Interactive technique for optimizing drug development from the pre-clinical phases through phase-IV

• US 20040107084A1
• Filed: 09/16/2003
• Published: 06/03/2004
• Est. Priority Date: 09/16/2002
• Status: Active Grant

• Current Assignee: Optimata Ltd.
• Original Assignee: Optimata Ltd.
• Inventors: Selitser, Vera, Arakelyan, Levon, Agur, Zvia
• Granted Patent: US 7,970,550 B2
• Time in Patent Office: Days
• US Class Current: 703/11
• CPC Class Codes: G16C 20/30 Prediction of properties of chemical compounds, compositions or mixtures
• CPC Class Codes: G16H 10/20 for electronic clinical trials or questionnaires
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders

Abstract

A method of performing interactive clinical trials for testing a new drug comprising performing a pre-clinical phase in which a computer model for pharmacokinetics and pharmacodynamics of the drug is created and adjusted based on in vitro studies and in vivo studies in animals. A phase I clinical research is performed in which a clinical trial on at least a single dose is performed in parallel with performing computer simulation studies using the computer model. The computer model is adjusted based on comparison of the results of the clinical research and the computer simulation. A maximal tolerated dose, minimum effective dose, and a recommended dose is determined based on the phase I clinical research in conjunction with the computer simulations. The drug is checked for cumulative effects and providing this information to the computer model. Multiple simulations are performed using the computer model with different doses and dosing intervals. An optimal protocol is determined for the most responsive patient populations and indications for a phase II clinical trial. Phase II clinical trial is performed where a number of small scale clinical trials are performed in parallel based on results of the above. The interim results are analyzed to choose the most promising regimens for continued clinical trials. Phase III clinical research is performed for chosen indications by chosen protocols. Phase IV studies are performed for post-marketing subpopulation analysis and long term product safety assessment.

Claims

1. A method of performing interactive clinical trials for testing a new drug comprising:

a) performing a pre-clinical phase in which a computer model for pharmacokinetics and pharmacodynamics of the drug is created and adjusted based on in vitro studies and in vivo studies in animals;

b) performing a phase I clinical research in which a clinical trial on at least a single dose is performed in parallel with performing computer simulation studies using the computer model;

c) adjusting the computer model based on comparison of the results of the clinical research and the computer simulation;

d) determination of a maximal tolerated dose, minimum effective dose, and a recommended dose based on the phase I clinical research in conjunction with the computer simulations;

e) checking the drug for cumulative effects and providing this information to the computer model;

f) performing multiple simulations using the computer model with different doses and dosing intervals;

g) determining an optimal protocol for the most responsive patient populations and indications for a phase II clinical trial;

h) performing phase II clinical trial where a number of small scale clinical trials are performed in parallel based on results of step g;

i) analyzing interim results to choose the most promising regimens for continued clinical trials;

j) performing phase III clinical research for chosen indications by chosen protocols; and

k) performing phase IV studies for post-marketing subpopulation analysis and long term product safety assessment.

2. The method of claim 1, wherein in step b, prior to each sub-step of the phase I trial, computer simulation is performed to predict results of the sub-step and the predicted results are compared to clinical results corresponding to the sub-step and the computer model is adjusted based on the comparison.

3. The method of claim 1, wherein a first decision whether to continue with the trial is made, stopping the trial if an adverse decision is made.

4. The method of claim 1, wherein results of step g are used to define indications and define sub-groups of patients most sensitive, susceptible and responsive to the drug.

5. The method of claim 4, wherein effective treatment protocol is defined for a subset of the subgroups.

6. The method of claim 1, wherein the computer model is adjusted based on whether the clinical research indicates a result higher than a threshold in at least one of pre-clinical, phase I and phase II studies.

7. The method of claim 1, wherein in step h, the small clinical trials are performed in parallel for a chosen indication by a chosen treatment protocol.

8. The method of claim 1, wherein in step i, the most promising trials are chosen for indications most sensitive to the drug administered via the most efficient protocol.

9. The method of claim 8, wherein in step i, a second decision whether to continue with the trial is made, stopping the trial if an adverse decision is made.

10. The method of claim 9, wherein the second decision is based on a prediction of safety profile of the new drug in the most promising trial compared with safety of pre-existing therapies.

11. The method of claim 9, wherein the second decision is based on a prediction of efficacy profile of the new drug in the most promising trial compared with efficacy of pre-existing therapies.

12. The method of claim 1, wherein step j is performed to prove safety of the drug.

13. The method of claim 1, wherein step j is performed to prove efficacy of the drug.

14. The method of claim 1, when hitherto unknown effects are discovered, the computer model is adjusted to obtain predictions for new protocols, patient populations and indications.

15. A method of performing interactive clinical trials for a new drug comprising a step of performing a pre-clinical phase in which a computer model for pharmacokinetics and pharmacodynamics is created and adjusted based on in vitro studies and in vivo studies in animals.

16. A method of performing interactive clinical trial for a new drug comprising a step of performing a phase I clinical trial wherein a dose-escalation trial is performed in parallel with computer simulation studies to predict results and the prediction is compared with clinical results and the comparing is used to adjust the computer model.

17. A method of performing interactive clinical trials for a new drug comprising:

developing a strategy for a next sub-step in phase I clinical trial in conjunction with simulated computer predictions.