of the co-investigators'roles in implementing the project is lacking. * The intervention component seems overly ambitious and is not particularly innovative nor is the process to develop the intervention described in any detail. * The use of in-depth interviews with 20 - 25 participants is appropriate, however the details on recruiting to obtain a balanced sample is not sufficiently explained. Either the first 20 - 25 cases are recruited or the investigators deliberately seek to obtain a balanced sample but the way it is described is neither of those. * There is mention of focus groups or in-depth interviews but there is no plan in place to run focus groups, there is any description of anyone with expertise running focus groups, and there is no plan to evaluate any data collected should focus groups be implemented. Focus groups are not necessary and seem only put into the application as the 'latest thing to do'thus weakening the application. In-depth interviews are adequate and you can't take 20 - 25 people and inconsistently decide to put some in focus groups (maybe) and some in-depth interviews and expect the data to be of any use. Also, should the investigators decide to run focus groups instead of in-depth interviews, 20 - 25 participants is unlikely to be a sufficient number. * Either choose to run focus groups or in-depth interviews. It appears that the investigator has little experience with either and her mentors have not assisted her with developing a coherent plan for data collection and analysis * The investigator makes assumptions that attrition will be decreased in the parent study while the intervention is vague which does not support that claim * The intervention as described does not sound innovative nor community based. It doesn't sound like it has been thought through It seems that the intervention component would be an ideal project to be proposed within the Partnership as a full project, once the initial pilot is complete. This would allow for data collection specific to the intervention that would enhance an R01 application in the future. 5. Environment: Strengths: * Infrastructure for recruitment is in place with the R01 study Weaknesses: * Discrepancy between locations of recruitment creates questions about whether there are sufficient potential subjects to recruit. The human subjects'description states that there are 750 patients seen at the colposcopy clinic in the Duke Community and Family Medicine clinic clinic yearly. If so, approximately 10% (per national statistics) or 75 of these will be diagnosed with C1N1. Of these, 30% (per investigators'descriptions) or approximately 22 will not follow up with recommended appointment. These are different numbers from those described in the majority of the application which are 4,000 diagnosed yearly with the investigators targeting the first 1,500, of which approximately 450 - 500 will not follow up. Presumably the parent study is conducted elsewhere however the numbers of potential participants and the locations of these participants is vague and does not assure the reviewer that there is sufficient population to achieve the goals of Aim 2 in one year. * The lack of cohesion in the proposal and the errors in the budget and justification seems to indicate that the investigator did not have the institutional or mentoring support that the partnership is supposed to provide. Additional Review Criteria Protections for Human Subjects: * Acceptable Inclusion of Women, Minorities and Children * Children do not usually get C1N1 and the disease and unusual cells may present differently CRTIQUE 3: Significance: 2 Investigator(s): 2 Innovation: 1 Approach: 1 Environment: 2 1. Significance: Strengths: * African American women suffer disproportionate rates of invasive cervical cancer morbidity and mortality than white women, and adherence to recommended follow-up visits to positive pap screens may contribute to this disparity. It is critical that adherence rates are increased in this population so that disparities in this disease will decrease. * Data generated will be used to develop a community-based intervention (managing and triage) that will reduce disparities in ICC incidence and mortality. * Findings from this study will influence attrition rates in the parent study. Weaknesses * No major weaknesses noted 2. Investigator(s): Strengths: * Dr. Wordlaw-Stinson (NCCU) is an assistant professor of medical sociology with interests in how social factors impact health outcomes among African American women. In particular, screening behavior for cervical and breast cancer. She will work with Dr. Hoyo in designing the project, conducting focus group interviews, and managing the studies implementation, analyses, and writing. * Dr. Hoyo (Duke) is an associate professor of epidemiology with expertise in epigenetics and cancer. She is well-funded and published in this area and will collaborate on the project and serve as the primary mentor. A detailed mentorship plan and letter have been included. * Dr. Yarnall (Duke) is an associate professor of obstetrics and gynecology. Her role on the project is to facilitate access to medical records, collecting specimens, and contribute to data interpretation and manuscript writing. She has worked with Dr. Hoyo on previous projects in this area. * Dr. Mooman (Duke) is an associate professor of epidemiology with expertise in women's health, particularly ovarian and breast cancer among African American and White women. She has collaborated with Dr. Hoyo on several projects and is well published in this area. Her role will be to assist in the recruitment and retention of study subjects and contribute to the analysis an interpretation of the data. * Dr. Murphy (Duke) is an assistant professor of molecular biology with expertise in the study of epigenetic silencing of genes in gynecologic malignancies. She has worked on funded projects in this area and has published in this area. Her role on the project will include assisting in the interpretation of HPV analysis, drafting and editing manuscripts, and provide overall direction for the laboratory aspects of the study. Weaknesses: * Dr. Smith's contribution to the project and biographical sketch do not refer to the project for the current proposal. * No statistician has been identified. 3. Innovation: Strengths: * First known study to comprehensively examine genetic, epigenetic, social and medical factors associated with progression of CIN1 to CIN2. Weaknesses No major weaknesses noted 4. Approach: Strengths: * Theoretically-based approach to increasing adherence. * Very well written and comprehensive. Weaknesses * No major weaknesses noted 5. Environment: Strengths: * The scientific environment, resources, and equipment as described appear to be sufficient for the work to be conducted successfully. Weaknesses * No major weaknesses noted Additional Review Criteria Protections for Human Subjects: * Informed consent, confidentiality, and IRB have all been adequately addressed. Inclusion of Women, Minorities and Children G2A. M1A. C3A. Targeting patients 25 and older because CIN1 clears more readily among women younger than 25 years. Budget and Period of Support: * Budget justification for Dr. Smith includes information referring to Dr. Charles, when It appears that it should be referring to Dr. Wordlawn-Stinson. Otherwise, appears acceptable. THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES: ADDITIONAL REVIEW CRITERIA: PROTECTION OF HUMAN SUBJECTS (Resume): HS30 INCLUSION OF WOMEN PLAN (Resume): G2A INCLUSION OF MINORITIES PLAN (Resume): M1A INCLUSION OF CHILDREN PLAN (Resume): C3A VERTEBRATE ANIMALS (Resume): A10 COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested. BUDGETARY OVERLAP: None ASSESSMENT: Fair PROJECT 1 - Racial Disparity in Barrett's Esophagus (Description as provided by applicant) Barrett's esophagus (BE), a prelimalignant disease predisposing to human esophageal adenocarcinoma (EAC), is known to predominantly afflict Caucasian Americans. Our preliminary data have shown that in human BE a series of genes and pathways are activated to mediate the process of intestinal metaplasia, and thatintestinal transcription factors (e.g., Cdxl and Cdx2) are crucial to this process. Both Cdx1 and Cdx2 are induced and expressed in esophageal epithelial cells through loss of promoter methylation. Transfection of Cdx2 into human esophageal squamous epithelial cells induces metaplastic changes in morphology and gene expression. In this proposal, we hypothesize that environmental factors, genetic factors, and potentially gene-environment interactions play crucial roles in the observed racial disparity in BE. Clinical data, gastric secretions, endoscopic biopsy samples and blood samples will be collected from Caucasian and African American patients to identify critical environmental and genetic factors leading to BE. We hypothesize that differential distribution of genetic risk factors make Caucasian Americans more susceptible to BE than African Americans. Understanding the pathogenesis of the lesion is vital to future attempts at preventing metaplastic and dysplastic changes in the esophagus.
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