CRITIQUE 1: Significance: 1 Investigator(s): 1 Innovation: 2 Approach: 2 Environment: 2 Overall Impact: Strengths * This application has stated goals and primary objectives that are linked to specific actions directed to identifying appropriate participants, collecting adequate data, and analyzing the data appropriately. The investigators appear to be well-qualified to carry this project to a successful conclusion. This investigative plan provides a good model for registries on a state-wide basis. Weaknesses * There are no processes described that indicate that this approach could provide valid nation-wide estimates of incidence, prevalence, and prognosis of the major categories of IBD. 1. Significance: Strengths * Plans are presented for addressing most of the limitations of prior research in this area (incomplete and/or inaccurate ascertainment of cases;inconsistent diagnostic criteria;incomplete follow-up). Weaknesses * No plans or evidence are presented that indicate that this approach could be expanded to provide a national registry for IBD. 2. Investigator(s): Strengths * The investigators come from several disciplines (medicine, psychology, genomics) who have extensive research experience and notable publications. Weaknesses * Management of such a complex of scientific undertakings requires a principal investigator with a strong scientific background and the demonstrated ability to manage experts in different disciplines and to ensure timely communications between the project leaders. 3. Innovation: Strengths * The plans and protocols for identifying genetic risk factors both as independent risk factors and potentially effect modifying factors are notable. As many of the problems with previous research have arisen from the wide variability in phenotype expression, these efforts offer a real possibility of characterizing more specific criteria for case definition, as well as increasing understanding of the apparent inconsistency in prognosis across populations. Weaknesses * There are reservations about the collection of biologic samples that will be collected and stored and analyzed in the future. While not uncommon, there have been ethical/sociopolitical issues associated with this practice. If genetic data are not to be shared with participants due to """"""""lack of knowledge"""""""" of clinical significance, participants must be aware that as more information is gained and developed into consistent theory, then these results will be shared and explained. 4. Approach: Strengths * The specific protocols for each of the arms of the investigation and include timelines with the active personnel specified for the different activities undertaken at each milestone point. Weaknesses * Caution is recommended when analyzing very large databases for large populations. Healthy skepticism about the differences between association and causation is a good thing. Also, cohort studies should be undertaken following validation of the Registry population through the proposed case-capture approach. * Power calculations should be presented that indicate that the use of the Rhode Island population for development of the registry would offer adequate numbers for productive analysis even when stratified on multiple demographic and clinical factors. 5. Environment: Strengths * The collaborating institutions are large, highly respected centers for clinical research and are staffed with appropriate support personnel. Weaknesses * The number of essential professional investigators calls for very strong scientific as well as administrative leadership and co-ordination. Protections for Human Subjects: Acceptable Risks and/or Adequate Protections * The consent form should include the possibility of future datasets being analyzed for genetic variation even though that information will not be shared for the duration of the proposed investigation. Data and Safety Monitoring Plan (Applicable for Clinical Trials Only): * Not Applicable Inclusion of Women, Minorities and Children: G1A - Both Genders, Acceptable M1A - Minority and Non-minority, Acceptable C1A - Children and Adults, Acceptable * Case subjects who are pregnant at the time of identification will be enrolled later (post-partum). Care should be taken that records and notes of specific care during the pregnancy are also consented for later investigation. Budget and Period of Support: Recommend as Requested Resource Sharing Plans: Acceptable
