Mr. DENSMORE. That is a difficult question to answer without doing some additional followup work. The main reason we have not followed up on the contracting activities is because of the Inspector General's work. We did not want to duplicate their efforts. Senator HAWKINS. Thank you, gentlemen. We appreciate your coming. Our final witness today will be Dr. Thomas Orme, president of Toxicology Paperwork and Information, Inc. Until recently, Dr. Orme served as manager of the NCI's bioassay and program resources branch. We welcome you, Dr. Orme, to this hearing. We look forward to your testimony. It would be helpful if you would summarize your prepared statement for us, please. STATEMENT OF THOMAS W. ORME, PH. D., PRESIDENT, Dr. ORME. Thank you, Senator Hawkins. I thank the full committee for the opportunity to comment on contracting procedures used by the National Cancer Institute. I have submitted a longer written statement. This shorter version, hopefully, will present the major points. I would like to confine my remarks to the bioassay system with which I was associated and indicate that I do not have firsthand knowledge of any of the other aspects of the NCI operations. In my report, I notice that I mention the bioassay program by a number of different names: bioassay program, the carcinogenesis testing program, the national toxicology program. These different names cause confusion to even me sometimes. I would like to indicate that at all times I am talking about the one continuous bioassay program that has been sponsored by the National Cancer Institute and has recently been detailed to Dr. David Rall at the National Institute of Environmental Health Sciences. The carcinogen bioassay is an experiment involving animals, usually rats and mice. It is currently one of the cornerstones of the Nation's effort to identify chemicals that cause cancer in man. Since the basic design of the carcinogen bioassay involves feeding high doses of chemicals to rats and mice under conditions which often do not simulate those of human exposure, some feel that the bioassay is necessarily crude, but worthy of support because it represents the most advanced technology available. I would like to read some remarks coauthored by Dr. Arthur C. Upton, former Director of the National Cancer Institute: There is no disagreement as to the limitations of the present routine tests. The choice is stark and clear. We can go forward with these crude tools as best we can, and they are far from useless as we will note below, or we can sit and do nothing while waiting for better. We believe it would be irresponsible to delay. We need guidance now. This statement was not released in the early 1970's. It appeared in the May 18, 1981, issue of Chemical and Engineering News. It summarizes why the NCI bioassay program failed to move forward under Dr. Upton's directorship, why it is scientifically a butt of criticism today, and why responsibility for it was transferred eventually to Dr. David Rall. There is, of course, no reason why the carcinogen bioassay should be a crude experiment. The better experiments involving animals are highly sophisticated. What Dr. Upton meant to say was that the carcinogen bioassay, conducted according to NCI guidelines published in 1976, is a crude experiment. Most scientists in the field of carcinogen identification have known for some time how to make animal experiments more informative, more sensitive, and more useful for assessing human risk. If any irresponsibility exists today, it is not the irresponsibility of delay but the irresponsibility of using crudely designed experiments to analyze important health problems when better experimental design is possible. The single greatest obstacle to progress in the field of experimental carcinogenesis is persistence of the NCI idea that bioassay design is invariant, that every test should be the same no matter what chemical is being tested, and that cookbook recipes should be followed dogmatically. In my written statement, I described a number of factors which contributed to experimental design inflexibility. Most of these have been addressed by Drs. Rall and Moore through the national toxicology program. I would like to draw your attention to several persistent problems in contracting procedure since this aspect of the national toxicology program is still largely controlled by NCI. In 1978, NCI was reorganized in a manner which deemphasized the importance of the research contract in favor of grant funding mechanisms. This change was, in part, a reaction to the abuse of research contracts to provide continuous noncompetitive, unreviewed support to favored institutions. The grant mechanism is inappropriate for most activities sponsored then by the carcinogenesis testing program and now by the national toxicology program because its emphasis on investigator initiative impedes Government efforts to coordinate planning, to monitor experiments in progress, to provide animal, chemical, and informational resources, to provide computer support, and to enforce compliance with health effects testing standards. Several large carcinogenesis testing program contracts with universities were phased out as a result of the deemphasis of the research contract mechanism, but most testing program activities were unaffected because they were supported by resource contracts. By definition, no investigator initiative is allowed in a resource contract. Hence, a favorable collaboration between Government scientists and private scientists in improving experimental design is practically excluded by arbitrary rules of contracting. There really is no better mechanism for supporting innovative carcinogen bioassays than a research contract which incorporates Government-imposed restraints, but allows for investigator initiative and experimental design. There is no reason why research contracts should not be awarded competitively, be subject to peer review, and expire on schedule. The classification of the carcinogen bioassay as a resource activity exempt from peer review by a chartered technical review com mittee insulated the carcinogenesis testing program from criticism which might have brought about desirable experimental design change. In the late 1970's, the program leadership correctly perceived that review by any of the existing chartered committees used by NCI to review basic research would have been hostile to the bioassay program and would have led to a recommendation for abolition of the program in favor of investigator initiated research. No attempt was made by NCI, however, to charter a technical review group sympathetic to the carcinogen bioassay and capable of reviewing the design of individual bioassays. Furthermore, no consistent policy was available to enlist the support of potential contractors in designing experiments. Such solicitation requires that the process of project planning be separated from the process of contract award. The advice of potential contractors in determining what should and can be done is often extremely important. On the other hand, bidders cannot be permitted to participate in the selection of a contractor. The concept of dual review is well-described in the NCI orange book on contracting procedures, but was rarely used by the carcinogenesis testing program. In my written statement, I have argued for individual review of the experimental design of large scale animal bioassays. This is by no means a simple task. If systematic review procedures are adopted, I hope Government officials will not abdicate leadership responsibilities in the process of seeking advice. Review committees should not meet so infrequently or be so illprepared to fulfill their mandate that implementation of experimental work is impeded. I have recommended that a permanent subcommittee of the national toxicology program's board of scientific counselors be created to review experimental design, that this subcommittee be authorized to engage ad hoc advisors as required since no single committee member can be expected to be an expert on the toxicity of more than a few chemicals, and that responsibility for informational support be delegated to chemical managers on a project-by-project basis. I believe this arrangement offers the legitimacy of review by a chartered review committee and avoids the excessive formality which makes some types of peer review cumbersome. Much has been said about the difficulties of buying research services in the medical sciences and how different it is than sending a rocket into space or building a battleship. These difficulties were not encountered in the carcinogenesis testing program because the existence of a fixed protocol made it possible to use precisely the same procurement mechanisms used by NASA and the Department of Defense. Buying 100 fixed protocol bioassays, like buying 100 identical helicopters, was much easier than buying 100 unique research projects. Now it is apparent that the fixed protocol bioassay is an obsolete weapons system. The consternation is great. Money has been appropriated. Contracts have been awarded. Foot soldiers have been trained. A vocal minority defends its continuance. But in a showdown, those whose safety is dependent on an obsolete weapons system will be in danger. Fortunately, the leadership of both the national toxicology program and the National Cancer Institute is aware of experimental design problems and needs only time and support to resolve them. Thank you again for the opportunity to address this committee. I would be happy to answer any questions. [The prepared statement of Dr. Orme follows:] 81-966 0-81--21 Statement of Thomas W. Orme, Ph.D. Toxicology Paperwork and Information, Inc. (Former Manager of the NCI Bioassay and Program Resources Branch and National Toxicology Program Pharmacologist) Abstract From 1977 to 1979 the National Cancer Institute suffered a leadership crisis which allowed the bioassay program to become a political football and to deteriorate in scientific quality. The crisis was eventually resolved by transfering responsibility for the program to Dr. David Rall, Director of the National Institute of Environmental Health Sciences and by creation of the National Toxicology Program. Carcinogenicity tests in rats and mice as described in the National Cancer Institute Guidelines for Carcinogen Bioassay in Small Rodents represented the best available technology for carcinogen identification in the early 1970's, but today they can no longer be considered reliable, cost-effective indicators of a human health hazard. Much of their value can be restored if proper consideration is given for each test chemical to the specific role of animal data in the human risk assessment process and to the need for preliminary in vitro tests and short term animal studies. There is currently an experimental design crisis, because an acceptable "cookbook" approach to human risk assessment comparable to the "cookbook" approach to bioassay design has not been found. Resolution of this crisis requires that each bioassay become a unique applied research project focused on the toxicity of a selected chemical or group of related chemicals, rather than a standard protocol test costing $600,000 which ignores current toxicological information and the unique properties of the test chemical. Emphasis should be placed on establishing basic principles in comparative toxicology on which theoretically sound assessments of risk to man can be grounded. The existence of an extensive toxicological information base would contribute to the development of new non-toxic products as well as to the continuing effort to identify actual chemical causes of cancer in man. Resolution of the experimental design problem also would contribute meaningfully to the solution of bioassay management problems, since it would restore confidence that "testing" is a scientific, rather than a political exercise. The National Toxicology Program has been addressing successfully the problem of experimental design in animal testing, but its personnel are hampered by an inheritance of poorly designed work in progress, little money for new ideas, and entanglement with the National Cancer Institute administrative structure. The National Cancer Institute, now under new leadership, is in a position to restructure its carcinogenesis program, but the funds necessary to do so are committed to the National Toxicology Program. Scientifically, both programs are worthy of support. Progress is limited only by the existing administrative morass. |