Traditional clinical trial end points and suggested modifications in low-resource settings
| Disease-related factors . | Traditional clinical end points . | Clinical end points for low-resource settings . |
|---|---|---|
| Recurrent pain episodes | Proportion of days with symptom exacerbation (SCDSM); annualized sickle cell crisis rate; annualized VOC events (number and length of hospital/ER visits, phone diary, home-health visits over time); time to first pain crisis; duration and severity of pain crisis | Electronic daily pain diary, phone tracking, plus hospitalization and emergency room visit rate; reduction in average visual analog score for pain |
| Disease amelioration | Measuring HRQoL; increase in Hb >1 g/dL from baseline; hemolysis biomarkers (total bilirubin, LDH, reticulocyte, total WBC, platelet count, CRP, plasma D-dimers laboratory values); frequency of SCD- related complications (VOC, ACS, hepatic and splenic sequestration, leg ulcers, priapism and stroke); changes in functional exercise capacity (6-min walk test) | Increase in baseline Hb >1 g/dL; decrease in frequency of SCD-related complications; changes in functional exercise capacity (6-min walk test); improved growth in children; locally relevant PROs |
| Hematologic responses | Increase in baseline Hb by 2 points; improvement in HbF from baseline | Increase in baseline Hb by 2 points, quite feasible; improvement in HbF from baseline, dependent on availability of HPLC machines, limits to tertiary centers |
| PROs | Symptom relief or HRQoL (multidimensional), including physical, functional, social, emotional, and spiritual QoL, as measured by QoL instruments | Lack of context-specific and culturally specific instruments that have demonstrated validity, reliability, and sensitivity to clinically important changes |
| Disease-related factors . | Traditional clinical end points . | Clinical end points for low-resource settings . |
|---|---|---|
| Recurrent pain episodes | Proportion of days with symptom exacerbation (SCDSM); annualized sickle cell crisis rate; annualized VOC events (number and length of hospital/ER visits, phone diary, home-health visits over time); time to first pain crisis; duration and severity of pain crisis | Electronic daily pain diary, phone tracking, plus hospitalization and emergency room visit rate; reduction in average visual analog score for pain |
| Disease amelioration | Measuring HRQoL; increase in Hb >1 g/dL from baseline; hemolysis biomarkers (total bilirubin, LDH, reticulocyte, total WBC, platelet count, CRP, plasma D-dimers laboratory values); frequency of SCD- related complications (VOC, ACS, hepatic and splenic sequestration, leg ulcers, priapism and stroke); changes in functional exercise capacity (6-min walk test) | Increase in baseline Hb >1 g/dL; decrease in frequency of SCD-related complications; changes in functional exercise capacity (6-min walk test); improved growth in children; locally relevant PROs |
| Hematologic responses | Increase in baseline Hb by 2 points; improvement in HbF from baseline | Increase in baseline Hb by 2 points, quite feasible; improvement in HbF from baseline, dependent on availability of HPLC machines, limits to tertiary centers |
| PROs | Symptom relief or HRQoL (multidimensional), including physical, functional, social, emotional, and spiritual QoL, as measured by QoL instruments | Lack of context-specific and culturally specific instruments that have demonstrated validity, reliability, and sensitivity to clinically important changes |
CRP, C-reactive protein; QoL, quality of life.