Example of outcome measures for chelator trials and their application for clinical practice now and in the future
Outcome . | Advantages . | Disadvantages . | Current status in clinical practice, 2006 . | Future status in clinical practice . |
|---|---|---|---|---|
| Death | Hard outcome; compelling for studies | Cannot be monitored for individuals in clinical practice | Cardiac disease is leading cause of death in thalassemia major | Remains ultimate outcome |
| Cardiac events | Hard outcome, compelling | Late event for individuals | Critical marker of clinical status | Remains crucial outcome |
| HIC by liver biopsy, both as intrinsic outcome and as surrogate for risk of cardiac disease and death19 | Gold standard to date; accurately reflects total body iron status; best assessment of fibrosis, hepatitis | Invasive and uncomfort able for patients; heterogeneous tissue iron cannot be assessed; less reliable for iron content in fibrosis or cirrhosis | Remains a critical tool but may not be so golden considering variability and new alternatives; imperfect surrogate for cardiac iron | Use may decline if R2 MRI becomes widely available |
| Cardiac iron by T2*; surrogate for risk of heart failure due to iron20,21 | Noninvasive measure of cardiac iron status. T2* < 8 ms associated with high risk of heart disease. | Not widely available; not yet proven that improved T2* by chelation improves cardiac disease or death from iron | Very helpful for patient assessment and follow-up at sites where study is available | Widespread use likely, if improvement correlates with improved clinical outcomes |
| HIC by MR; R2 “Ferriscan” approved by FDA, other methods under study | Noninvasive, potentially more accurate24 | As of 2006, not widely available | Ferriscan requires commercial license; few United States sites signed on to date | Use likely to increase if commercial hurdles are overcome |
| HIC by SQUID22,23 | Validated in clinical studies in comparison to liver biopsy | Expensive instruments, limited availability (4 in world); not directly comparable to biopsy because of calibration variability | Good alternative to biopsy for patients who live close to instruments | Likely to wane except for study settings if MRI methods become widespread and useful |
| Serum ferritin level; surrogate measure of HIC | Noninvasive, inexpensive | Highly variable; acute-phase reactant and affected by liver disease; single measures inadequate for assessment of current status | Widely available and used; running average over 6 months reliable for trends | Likely to remain as a first-line monitoring tool between more expensive HIC assessments |
Outcome . | Advantages . | Disadvantages . | Current status in clinical practice, 2006 . | Future status in clinical practice . |
|---|---|---|---|---|
| Death | Hard outcome; compelling for studies | Cannot be monitored for individuals in clinical practice | Cardiac disease is leading cause of death in thalassemia major | Remains ultimate outcome |
| Cardiac events | Hard outcome, compelling | Late event for individuals | Critical marker of clinical status | Remains crucial outcome |
| HIC by liver biopsy, both as intrinsic outcome and as surrogate for risk of cardiac disease and death19 | Gold standard to date; accurately reflects total body iron status; best assessment of fibrosis, hepatitis | Invasive and uncomfort able for patients; heterogeneous tissue iron cannot be assessed; less reliable for iron content in fibrosis or cirrhosis | Remains a critical tool but may not be so golden considering variability and new alternatives; imperfect surrogate for cardiac iron | Use may decline if R2 MRI becomes widely available |
| Cardiac iron by T2*; surrogate for risk of heart failure due to iron20,21 | Noninvasive measure of cardiac iron status. T2* < 8 ms associated with high risk of heart disease. | Not widely available; not yet proven that improved T2* by chelation improves cardiac disease or death from iron | Very helpful for patient assessment and follow-up at sites where study is available | Widespread use likely, if improvement correlates with improved clinical outcomes |
| HIC by MR; R2 “Ferriscan” approved by FDA, other methods under study | Noninvasive, potentially more accurate24 | As of 2006, not widely available | Ferriscan requires commercial license; few United States sites signed on to date | Use likely to increase if commercial hurdles are overcome |
| HIC by SQUID22,23 | Validated in clinical studies in comparison to liver biopsy | Expensive instruments, limited availability (4 in world); not directly comparable to biopsy because of calibration variability | Good alternative to biopsy for patients who live close to instruments | Likely to wane except for study settings if MRI methods become widespread and useful |
| Serum ferritin level; surrogate measure of HIC | Noninvasive, inexpensive | Highly variable; acute-phase reactant and affected by liver disease; single measures inadequate for assessment of current status | Widely available and used; running average over 6 months reliable for trends | Likely to remain as a first-line monitoring tool between more expensive HIC assessments |
HIC indicates hepatic iron content; and SQUID, superconducting quantum interference device.