++
In 1973, patients with sickle cell disease (SCD) due to homozygosity for hemoglobin S (HbSS) were estimated to have a median life expectancy of slightly more than 14 years,1 and thus, the disease was essentially a disease of childhood. However, in the observational Cooperative Study of Sickle Cell Disease (CSSCD), data collected between 1977 and 1988 showed that approximately 85% of children with HbSS lived to adulthood.2 Furthermore, in the CSSCD, child mortality peaked early, occurring among children aged 1 to 3 years, and was due predominantly to infections such as Streptococcus pneumoniae sepsis. Since the CSSCD natural history study, hallmark interventional clinical trials have significantly impacted the disease’s natural history by establishing standards of care, helping prevent serious complications, and improving quality of life and survival in SCD. In this chapter, we first review those clinical trials that have had major impact on clinical practice and patient survival (Figure 24-1 and Table 24-1). We also summarize the major observational studies that have substantially affected clinical practice in the care of patients with SCD in Table 24-2. Subsequent sections in this chapter address the key achievements and challenges of clinical trials in SCD.
++++