. 2 OMB's Frequently Asked Questions on PART, number 32, specifically addresses programs mandated by statute, stating: "If statutory provisions impede effectiveness - for example, if resources arc not targeted effectively or spread too thinly to have an impact - one result of a PART review may be recommendations for legislative changes." Protected Document - Subject to Protective Order 1 of 11 IMERYS 099497 MSRY6099497 Jul 24 04 03:42a p.3 Center for Regulatory Effectiveness Brief General Background on the RoC Program Preparation o f the RoCs was mandated by Congress in 1978 as a small part o f large public health legislation.3 The RoCs provide lists o f substances or agents which have been determined by HHS to be "known human carcinogens" or "reasonably anticipated human carcinogens", along with a summary o f the scientific information supporting the determination and information on exposure sources. The statute also requires the RoCs to provide an evaluation o f the efficacy o f any current regulatory standards; however, its discussed below, that portion of the mandate has not been followed. Initially, the legislation required a report every year; in 1993 that was changed to every two years. HHS is currently about to publish the 11thRoC, and it has begun work on the 12thRoC by announcing 21 new nominations for listing, and by soliciting public comments on each. Each nomination o f a substance or agent for listing in the RoCs requires preparation o f a detailed "background document" by expert outside consultants and NIEHS staff, review by four separate committees, and extensive public comments, before the Director and the Secretary make a listing decision for publication in the next edition o f the RoC.4 While the RoC program is administered by NIEHS under delegation from the Secretary o f HHS, the RoC program has an inter-agency dimension as part o fthe National Toxicology Program.5 The NTP "core" agencies are all HHS agencies -- NIEHS, NIOSH (part o f CDC), and NCTR (the National Center for Toxicological Research, which is part o f FDA) - and a number o f non-core agencies participate through membership on the NTP Executive Committee and the NTP Board of Scientific Counselors. Those non-core agencies are ATSDR (HHS), CPSC, EPA, NCEH (CDC), NCI (NIH), NIH, and OSHA (Dept o f Labor). Several public reviews o f the RoC program have been conducted - in 1994-96,1999, and 2004 - however, those reviews have addressed mainly issues o f stakeholder input and the listing criteria, not the PART questions discussed below. To the best o f our knowledge, there has been no Congressional oversight or GAO review of the RoC program since the original legislation in 1978. The following OMB PART questions are clearly relevant to the RoC program and should, we believe, be addressed in connection with the FY 2007 NIH budget justification and performance plan. The specific PART questions below are taken directly from the OMB PART guidance. 3 42 U.S.C. 241(b)(4). 4 The listing review procedures are explained on the RoC portion of the NTP website. 5 The Director o f NIEHS is also Director of the NTP. Administration of the RoC program by the Director affects his or her ability to focus on the research aspects of the NTP.2 2 Protected Document - Subject to Protective Order 2 of 11 IMERYS 099498 1MERYS099498 Jul 24 04 03:44a p.a C enter for Regulatory Effectiveness It also appears that NIEHS fails to consult with other federal agencies prior to nominating substances for listing in the RoCs, thus leading to the sort o f situations described above with regard to asphalt fumes and atrazine. 1.5: "Is the program design effectively targeted, so that resources will reach intended beneficiaries and/or otherwise address the program's purpose directly?" This has been addressed above. The RoC program does not have a defined target, and it is not targeted to provide sound information to the American public, as Congress intended. 3.5: "Does the program collaborate and coordinate effectively with related programs?" Assuming "related programs" includes programs by other Federal agencies and State and international health and science organizations to evaluate substances for carcinogenicity and regulate exposure, the RoC program does not collaborate and coordinate effectively. This is shown by the controversy involved in the recent nominations of atrazine and asphalt fumes for listing in the 12* RoC, as discussed above (under 1.3). Whatever formal collaboration and coordination with other federal agencies occurs during the RoC program does not occur until the NTP Executive Committee meets to review individual nominations. Since the review by the NTP Executive Committee is the fourth committee review in the RoC review process, nominations have usually acquired too much momentum by that point for the Executive Committee to conduct an impartial evaluation. In addition, NIEHS recently announced, in its response to public comments from its 2004 process review, that the NTP Executive Committee reviews only RoC "policy" issues. 4.4: "Does the performance of this program compare favorably to other programs, including government, private, etc., with similar purpose and goals?" Assuming performance is measured in terms o f the Congressional intent, which was that the RoCs should disseminate useful risk information to the American public, the RoC program, by its own admission, does not produce any performance results. Programs o f other federal agencies arguably provide far more useful performance results by providing risk information; however, even that risk information is usually not objective scientific information because the scientific data are intermixed with policy-driven assumptions allegedly health-protective precautionary assumptions) in such a way that they cannot be disentangled. The RoCs could provide superior information by providing objective information on levels of exposure at which substances are "known" or "reasonably expected" to cause cancer, but they do not do so. 4.5: "Do independent evaluations of sufficient scope and quality indicate that the program is effective and achieving results?" Since federal regulatory agencies evaluate the same substances for carcinogenicity and promulgate exposure standards, and since the RoCs do not evaluate the efficacy o f those standards as mandated by Congress, it appears impossible to determine whether the RoCs are producing any o f the results intended by Congress beyond those produced by the regulatory agencies.8 8 Protected Document - Subject to Protective Order 3 of 11 IMERYS 099499 Pltf_IMERYS_00WERY8099499 Jul 24 04 03:43a p. 5 C enter for Regulatory Effectiveness prominent toxicologists wrote to Secretary Shalala in 1999 to point out that the RoCs are confusing and ineffective because they do not provide to the public the crucial information on the level of exposure to a particular substance or agent which is "known" or "reasonably anticipated" to cause cancer. They also questioned whether this absence o f useful information was intended by Congress, and whether the resources currently devoted to preparing the RoCs might be better invested in basic health research. A copy o fthis 1999 letter to Secretary Shalala is attached. The issue had also been raised earlier in July 1999 by members o f the scientific community attending The Toxicology Forum in Aspen, CO at which the subject was on the agenda and the NTP Director and RoC staff were present to hear comments. Stakeholders also raised the issue during the 1999 review, and during the 2004 review as well. Nevertheless, NIEHS has never responded by addressing the legislative intent, and has only stated that it believes the RoC background documents provide sufficient information on exposure and dose. Since the background documents are not part of the RoCs, and it is very unlikely that they are read by members o f the general public, this is not an adequate response.8 In addition, the 1978 Congressional mandates require that the RoCs provide information on the extent to which any current federal regulatory standards reduce risk, but the RoCs fail to do this. They only present infoimation on the standards themselves, not the extent to which they reduce risk. The standard Introduction to the RoCs indicates that this failure to provide relevant information on exposure or dose and the efficacy of regulations is not based on considerations regarding utility or science, but rather on policy assumptions. The Introduction states, in essence, that the Agency has adopted the assumption that any reduction in exposure will decrease the incidence o f cancer, and that this assumption is "the basis of current regulatory policies" employed throughout the federal government.98 Such a statement is not only a policy-based, rather than scientific, statement, but is also clearly inaccurate. Current regulatory policy is based on attempting to determine levels o f exposure which are considered "safe". The stated assumption on which the RoCs are based is reflective of the old "Delaney Clause" regulatory approach, which was repealed by Congress when it enacted the Food Quality Protection Act in 1996. A review o fthe legislative history, which has consistently been avoided by the Agency, shows that Congress intended that the RoC's provide useful "risk" information to the public which they could employ in their daily lives, directly contrary to the approach adopted by the Agency. The 1978 House report on the original legislation for the RoC contains the following 8 Stakeholders have also raised the issue that the listing criteria for the " known" category are unclear, both as interpreted by the agency and as actually applied to certain substances, such as dioxin. We have not addressed that issue in this letter, since it is not primarily a PART issue, although it does pertain to the effectiveness o f the RoC program. 9 Introduction to the 11th RoC at p. 4. 4 Protected Document - Subject to Protective Order 4 of 11 IMERYS 099500 Pltf IMERYS 0MEBYS099500 Center for Regulatory Effectiveness statem en ts.10* (T here w a s nothing pertaining to th e R oC legislation in the S enate rep o rt.) The Reports "must include. . . an evaluation o f the efficacy o f existing regulatory standards designed to reduce or eliminate exposure to carcinogens." At 22. This could not be done without an evaluation o f the level of exposure known or reasonably anticipated to cause cancer. This directive is also contained in the plain language of the statute. The RoCs do not do this. "If an individual recognizes a substance on the list to which he or she suspects that significant exposure occurred, then measures could be taken though medical examination or other screening procedures to detect cancers before they become malignant." Id. (emphasis added). Presumably, Congress meant that the public could gauge the significance o f their exposure based on information provided in the RoCs on the levels of exposure known or reasonably anticipated to cause cancer. "The relative toxicity o f such agents should be described, to the extent such information is know n. . . the levels o f exposure to be expected from certain occupations, geographic areas, foods or consumer goods, and the identification o f subpopulations expected to be at higher than average risk (for example . . . ) . " At 28 (emphasis added). Toxicity is a function of the level of exposure (or dose --internal exposure). Obviously, higher than average risk cannot be ascertained unless the RoCs assess an average level o f risk, which they do not, since they only provide "hazard" information (Le., whether there is a danger at some level o f exposure, which, as studied, might be a level orders o f magnitude higher than an average level o f exposure). On the floor o f the House, Congressman Rogers, Chair o f the Subcommittee on Health and Environment, where the RoC legislation had originated, further explained the intent behind the legislation on behalf o f the full Committee on Commerce: It is the committee's intent that any such list [the RoC listings] include. . . any uncertainties in the data yet to be resolved, and where possible, estimates the [sic] magnitude o f the risk each [substance, etc.] poses. . . . Information concerning the relative risk posed by each substance and the quality of data will be made unequivocably [sic] clear to the reader." Cong. Rec., Oct. 10,1978, 34938 (emphasis added). The RoCs do not provide any information on the magnitude of risk or relative risk. Mr. Rogers' explanation was the only explanation made during floor consideration before passage. 10 H.R. Rep. No. 1192, 95th Cong., 2d Sess., 22-23, 28, 45 (May 15, 1978). 5 Protected Document - Subject to Protective Order 5 of 11 IMERYS 099501 Pltf IMERYS 0MEBYS099501 Jul 24 04 03 s43a p.7 C enter for R egulatory Effectiveness The joint House-Senate explanation of the legislation reflects that the final legislation was based on the House bill, since the Senate bill contained no comparable provisions. Cong. Rec., Oct. 14, 1978, 38653, 38657-58. It therefore appears that the RoC program is currently being conducted in a manner contrary to Congressional intent and so that it lacks the utility to the public that was intended by Congress. 1.2: "Does the program address a specific and existing problem, interest, o r need?" Cancer is certainly a problem, but the RoCs do not "address" that problem in a meaningful way, as intended by Congress. 13 : "Is the program designed so that it is not redundant or duplicative of any other Federal, State, local or private effort?" Numerous other federal agencies (such as EPA, OSHA, FDA, ATSDR, and CPSC), as well as State and international agencies11, conduct risk assessments for the same substances as are listed in the RoCs, and many o f them have promulgated regulatory standards, guidance levels, bans, or labeling requirements based on that risk information The type of "hazard" information contained in the RoC listings is routinely supplied as a part ofthose risk assessments. The RoCs provide hazard information which is redundant and duplicative ofthe hazard information contained in, or underlying, those risk assessments conducted by other agencies under other programs. The cancer risk assessments conducted by regulatory agencies usually result in quantitative estimates o f risk which are based to a significant degree on assumptions rather than scientific knowledge, including significant assumptions which are policy-driven. Examples would include the assumption o f low-dose linearity of dose-response for putative carcinogens and the resolution of inconsistent data or data gaps by selecting "conservative" (i.e.rpresumably more health-protective) data as the determinative data. The RoCs could avoid redundancy and duplication by providing basic factual information which has not been influenced by policy and which does not purport to determine a specific numerical estimate of risk at a certain exposure level (for example, a risk o f 3 x 10'5at an exposure level o f 6 parts per billion). They could do this by simply stating factually the exposure levels at which studies have shown there is a causal relationship with cancer, or at which it appears it is credible that there is a causal relationship. As the Agency itself has already pointed out, such information is contained in the background documents, so that incorporating it into the RoC listing information would not involve any significant extra effort. It should be pointed out that the RoCs are not only duplicative and redundant12, they also 11 The listings and information in the RoCs large duplicate the listings and information provided by the cancer monographs produced by the WHO's International Agency for Research on Cancer ("IARC"). Scientists from U.S. federal agencies frequently participate in preparing the IARC monographs. 12 Another example of potential duplication is the petition currently pending before FDA to require a cancer warning label on cosmetics containing talc. NIEHS recently nominated cosmetic talc for listing in the 12th RoC. 6 Protected Document - Subject to Protective Order 6 of 11 IMERYS 099502 Pltf IMERYS 0MEBYS099502 C enter for Regulatory Effectiveness sometimes conflict with information provided by other federal agencies. For example - - The RoCs list "Alcoholic Beverage Consumption" as a "known human carcinogen".13 At the same time, the Dietary Guidelines for Americans, producedjointly by HHS and USDA, inform the public that moderate consumption of alcoholic beverages is not harmful, and a label for alcoholic beverages mandated by the Bureau o f Alcohol, Tobacco, and Firearms refers the public to the Dietary Guidelines. - After the 9thRoC listed 2,3,7,8-TCDD (often referred to as "dioxin" or TCDD) as a known human carcinogen (based on studies o f humans highly exposed as a result of industrial accidents, as well as animal and in vitro data), EPA also proposed to classify TCDD as a known human carcinogen, but a majority o fits Science Advisory Board disagreed, and the National Academies are now conducting a study on the possible risks o f TCDD. - NIEHS has nominated the widely-used herbicide atrazine for listing in the 12thRoC. EPA has objected to the nomination in a public comment letter (posted on the NTP website) because EPA and its Scientific Advisory Panel had just completed an intensive review of atrazine and had decided that it was not carcingenic. The EPA letter states that "the effort proposed by NTP [to review atrazine for possible listing in the 12* RoC] would be duplicative of work already performed by EPA, as well as work EPA has committed to perform in the future." - In the late 1990s, NIOSH and the Interagency Committee on Chemical Evaluation and Coordination decided that additional studies o f asphalt fumes were needed in order to make a determination o f carcinogenicity. This decision was concurred in by other agencies such as WHO and Cal/OSHA. The recommended studies are currently under way. Nevertheless, this year NIEHS nominated asphalt fumes for listing in the 12* RoC. 1.4: "Is the program design free of m ajor flaws that would limit the program 's effectiveness or efficiency?" The failure o f the RoCs to provide the public with information on the levels o f exposure which are "known" or "reasonably anticipated" to cause cancer is such a major flaw, and it renders the RoCs essentially useless and misleading to the public. 13 At the insistence o f its external peer review committee, the Agency included in the listing information the statement that " [s]tudies indicate that the risk o f cancer is most pronounced among smokers and at the highest levels o f consumption." This may be the only reference to risk and exposure levels throughout the RoCs. Nevertheless, it still indicates that alcoholic beverages are known to cause cancer at any (low) level o f consumption, which is inaccurate and misleading. 7 Protected Document - Subject to Protective Order 7 of 11 IMERYS 099503 Pltf IMERYS 0MEBYS099503 C enter for Regulatory Effectiveness Our review o f these PART questions as applied to the RoC Program, presented below, indicates that there are serious problems with the program and that it is difficult to justify continued funding. . OMB PART Questions Particularly Pertinent to the RoC Program 1.1: "Is the program purpose clear?" This is perhaps the central question. For a long time the RoCs have been regarded as very puzzling in this regard. In their Introductions, at the very outset, the RoCs state that each edition is "an informational scientific and public health document" that "serves as a meaningful and useful compilation of data on [carcinogenicity o f various substances and agents]." However, immediately following this statement is another, contradictory, statement that "[l]isting o f substances in the RoC . . . does not establish that these substances present carcinogenic risks to individuals in their daily lives." In other words, the RoCs do not provide information on carcinogenicity that is useful to the public, but they nevertheless claim to be a "meaningful and useful" scientific and public health document. The program purpose is therefore not clear. A review of the listing information provided by the RoCs will quickly show that data critical to making the RoCs an accurate and useful public health document are missing. The RoCs do not provide the critical data on the level o f exposure at which a substance is "known" to cause cancer or "reasonably anticipated" to cause cancer. Instead, the RoC listings provide only "hazard" information, rather than "risk" information, and thereby indicate to the public that any degree of exposure to the substance is "known" or "reasonably anticipated" to cause cancer.6 Such an approach is not regarded as scientifically valid and useful by the scientific community, and other federal public health agencies provide the public with "risk" information and use "hazard" information as only a preliminary screening tool in the risk evaluation process. By failing to provide information on levels of exposure or dose "known" or "reasonably anticipated" to cause cancer, the RoCs not only lack utility, they are also likely to be misleading to the public.7 During the public review process o f the RoC program in 1999 this problem with the RoCs was pointed out by members o f the scientific community and stakeholders. For example, eleven 6 "Hazard" information is information which indicates that a substance is dangerous at some level o f exposure and dose -- levels which might have little or no relevance to the public because the danger was observed in connection with industrial accidents or worker exposures that occurred far in the past but which are no longer allowed. "Risk" information indicates the level o f danger at a particular level or exposure or dose, and is usually used to determine a level o f exposure which is "safe" or which presents an insignificant risk. 7 Information disseminated to the public which lacks "utility" violates the Data Quality Act and its implementing guidelines. 44 U.S.C. 3516, note; 67 FR 8452, 8459, Feb. 22, 2002 (OMB guidelines for federal agencies - the HHS guidelines conform to the OMB guidelines with regard to the "utility" requirement). 3 Protected Document - Subject to Protective Order 8 of 11 IMERYS 099504 Pltf IMERYS 0MEBYS099504 Jul 24 04 03:44a p . 10 C enter for Regulatory Effectiveness Conclusions and Recommendations The RoC program as currently conducted does not carry out the Congressional intent for the program and is not effective in providing useful information. Continued funding o f the RoC program detracts from the resources available for funding o f HHS and NIH research, and therefore its justification should be carefully examined. The PART was created for just such an evaluation, and numerous PART questions are applicable to the RoC program. We recommend that the PART therefore be employed as intended to evaluate the Report on Carcinogens program. Thank you for your consideration o f this recommendation. We would appreciate knowing whether the Agency will adopt this recommendation. Sincerely, William G. Kelly, Jr. y CRE Western Representative Attachment cc w. att: Bill Beldon, Deputy Assistant Secretary for Budget Art French, Acting Director, Division o f Budget Policy, Execution & Review9 9 Protected Document - Subject to Protective Order 9 of 11 IMERYS 099505 1MERYS099505 Jul 24 04 03:44a p. 11 The University of Kansas Medical Center School of Medicine Department o f Pharmacology, Toxicology and Therapeutics 11 September 1999 The Honorable Donna E. Shalala Secretary Department of Health and Human Services 200 Independence Ave., SW Washington, DC 20201 Dear Madam Secretary: We understand that your Department is currently inviting public comment on issues associated with the biennial Reports on Carcinogens. As members of the medical and scientific communities, we are writing to express briefly our principal concerns. The manner in which information is conveyed to die public through the Reports is confusing. On the one hand, the Reports state that the listing of a substance is not to be taken to indicate that it poses a risk to persons in their daily lives. On the other hand, labeling a substance as a "known" or "reasonably anticipated" carcinogen is almost certain to be understood to indicate that such substance either definitely will cause cancer to exposed persons, or is likely to. And the Introductions to the Reports themselves indicate that their purpose is to affect personal choices and reduce exposures, based on the assumption that anv reduction in exposure will bring about a reduction in the incidence of cancer. The level of exposure and consequently the dose to an individual of any substance are crucial in determining whether the effect on that individual will be beneficial, innocuous, or harmful. Yet such information is not communicated by the Reports. We think it is time to question seriously whether Congress intended the Reports to be so confusing and lacking in useful information, or whether Congress needs to revisit the directions it gave to the Agency. If the Reports cannot provide more useful information to the public, perhaps they should be discontinued and the resources better invested in basic research into causes and treatments for disease. We commend you and your staff for seeking public comment on these issues, and we trust that you will understand that we offer these views in a constructive spirit. Respectfully, 3901 Rainbow Blvd., Kansas City, Kansas CC100-7417* (913) 5S8-7l40Fax (913)588-7501 http://www.kume.edu/research/medicine/pharmacology/dhp.html e-mail address: jdouli@kumc.edu Protected Document - Subject to Protective Order 10 of 11 IMERYS 099506 1MERYS099506 Jul 24 04 03:45a p . 12 William O. Bemdt, Ph.D, Prof. & Vice Chanceler of Academic Affairs Univ^r^ity gfN/as|ca Medic^^ent-er... Joseph F. Borzelleca, Ph.D. Past President, Society of Toxicology Professor Emeritus Department of Pharmacology and Toxicology ( L. , , Z Z Z . ,/ ivledical College oVirginia Curtis D. Klaassen, Ph.D. Past President, Society of Toxicology Professor Department of Pharmacology, Toxicology and Therapeutics U niv^it^^fK a^s^jyledical Center ^ Z James E. Klaunig, Ph D. Director of Toxicoloj Indiani University ScMrolj John Doull, M.D., Ph.D. Past President, Society of Toxicology Professor Emeritus Department o f Pharmacology, Toxicology and Therapeutics U niversity^ isas Medical tender w zX z Jay I. Goodman, Ph.D. President, Society of Toxicology Professor Department of Pharmacology and Toxicology Michigan State University Philip S. Guzelian, M.D. Professor and Head Department of Medical Toxicology University of Colorado Health Sciences Center Karl K. Rozman, Ph.D. Professor Department offTFranriacology, Toxicology and Therapeutics University of Kansas Mhdical Center James A. Swenberg, DVM, Ph.D., DABT Prof. &. Chairman Dept of Environmental Sciences Past President, American College o f Toxicology Professor Emeritus University of Texas Health Sciences Center at San Antonu/ --Z z S Hanspeter R. Witschi, M.D. Professor Institute for Toxicology and Environmental Health University of C ^ fo rp iilfD a v is^ Protected Document - Subject to Protective Order 11 Of 11 IMERYS 099507 PltfJMERYS O O O ^ ^ 099507