Table 1.
Key Changes Needed to Implement Customized Combination Therapy
| Current Model | Patient-centric model with customized combinations | Oversight areas that would be affected | Comment | |
|---|---|---|---|---|
| Diagnosis | Patients are grouped together based on a histologic or molecular characteristic in order to be treated with a drug or combination of drugs | Combinations of drugs are tailored to each patient’s molecular portfolio | Internal review boards, guidelines for practice, payors, Food and Drug Administration (FDA) | |
| Therapy Decisions/Molecular Tests | Histologic diagnosis and/or companion diagnostics of single genes are used to determine treatment | Panel of genes are interrogated in order to determine treatment | CLIA, FDA | |
| Molecular Tests | Tests are locked down and cannot be changed after approval | Tests are dynamic and incorporate new knowledge as it develops | CLIA, FDA | |
| Safety of Therapy | Safety of new combinations of cancer drugs are determined by Phase I testing | Safety of new combinations of drugs are determined by validated algorithms | Internal review boards, guidelines for practice, payors, FDA | Combinations of drugs without phase I are already routinely given to patients with multiple illnesses aside from cancer |
| Clinical Research | The safety and efficacy of drugs or combinations are tested. The drug or combination of drugs is the same for all patients on the trial |
The safety and efficacy of a strategy is tested (strategy is molecular matching with customized combinations). While the strategy remains consistent between patients, the drugs may be different for the patients on the trial |
Internal review boards, guidelines for practice, payors, FDA | Novel statistical methods will be needed |
| Drug approval | Safety and efficacy in large randomized trials needed in histologically defined disease | Safety data needed. Trials for efficacy may be small and approval may not be limited by histology | FDA | |
| Access to drugs | Patients can access drugs after approval based on large randomized trials | Patients will be able to access drugs if they meet requirement that strategy of matching has been used to choose the drugs | FDA, payors |