It is recognized that even with a clinical network, the number of patients with Cooley's anemia who can be enrolled in a research protocol is likely to be small. Therefore, although a randomized clinical trial may be the preferred way of assessing the clinical benefits of a new therapy, it may not be feasible in some instances, even using biomarkers or other surrogate outcome measures. Depending upon the specific questions being addressed, other study designs might be appropriate. These might include pre- and post-treatment assessment or historical control studies. In all cases, the proposed design, including sample size, would be evaluated by the Protocol Review Committee.