From: A methodological framework for drug development in rare diseases
Steps | Approaches | Methods |
---|---|---|
Step 1 | Use available knowledge | Bibliography |
(i) Pathophysiology, diagnosis, therapeutics, pharmacology | ||
(ii)Discursive and mathematical models for the disease | ||
(iii)Discursive and mathematical models for the drug effect(s) | ||
Individual epidemiological and RCT databases | ||
(i) Statistical approaches for analysis | ||
(ii) Identify prognostic biomarkers | ||
(iii) Identify N potential drugs (or therapeutic strategies) for evaluation in phase III RCTs | ||
(iv) Identify predictive biomarkers for these N drugs (e.g. interactions between patient characteristics and drug efficacy) | ||
(v) Validate drug-disease models | ||
Step 2 | Drug-disease modeling for the N treatments identified above | Treatment 1: (Disease model + Drug effect model 1) |
Treatment i: (Disease model + Drug effect model i) | ||
Treatment N: (Disease model + Drug effect model N) | ||
Step 3 | Drug-disease modeling for the N treatments above in patients whose characteristics may interact with drug efficacy | Treatment 1: (Disease model + Drug effect model 1) in patients whose specific characteristics interact with treatment effect 1 |
Treatment i: (Disease model + Drug effect model i) in patients whose specific characteristics interact with treatment effect i | ||
Treatment N: (Disease model + Drug effect model N) in patients whose specific characteristics interact with treatment effect N | ||
Step 4 | Experimental RCT design modeling (including orthogonal approaches) for N conditions above | P experimental designs *N situations |
Step 5 | Simulate these N*P options | Results ordered in terms of potential efficacy, adverse events, number of needed patients, cost (including trial duration) |
Step 6 | Identify the most relevant drugs to be evaluated in phase III RCTs and the RCT design to be used for each of them | Multiple-criteria decision analysis approaches |