Distributed randomization and supply management in clinical trials

Patent metadata

Field	Value
Publication number	US-2016267255-A1
Application number	US-201615159550-A
Country	US
Kind code	A1
Filing date	May 19, 2016
Priority date	Jun 12, 2010
Publication date	Sep 15, 2016
Grant date	—

Abstract

A distributed clinical trial system that provides configurability, reusability and integration of randomization for different clinical trials with various electronic data capture (EDC) systems. The distributed clinical trial system includes a method of randomizing subjects in a multi-arm clinical trial. In accordance with a method, a subject identifier and a trial identifier are received from an EDC system. The trial identifier indicates the multi-arm clinical trial and the subject identifier indicates a subject enrolled in the multi-arm clinical trial. A randomization design algorithm for the multi-arm clinical trial is retrieved from a database using the received trial identifier. The randomization design algorithm is executed. The randomization design algorithm randomizes the subject to an arm of the multi-arm clinical trial, assigning the subject identifier to an arm identifier that indicates the arm of the multi-arm clinical trial to which the subject has been randomized

First claim

1 . A method of randomizing subjects in a multi-arm clinical trial, the method comprising:
receiving, by a computing system, at least a subject identifier and a trial identifier from an electronic data capture system, the subject identifier indicating a subject enrolled into the multi-arm clinical trial, the trial identifier indicating the multi-arm clinical trial into which the subject is enrolled; selecting at runtime, by the computing system, a randomization design algorithm for the multi-arm clinical trial from a database using the trial identifier, the database storing a plurality of randomization design algorithms associated with respective trial identifiers for a plurality of multi-arm clinical trials; and executing, by the computing system, the randomization design algorithm as selected that randomizes the subject to an arm of the multi-arm clinical trial, the randomization design algorithm assigning the subject identifier to an arm identifier that indicates the arm of the multi-arm clinical trial to which the subject has been randomized.

2 . The method of claim 1 , further comprising transmitting an assignment indicator to the electronic data capture system, the assignment indicator indicating that the subject has been randomized.

3 . The method of claim 1 , further comprising maintaining the trial identifier, subject identifier and arm identifier for the multi-arm clinical trial in a runtime database.

4 . The method of claim 1 , further receiving a trial site identifier and a value associated with a state of the subject in at least one randomizing factor, the trial site identifier indicating a trial site in which the subject was enrolled into the multi-arm clinical trial.

5 . The method of claim 4 , wherein randomizing the subject comprises for each arm in the multi-arm clinical trial:
determining a trial imbalance in subjects assigned in the multi-arm clinical trial when the subject is randomized to a selected arm of the multi-arm clinical trial; determining a site imbalance in subjects assigned to the selected arm; determining for each of the at least one randomization factor, a state imbalance in subjects in the multi-arm clinical trial that share the state with the subject; determining strata imbalance in subjects in the multi-arm clinical trial that share the strata with the subject; and generating a weighted sum of imbalances.

6 . The method of claim 5 , wherein randomizing the subject further comprises:
determining that there are two or more arms with a lowest weighted sum of imbalances; and assigning randomly the subject identifier to one of the two or more arms with the lowest weighted sum of imbalances.

7 . The method of claim 5 , wherein randomizing the subject identifier further comprises:
determining that there is one arm with a lowest weighted sum of imbalances; determining a set of one or more arms with a next lowest weighted sum of imbalances; and assigning randomly the subject identifier to one arm from the one arm with the lowest weighted sum of imbalances and the set of one or more arms with the next lowest weighted sum of imbalances.

8 . The method of claim 7 , wherein assigning randomly the subject identifier comprises:
determining whether a second-best probability percentage has been defined in the randomization design algorithm; and assigning randomly the subject identifier to the one arm in the set of one or more arms with the next with lowest weighted sum of imbalances in accordance with the defined second-best probability percentage.

9 . The method of claim 1 , further comprising:
receiving one or more simulation metrics associated with the randomization design algorithm, the randomization design algorithm including one or more randomization metrics; and executing a simulation of the randomization design algorithm based on the one or more simulation metrics before assigning the subject identifier to the arm identifier.

10 . The method of claim 9 , further comprising:
adjusting at least one of the one or more randomization metrics in the randomization design algorithm; and executing a simulation of the randomization design algorithm based on the one or more randomization metrics as adjusted before assigning the subject identifier to the arm identifier, the randomization design algorithm reducing a number of subjects necessary for multi-arm clinical trial.

11 . A system to randomize subjects in a multi-arm clinical trial, the system comprising:
a computing device; and a machine-readable medium comprising instructions that, when executed by the computing device, cause the computing device to perform operations comprising:
receiving at least a subject identifier and a trial identifier from an electronic data capture system, the subject identifier indicating a subject enrolled by the electronic data capture system into the multi-arm clinical trial, the trial identifier indicating the multi-arm clinical into which the subject is enrolled;
selecting at runtime a randomization design algorithm for the multi-arm clinical trial from a database using the trial identifier, the database storing a plurality of randomization design algorithms associated with respective trial identifiers for a plurality of multi-arm clinical trials; and
executing the randomization design algorithm as selected that randomizes the subject to an arm of the multi-arm clinical trial, the randomization design algorithm assigning the subject identifier to an arm identifier that indicates the arm of the multi-arm clinical trial to which the subject has been randomized.

12 . The system of claim 11 , wherein the operations further comprise transmitting an assignment indicator to the electronic data capture system, the assignment indicator indicating that the subject has been randomized.

13 . The system of claim 11 , further comprising a runtime database maintaining the trial identifier, subject identifier and arm identifier for the multi-arm clinical trial.

14 . The system of claim 11 , wherein the operations further comprise receiving a trial site identifier and a value associated with a state of the subject in at least one randomizing factor, the trial site identifier indicating a trial site in which the subject was enrolled into the multi-arm clinical trial.

15 . The system of claim 14 , wherein for each arm in the multi-arm clinical trial the operations further comprise:
determining a trial imbalance in subjects assigned in the multi-arm clinical trial when the subject is randomized to a selected arm of the multi-arm clinical trial; determining a site imbalance in subjects assigned to the selected arm; determining for each of the at least one randomization factor, a state imbalance in subjects in the multi-arm clinical trial that share the state with the subject; determining strata imbalance in subjects in the multi-arm clinical trial that share the strata with the subject; and generating a weighted sum of imbalances.

16 . The system of claim 15 , wherein the operations further comprise:
determining that there are two or more arms with a lowest weighted sum of imbalances; and assigning randomly the subject identifier to one of the two or more arms with the lowest weighted sum of imbalances.

17 . The system of claim 15 , wherein the operations further comprise:
determining that there is one arm with a lowest weighted sum of imbalances; determining a set of one or more arms with a next lowest weighted sum of imbalances; and assigning randomly the subject identifier to one arm from the one arm with the lowest weighted

Assignees

• Medidata Solutions Inc

Inventors

• Young Benjamin
• Devries Glen
• Fenster David
• Lebowitsch Jonathan

Classifications

• G06Q10/083

  Shipping · CPC title

• G06F19/363 Primary

  Physics · mapped topic

• G16H20/13

  delivered from dispensers · CPC title

• G16H10/20 Primary

  for electronic clinical trials or questionnaires · CPC title

• G16H70/40

  relating to drugs, e.g. their side effects or intended usage · CPC title