End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings

Abstract

To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non–patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.

Cardiovascular phenotypes predict clinical outcomes in sickle cell disease: An echocardiography‐based cluster analysis

“…4,16 In the context of high cardiac output, altered microvascular function and chronic anemia, the current thresholds of echocardiography parameters provided by the recent recommendations on diastolic function are questionable for SCD profiles. 17,18 Using unsupervised analysis based upon the integration of cardiac remodeling, systolic and diastolic function together with TRV measurement, we aimed to improve cardiac phenotyping and provide new insights on heart involvement in SCD. 19 Using Etendard cohort data, 2 we hypothesized that a cluster analysis might allow identification of SCD groups based on cardiac phenotypes, which might predict prognosis beyond the different clinical profiles.…”

The effect of intensity of conditioning regimen on the outcome of HSCT in children with sickle cell disease

“…A proposal on measurement of specific endpoints to assess the cure of SCD was recently published. 33 The burden of SCD in Saudi Arabia is high and the demand for HSCT is large. Approximately 15%-20% of SCD patients in Saudi Arabia are candidates for HSCT.…”

What is the future of patient-reported outcomes in sickle-cell disease?

“…Although there are great benefits to the increased use of PROs in clinical research and clinical practice, there are additional challenges to the incorporation of patient reported outcomes in low-resource settings. As a SCD community, we cannot forget that the largest burden of this disease lies in developing countries like sub-Saharan Africa, where there is limited access to health care [115][116][117]. Survival in SCD patient in these areas lags far behind the norms in the US and the immediate priority in many of these countries is to set up newborn screening in order to limit early mortality from infections and severe disability due to stroke.…”