Common use of Randomization Schedule Clause in Contracts

Randomization Schedule. The Project statistician will generate a randomization schedule according to the study design specified in the protocol. Electronic copies of the randomization will be created for loading into the clinical database at the time of database closure. Electronic and paper copies of the randomization are stored in a secured location in accordance with Omnicare CR SOPs. Fees include verification and review by a senior biostatistician. Design of Table Shells (Mocks) The statistical plan will include a set of formatted shells for all data displays (data listings, summary tables and graphics) planned for the study, which will be prepared with input from the Clinical Writing Department. If formatted data displays are not required, a detailed table of contents of SAS generated data displays will be included. Programming/QC of Data Displays The process to programming actual data displays (data listings, summary tables and graphics) at Omnicare CR is methodical and stepwise in description. **** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended. The process begins with the rules and requirements stated in the Protocol, Statistical Analysis Plan and Mock Data Displays. The annotated mocks drive the specifications for derived datasets definitions document, the programming of those datasets and the development and production of the data displays. The derived dataset specifications document follows the format presented by the FDA guidance concerning regulatory submissions in electronic format. Derived dataset structures can be created to client specifications. If specifications are not provided then programming defaults to CDISC standard structures in SAS transport file format. As the mocks is the specification for all programming output, any changes to data display formats or raw database after approval and programming initiation could result in additional charges. The biometrics staff will use a combination of independent programming, hand tabulations from supporting listings, and programming verification to ensure the accuracy and completeness of tables, listings, and statistical results. Products developed in SAS are validated for accuracy through a double programming process and these processes are outlined in the departmental SOPs and guidelines. The status of a SAS program’s development is monitored through an internal tracking system which stores the individuals involved with a given product, comments for program and output issues, when the programmed files are ready for QC and when the person validating the results states that the product has passed QC. All report data displays will be verified for accuracy and internal consistency among data displays. A quality control binder, including the quality control strategy for each data display and audit trail, will be included in the Project file. Programmatic Evaluability/Outcome Patient evaluability criteria and relevant algorithms will be developed for the study by Omnicare CR and presented to Sponsor for review and approval. These algorithms will be programmed using SAS to identify evaluable patients. Biostatisticians will verify the accuracy of the output with independent programming and review of individual patient data. Final decisions regarding patient evaluability will require approval by the Sponsor; patient evaluability is performed once for each patient in the study. Data listings for each patient’s evaluability status and supporting data will be prepared and submitted to Sponsor for classification prior to breaking the blind. Data classification meetings may be held either in person or via teleconference. Statistical Analysis Omnicare CR staff biostatisticians will perform statistical analysis, in accordance with the approved statistical analysis plan. The analysis includes verification of assumptions needed for statistical inference, determination of investigator-by-treatment interaction, and examination of outlying data points. Statistical findings which may not be appropriate for the body of the clinical report (e.g., tests for interaction, data distribution issues, etc.), deviations from the planned analyses, and additional exploratory analyses will be included in a statistical appendix to the clinical report. **** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended. The Project statistician will also review the clinical report to ensure appropriate representation of statistical methodology and inference. FDA Item 11 Additional data definition documentation for all derived datasets can be provided to support the FDA requirements for submitting to the agency. The file produced would be named define pdf matching the guidance titled Regulatory Submissions in Electronic Format; New Drug Applications. Datasets are provided in SAS version 5-transport format. Standard Data Transfer At the conclusion of the study, Omnicare CR will transfer, the Project database to Sponsor in standard Omnicare CR SAS data sets using Omnicare CR standard naming conventions and format. Customized data transfers, or interim database closes and transfers, can be accommodated on request at an additional fee.

Randomization Schedule. The Project statistician will generate a randomization schedule according to the study design specified in the protocol. Electronic copies of the randomization will be created for loading into the clinical database at the time of database closure. Electronic and paper copies of the randomization are stored in a secured location in accordance with Omnicare CR SOPs. Fees include verification and review by a senior biostatistician. Design of Table Shells (Mocks) The statistical plan will include a set of formatted shells for all data displays (data listings, summary tables and graphics) planned for the study, which will be prepared with input from the Clinical Writing Department. If formatted data displays are not required, a detailed table of contents of SAS generated data displays will be included. Programming/QC of Data Displays The process to programming actual data displays (data listings, summary tables and graphics) at Omnicare CR is methodical and stepwise in description. **** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 24b-2 of the Securities Exchange Act of 19331934, as amended. The process begins with the rules and requirements stated in the Protocol, Statistical Analysis Plan and Mock Data Displays. The annotated mocks drive the specifications for derived datasets definitions document, the programming of those datasets and the development and production of the data displays. The derived dataset specifications document follows the format presented by the FDA guidance concerning regulatory submissions in electronic format. Derived dataset structures can be created to client specifications. If specifications are not provided then programming defaults to CDISC standard structures in SAS transport file format. As the mocks is the specification for all programming output, any changes to data display formats or raw database after approval and programming initiation could result in additional charges. The biometrics staff will use a combination of independent programming, hand tabulations from supporting listings, and programming verification to ensure the accuracy and completeness of tables, listings, and statistical results. Products developed in SAS are validated for accuracy through a double programming process and these processes are outlined in the departmental SOPs and guidelines. The status of a SAS program’s development is monitored through an internal tracking system which stores the individuals involved with a given product, comments for program and output issues, when the programmed files are ready for QC and when the person validating the results states that the product has passed QC. All report data displays will be verified for accuracy and internal consistency among data displays. A quality control binder, including the quality control strategy for each data display and audit trail, will be included in the Project file. Programmatic Evaluability/Outcome Patient evaluability criteria and relevant algorithms will be developed for the study by Omnicare CR and presented to Sponsor for review and approval. These algorithms will be programmed using SAS to identify evaluable patients. Biostatisticians will verify the accuracy of the output with independent programming and review of individual patient data. Final decisions regarding patient evaluability will require approval by the Sponsor; patient evaluability is performed once for each patient in the study. Data listings for each patient’s evaluability status and supporting data will be prepared and submitted to Sponsor for classification prior to breaking the blind. Data classification meetings may be held either in person or via teleconference. Statistical Analysis Omnicare CR staff biostatisticians will perform statistical analysis, in accordance with the approved statistical analysis plan. The analysis includes verification of assumptions needed for statistical inference, determination of investigator-by-treatment interaction, and examination of outlying data points. Statistical findings which may not be appropriate for the body of the clinical report (e.g., tests for interaction, data distribution issues, etc.), deviations from the planned analyses, and additional exploratory analyses will be included in a statistical appendix to the clinical report. **** Certain confidential information contained in this document, marked with four asterisks, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 406 24b-2 of the Securities Exchange Act of 19331934, as amended. The Project statistician will also review the clinical report to ensure appropriate representation of statistical methodology and inference. FDA Item 11 Additional data definition documentation for all derived datasets can be provided to support the FDA requirements for submitting to the agency. The file produced would be named define pdf matching the guidance titled Regulatory Submissions in Electronic Format; New Drug Applications. Datasets are provided in SAS version 5-transport format. Standard Data Transfer At the conclusion of the study, Omnicare CR will transfer, the Project database to Sponsor in standard Omnicare CR SAS data sets using Omnicare CR standard naming conventions and format. Customized data transfers, or interim database closes and transfers, can be accommodated on request at an additional fee.