Table 2. The Framework to Identify Models of Disease (FIMD).
Questions per validation parameter, and weight of each question and domain according to the same weighting system, in which the total of 100 points is divided equally by the eight domains, and then equally by each question within a domain.
| Weight | |
|---|---|
| 1. EPIDEMIOLOGICAL VALIDATION | 12,5 |
| 1.1 Is the model able to simulate the disease in the relevant sexes? | 6,25 |
| 1.2 Is the model able to simulate the disease in the relevant age groups (e.g. juvenile, adult or ageing)? | 6,25 |
| 2. SYMPTOMATOLOGY AND NATURAL HISTORY VALIDATION | 12,5 |
| 2.1 Is the model able to replicate the symptoms and co-morbidities commonly present in this disease? If so, which ones? | 2,5 |
| 2.2 Is the natural history of the disease similar to human’s regarding: 2.2.1 Time to onset |
2,5 |
| 2.2.2 Disease progression | 2,5 |
| 2.2.3 Duration of symptoms | 2,5 |
| 2.2.4 Severity | 2,5 |
| 3. GENETIC VALIDATION | 12,5 |
| 3.1 Does this species also have orthologous genes and/or proteins involved in the human disease? | 4,17 |
| 3.2 If so, are the relevant genetic mutations or alterations also present in the orthologous genes/proteins? | 4,17 |
| 3.3 If so, is the expression of such orthologous genes and/or proteins similar to the human condition? | 4,16 |
| 4. BIOCHEMICAL VALIDATION | 12,5 |
| 4.1 If there are known pharmacodynamic (PD) biomarkers related to the pathophysiology of the disease, are they also present in the model? | 3,125 |
| 4.2 Do these PD biomarkers behave similarly to humans’? | 3,125 |
| 4.3 If there are known prognostic biomarkers related to the pathophysiology of the disease, are they also present in the model? | 3,125 |
| 4.4 Do these prognostic biomarkers behave similarly to humans’? | 3,125 |
| 5. AETIOLOGICAL VALIDATION | 12,5 |
| 5.1 Is the aetiology of the disease similar to humans’? | 12,5 |
| 6. HISTOLOGICAL VALIDATION | 12,5 |
| 6.1 Do the histopathological structures in relevant tissues resemble the ones found in humans? | 12,5 |
| 7. PHARMACOLOGICAL VALIDATION | 12,5 |
| 7.1 Are effective drugs in humans also effective in this model? | 4,17 |
| 7.2 Are ineffective drugs in humans also ineffective in this model? | 4,17 |
| 7.3 Have drugs with different mechanisms of action and acting on different pathways been tested in this model? If so, which? | 4,16 |
| 8. ENDPOINT VALIDATION | 12,5 |
| 8.1 Are the endpoints used in preclinical studies the same or translatable to the clinical endpoints? | 6,25 |
| 8.2 Are the methods used to assess preclinical endpoints comparable to the ones used to assess related clinical endpoints? | 6,25 |