Table 2.
Comparison of traditional and modern frameworks for calculating synergy. *CI has two equations for synergy in the original derivation22, for the mutually exclusive and mutually non-exclusive case. The mutually exclusive case has been widely adopted and is the model compared here. The concentration-dependent synergy of Bliss and Loewe are explored in Supplemental Section “Interactive MuSyC Jupter Notebook”, Figs. S12–S16, and Supplemental Code 1, an interactive Jupyter Notebook. This notebook shows how different MuSyC synergy parameters may be reflected at specific concentrations of Bliss or Loewe synergy.
| Dose Equivalence Principle | Multiplicative Survival Principle | Other | Multiple | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Loewe | BRAID | Hill PDE | GPDI (Loewe) | Combination Index* | Bliss | Effective Dose | ZIP | GPDI (Bliss) | HSA | GPDI (HSA) | MuSyC | |
| Defined for arbitrary metrics of drug effect (not just percent data) | ✓ | ✓ | – | ✓ | – | – | – | ✓ | ✓ | ✓ | ✓ | |
| Does not require all drugs to be equally efficacious | – | ✓ | ✓ | ✓ | – | ✓ | – | – | ✓ | ✓ | ✓ | ✓ |
| Synergy is concentration independent | – | ✓ | – | – | – | – | ✓ | – | – | – | – | ✓ |
| Synergy is related to traditional dose-response parameters | – | – | – | ✓ | – | – | ✓ | – | ✓ | ✓ | ✓ | ✓ |
| Satisfies the sham experiment | ✓ | ✓ | ✓ | ✓ | ✓ | – | – | – | – | – | – | – |