A multi-center study of cystic fibrosis: Assessment of institutional review and a comparison of longitudinal data from multiplex and simplex families

Recruitment began for a 116-center twin and sibling genetic epidemiology study of factors modifying the severity of cystic fibrosis in 1999. It became apparent that obtaining center-by-center institutional review board (IRB) approval for this large multi-center observational study was taking an inordinate amount of time, creating confusion, and resulting in multiple disparate consent forms. During this time, we also discovered a lack of information regarding the comparability of cystic fibrosis patients who had another affected family member with cystic fibrosis patients who were the only affected family member. We undertook two supplementary studies.;The first involved collecting descriptive data on each center, examining correspondence between the IRB and the center investigator, and reviewing consent forms used by each center. The goal of this IRB study was to determine causes of confusion and to assess differences in consent forms used for this study. It was Hypothesized that because this study involved genetic factors, the IRB approval process was unduly slow. Excessive variation in IRB review of a multi-center study can cause variability in the level of protection afforded to participants. Documenting this variability offers support for revising the current procedures for IRB review for multi-center genetic studies.;The second study was a longitudinal comparison between delF508 homozygous cystic fibrosis patients with and without another affected family member selected for comparison from a CF patient registry. Two phenotypic variables of interest for the clinical course of cystic fibrosis, body mass index and percent predicted forced expiratory volume in I second were examined. The patients who had siblings were hypothesized to be similar to those who did not for these two variables. Regression analysis was conducted using the generalized estimating equations method. A statistical tool specific for assessing similarity, equivalence analysis, was used to determine the comparability of these two groups for the two variables. In research, it is important to know the extent to which an inference may be extended beyond a study population. Any lack of similarity between patients with affected siblings and those without has implications for the design and interpretation of future studies of cystic fibrosis.