Full Text AG-96-001 TRIAL OF A COGNITIVE INTERVENTION FOR OLDER ADULTS NIH GUIDE, Volume 24, Number 34, September 29, 1995 RFA: AG-96-001 P.T. 34, CC Keywords: Aging/Gerontology Cognitive Development/Process Clinical Trial National Institute on Aging National Institute of Nursing Research Letter of Intent Receipt Date: January 15, 1996 Application Receipt Date: March 20, 1996 PURPOSE This Request for Applications (RFA) seeks applications to pursue a cooperative field trial of a cognitive or related perceptual intervention to maintain and promote independent functioning among older adults. This RFA targets older adults who are at increased risk for loss of independence through hospitalization, need for formal care, or other major restrictions in quality of life. A number of recent findings have indicated some promise of preventing or postponing declines in critical activities of daily living through intervention to improve cognitive or related perceptual abilities and skills. However, differences in the outcome measures examined, the kind of intervention chosen, and the samples tested indicate that it is not possible to generalize from individual findings to reach consensus on the success or failure of these techniques. The objective of this project is to stimulate researchers to develop a cooperative trial investigating whether a common cognitive intervention conducted by several sites simultaneously can improve functioning or postpone decline in different samples of subjects, varying in racial, ethnic, gender, socioeconomic, and cognitive characteristics. The common protocol will then allow a consensus assessment of the success of this approach with respect to the likelihood of preventing or postponing the loss of independence, need for formal care, or other major restrictions in quality of life. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priorities. This RFA, Trial of a cognitive Intervention for Older Adults, addresses several priority areas including chronic disabling conditions, physical activity and fitness, and unintentional injuries as they relate to older people. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202/512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT The support mechanism for these awards will be the cooperative agreement (U01), an assistance mechanism in which substantial NIH scientific involvement with the awardee is anticipated during performance of the activity, as outlined in the award. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipients in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships, and governance of the study to be funded under the cooperative agreements are discussed later in this document under the section "Terms and Conditions of Award." Five years of support should be requested. At that time, depending on the results of the exploratory trial, a second RFA may be issued to pursue a full-scale trial of the intervention. FUNDS AVAILABLE Field Sites It is estimated that $1,380,000 in total costs will be available in the first year for start-up costs associated with the field sites. Funds available for the field sites in the second and subsequent years are expected to increase to $2,700,000 in total costs. These funds are expected to support five to seven sites at an average cost of $450,000 in total costs. Site-specific protocols will be allowed, but will have a maximum of $50,000 in total costs each per year. The purpose of the maximum amount is to protect the integrity of funding for the common protocol. Coordinating Center In the first year, up to $80,000 will be available for start-up costs associated with the coordinating center. In the second year up to $200,000 is expected to be available. In the third year these funds are expected to increase to $400,000 and in the fourth and fifth years the available funds are expected to be $600,000. All estimates are expressed as total costs. These funds will support one coordinating center. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of NIA and the NINR, the award of cooperative agreements pursuant to this RFA is contingent on the availability of funds for this purpose. RESEARCH OBJECTIVES Background The long-term goal of this initiative is to reduce the increasing public health problems of need for formal care, hospitalization, and substantial loss of independence in the Nation's growing number of older persons. Persons over the age of 65 account for almost half of all days of care in short stay hospitals and constitute the majority of residents of nursing homes. Interventions that can postpone or prevent hospitalization or formal care, therefore, have much to contribute both to public health and to the quality of life among older people. The immediate goal of this initiative is to examine the effects of perceptual and cognitive interventions on more proximal outcome measures that are associated strongly with hospitalization and need for formal care. The impetus for this trial comes from (a) the recent success of a number of different cognitive, or related perceptual, intervention techniques at enhancing some aspects of ability or functioning; (b) the increasing evidence that cognitive factors are associated with key public health outcomes such as hospitalization and death; and (c) the increasing need to find preventative techniques that successfully maintain the quality of life of the older population. Studies reporting success with laboratory-based interventions include: Interventions to increase scores on intellectual abilities (e.g., Baltes & Willis, 1982; Labouvie-Vief & Gonda, 1976; Hayslip, 1989; Hayslip, Maloy, & Kohl, 1995; Willis, 1987); techniques to improve speed of reaction (Baron & Mattila, 1989); training to boost functional perceptual abilities (Ball, Beard, Roenker, Miller, & Griggs, 1988) and training on various aspects of memory (Greenberg & Powers, 1987; Yesavage, 1985). Several studies have also identified a relation between the abilities and skills being intervened on and performance on everyday activities of critical importance to independent functioning (Leirer, Morrow, Pariante, & Sheikh, 1988; Owsley, Ball, Sloane, Roenker, & Bruni, 1991; Ball, Owsley, Sloane, Roenker, & Bruni, 1993). Recent research has confirmed earlier findings of an association between decline in cognitive functioning and measures of hospitalization, need for formal care, and mortality. Analyzing data from the Longitudinal Study on Aging, Wolinsky and Johnson (1991) found that a factor they call advanced activities of daily living (advanced ADL) was uniquely associated with bed-disability days, hospital contact and mortality. The advanced ADL measure was constructed to focus on cognitive capacity and included measures of telephone communication and planning for the future. Several studies using a range of measures of cognitive impairment have established associations with quality of life of family members and risk of institutionalization (e.g., Branch & Jette, 1982). More recently, Kelman, Thomas, and Kennedy (1994) have identified an association between both mild and severe cognitive impairment and mortality in community-dwelling elderly. Swan, Carmelli, and LaRue (1995) reported that performance on the digit-symbol substitution test was associated with five-year mortality in their sample of older men. The association remained after adjustment for age, education, baseline serum cholesterol, and blood pressure. The association was of the same order as that of a subgroup of subjects with a history of cancer. The above promising findings demonstrate the success of cognitive interventions at improving performance in activities of daily living, and illustrate the now clear links between decline in cognitive function and subsequent hospitalization, need for formal care, and mortality. Nevertheless, no clear consensus exists on the likelihood of success of cognitive interventions at reducing the public health problems of hospitalization and need for formal care in the older population. Differences in the outcome measures examined, the interventions tested, and the samples recruited have made generalizations across different findings impossible. This trial seeks to address these problems by testing a planned intervention on defined samples using common outcome measures. Therefore, the trial will explore whether site-specific variations or specific sample characteristics limit the applicability of the findings. Study Design The scientific goal of the trial is to test the efficacy, using field measures of functioning, of a cognitive or related perceptual, motivational and attitudinal intervention that has previously been found to be successful at improving functioning under laboratory or small-scale field conditions. The focus should be on older adults who are identified to be at risk of loss of independence from causes to which the variables under study contribute. The particular protocol to be developed must provide tests of theories linking changes in degree of independence, to increases or decreases in intellectual and perceptual strategies and processes. Therefore, in order to retain the advantage of a multisite field trial, yet capitalize on the interventions already found to be successful in laboratory studies (see below), the trial should focus on a class of outcome measures that are basic to living independently, have a strong cognitive component, and whose decline has been associated with loss of independence. These significant everyday tasks include, but are not limited to: communicating via the telephone, remembering key events and activities (e.g., remembering to eat, remembering to take medication), and financial planning and management. The intended subject populations must be living largely independent of formal care at the point of entry into the study. Improvement, or postponement of decline, in the activities of daily living (telephone communication, financial management, etc.) should be the primary outcome variable. The final protocol will be designed to allow maximum power on tests of the intervention on this class of variables. Investigators are also encouraged to develop tests for secondary outcome variables, such as hospitalization, need for formal or informal assistance, disability, morbidity, or mortality. However, power calculations should be based on the primary indicator (or indicators) of outcome. The common intervention should involve training of basic abilities or skills, or training on factors expected to boost such basic abilities or skills. Thus, the study should not intervene directly on the outcome variables. The study should include intermediate examinations of maintenance of training effects on the basic abilities and skills. Failure to show maintenance of these effects may be considered a reason to stop the trial. These tests do not substitute for final analyses of the effects of the intervention on the primary outcome variables. Such a test should be planned to be conducted at a time beyond the initial intervention determined by power calculations on differences in the expected relative rate of decline among experimental comparison groups. Particular sites may also propose studies that are planned as site- specific. These studies should be planned to complement or extend the multisite protocol. For example, they may address issues of the specificity of transfer. They may compare the efficacy of training versus cuing (or other environmental support) as a means of maintaining or increasing competence in critical everyday tasks. They may compare the efficacy of intervening on basic abilities alone versus on outcome variables alone, or in combination with training on basic abilities. Such separate hypotheses must be integrated with the planned cooperative project in such a way that their investigation does not compromise the integrity of the cooperative trial across sites. Each application (except for the coordinating center) should propose one intervention as its candidate for the cooperative trial as a whole. The intervention should be designed to improve performance on outcomes that: (a) rely on intact cognitive functioning; and (b) are critical for maintaining independence. These outcomes include but are not limited to: telephone communication, financial management and planning, and remembering key events or instructions. Subsequently, a common protocol will be developed by the steering committee combining the best features of the proposed protocols; this intervention will be used by all field sites. The outcome measures must be justified by: (a) an analysis showing the degree to which the intervened abilities or skills are related to the outcome being measured; (b) their association with direct measures of loss of independence or disability, morbidity or mortality (e.g., hospitalization, need for formal care, bed- disability days); and (c) their estimated sensitivity to tests of the effect of the proposed intervention. Applications must address the issue of the likelihood of transfer of training from the cognitive abilities and skills examined to the primary outcomes proposed. Several recent studies have found that although training is successful at boosting cognitive abilities, transfer to other skills is limited (e.g., Dittman-Kohli, Lachman, Kliegl, & Baltes, 1991, Neely & Backman, 1995). Applications must offer a theoretical rationale as to why transfer would be expected. If the proposed outcome assessment is limited to self- or proxy- report of functioning, the particular self-report or proxy-report surveys used must previously have been validated against relevant outcomes. Simulations may be used as manipulation checks or to provide additional measurement of the outcome. However, the primary outcome measures upon which the intervention is evaluated must be a clearly delimited set, justified by the criteria described above. The intervention that is adopted for this trial as a whole will be conducted cooperatively by all field sites participating in the trial. Therefore, in order to ensure uniform administration across sites, investigators must propose standardization criteria for assessing baseline and follow-up performance on the outcome measures as well as standardization criteria for implementing the intervention. The initiative will examine an intervention designed to prevent, or reduce the risk of, future loss of independence rather than rehabilitate older adults who are already dependent. Therefore, subject groups should be selected who are at recognizable risk of loss of independence but who are living independently at the point of entry into the study. Relevant risk factors can include demographic and social, as well as cognitive factors. Applications may propose screening and eligibility criteria to identify target subjects. The criteria should be expected to eliminate both those who are at little risk of loss of independence over the term of the study and those who, because of a prevailing disease or medical condition (e.g., Alzheimer's disease), would be poor candidates for intervention. However, costs of screening must be carefully controlled to accommodate the overall budget for the study. Investigators may wish to consider collaborating with sites in which there are studies ongoing that use well described samples whose cognitive abilities are already known. Such collaboration may substantially reduce the costs of screening. This initiative is focused on an assessment of the intervention at a substantial interval after treatment. Therefore, proposed designs must be able to accommodate attrition as well as test the efficacy of the treatment on those subjects who adhere to instructions throughout the testing period. Potential applicants should be familiar with appropriate methodological approaches to minimizing attrition, should indicate the expected amount of attrition, and should justify the approach to minimizing attrition that they propose to adopt. Because this field trial is preliminary, power calculations on the primary outcome measures should be based on the number of subjects expected to complete the study, rather than the total number recruited into the study. However, attrition rates substantially higher than expected will be considered a reason to stop the study. Moreover, because the initiative focuses on a delayed assessment, the design for the multisite trial should include intermediate tests of maintenance of the intervention on the targeted basic abilities. The design may also include strategies to ensure maintenance of the intervention's effects, including booster training sessions. SPECIAL REQUIREMENTS A coordinated multisite protocol is dictated by the need to have a planned intervention examined on a defined sample using a common set of outcome measures. The terms and conditions section describes the elements and organization required to assure that a common protocol can be agreed upon, and that recruitment and operating procedures are standardized across intervention sites. Multiple intervention sites will conduct the common protocol. A coordinating center will interact with the intervention sites to ensure the smooth conduct of the trial and to organize data collection and analysis. A steering committee will be the main decision-making body for the trial. An advisory panel, chosen by the steering committee, will provide advice to the committee on the performance of particular sites and on the progress of the trial. These intervention sites may also run site-specific studies designed to complement the multisite protocol. Such studies will not be part of the multisite protocol. The following terms and conditions will be incorporated into the award notice. Terms and Conditions of Award The following special Terms of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92 and other HHS, PHS and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is a cooperative agreement (U01). Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the collaborative aspects will be shared among the awardees and the NIA/NINR scientific coordinators. 1. Organizational Components Intervention Sites An intervention site is one of several institutions that will receive awards for conducting the multisite protocol under this RFA. The Principal Investigator at each applicant intervention site is encouraged to form a multidisciplinary team, including a senior staff member or consultant who has expertise in clinical trials. Each intervention site will be responsible for recruiting subjects, collecting data using the common protocol, and submitting data to the coordinating center. Intervention site may conduct site specific studies. Coordinating Center The coordinating center will interact with the intervention sites, an advisory panel, and the NIA/NINR scientific coordinators on a variety of topics ranging from seeking and compiling information, to providing technical assistance, to conducting cross-site analyses. In consultation with other organizational components, the coordinating center will have the primary responsibility for instrument development and testing activities (e.g., compiling the listing of proposed common measures; reviewing the literature and assessing the advantages and disadvantages of different measures for common study variables; conducting psychometric analyses on the common data set; and making recommendations at the end of the study about the most parsimonious set of measures to be archived). Moreover, the coordinating center will be responsible for tracking recruitment and retention across the different sites, and advising the sites on strategies for enhancing recruitment/retention, especially in minority populations. The coordinating center will also ensure that data collection is standardized, and will manage and analyze the common data set. This work will also include setting up data collection systems at the different intervention sites and visiting the sites to set up these data systems. The coordinating center will also provide certain support functions. It will develop a cross-project manual of procedures, maintain a directory of intervention sites' staff, arrange all conference calls and meetings, and facilitate information exchange among the sites and NIH, and with the general research community. Steering Committee A steering committee, composed of one principal investigators from each field site, the principal investigator at the coordinating center, and the NIA/NINR scientific coordinators, will be the main governing body of the study. The steering committee will elect a chair from among the principal investigators. The steering committee may also establish subcommittees to oversee major operational components of the study. One vote will be given to each principal investigator and to the NIH. The steering committee will meet at least every six months. The steering committee will have overall responsibility for the multisite intervention and will review, for inclusion in the protocol, proposals from its members for any modifications designed to facilitate any aspect of recruitment, design, or analysis. The steering committee will specify the common data set to be collected, using the information in this RFA as a guide. With the advice of coordinating center staff, it will specify procedures and frequency of data submission to the coordinating center. It will specify rules concerning access to data generated from the multisite protocol. The steering committee will establish a publications subcommittee to advise on publication and presentation of data collected through the multisite protocol. The chair of the steering committee will also serve as the chair of the publications subcommittee. The publications subcommittee will review all proposed presentations and publications using data from the common protocol. The subcommittee will be responsible for setting standards and guidelines for presenting and publishing data from the common protocol. The subcommittee will also advise on public information dissemination activities regarding the common data set. These requirements are not intended to jeopardize individual investigators' rights to their own data, but are intended to facilitate data sharing and collaborative work. Advisory Panel An advisory panel will be selected by the steering committee to serve in an advisory capacity to the study and all its organizational components. The functions of this panel include reviewing the multisite intervention protocol and making suggestions to the awardees and the NIA/NINR scientific coordinators; monitoring individual site performance, using material provided by the coordinating center and through site inspections; advising the steering committee on design and protocol changes requested by individual investigators; reviewing site-specific protocols and advising on disagreements regarding site-specific studies; and advising the awardees and NIA/NINR scientific coordinators regarding analyses and publications arising from the multisite protocol. The panel will also serve as a data and safety monitoring board for the multisite protocol. In that capacity panel members will monitor the protocol at individual sites for possible adverse effects associated with the design and for variations from prevailing NIH policy on treatment of human subjects. The panel will consist of at least six experts in relevant behavioral, clinical, statistical, and bioethical fields and will convene at least once a year. The experts must be independent of all components of all sites participating in the multisite protocol and be free from conflicts of interest with awardees. A chair will be elected by members of the advisory panel with input from the NIA/NINR scientific coordinators. The chair of the steering committee, the principal investigator of the coordinating center, and the NIA/NINR scientific coordinators will all participate as non-voting members during each panel meeting. Interim conference calls and other correspondence may be necessary between meetings. Two panel members will visit each of the field sites and the coordinating center twice during the course of the multisite protocol. The members will report back to the full advisory panel on the site's compliance with data collection and record keeping procedures and with safety and ethical issues concerning human subjects. 2. Responsibilities Awardee Rights and Responsibilities Awardees individually propose a research design for the common protocol and collectively decide on the design for the common protocol. They are responsible for data analysis. Through the steering committee, they are responsible for changes in the direction of the project and the scope of activities at particular sites. Through a publications committee, they are responsible for preparing publications from the multisite protocol. The individual awardees are responsible for recruitment and retention at their own sites. The coordinating center awardee is responsible for developing and updating a manual of operations and for quality control at the different field sites. Awardees will retain custody of and have primary rights to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. NIH Staff Responsibilities The NIH scientific coordinators will have substantial scientific/programmatic involvement during conduct of the activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants. Such assistance is intended to facilitate, not to direct, the design, implementation and analysis of the trial. Awardees agree to accept assistance from the NIA/NINR scientific coordinators in: o providing technical assistance for developing the common protocol for the multisite intervention, and for formulation or consideration of refinements and adjustments to the study objectives, design and protocol; o monitoring of performance issues involved in recruitment, follow- up, quality control, adherence to protocol, and attainment of study objectives; o assistance in analysis and reporting of the multisite intervention study results; o assistance in identifying subject-matter and financial experts to help the steering committee; o assistance in locating potential replacements for key personnel involved in the project. The NIA/NINR scientific coordinators may also provide advice on statistical requirements. In instances where the NIA/NINR scientific coordinators has had significant input into study design and analysis, and in accordance with publication guidelines developed by the publications committee, and with NIH policies regarding staff co-authorship of publications resulting from extramural awards, he/she may cooperate with awardees as a co- author in preparing manuscripts that report results from these studies. As part of these duties, the NIA/NINR scientific coordinators will meet at least three times with other steering committee members in the first year of the award, and at least twice a year in subsequent years. The scientific coordinator will also meet at least once a year with advisory panel members. Collaborative Responsibilities Development and monitoring of common protocol. The awardees, with the assistance of such other experts as are deemed necessary by the steering committee, shall develop, within six months of the official start date of the awards, a single common protocol for multisite testing of the intervention, drawing upon the best aspects of the applicants' proposals. The protocol will be reviewed by an advisory panel that is chosen by the steering committee. The advisory panel will recommend changes to the steering committee not later than three months after receiving it. The steering committee will then decide on the final form of the protocol. Awardees will be required to accept and implement the common protocol and procedures approved by the steering committee. Following implementation of the protocol, the steering committee will meet at least twice a year, once may be by teleconference, to consider progress at individual sites, progress in the multisite protocol as a whole, and any modifications to the protocol either at individual sites or across all sites. The steering committee will consider advice from the advisory panel as well as input from steering committee members in making decisions regarding the common protocol. Site-specific studies. Individual awardee investigators who conduct site-specific studies in conjunction with the overall trial must submit any proposed study, or modification to a study, to the steering committee regardless of whether the study or modification is considered to affect the management or implementation of the common intervention protocol. Before approving a single-site protocol, the steering committee will determine whether the proposal complements or extends the overall project, and whether it interferes with the common protocol. The $50,000 maximum funds for a site-specific study may be reduced by the steering committee. Arbitration Process Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIH may be brought to arbitration. An arbitration panel will be composed of three members - one selected by the steering committee (the NIH representative will not vote) or by the individual awardee in the event of an individual disagreement, a second member selected by the NIH, and the third member selected by the prior two selected members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR 50, Subpart D, and HHS regulations at 45 CFR Part 16. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by January 15, 1996, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of the key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIH staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to: Dr. Jared B. Jobe Behavioral and Social Research National Institute on Aging Gateway Building, Room 533 7201 Wisconsin Avenue, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-3137 FAX: (301) 402-0051 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3034, Bethesda, MD 20892-7762, telephone 301/710-0267, girg@drgpo.drg.nih.gov; and from the program administrator listed under INQUIRIES. The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. With the exception of coordinating center applications (see below), instructions in the PHS-398 form should be followed as if the application were a regular (R01) research grant request. Additional Information The information below is requested in addition to the requirements in the PHS 398 package. With the exception of the budget information, all additional information described below should be presented as part of the research plan, which is limited to no more than 25 pages. 1. Choice of Outcome Variables As part of the proposed common intervention each application must propose primary outcome variables that are: (a) measures of activities of daily living; and (b) have a strong cognitive or perceptual component. In particular, applications must offer empirically supported models of the relation between the outcome variables and the cognitive or perceptual abilities and skills being trained. Estimates of the effects of the intervention on these outcome variables must yield sufficient power so that a multisite trial with the budget structure and amount shown under FUNDS AVAILABLE can provide an adequate test of the hypotheses on these outcome variables. 2. Multisite and Single-site Interventions Any intervention proposed by an applicant as the common protocol must be justified by prior published work. These studies must be directly related to the proposed intervention and allow estimates of the likely size of effect of the intervention on samples to be recruited through this trial. Such prior publications are not necessary for interventions proposed as single-site studies. As with a conventional grant, however, theoretical rationale, supporting literature, and some supporting pilot data are an advantage. 3. Sample Population The application must specify the desired sample characteristics (e.g., age, sex, ethnic status, health-status) and size of the multisite sample required to test the proposed multisite intervention. The application must also specify characteristics of the sample to be recruited at the local site. The application must specify the particular recruiting strategies to be used to attract target subjects and any special outreach procedures that will be used to ensure retention of diverse subject groups in the common protocol. If the applicant is proposing collaboration with other investigators who have already recruited well-defined samples to ongoing studies, the letter of collaboration from the principal investigator of such studies must specify the numbers of subjects available for the study and their demographic profile. 4. Screening Instruments Any screening instruments that are proposed for the cooperative trial must be justified both in terms of reliability of measurement and validity in relation to the target subject populations. Estimates of the proportion of subjects who would be excluded through these instruments, and the costs of recruiting replacement subjects should be clearly indicated. 5. Data Analysis The data analysis section should describe both the specific analyses to be performed on site-specific studies, and the analytic plan that yields the power estimates on which the proposed multisite intervention is based. A limited set of primary outcome variables must be identified in the analysis plan. 6. Cooperation The applicant must indicate a willingness to work cooperatively with the NIA/NINR scientific coordinators, the data coordinating center, fellow principal investigators, and the advisory panel in pursuing the research project. 7. Organizational Structure An organizational structure for the intervention site should be described in the application, designating lines of responsibility and authority. 8. Budgeting The applicants should prepare a detailed budget for the first twelve months of the project at the applicant's institution (including sub- contracts). The applicants should assume that data collection does not begin until the tenth month of the project. During the first nine months, funds should be budgeted for the principal investigator, and two other investigators to travel to three steering committee meetings in Bethesda. Funds should also be budgeted for one meeting a year subsequent to that in Bethesda. Applicants should also prepare a budget for the investigator's site-specific costs in all years of the cooperative agreement. Finally, the applicant should prepare a budget for all years of the proposed cooperative intervention across all sites. The budget should reflect all costs of the multisite trial across all sites. Investigators are not required to identify all sites in their application. Costs should be projected using direct costs at the applicant site as the base. Applicants should use a 50 percent indirect cost rate to estimate total costs at sites other than those identified in the application. Acceptance of funding under this RFA implies agreeing to be a participant site for the multisite field trial. 9. Advisory Panel Candidates should not be contacted or recruited to serve on the advisory panel or be named prior to the onset of the project. However, applicants are encouraged to specify areas of expertise appropriate for representation on the panel. Advisory panel members will be reimbursed for necessary travel and attendance at advisory board meetings, but will not receive consultant fees for input to individual projects. Travel funds for members of the panel are to be included as a line item in the coordinating center budget. Special Instructions for Coordinating Center Applications Two completely different applications, with different principal investigators, must be submitted if an institution seeks selection both as an intervention site and as the coordinating center. The coordinating center will provide expertise in multisite field trial design, in the data management and communication associated with such trials, and with multivariate statistical techniques required for analysis and reporting of the results. It is essential that applicants show such expertise among the personnel selected for the coordinating center. Completion of PHS 398 The data coordinating center applications should use the form PHS 398 (rev.5/95). However, the following procedures should be applied in completing it. 1. Human Subjects The data coordinating center is not responsible for Institutional Review Board review of human subject protocols. That is the duty of the individual sites. 2. Budget Both the detailed budget for the first year and the full budget for all years should reflect only costs specific to the data coordinating center. The first year budget should assume that data collection begins in the tenth month of the award. The budget should include projected costs of travel by the advisory panel to the individual field sites and to Bethesda. The budget should include funds for one annual visit to Bethesda by the advisory panel (assume six members of the committee), and funds for two site-visits to each of the field sites by two panel members across the five years of the trial. 3. Research Plan This section should reflect plans for data management (including entering, editing, and storing of data); plans for data archiving; plans for establishing an effective communication network among the different project sites; plans for producing forms, protocols, and a manual of operations for the multisite trial; plans for receiving information from the sites on a regular basis; and plans for integrating that information and providing summaries to the sites, the NIA/NINR scientific coordinators, and the advisory panel. The section should also discuss strategies for enhancing recruitment and retention of subjects at intervention sites, especially among minority populations. This section should also discuss succinctly the alternative benefits of different approaches to data analysis. (The data coordinating center will provide a key role in the design of the multi-phase trial at the start of the project. The center will provide key expertise on how best to integrate the data from the different sites, on the costs to data quality of individual site variation in project design, and on the advantages and disadvantages of different methods of pooling data. These and other relevant issues must be discussed in the application.) All applicants, including coordinating center applicants, must submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies, in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to: Dr. Michael Oxman Scientific Review Office National Institute on Aging Gateway Building, Room 2C212 7201 Wisconsin Avenue, MSC 9205 Bethesda, MD 20892-9205 Applications must be received by March 15, 1996. If an application is received after that date it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and responsiveness by NIA/NINR. Incomplete applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIA in accordance with the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the national advisory councils of NIA and NINR. Review Criteria: Field Sites Both the proposed multisite intervention and single-site studies will be evaluated for: o scientific significance and originality of the proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to conduct the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in perceptual and cognitive functioning and aging; o availability of the resources necessary to conduct the proposed research; o appropriateness of the proposed budget; o adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will be evaluated. The initial review group will also examine the provisions for the protection of human and animal subjects and the safety of the research environment. The proposed multisite intervention will be evaluated for the following additional criteria: o a demonstrated need for the intervention in the proposed target population; o evidence that the intervention has worked in prior small-scale or laboratory studies; o a theoretical rationale that links the targeted basic abilities to the primary outcome measures proposed; o a recruitment strategy that shows how appropriate numbers of suitable subjects can be recruited for the intervention and retained in the study. The recruitment strategy must include a description of procedures to ensure adequate recruitment and retention of women and minority subjects; o evidence of prior experience with multisite clinical or field trial studies; o the time commitment of the principal investigator should be sufficient both to ensure personal supervision of the day-to-day running of that field site and to ensure time to work cooperatively with the coordinating center, principal investigators of other field sites, the advisory panel, and the NIA/NINR program administrators; o demonstrated willingness of the principal investigator and staff to work collaboratively with the coordinating center, the other principal investigators, the advisory panel and the NIA program administrator. Review Criteria: Coordinating Center: o adequacy of the proposed operating procedures for the management of the multisite intervention; o adequacy of the proposed plans for data management and archiving, and for communication among field sites and the coordinating center; o appropriate discussion of alternative procedures for data analysis; o leadership ability, relevant experience in appropriate areas, and scientific stature of the principal investigator. The time commitment of the principal investigator must be sufficient both to supervise the coordinating center staff and to liaise with principal investigators of field sites, the advisory panel, and the NIA/NINR program administrators; o qualifications and experience of other staff of the coordinating center, and their investment of time in the project. It is important that some coordinating staff show prior experience in data analytic and project-coordinating aspects of the management of a multisite field trial; o Commitment from the host institution to the coordinating center's activity and availability of appropriate facilities for the activities proposed; o The appropriateness of the budget. AWARD CRITERIA Awards will be made on the basis of the availability of funds with consideration being given to the compatibility of the different projects funded and the overall representation of women and minorities across the sites selected. Primary weight will be given to results obtained through the NIH peer review mechanism. Schedule Letter of Intent Receipt Date: January 15, 1996 Application Receipt Date: March 15, 1996 Review by Advisory Councils: September, 1996 Anticipated Award Date: September 30, 1996 INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Jared B. Jobe Behavioral and Social Research National Institute on Aging Gateway Building, Room 533 7201 Wisconsin Avenue, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-3137 FAX: (301) 402-0051 Email: Jared_Jobe@nih.gov Dr. J. Taylor Harden Extramural Programs National Institute of Nursing Research Natcher Building 45, Room 3AN-12 45 Center Drive, MSC 6300 Bethesda, MD 20892-6300 Telephone: (301) 594-6906 FAX: (301) 480-8260 Email: THarden@ep.ninr.nih.gov Direct inquiries regarding fiscal matters to: Mr. David Reiter Grants and Contracts Management National Institute on Aging Gateway Building, Room 2N212 7201 Wisconsin Avenue, MSC 9205 Bethesda, MD 20892 Telephone: (301) 496-1472 Email: David_Reiter@nih.gov Bibliography Ball, K., Beard, B.L., Roenker, D.L., Miller, R.L., & Griggs, D.S. (1988). Age and visual search: Expanding the useful field of view. Journal of the Optical Society of America, 5, 2210-2219. Ball, K., Owsley, C., Sloane, M.E., Roenker, D.L., & Bruni, J.R. (1993). Visual attention problems as a predictor of vehicle crashes in older drivers. Investigative Ophthalmology and Visual Science, 34, 3110-3123. Baltes, P.B., & Willis, S.L. (1982). Plasticity and enhancement of intellectual functioning in old age: Penn State's Adult Enrichment Project (ADEPT). In F. I. M. Craik & S. Trehub (Eds.) Aging and Cognitive Processes (pp. 353-390). New York: Plenum Press. Baron, A., & Mattila, W. R. (1989). Response slowing of older adults: Effects of time limit contingencies on single and dual task performances. Psychology and Aging, 4, 66-72. Branch, L. G., & Jette, A. M. (1982). A prospective study of long- term care institutionalization among the aged. American Journal of Public Health, 72, 1373-1379. Dittman-Kohli, F., Lachman, M. E., Kliegl, R., & Baltes, P. B. (1991). Effects of cognitive training and testing on intellectual efficacy beliefs in elderly adults. Journal of Gerontology: Psychological Sciences, 46, P162-164. Greenberg, C., & Powers, S. M. (1987). Memory improvement among adult learners. Educational Gerontology, 12, 385-394. Hayslip, B., Jr., (1989). Alternative mechanisms for improvements in fluid ability performance in older adults. Psychology and Aging, 4, 122-124. Hayslip, B. Jr., Maloy, R. M., & Kohl, R. (1995). Long-term efficacy of fluid ability interventions with older adults. Journal of Gerontology: Psychological Sciences, 50B, P141-149 Kelman, H. R., Thomas, C. Kennedy, G. J., & Cheng, J. (1994). Cognitive impairment and mortality in older community residents. American Journal of Public Health, 84, 1255-1260. Labouvie-Vief, G., & Gonda, J. N. (1976). Cognitive strategy training and intellectual performance in the elderly. Journal of Gerontology, 31, 372-382. Leirer, V. O., Morrow, D. G., Pariante, G. M., & Sheikh, J. I. (1988). Elders' nonadherence, its assessment, and computer assisted instruction for medication recall training. Journal of the American Geriatrics Society, 36, 877-884. Neely, A. S., & Backman, L. (1995). Effects of multifactorial training in old age: Generalizability across tasks and individuals. Journal of Gerontology: Psychological Sciences, 50B, P134-140. Owsley, C., Ball, K., Sloane, M. E., Roenker, D. L., & Bruni, J. R. (1991). Visual/cognitive correlates of vehicle accidents in older drivers. Psychology and Aging, 6, 403-415. Swan, G. E., Carmelli, D., & LaRue, A. (1995). Performance on the digit-symbol substitution test and 5-year mortality in the Western Collaborative Group Study. American Journal of Epidemiology, 141, 32-40. Willis, S. L. (1987). Cognitive training and everyday competence. In K.W. Schaie (Ed.), Annual Review of Gerontology and Geriatrics, 7, New York: Springer. Wolinsky, F. R., & Johnson, R. J. (1991). The use of health services by older adults. Journal of Gerontology: Social Sciences, 46, S345- S357. Yesavage, J. A. (1985). Nonpharmacologic treatments for memory losses with normal aging. American Journal of Psychiatry, 142, 600-605. AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.866. Awards are made under authorization of the Public Health Service Act, Title IV, Part A Section 301 (42 USC 241) and administered under PHS grant policies and Federal Regulations, most specifically at 42 CFR Part 52 and 45 CFR Parts 74 and 92. Special Terms of Awards applying to projects funded in response to this RFA are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administrative regulations at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH grant administration policies. Awardees will maintain custody of, and primary rights to, their data developed under their awards, subject to Government rights of access, consistent with current HHS, PHS, and NIH policies. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. .
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