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treatment with hormones which was being described a short while ago, which now appears may give us a good attack on the disease when it spreads beyond its localized areas. In other words, in those patients who are no longer amenable to our standard treatments which are in general the only methods of cure.
The agencies to which these proposals were made or to which inquiries were made regarding the so-called method for control, were not set up to answer nor did they have the information to give the individuals who might request this information. Also there is the situation that these independent agencies might feel that they were not justified in talking for anyone else, and as I understand this-having come into this picture somewhat later-about 2 years was spent by a very good committee who devoted a lot of time as to the wisdom of this type of committee. Could it accomplish what it was set up to do? It was then decided that this committee should be set up and this was done under the auspices of the National Research Council.
The committee was established in November 1950, and the first meeting of the committee was on February 1, 1951. There were few suggestions and proposals as to what the committee might be expected to do by the sponsoring agencies, which I shall name: The American Association for Cancer Research, the American Cancer Society, the Damon Runyon Memorial Fund, the National Cancer Institute, and the Food and Drug Administration. They all lend their sponsorship and assist in every possible way. I think I neglected to mention the American Medical Association.
The committee has complete leeway to approach this problem on a completely unbiased basis, so that we do not owe anything to anybody. We are a group of individuals who are independent in their own rights, who have no obligation to any of these sources, although we ourselves avail ourselves of the opportunities to receive money for research in our own areas for control of cancer.
The committee membership is composed of a variety of individuals with different disciplines, some with a specific point of view and others who have the ability to understand the problem from a broad horizon. I would like to cite here for the record the Principles and Procedures for Evaluation of Proposals and the Tentative Criteria for Cancer Diagnosis and Therapy.
The CHAIRMAN. We will be happy to have these materials for the record.
(The material referred to follows:)
PRINCIPLES AND PROCEDURES FOR EVALUATION OF PROPOSALS, JULY 1953 Committee on cancer diagnosis and therapy, division of medical sciences, National Research Council, Washington, D. C.
The committee on cancer diagnosis and therapy was initiated by the National Research Council to evaluate proposals and claims for the diagnosis and therapy of cancer, in response to the request of seven national agencies to which such problems were usually referred. These agencies, having greatly diversified activities, recognized the need for the creation of an independent advisory body charged with the collection and evaluation of information in respect of such proposals and claims. The primary objective of the committee is to determine the efficacy of various proposals for the diagnosis and treatment of cancer, and to provide information, advice, and opinions to the organizations that sponsor and support its activities.
I. GENERAL PRINCIPLES AND DEFINITIONS
1. General principles are established. Policies and procedures are necessarily tentative, inasmuch as flexibility is essential to enable the committee to meet widely varying situations. Exceptions or changes can be made at any time by a majority vote of the committee.
2. Every procedure adopted should embody the action of the committee as a group, rather than action as individuals.
3. The primary function of the committee on cancer diagnosis and therapy is to evaluate the efficacy of proposals in this field and to render an opinion to the sponsoring agencies. There are three opinions that can be rendered: (a) The proposal has merit.
(b) The proposal has no merit.
(c) There are not sufficient data to enable the committee to form an opinion in regard to the efficacy of the specific agent or procedure. Under such circumstances:
B. Objectives of the committee
1. To supply an opinion in answer to a request from a sponsoring agency. 2. To supply an opinion to the sponsors on matters deemed important by the committee or the chairman of the division of medical sciences.
3. To provide a central office for the collection of information concerning proposed diagnostic or therapeutic procedures for cancer, and to make a factual summary available, when requested by sponsors or the committee. The executive secretary makes this summary. In such a summary, it should be clearly stated that any ideas expressed therein are not those of the committee; that committee views are stated only in its final opinion.
4. Inquiries that do not come through the committee, the sponsors or the division may be referred to a sponsoring agency or to other sources of information.
The following terms are employed in these procedures:
1. Proponent: A person who claims to have a new test or therapy for cancer. 2. Proposal: The test or therapy that is advocated by the proponent.
3. Exponents: The persons who have taken up the claims of the proponent and are using the procedure.
4. Sponsors: The sponsoring agencies.
5. Request: The formal request for advice or an opinion; this may be submitted by the sponsors, the chairman of the division of medical sciences, or members of the committee.
6. Investigator: A scientist or clinician who may assist the committee by conducting a laboratory or clinical study.
7. Consultant: A specialized individual with specific techniques or training whose advice or opinion is sought by the committee.
8. Observer: An individual who at the request of the committee may visit a proponent or exponent to secure information.
If there is urgency and need for further study, and if mutual agreements with proponents and investigators permit, more data will be accumulated. If the need for a study has diminished, or if it is not possible to reach a mutually satisfactory agreement, a report will be drafted, as specified in IV. C. 2.
II. SELECTION OF INVESTIGATORS, CONSULTANTS, AND OBSERVERS
A. Panels of investigators
Lists are compiled upon :
1. Recommendations from sponsors.
2. Members of committees, panels, and study sections of the Division of Medical Sciences or of the sponsoring agencies.
3. Recommendations from members of the committee or from members of the panels.
4. Recommendations from other investigators who know the qualifications of individuals.
B. Selection of observers, consultants, and idnvestigators
Observers, consultants, and investigators are selected from the panels by the chairman of the committee in consultation with the executive secretary.
C. Arrangements with investigators
Consultants and investigators remain anonymous, unless the committee decides that exceptional circumstanses make another course advisable. arrangements are made through the committee.
III. SPECIFICATIONS FOR ASSEMBLY OF INFORMATION
A. Information on therapeutic procedures to be requested from proponent
1. Therapeutic agent(s):
(a) Method of manufacture, preparation, and sterilization.
(b) Composition and chemical or other specifications.
(c) Stability and data on deterioration.
(d) Method of standardization, including controls and checks.
(e) Method of assay for potency.
(f) Other pertinent laboratory data.
(g) Animal toxicology and pharmacology.
(h) Human toxicology and pharmacology, including patient acceptability, the toxic reactions that may be encountered, and pertinent information concerning the relative frequency, intensity, and type of such reactions.
2. Clinical usage:
(a) Dosage, including method and frequency of administration.
(b) Criteria for selection and for clinical usage of the agent(s).
(c) Time after initiation of therapy that one may expect:
(1) Favorable subjective response and its nature.
(2) Favorable objective response and its extent.
(d) Length of time during which treatment should be continued before it may be assumed that favorable response is not probable.
(e) Advantages and disadvantages of the new agent as compared to those already in clinical use.
3. Therapeutic results:
(a) Number and type of patients for whom the agent (s) has been employed, including:
(1) Total number of patients treated.
(2) Total number of patients for whom the time was too brief for favorable response to be evident.
(3) Number of patients who have received treatment for the period of time considered necessary for evaluating efficacy of the specific therapy.
(4) Information on the type and extent of the last previous therapy given to each case, and the length of time that intervened between such treatment and initiation of the therapy under study.
(b) Clinical results obtained, including the number and types of cases that have shown favorable or unfavorable response. Details should be given concerning the objective or subjective nature of these responses, and also their consistency and duration.
(c) Other investigators who have employed this mode of therapy.
4. Published reports:
(a) List and reprints of proponent's publications concerned with this therapeutic agent(s).
B. Information on diagnostic procedures to be requested from proponent 1. Type of procedure.
2. Agents and reagents employed, with data on:
(b) Methods of preparation and standardization. (c) Stability.
3. Explicit directions for carrying out the test.
4. Diagnostic results, including:
(a) Number and types of cases that were tested:
(1) Cancer-with basis for diagnosis, type of neoplasm, and stage of the disease.
(2) Controls-normal individuals and other diseases.
(b) Number of tests done under each of the above three categories, with results expressed in numbers and percentages.
5. Results obtained by other investigations using this test.
6. Published reports:
(a) List and reprints of proponent's publications concerned with this diagnostic procedure.
(a) Information on the proposal and the therapeutic or diagnostic agent(s), procedure, and results furnished by proponent, as detailed under III A and B. (b) Information on the proposal obtained from the sponsors, other responsible organizations or individuals and from publications.
2. Financial data:
(a) Expense of the test or therapy.
(b) Support for the proposal.
3. Reports of previous investigations.
(a) Biographical information.
(b) Results obtained by use of the procedure.
(c) Copies or abstracts of pertinent publications.
6. Organizations and institutions:
(a) Information on scientific, legal, and financial aspects as related to the proposal.
(b) Additional personnel concerned with the proposal.
D. Basic information for clinical investigators
1. Statement of policy of the committee.
2. Arrangements for the specific study.
3. Criteria formulated by the committee and approved by the proponent. 4. Scientific biography of proponent.
5. Brief historical background of the proposal.
6. Therapeutic agent-composition, manufacture, etc.
7. Safety factors-pharmacology, toxicology, sterility.
8. Clinical usage, including the criteria and directions given by the proponent. 9. Times and nature of response.
10. Therapeutic results reported by proponent and others.
A. The request
IV. STIPULATIONS IN RELATION TO SPECIFIC TERMS
1. The request must be officially presented:
(a) By the sponsors-in writing.
(b) By the committee members-in writing between meetings, or as a motion at the time of the meeting.
(c) By the Chairman of the Division of Medical Sciences.
2. Requests for opinions from the proponents or others than the sponsors, the Divisions or committee members must be referred to the sponsors for preliminary review.
3. All sponsors are notified simultaneously concerning the committee action on a request.
B. The proposal
1. The proposal must be of unestablished or controversial nature.
2. Information on the nature of the proposal must be available.
3. In order to avoid duplication of effort, except in unusual circumstances: (a) The proposal must not be in the process of being tested or evaluated by any of the sponsors.
(b) After the committee has initiated a study, it is understood that the sponsors will not initiate an independent study of this proposal except with the consent or by the request of the committee.
(c) If another evaluation of the same proposal is in process at the time the request is received, or has been previously undertaken by independent qualified investigators, consideration should be given thereto and to the need and advisability of assisting a current investigation.
4. A preliminary estimation of the urgency and need for an evaluation of a proposal should be made by the sponsors and committee members. These views will guide the committee in the decision concerning acceptance of the request.
Both the preliminary estimation and the priority rate to be assigned an investigation should be based on such factors as:
(a) Acuteness of the problem nationally.
(c) Scientific status of proponent and of proposal. The purpose of this procedure is to permit the committee to devote its major efforts to the more urgent proposals. At any stage in an investigation, at the discretion of the chairman, an expression of views may again be sought and a change in the priority rate be made.
C. Reports to sponsors
1. An interim progress report on an investigation may be requested by a sponsor at any time. When prepared, it will be sent to all sponsoring agencies. Further use of this report should be decided by the sponsors, preferably by mutual agreement.
2. If an inquiry has reached an impasse, due to inability of the proponent and the committee to reach an agreement, and further progress appears improbable, a report will be drafted. It will include information on the steps taken, the factual findings and whatever conclusions can be based on available data.
3. Reports will be circulated to the committee. The approval of the committee, the Chairman of the Division, and the legal adviser of the National Academy of Sciences, are required for a report to become official.
D. The opinion
1. The opinion of the committee is formulated by the members, either at a meeting or by mail.
2. A majority of the committee members must agree with the opinion. The minority may formulate a minority opinion, if desired.
3. If there is not agreement on formulation of an opinion, the inquiry will be reassessed for the purpose of determining what further steps, if any, should be taken.
V. PROCEDURES FOR EVALUATION OF PROPOSAL
A. Vote regarding acceptance of request
1. An opinion on a proposal may be requested from the committee whenever: (a) Information on the nature of the proposal and the indications for a study are available.
(b) Views of sponsors and members concerning the urgency of the proposal are known.
(c) Inquiries have been made concerning other past or current evaluation studies.
2. Acceptance of request includes assignment of priority rating by the Committee.
3. The sponsors are notified concerning the committee's action on a request.
B. Steps to secure cooperation and information
1. Proponent is contacted.
(a) Letter requests cooperation.
(b) Statement of policy is included with letter.
(c) If reply is favorable, further steps are taken.
2. Proponent is requested to present his data, claims, criteria, and evidence as detailed in III A or B.
3. A survey is compiled as specified in III C.
4. Panel or a representative, appointed by the chairman and representing the committee, visits the proponent:
(a) To establish mutually acceptable basis for further study.
(b) To secure further information.
(c) To discuss criteria, provision of agents and a plan of study.
5. There is sent to the committee:
(c) A sheet for expression of views regarding adequacy of data and for further comments.
6. If data are deemed deficient, requests may be made for :
(a) Additional evidence to be assembled by proponent.
(b) Advice or assistance of special observers or consultants for specific problems (i. e., chemist, pharmacologists, clinician for review of records, etc.).