and Human Services (HHS)
EXPIRED
CLINICAL TRIALS NETWORK FOR FEMALE PELVIC FLOOR DISORDERS Release Date: July 13, 2000 RFA: HD-00-013 (This RFA has been reissued, see RFA-HD-05-019) National Institute of Child Health and Human Development (http://www.nichd.nih.gov) Letter of Intent Receipt Date: October 3, 2000 Application Receipt Date: November 28, 2000 PURPOSE The Center for Population Research (CPR) of the National Institute of Child Health and Human Development (NICHD) invites applications from investigators willing to participate with the NICHD in a multicenter cooperative program designed to conduct clinical trials investigating female pelvic floor disorders, including pelvic organ prolapse, urinary incontinence, and fecal incontinence. The objective of this program is to facilitate research related to these problems by maintaining a network of Clinical Sites and a Data Coordinating Center (DCC) that, by rigorous patient evaluation using common protocols, can study large numbers of patients and provide answers more rapidly than individual sites acting alone. HEALTHY PEOPLE 2010 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of Healthy People 2010, a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain Healthy People 2010 at http://www.health.gov/healthypeople. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic 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. The need for continuous and active communication among the sites dictates that only institutions in the United States will be eligible to apply. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. An institution may apply for both a Clinical Site and the Data Coordinating Center (DCC) grant, however, separate applications are required and the DCC application must include a specific plan for maintaining the independent operation of each unit (e.g., confidentiality of study-wide data). MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) cooperative research project grant (U01) and cooperative clinical research grant (U10) award mechanisms, assistance mechanisms (rather than acquisition mechanisms) in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients activity by involvement in the activity 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 cooperative agreements are discussed below under Terms and Conditions of Award. The Data Coordinating Center will be supported by a U01 award and the Clinical Sites (described below) by U10 awards. The anticipated award date is July 1, 2001. FUNDS AVAILABLE The NICHD intends to commit approximately $3 million in total costs [direct plus Facilities and Administrative (F&A) costs] in FY 2001 to fund six to eight new grants for Clinical Sites and one new grant for a Data Coordinating Center. Applicants for the Data Coordinating Center grant may request a project period of up to five years and a budget for direct costs of up to $600,000 per year. Applicants for a Clinical Site may request a project period of up to five years and a budget for direct costs of up to $200,000 per year. Because the nature and scope of the research proposed may vary, it is anticipated that the size of each award also will vary. Although the financial plans of the NICHD provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. At this time, it is not known if this RFA will be reissued. RESEARCH OBJECTIVES Background Within the mission of NICHD, as part of the broad topic of reproductive health, priority has been given to research on pelvic floor disorders in women. To this end, the Contraception and Reproductive Health Branch of the Center for Population Research (CPR), NICHD, supports research on pelvic floor disorders affecting the reproductive system and other pelvic organs. The term pelvic floor disorders refers to a group of clinical conditions that includes pelvic organ prolapse, urinary incontinence, fecal incontinence, and other sensory and emptying abnormalities of the lower urinary and gastrointestinal tracts. It is estimated that one or more of these conditions affects up to one-third of adult women. Almost 10 percent of women will undergo surgery for urinary incontinence or pelvic organ prolapse during their lifetime, and 30 percent of those having surgery will have at least two surgical procedures to try to correct the problem. With the steady increase in the population of older women, the national cost burden related to pelvic floor disorders is large in terms of direct health care costs, lost productivity, and decreased quality of life. Pelvic floor disorders result in significant morbidity, both in women of reproductive age and postmenopausal women. Many of these conditions lead to hysterectomy or other major surgery. In some cases, alternative management strategies might have been effective, but were not understood, accessible or affordable. Outcomes of surgical treatment have not been well documented, for some procedures, initial claims of effectiveness have not been supported by data from long-term follow-up. In September 1998, the NICHD, in collaboration with the Office of Research on Women’s Health, the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Office of Rare Diseases, held a workshop to examine the state of basic, epidemiological, and clinical research addressing pelvic floor disorders in women. A consensus emerged that underscored the lack of a substantive knowledge base related to these disorders and directions for future research to remedy these deficiencies were discussed. Few data were available on clinical management of pelvic floor disorders, and the validity of conclusions was limited by lack of standardization in defining conditions and reporting outcomes, small sample sizes, mostly retrospective study designs, and high rates of loss to follow- up. There is no consensus as to the threshold for intervention and the rationale for selection of treatment for particular clinical conditions has not been established. From the proceedings of the 1998 workshop, NICHD has developed a set of initiatives in this field related to basic science, epidemiologic, and clinical research on pelvic floor disorders in women. The overall goal is to advance the state of knowledge regarding the pathophysiology of pelvic floor disorders and to address the need for rigorous controlled evaluation of diagnostic and therapeutic practices for these disorders. In December 1999, NICHD and other NIH institutes sponsored a Workshop on Terminology for Researchers in Female Pelvic Floor Disorders. During this workshop, recommendations were made for standardization of terminology regarding definitions of the conditions included under the general term pelvic floor disorders, for definitions of outcomes after intervention, and for minimum data set collection for research studies. All NIH grant applications related to pelvic floor disorders are required to use these standard terms. Interested applicants should request a copy of the proceedings of the Terminology Workshop from the program staff listed under INQUIRIES, below. Use of the cooperative agreement mechanism for this initiative has many advantages. The NICHD staff participant will contribute scientifically to consensus decision-making and to maintaining balance among the participants. Expert statistical consultation in experimental design and analysis is provided to assist during protocol development and data analysis. In this way, the research group can identify issues with a high degree of objectivity, develop well-designed protocols, and provide a large patient base, so that tests and treatments can be evaluated more rapidly and with greater statistical validity than would be otherwise possible for individual centers. The anticipated efficiency of communication among investigators and dissemination of information to practitioners and the public will lead to more effective patient care and to more economical use of resources. Objectives and Research Scope There are many controversies in the field of pelvic floor disorders that would lend themselves to cooperative study. The scope includes clinical problems in pelvic organ prolapse, urinary incontinence, and fecal incontinence. The following should by no means be viewed as exhaustive, and are intended only as broad examples of research topics relevant to this RFA: o Outcomes of different surgical procedures or non-surgical versus surgical treatment for pelvic organ prolapse, urinary incontinence, and/or fecal incontinence: Controlled trials to compare outcomes by cure rate and functional status (such as quality of life, sexual function, and urinary and lower gastrointestinal tract function). o Diagnostic testing: Indications and expected versus actual benefit of diagnostic testing in patients with pelvic floor disorders, such as use of urodynamic testing in patients with urinary dysfunction, use of ancillary imaging tests such as video urodynamics, ultrasound (pelvic, perineal, anal), magnetic resonance imaging, or defecography. o Timing of intervention, either surgical or nonsurgical: Controlled trials to compare outcomes of early (anatomic abnormalities that may be asymptomatic) versus later (symptom-driven) intervention. o Postoperative management to maximize recovery and minimize recurrence of pelvic floor disorders: Controlled trials of different postoperative management strategies after surgical treatment for pelvic organ prolapse, urinary incontinence, and/or fecal incontinence. Because the prevalence of pelvic floor disorders is substantially greater in women than in men and because treatment of pelvic floor disorders is markedly different in men and women, participation in the clinical protocols planned under this initiative will be restricted to adult women. Since this list is not meant to be all-inclusive, prospective applicants are encouraged to discuss their ideas for applications with the program staff listed under INQUIRIES. Study Design While other study designs will be considered as appropriate to the research question, randomized trials are the preferred approach. The Network will include approximately eight Clinical Sites supported by U10 awards, and a Data Coordinating Center (DCC) supported by a U01 award. The Clinical Sites will recruit, evaluate, and treat the participants in any or all of the clinical studies supported by the Network. The DCC will have primary responsibility for data collection and management for each trial. A member of the NICHD program staff, serving as Project Scientist, will cooperate with the funded Principal Investigators in designing and executing protocols to optimize management in these areas. As discussed in more detail under Terms and Conditions of Award, below, collaborative responsibilities among the investigators at Clinical Sites, the DCC, and the NICHD will be facilitated by a Steering Committee, a Clinical Trials Advisory Board, and a Data Safety and Monitoring Committee. Timetable It is anticipated that the program will conduct its activities according to the following general outline: Phase I (First Six Months of Study): Protocol Development Initially, the Advisory Board and Steering Committee (see section on Collaborative Responsibilities under Terms and Conditions of Award ) will review and identify issues of importance in pelvic floor disorders. They will consider items proposed for study by the Network from among those listed above in Objectives and Research Scope and others. The Advisory Board and Steering Committee will rank in priority order a series of issues that are substantive, lie within the scope of existing technical capability, lend themselves to multicenter evaluation, involve sufficient numbers of patients to be of consequence in terms of morbidity, and address significant public health needs. In this and subsequent activities, the Steering Committee will attempt to use electronic and telecommunications whenever possible. From the list of important issues, the Steering Committee will generate protocols and agree on lead sites for the protocols. Each protocol is to be acceptable to the participants, adequate for appraisal of the research issues defined, and amenable to data collection in a single format acceptable to all sites. Satisfactory controls will be incorporated, and attention will be given to maximize the number of studies possible with minimal data collection. Protocol subcommittees may be appointed to develop protocols more efficiently. Phase II (Second Six Months of Year 01, Years 02-05): Protocol Implementation Participating Clinical Sites will incorporate the protocols into the clinical management of those patients selected for study. The Clinical Sites will supervise the collection of data with adequate attention to the fidelity of records and transcription, and will provide information in uniform data format for analysis. The mode of data transmission and analysis will be determined by the Steering Committee in conjunction with the recommendations of the DCC. Data summaries will be provided to the Data Safety and Monitoring Committee (see section on Collaborative Responsibilities under Terms and Conditions of Award ) on a semi-annual basis, or as indicated by study development. Format and content of final reports and the dissemination of information to the scientific community will be determined by the Steering Committee. Beginning approximately six months after the start of data collection, the Data Safety and Monitoring Committee will examine the aggregated data and make recommendations to NICHD on the need to modify or terminate studies, as described above. As studies are terminated, the Advisory Board and Steering Committee will be expected to initiate identification of new issues and the institution of new protocols. SPECIAL REQUIREMENTS Because protocols for investigation will not be written until after awards are made, it is not possible for applicants to propose the exact work that they would actually carry out if funded. Therefore, to provide peer reviewers and NICHD staff with sufficient information regarding the capabilities of the investigators, each applicant must submit a concept protocol for a new study. The applicant should note carefully that the concept study proposed may or may not actually be adopted by the Network as one of its protocols. The proposal is requested to serve as an indicator of the applicant’s ability to participate in the development and design of protocols for cooperative clinical investigations. It is anticipated that the Steering Committee and Advisory Board will include the concept protocols submitted by the funded Clinical Sites and DCC in their consideration of topics for actual protocols. For the purposes of this RFA only, it is suggested that the concept protocol address one of the following topics: o Controlled trials for comparison of outcomes after surgical treatment of pelvic floor disorders (pelvic organ prolapse, urinary incontinence or fecal incontinence). o Indications and benefits of diagnostic testing in pelvic floor disorders. o Timing of intervention for pelvic floor disorders. o Postoperative management strategies to maximize recovery and minimize recurrence of pelvic floor disorders. The protocol should be written specifically for this Network and will be a key factor in evaluation of the application. Applicants should outline the rationale and background of the proposed study, study design and protocol, eligibility criteria, and initial sample size and power analyses. Minimum Requirements for Clinical Site Applicants: 1. Participants must be based in departments providing both inpatient and outpatient health care for women. 2. The Principal Investigator and research team at each Clinical Site must have a history of previous successful clinical research. 3. The Principal Investigator should be able to make a substantive, long-term commitment of effort to Network responsibilities. The clinical investigators at each Clinical Site must include a urogynecologist and a urologist with demonstrated training and experience in the diagnosis and treatment of pelvic floor disorders in women. It is expected that either a urologist or a urogynecologist will serve as the Principal Investigator for a Clinical Site. 4. The Clinical Site must demonstrate willingness and ability to participate in a cooperative manner with other Clinical Sites and with the DCC in the delineation of research protocols, statistical methods, uniform data collection, and data transfer. Applications from institutions that have a General Clinical Research Center (GCRC) funded by the National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator should be included with the application. Applicants may wish to propose a consortium of institutions as a multicenter Clinical Site. If so, a single application, with one Principal Investigator, should be submitted by an applicant institution on behalf of all institutions that compose that Clinical Site. It is not necessary for each institution constituting a multicenter Clinical Site to have a urogynecologist and a urologist as clinical investigators, the Clinical Site as a whole must have a urogynecologist and a urologist as clinical investigators and it is expected that one will serve as the Principal Investigator. Minimum Requirements for Data Coordinating Center (DCC) Applicants: 1. The applicant must have demonstrated prior experience as a Coordinating Center in multicenter studies. 2. The Principal Investigator, with other staff, must have appropriate biostatistical, data management, and coordination expertise. 3. The applicant must have the ability to assist in designing protocols and the data collection system, including transmission via the Internet. 4. The applicant must demonstrate the willingness and ability to cooperate with the Clinical Sites and NICHD staff in all design, data collection, and analysis functions. Budget Requirements The budget must reflect the phases of the project as described under Application Instructions, below. Terms and Conditions of Award The following Terms and Conditions of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations in 45 CFR Parts 74 and 92 and other HHS, PHS and NIH grant administration policies. The administrative and funding instrument used for this program is a cooperative agreement (U01, U10), an assistance mechanism, (rather than an acquisition mechanism) in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH’s purpose is to support and stimulate the recipient’s activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardee(s) and the NICHD Project Scientist. Cooperative agreements are subject to the same administrative requirements as grants. A Program Officer from the Contraception and Reproductive Health Branch, Center for Population Research, NICHD, separate from the Project Scientist, will exercise normal program stewardship. Business management aspects of these awards will be administered by the NICHD Grants Management Branch in accordance with HHS, PHS, and NIH grant administration requirements. Awardee Rights and Responsibilities In collaboration with the other awardees and with assistance from the NICHD Project Scientist, awardees will have primary and lead responsibilities to: 1. Define research objectives and approaches. 2. Plan the design and implementation of the clinical protocols. 3. Conduct the studies including participant recruitment and follow-up. 4. Collect and analyze the data. 5. Publish the results, conclusions, and interpretations of studies. 6. Modify or delete protocols, and add new protocols, subject to NICHD approval. Awardees will retain custody of and primary rights to data from their Clinical Site developed under the award, subject to current Government policies regarding rights of access. The awardees agree to accept the advisory role of the Clinical Trials Advisory Board, the coordinating role of the Steering Committee, and the cooperative nature of the group process. NICHD Staff Responsibilities The NICHD Project Scientist will have substantial scientific-programmatic involvement during conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants, as described below. 1. Assist in and facilitate the development of study protocols. 2. As a voting member of the Steering Committee, review and comment on each stage of the program before subsequent stages are started, including options of modification or termination by mutual consent between the Network and NICHD. 3. Assist in maximizing cooperation among the units and help redirect efforts, if necessary. The NICHD Project Scientist may determine jointly with the awardees the need to add clinical sites for the purpose of increasing patient accrual. 4. Assist, through review, comment, analysis, and, where appropriate, co- authorship, in reporting results to the community of investigators and health care recipients. The NICHD Program Officer will exercise normal program stewardship, as described below. 1. Retain the option to withhold support of a participating unit, if technical performance requirements such as compliance with the protocol, meeting patient enrollment targets, and adherence to uniform data format are not met. Continued support will be contingent upon meeting these requirements. 2. Continuous review of all activities to ensure objectives are being met. 3. Redirecting activities or improving the cooperation and performance of participating institutions. 4. Ensuring that the scientific progress of the cooperative agreement is commensurate with the funds provided to each of the sites. If recruitment or cost containment becomes an issue, funding on a cost per patient may be implemented if necessary. Collaborative Responsibilities 1. Steering Committee: The Steering Committee will be the main governing body of the study and will have primary responsibility for developing research protocols by consensus, supervising the conduct of the studies, and reporting results. The Steering Committee will consist of the Principal Investigators (one from each Clinical Site), the Principal Investigator of the DCC, and the NICHD staff Project Scientist. Each member of the Steering Committee will have one vote. The chairperson, who will be someone other than the NICHD Project Scientist, will be designated by the Steering Committee. A member of the NICHD grants management staff will serve as advisor to the Committee. Subcommittees will be established by the Steering Committee, as it deems appropriate. Awardees will be required to accept and implement the common protocols and procedures approved by the Steering Committee. 2. Clinical Trials Advisory Board: An independent Clinical Trials Advisory Board will advise the Steering Committee in identifying and setting priorities for research topics on pelvic floor disorders appropriate for study by the Network. Such topics would be of high public health impact, amenable to rigorous scientific approaches, and clinically feasible. The Advisory Board, chosen by the NICHD with the advice of the Steering Committee, will include members with expertise in clinical trial design, biostatistics, epidemiology, gynecology, urology, and urogynecology, as well as the Chair of the Steering Committee and the NICHD Project Scientist. The Advisory Board will evaluate the overall hypotheses and scope of planned trial protocols, with additional ad hoc scientific and/or clinical experts as needed. 3. Data Safety and Monitoring Committee: A Data Safety and Monitoring Committee (DSMC) convened by the NICHD will have responsibility for reviewing the safety of ongoing clinical trials and will advise on their conduct. Members of the DSMC will be chosen by the NICHD with the advice of the Steering Committee, and will include one member representing the lay community. The DSMC will meet at least every six months, either in person or by conference call. The DSMC will monitor data collection and analysis by the DCC, including any reports of adverse events. When appropriate, the DSMC will conduct interim evaluations of the data with respect to the need to terminate studies, either because the data suffice to answer the research questions posed, data collection provides support for an alternative study initiative, or because experience has proven that the research is not feasible. Arbitration Any disagreement that may arise on scientific/programmatic matters, within the scope of the award, between award recipients and NICHD may be brought to arbitration. An arbitration panel will be composed of three members: one selected by the Steering Committee (with the NICHD Project Scientist not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by NICHD staff, and a third member selected by the first two members. The decision of the arbitration panel, by majority vote, will be binding. This special arbitration procedure in no way affects the right of an awardee to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulation 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 are provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). 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 in the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994, and available on the Internet at: http://grants.nih.gov/grants/guide/notice-files/not94-100.html. Because the prevalence of pelvic floor disorders in women is substantially greater than in men and because treatment of pelvic floor disorders is markedly different in men and women, participation in the clinical protocols planned under this initiative will be restricted to adult women. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that children (i.e., individuals under the age of 21) must be included in all human subject research, conducted or supported by the NIH, unless there are scientific and/or ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects," published in the NIH Guide for Grants and Contracts, March 6, 1998, and available on the Internet at: http://grants.nih.gov/grants/guide/notice-files/not98-024.html. URLs IN NIH GRANT APPLICATIONS OR APPENDICES All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. LETTER OF INTENT Prospective applicants are asked to submit 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 other key personnel and participating institutions, and the number and title of this RFA. 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 NICHD staff to estimate the potential review workload and plan the review. The letter of intent is to be sent to Dr. Anne M. Weber at the address listed under INQUIRIES, below, by October 3, 2000. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research, on the Internet at http://grants.nih.gov/grants/funding/phs398/phs398.html, and from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-710-0267, E-mail: [email protected]. Open Information Forum for Prospective Applicants A one-day open information forum will be held for prospective applicants, approximately four to six weeks after issuance of this RFA. For prospective applicants who cannot attend the forum in person, conference call capability will be provided. At this forum, NICHD program staff will address any questions that prospective applicants might have regarding the clinical or scientific concepts of the RFA. Attendance is not required and is not a pre- condition for submission of an application. Prospective applicants may obtain additional information regarding the time, date, and location of this forum at http://www.nichd.nih.gov/RFA/HD-00-013/HD-00-013.htm or may contact the NICHD program staff listed under INQUIRIES. Applicants planning to attend the meeting or to participate in the conference call are asked to submit their questions in writing to the NICHD program staff listed under INQUIRIES at least one week in advance of the forum. A list of questions asked during the forum and a written summary of the responses from NICHD program staff will be posted following the meeting at http://www.nichd.nih.gov/RFA/HD-00-013/HD-00-013.htm or will be provided to persons who request it. Application Instructions For Clinical Site and DCC applications, the concept protocol should be presented in the Research Plan section of the PHS 398 within the standard 25- page limit. The concept protocol should reflect the requirements stated in the "SPECIAL REQUIREMENTS" section above. The following should be addressed or included in Clinical Site applications: 1. The application should include a summary of prior research experience. Specifically, contributions in key areas such as protocol design, patient recruitment and retention, data analysis and interpretation, and publication are important. Research on pelvic floor disorders in women is especially relevant. 2. Ability to enroll and retain sufficient numbers of patients with pelvic floor disorders for meaningful studies should be documented, including plans for recruitment of minority/ethnic women and plans to minimize loss to follow- up. Applications should state the numbers of patients seen annually for the different types of pelvic floor disorders (including, but not necessarily limited to, patients with pelvic organ prolapse, urinary incontinence, and fecal incontinence). 3. Key personnel should include physician staff representing several areas of expertise, either based in the participating department or available as collaborators. These areas could include obstetrics, gastroenterology, colorectal surgery, radiology, and physical therapy. In addition, an experienced full-time research nurse (study coordinator) must be among the key personnel. Additional research nursing staff and clerical staff (e.g., data entry clerk) should be available as appropriate for the proposed study. Established research teams should describe their current program with any plans for change related to this application, newly formed teams should describe their plans for development and implementation of the team"s program for interaction and collaboration. Description of the team should include sufficient commitment of staff time for satisfactory conduct of the study. 4. The application should describe available laboratory and radiology facilities for appropriate testing of study participants, in such areas as urodynamics, ultrasound, contrast studies such as defecography, and other radiological and related techniques that may be required to diagnose and follow the conditions under study. 5. Institutional and departmental commitment to this program must be demonstrated, including adequate space in which to conduct clinical and research activities. 6. The application must demonstrate willingness and ability to cooperate with other Clinical Sites, the DCC, and NICHD staff in all design, data collection, and analysis functions. For those applicants with previous experience in multicenter studies (especially randomized trials) using common protocols, this experience should be documented. For applicants without previous experience, the capability and willingness to work with other centers on common protocols should be described. 7. As noted above, all grant applications related to pelvic floor disorders are required to use the standard terminology as recommended at the NIH Terminology Workshop for Researchers in Female Pelvic Floor Disorders held in December 1999. The following should be addressed or included in Data Coordinating Center applications: 1. The application should include documentation of adequate and appropriate resources (in addition to personnel) to fulfill all DCC responsibilities. 2. The application must demonstrate experience in developing and monitoring quality control. 3. The DCC will report to the Data Safety and Monitoring Committee at least every six months regarding accumulating data and the Clinical Sites performance. The application should document the ability to meet such reporting deadlines as well as the overall timetable. 4. The application must include a plan detailing methods of data receipt, analysis, quality control, and reporting, including communications with administrative and clinical personnel. 5. There should be evidence of strong institutional support for the study, including adequate space for data analysis and management activities. An organizational structure for the study should be developed in the application, delineating lines of authority and responsibility for dealing with problems in all general areas. 6. The application must demonstrate willingness and ability to cooperate with the Clinical Sites and NICHD staff in all design, data collection, and analysis functions. 7. If an institution applies for both a Clinical Site and the DCC, the DCC application must address the issue of how the DCC would maintain operational independence if both were funded (for example, maintenance of blinding for investigators involved at the Clinical Site and the DCC). 8. As noted above, all grant applications related to pelvic floor disorders are required to use the standard terminology as recommended at the NIH Terminology Workshop for Researchers in Female Pelvic Floor Disorders held in December 1999. Budget Requirements All applications must include an adequately justified year-by-year budget, reflecting the changes in proposed activities as the studies progress through their various phases. Since the project proposed in the grant application may not be adopted by the Network, development of the budget should be viewed as estimated. During the first six months, the budget will be for development of the protocols, manuals of procedures, and data collection forms for the studies. The database will be created by the DCC during this time. During the second phase of the study (the second six months of Year 01, and Years 02-05), the budget should reflect recruitment of a full complement of participants for the clinical trials plus follow-up of these participants over the time course of study. Interim data analysis, preparation of reports to the Steering Committee and Advisory Board, and writing of papers for publication will be performed during this phase. Budget Requirements for Clinical Site Applications For a Clinical Site, the budget should request support for the minimum number of full-time and/or part-time staff needed to successfully carry out the proposed trial. The personnel list should include a Principal Investigator, co-investigator(s), study coordinator, and data entry clerk. The budget should request a minimum of 10 percent effort for the Principal Investigator. For the first six months, the travel budget should be estimated based on travel for two key investigators from each Clinical Site (the Principal Investigator and one co-investigator) to attend two-day, monthly meetings of the Steering Committee in the Washington, DC area. The second phase of the study (the second six months of Year 01, and Years 02- 05) will require meetings of the Steering Committee approximately every four months for one to two days in the Washington, DC area. The travel budget should be estimated based on travel for the Principal Investigator plus, if desired, one additional co-investigator, from each Clinical Site. In addition, travel for centralized training of the study coordinator and data entry clerk must also be budgeted (assume central training for one to two days to be held in the Washington, DC area annually during Years 01-05). Therefore, the travel budget for the first year should include eight Steering Committee meetings for up to two people from each site (six in the first six months, and two in the second six months of Year 01), and one meeting for centralized training for two people. The travel budget for the second, third, fourth, and fifth years should include three Steering Committee meetings per year for up to two people from each site, and one meeting per year for centralized training for two people. Budget Requirements for Data Coordinating Center (DCC) Applications For a DCC, the budget should request support for the minimum number of full- time and/or part-time staff needed to successfully conduct the proposed trial. The Personnel list should include a Principal Investigator, co- investigator(s), statistician(s), computer programmer(s), and data manager(s). Travel by DCC staff (the Principal Investigator and one additional person) for the following meetings should be budgeted (all meetings will be held in the Washington, DC area except the site visits). In Year 01, there will be a total of 17 trips: eight Steering Committee meetings (six meetings in the first six months and two meetings in the second six months), one Clinical Trials Advisory Board meeting, plus site visits to each of eight Clinical Sites before initiation of the first protocol. For each year in Years 02-05, there will be a total of 12 trips each year: three Steering Committee meetings, one Clinical Trials Advisory Board meeting, plus site visits to each of eight Clinical Sites each year. Submission Instructions The RFA label available in the PHS 398 (rev. 4/98) application form must be stapled to the bottom of the face page of the application and must display the RFA number HD-00-013. A sample RFA label is available at http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Please note this is in the pdf format. 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 2 of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies, in one package to: CENTER FOR SCIENTIFIC REVIEW 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 should be sent to: L.R. Stanford, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03, MSC 7510 Bethesda, MD 20892-7510 Bethesda, MD 20852 (for express/courier service) Telephone: (301) 496-9254 Applications must be received by November 28, 2000. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) 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 CSR 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 the CSR and for responsiveness to the RFA by NICHD staff. Incomplete and/or non- responsive 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 NICHD in accordance with the review criteria stated below. As part of the initial merit review, all applications will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific merit will be discussed, assigned a priority score, and receive a second level review by the National Advisory Child Health and Human Development (NACHHD) Council. Review Criteria for the Evaluation of All Applications The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. (1) Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) Innovation: Does the project employ novel concepts, approaches, or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? (5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support in such areas as fiscal administration, personnel management, space allocation, procurement, planning, equipment, and budgeting? o Demonstrated willingness to work and cooperate with other units in the Network (Clinical Sites and Data Coordinating Center) and the NICHD as summarized in this RFA. o Adequacy of administrative, clinical, and data organizational management facilities as described in the minimum requirements. In addition to the above criteria, in accordance with NIH policy, all applications also will be reviewed with respect to the following: o The adequacy of plans to include minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects also will be evaluated. o The reasonableness of the proposed budget and duration in relation to the proposed research. o The adequacy of the proposed protection for humans, animals or the environment, to the extent they may be adversely affected by the project proposed in the application. Review Criteria for the Evaluation of Clinical Site Applications In addition to the review criteria for all applications, Clinical Site applications will be evaluated according to the following: o Innovation The final study protocols will be developed collaboratively by the Steering Committee. Thus, in reviewing the concept protocol, the peer review group will focus on evidence that: 1. The applicant possesses the knowledge necessary to contribute meaningfully to the final designs, including understanding of the scientific, ethical, and practical issues underlying the proposed study. 2. The applicant demonstrates knowledge of the potential problems associated with the conduct of the proposed study, and identifies solutions or alternatives. 3. Justification of the proposed sample size is provided. o Investigator 1. The application provides evidence of the investigator’s training, experience, scientific, clinical, and administrative abilities, academic productivity, and specific competence relevant to the operation of a Clinical Site. 2. Clinical Site applications provide evidence of a successful clinical research team. Review Criteria for the Evaluation of Data Coordinating Center (DCC) Applications In addition to the review criteria for all applications, DCC applications will be evaluated according to the following: o Innovation The final study protocols will be developed collaboratively by the Steering Committee. Thus, in reviewing the concept protocol, the peer review group will focus on evidence that: 1. The applicant possesses the knowledge necessary to contribute meaningfully to the final designs, including understanding of the scientific, ethical, and practical issues underlying the proposed study. 2. The applicant demonstrates knowledge of the potential problems associated with the conduct of the proposed study, and identifies solutions or alternatives. 3. Justification of the proposed sample size is provided, in addition to proposed plans for data collection, management, editing, processing, analysis, and reporting. o Investigator 1. The application provides specific evidence of experience and qualifications of team members who would be responsible for data quality and management activities. 2. The application documents knowledge and experience in areas relevant to the conduct of collaborative clinical research, especially randomized clinical trials. This includes the adequacy of the approach to developing a cooperative relationship among the Clinical Sites and exercising appropriate leadership in matters of study design, data acquisition, data management, data quality, and data analysis. o Environment 1. Experience of DCC personnel in utilizing procedures that ensure the safety and confidentiality of all records. 2. Adequacy of the proposed facility, technical hardware, and space, and appropriateness of the organizational and administrative structure of the proposed DCC. SCHEDULE Letter of Intent Receipt Date: October 3, 2000 Application Receipt Date: November 28, 2000 Peer Review Date: February-March 2001 Council Review: June 2001 Earliest Anticipated Start Date: July 1, 2001 AWARD CRITERIA Criteria that will be used to make award decisions include scientific merit (as determined by peer review), availability of funds, and programmatic priorities. 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: Anne M. Weber, M.D., M.S. Center for Population Research National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8B13C, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 435-6972 FAX: (301) 480-1972 E-mail: [email protected] Direct inquiries regarding fiscal matters to: Mr. Michael Loewe Grants Management Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17J, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 435-7008 FAX: (301) 402-0915 E-mail: [email protected] AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.864, Population Research. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act, as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 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 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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