minority women who have some of the Nation's worst statistics in breast and other cancers, a point of particular concern to NCI.

Still others are very concerned by the total cost of the proposal in an era of restricted resources. The original proposal required a commitment of $10 million to $15 million per year for about 10 years. This funding is equivalent to about 60 to 70 traditional investigator-initiated research grants (R01's) per year; or about six to ten core grants to Cancer Centers (P30's); or it is approximately equivalent to the funding of the entire Community Clinical Oncology Program (CCOP). By way of contrast, the CCOP supports over 50 community-based clinical and prevention and control research programs, participating jointly in some 400 research protocols involving over 5,000 cancer patients and 6,000 prevention and control subjects.

NCI Position

The National Cancer Institute has examined these issues and marked the following conclusions. First, with respect to the impact of following the nutrition guidelines on the trial, NCI staff have formulated the trial design to account for significant dietary behavior change on the part of the control group, who will receive full information on diet and cancer. The relationship between diet and cancer is not completely understood, and that is one of the main reasons NCI has considered launching this trial. The NCI feels, however, that following the dietary guidelines is a prudent choice at this point in time.

NCI

Secondly, whether the potential effect of a change in diet on cancer might be due to the change in calories consumed or due to a reduced intake of fat is an important scientific question. However, from a practical point of view, lowering fat in the diet reduces both fat and total calorie intake. NCI studies implicate both as having a critical role in mammary tumor development. believes that a large-scale study of such size, cost and complexity can only be conducted once, and therefore must be designed to maximize the utility of its results. A dietary modification that has both the greatest potential to reduce cancer and is broadly achievable by the American population is the best intervention strategy. Clearly, there are many tradeoffs that need to be made in the design of such a study and there may be reasonable people with differing views of the issue. This is part of science and the core of the scientific process.

Thirdly, dietary intervention methods must be properly tested and adapted to meet the economic and cultural framework of poor and minority women, who suffer the most from breast cancer. The recommendations from the NCAB and from the Workshop also stress this point. The prior feasibility study was not of the scale to develop interventions (strategies, techniques, and materials) specific to either the Hispanic or Black populations. NCI's studies should be sensitive to the cultural diversity of American women. A decade of cancer control research has made it abundantly

clear that to achieve change, whether in smoking behavior, cancer screening behavior, or dietary behavior, it is essential to understand and tailor methods to the specific target population. It is also essential that no major population subgroup be disenfranchised from participation in our studies. A secondary but important goal of any large scale dietary intervention study is to facilitate clinical research and training opportunities at the various study-centers. Therefore, study-centers should be open to participation by health care professionals from minority and underserved communities. It is also important that the developmental aspect of the study take place even if the NCAB has not focused on the feasibility study in its recommendation. A feasibility study is necessary not only to address the development of techniques and materials, but also to identify the barriers to full participation in the study by these populations.

These studies must include and be germane to those who suffer most from cancer. This is the rationale for our

population-specific emphasis, and the reason NCI endorses the feasibility study to test methods for including Black and Hispanic women in the dietary intervention study.

The recommendations of the NCAB, and the steps being taken by NCI permit the evaluation of intervention methods with respect to the broadest group possible who should benefit from the dietary intervention. In addition, they enable the identification of the best centers, those most suited to compete to perform this study. Every large-scale study includes the subsidiary but important goal of training clinical researchers and it is important to ensure minority participation in this opportunity. The NCI is committed to designing its research to be as applicable as possible to the broadest segment of the American people.

Current Status

NCI is now moving forward based on the recommendations of the DCPC BSC and the NCAB. Requests for Proposals (RFPs) are being issued to identify three clinical centers and a coordinating center to participate in the "Women's Health Trial: Feasibility Study in Minority Populations." One of the clinical centers will have 50 percent or greater representation of Black American women, one will have 50 percent or greater representation of Hispanic women and one will be representative of the U.S. population, including all minorities. The feasibility study will enroll 2,250 women representing all economic levels. It is anticipated that enrollment will begin in the Summer of 1992. The feasibility study is a three-year study and will be conducted by NCI in collaboration with NHLBI.

Policy Advisory Committee: A Policy Advisory Committee will provide oversight of trial operations and scientific progress. Members to be appointed will consist of a subcommittee of the Division of Cancer Prevention and Control's Board of Scientific Counselors and outside experts in clinical trials, biostatistics, nutritional science, behavioral science, cardiovascular disease

and lipids, medical ethics, and other appropriate medical specialties. Their responsibilities will include trial protocol review, periodic evaluation of trial progress including recruitment, compliance to protocols and making recommendations to NCI, NHLBI and their advisory groups as to whether or not the trial should proceed as planned.

Decision Point: A decision to undertake a full-scale trial shall await the results of the feasibility study and review by the National Cancer Institute, National Heart, Lung and Blood Institute and their advisory boards. If the feasibility study is successful, as judged by successful recruitment and dietary adherence, and a decision is made to implement a full-scale trial, women participating in the feasibility study would continue as part of the full-scale trial. The primary objectives of the full-scale trial are to determine whether a low-fat dietary pattern can reduce 1) breast cancer incidence, 2) combined breast cancer and colorectal cancer incidence, 3) fatal and non-fatal coronary heart disease incidence, and 4) total mortality. The full-scale trial would enroll 24,000 women at 12 Clinical Centers with 60 percent randomized to the control group and 40 percent to the intervention group. Women enrolled in the full-scale trial would be followed for a minimum of 13 years and a maximum of 15 years.

DIETARY STUDY ISSUES

Dr. BRODER. In brief, there are essentially two or three camps that have strong feelings on this point of view.

The diet fit study that you are discussing is a prospective randomized trial to test whether a reduction in fat would have significant benefits to women in terms of cancer reduction and reduction of heart disease and vascular disorders.

In brief, there is a school of scientists and laypeople who feel that the answer is known that a reduction in fat with the evidence at hand is something that we should already be adopting, and this school of thought feels there is a strong data base for asking for a reduction so that individuals consume no more than 30 percent of their calories as fat, and, therefore, there is no need to study this issue. The answer is known. And this group, therefore, is not in favor of this study because they feel we should simply be using our educational resources and our informational resources and so on to address this point.

There is another group which feels that the answer is not known, but the particular protocols that have been suggested are not going to give an answer.

There is sentiment in some quarters of our scientific community that there is a strong difference between animal fat and dairy fat, and that you cannot just link all fats together, and that one has to be careful in designing a study that one does not get the wrong answer by not controlling for that variable.

There is another group that feels that it is total calories that count and not just the fat per se.

I am giving you a flavor of some of the differences, but the most significant concern that I personally feel is that we do not have an

adequate preliminary data base on poor and minority women as to whether we have enough cultural sensitivity and appropriateness in addressing how one would implement a low-fat diet for that group. Poor women and minority women have the worst cancer statistics and, therefore, from my own personal point of view, it would be unthinkable that we could make a large scale commitment without ensuring that we have done our homework and that we understand how to do fat reduction interventions in that population and make such individuals integrally part of the studies.

FEASIBILITY OF DIETARY INTERVENTION IN TARGET POPULATIONS

Therefore, what the Institute has done is set up a feasibility study over approximately 3 years. The NCI has committed a total out-year cost of about $7.5 million to do a feasibility study in minority and poor women and to ask whether we can do a culturally appropriate dietary intervention in those groups, and then reassess our position. I cannot give you a commitment today that we will do the large scale diet fit intervention study. There are some technical and scientific issues that for purposes of time I am not sharing with you, but I would be happy to give them to you for the record.

Senator HARKIN. I guess what I hear you saying is that you are doing a review right now.

Dr. BRODER. Sir, we are doing a feasibility study. We actually will launch a feasibility study in poor and minority women. If you ask: Can you do a low-fat intervention? The answer is, yes. It is possible to get certain women to participate in a study and effectively reduce the percentage of their total caloric intake that is fat to 30 percent or to 20 percent or 25 percent, whatever the goal is. But, if the question is also whether this can be done in certain target populations where we have a special need-these issues have not been resolved. I do not think that you can say that the answer is yes. What you do in an educated middle-class community is not necessarily what you would do in an impoverished or minority community. I feel this is a gap. We have to address this point and see whether we can effectively do the study in this group. And that is the feasibility study, to determine whether we can accomplish this goal, and then, if so, how to do it. And again, there are many issues that I am still leaving off for purposes of time. But this study will be underway.

FARM CHEMICALS AND CANCER

Senator HARKIN. Are you doing any studies to look at the possible link between the use of farm chemicals and the increased type of cancers like non-Hodgkin's lymphoma and leukemia that's higher in midwestern farming States?

Dr. BRODER. Yes, sir, we are. In fact, our Division of Cancer Etiology has made a special effort to study these issues and has studied in particular a chemical referred to as 2,4-D. And in fact, I can take great pride in saying that the Division of Cancer Etiology was instrumental in helping to adopt some commonsense but terribly effective ways of dealing with this problem of lowering the exposure of farmers and agricultural workers. And we believe that with

some of the sound recommendations that have been made, that we can minimize, not necessarily eliminate entirely, but minimize to a very significant degree the risks that are attached with 2,4-D and the risk of non-Hodgkin's lymphoma.

NEW TECHNOLOGIES FOR INFORMATION DISSEMINATION

And in addition, we have done as much as we can to disseminate this. I have brought some of the technologies that we use for disseminating knowledge. We have compact disks that we can put our information services on that can be put into what is called a CD read-only memory computer, and individuals can get the latest information that we have. This little disk can hold 350 books worth of knowledge. And we feel this is a cost-effective way, and we are using these types of technologies to get the word out and to make sure that we are reaching communities both in the United States and in other countries as well.

QUESTIONS SUBMITTED BY THE SUBCOMMITTEE

Senator HARKIN. Thank you very much, Dr. Broder. There will be some additional questions from various Senators which we will submit to you for your response.

[The following questions were not asked at the hearing, but were submitted to the Institute for response subsequent to the hearing:]