Table 1.
Preclinical Grading Scale
| Animal species in which efficacy* has been demonstrated | Points |
|---|---|
| Primate model of traumatic SCI | 8 |
| Large animal model of traumatic SCI (dog, cat, rabbit, pig, sheep) | 6 |
| Rat model of traumatic SCI | 4 |
| Mouse model of traumatic SCI | 2 |
| Maximum score: | 20 |
| Injury paradigms in which efficacy* has been demonstrated | Points |
| Cervical contusion SCI models | 6 |
| Thoracic contusion SCI model | 3 |
| Cervical clip compression SCI model | 6 |
| Thoracic clip compression SCI models | 3 |
| Cervical partial transection sharp SCI model | 1 |
| Thoracic partial transection sharp SCI model | 1 |
| Maximum score: | 20 |
| Time window of efficacy* | Points |
| Efficacy demonstrated with a treatment delay of 12 h or more | 8 |
| Efficacy demonstrated with a treatment delay of 4 h or more, but less than 12 h | 6 |
| Efficacy demonstrated with a treatment delay of 1 h or more, but less than 4 h | 3 |
| Efficacy demonstrated when treatment given immediately at the time of injury or within less than 1 h | 2 |
| Efficacy demonstrated when treatment is given prior to injury | 1 |
| Maximum score: | 20 |
| Demonstration of “clinically meaningful” efficacy | Points |
| THORACIC SCI MODEL: Achievement of plantar weight support (i.e., BBB of 9) versus controls that do not, or the achievement of consistent forelimb–hindlimb coordination (i.e., BBB of 14) versus controls that do not, in a study with associated improvements in non-behavioral outcomes (e.g., tissue sparing). | 4 |
| THORACIC SCI MODEL: Significant improvement in other locomotor or motor behavioral tests (e.g., quantitative gait analysis, inclined plane, swimming) or other non-motor behavioral tests (e.g., pain, autonomic dysreflexia) in a study that also demonstrates associated improvements in non-behavioral outcomes (e.g., tissue sparing). | 4 |
| CERVICAL SCI: Significant improvement in some motor function test (e.g., food-pellet reaching, grasping, quantitative “gait” assessment) in a study that also demonstrates associated improvements in non-behavioral outcomes. | 4 |
| CERVICAL SCI: Significant improvements in other non-motor behavioral tests (e.g., pain, autonomic dysreflexia) in a study that also demonstrates associated improvements in non-behavioral outcomes. | 4 |
| DOSE RESPONSE: Demonstrated in a single study using either the thoracic or the cervical SCI model. The dose “response” is defined by improvements in either behavioral or non-behavioral outcomes with changing doses of the therapy. | 4 |
| Maximum score: | 20 |
| Independent reproducibility/replication | Points |
| More than 10 independent laboratories report on the beneficial effects of the therapy | 20 |
| 5–10 independent laboratories report on the beneficial effects of the therapy | 12 |
| 3–4 independent laboratories report on the beneficial effects of the therapy | 7 |
| 2 Independent laboratories report on the beneficial effects of the therapy | 3 |
| 1 independent laboratory reporting on the beneficial effects of the therapy | 0 |
| 1 independent laboratory reports on the negative results on the therapy | −3 |
| 2–3 independent laboratories report on the negative results of the therapy | −7 |
| 4–9 independent laboratories report on the negative results of the therapy | −12 |
| More than 9 independent laboratories report on the negative results of the therapy | −20 |
| Maximum score: | 20 |