StudyDoc Report Writing Manager

Transcription

1 2016 LabIntegrity Inc. 1

2 Table of Contents 1. Overview 2. Return On Investment (ROI) 3. StudyDoc Home 4. Data Integrity Features 5. Method Validation Tables 6. Sample Analysis Tables 7. Tox and Custom Tables 8. Report Tables Configuration a. Automatic Method Validation Sample Assignment 9. Report Features a. Report Writer Aids b. Automated Formatting i. Hyperlinks ii. Non-Breaking Spaces 10. Field Codes a. Study-Specific Field Codes b. Table-Specific Field Codes 11. Appendices and Figures a. Sciex Analyst Chromatograms 12. Additional Modules a. Outlier Evaluator b. Review Analytical Runs c. Review Validated Method d. Method Validation Summary Table e. Report Template Configuration f. Analytical Reference Standards Table g. Contributing Personnel Table h. Signature Blocks i. QA Event Table j. Sample Receipt Record Management k. Hooks to additional data stores 2016 LabIntegrity Inc. 2

3 Overview LabIntegrity Inc. 3

4 StudyDoc Manager collates, organizes, and creates reports from preclinical (or Good Lab Practices GLP) study data, using data from the Thermo Scientific Watson database and metadata from the StudyDoc database. StudyDoc minimizes if not eliminates the process of merging and recombining and/or cutting and pasting to prepare a GLP Final Report. Automatic Retrieves data from the Thermo Scientific Watson database. Processes it using the StudyDoc Table Engine and the StudyDoc Field Code Engine Combines it with boilerplate text and formats using StudyDoc s Controlled Microsoft Word templates Adaptable Enables flexible template control, allowing creation of one template for each report type Automatically fills in customized reports, allowing for single template to be used for single or multi-analyte studies. Supports multiple concentration ranges and multiple matrices for complex studies. Users can configure Figures, Appendices and Attachments to be included in the Final Report. Incorporates Gubbs Inc ChromReporter to include Sciex Analyst chromatograms. Designed for Compliance Uses LockSection and graphical table functions to allow section-specific data protection of automatically generated reports. Gives Full 21 CFR Part 11 support (security, electronic signatures, and auditing) Watson Data StudyDoc Table Preferences StudyDoc Table Engine StudyDoc Controlled Microsoft Word Template Sample Table Assignment StudyDoc Template Settings StudyDoc Field Code Engine Automated Report Figure 1: Data from Watson and settings from StudyDoc are automatically processed and combined with a template to produce an automated report in minutes. The StudyDoc Table Engine At the core of StudyDoc is its Table Engine, which builds tables from Watson data. The user can have full control over: Table Presentation (orientation, statistical calculation methods, significant digits, etc.) Samples within tables (auto-assigned by default for standard tables) Treatment of special values (outlier values, rejected samples, etc) 2016 LabIntegrity Inc. 4

5 The StudyDoc Field Code Generator The key to StudyDoc s flexibility as automated reporting software is its field code generator. All key values present in the studies and imported through StudyDoc are converted into field codes. In addition, the results of the Table Engine are converted into field codes, such that the complete section of tables, any individual table, or any table- specific statistical data can be put anywhere in the final document template. Specific references to tables in the form of hyper-links are also available. Bold, italic, hyperlinked.docx The field code generator gives LabIntegrity s clients complete control over the text sections of their reports. This allows: Rapid conversion of pre-existing reports into StudyDoc templates The ability to lock tables (through locking field codes) such that their contents cannot be manipulated, even if other sections of the document are edited. The ability to add text sections discussing multiple analytes and their characteristics. Admins can create custom field codes for information that is not contained in Watson or StudyDoc. The field code generator gives LabIntegrity s clients complete control over how the text sections of their reports are generated. Select Watson Study Select StudyDoc Template Assign Samples to Special Tables (if needed) Generate Report The Microsoft Word Report Template: Samples in this project were analyzed for [ANALYTE] according to [SUBMITTEDBY] Laboratory Method (LM) [LABMETHODNAME], [LABMETHODNUMBER]. This method employs [METHODASSAYPROCEDUREDESCRIPTION]. This method was validated for the analysis of [ANALYTE] in [SAMPLESIZE] [SAMPLESIZEUNITS] [ANTICOAGULANT] buffered [SPECIES] [MATRIX] over a concentration range of [LLOQ] [LLOQUNITS] to [ULOQ][ULOQUNITS] Final Report: Samples in this project were analyzed for Verapamil and Reserpine according to acro Division, Inc. Laboratory Method (LM) Standard Study, 7201B. This method employs protein precipitation. This method was validated for the analysis of Verapamil and Reserpine in 20 µl K2-EDTA buffered rat plasma over a concentration range of 1.00 ng/ml to 1000 ng/ml Figure 2: (left) Simple workflow from Watson data to final report. (right) Example of field code 2016 LabIntegrity Inc. 5

6 substitutions performed in the final report by the field code engine. Document Content Management and Version Control StudyDoc offers complete document content management and version control of Microsoft Word Report Templates and StudyDoc output (drafts, sections, individual tables and Final Reports). StudyDoc documents (Microsoft Word Report Templates and StudyDoc output) are stored in the StudyDoc database. Document viewing, modification and printing are restricted to users with appropriate permissions. Documents are created/modified within the StudyDoc application. If 21 CFR Part 11 compliance is enabled, modification audit trail entries are recorded including identification of modifier and date of modification. All document modifications are version controlled. Users may compare versions of documents, make modifications as necessary and save as a new version. Figure 3: StudyDoc Document Control Window LabIntegrity Inc. 6

7 21 CFR Part 11 Compliance StudyDoc can be configured to be 21 CFR Part 11 compliant including user account assignments, electronic signatures and audit trails. Audit trails keep track of any changes made in the report generation process. Electronic signatures allow the software to restrict any fraudulent StudyDoc changes. The 21 CFR Part 11 compliance feature can be configured as a silent audit trail without an electronic signature prompt. User Groups and Permissions StudyDoc permissions allow for strict access-and control of reporting features, including the ability to adjust the types of tables in a report, and the ability to create newer versions of the report templates. StudyDoc permissions are governed by Permission Groups. Permission Groups are configured by an administrator; groups are then assigned to individual user accounts. Figure 4: StudyDoc Permissions Manager LabIntegrity Inc. 7

8 Automatic Method Validation Sample Assignment Method Validation studies typically involve at least specific assays including but not limited to: 1. Calibration Curve a. Accuracy and Precision 2. QC a. Accuracy and Precision 3. Recovery and Matrix Factor 4. Matrix Effects 5. Dilution Linearity 6. LLOQ Analysis 7. Carryover 7. Selectivity 8. Sensitivity 9. Reinjection Reproducibility 10. Stability a. Freeze and Thaw b. Bench-Top c. Long-Term d. Stock Solution e. Processed Sample (autosampler) 11. Hemolyzed Matrix Typically users must manually select these samples in Watson, generate a text file output, then copy/paste/format this table. Some assay types (e.g. Recovery and Matrix Factor) are not available in Watson. StudyDoc allows users to similarly assign samples to assay tables, including Recovery and Matrix Factor tables, not provided by Watson. Alternatively, users may use StudyDoc s Automatic Method Validation Sample Assignment feature. StudyDoc allows users to assign and/or exclude Sample Name and Analytical Run Description text fragments to specific tables, which allows StudyDoc to automatically assign samples to specific assay tables. Figure 5: StudyDoc Auto-Assign Samples Feature 2016 LabIntegrity Inc. 8

9 2 Return On Investment (ROI) 2016 LabIntegrity Inc. 9

10 Return On Investment (ROI) Because of the manual nature of non-automated Final Report processes, an inordinate amount of time is spent manually copying/pasting/formatting/hyperlinking text. In addition, a large number of Quality Control (QC) and Quality Assurance (QA) events are needed to ensure accuracy and data integrity. The cost savings of automating Final Report generation are real. Below is a table of an estimation of these cost benefits, which does not include the tangible benefits of being able to quickly close out a study and start a new study LabIntegrity Inc. 10

11 3 StudyDoc Home 2016 LabIntegrity Inc. 11

12 StudyDoc Home StudyDoc can retrieve data from either the Watson database or a Watson Archived Study Microsoft Access file (.mdb). Interacting with the Watson Archived Study is desirable during StudyDoc evaluation since the validated Watson database is not touched. StudyDoc is available as a fully-functional trial version that interacts solely with Watson Archived Studies for ease of evaluation. Figure 5: StudyDoc Home Page LabIntegrity Inc. 12

13 When a new study is loaded in StudyDoc, the user is prompted to apply a Study Template. The Study Template will tell StudyDoc the type of study (Method Validation, Sample Analysis). In addition, StudyDoc will apply the underlying metadata, configuration settings, and tables contained in the study configured as the Study Template LabIntegrity Inc. 13

14 4 Data Integrity Features 2016 LabIntegrity Inc. 14

15 StudyDoc Data Integrity Features One of the most important issues in GLP Final Report is maintaining the integrity of the data as it resides in the Microsoft Word document. The uncontrolled nature of the Word document requires either the use of a commercial Document Management System (DMS) or the implementation of a manual Windows directory scheme that entails restricted access to users, report writers and Quality Assurance (QA) personnel. The latter typically involves a high level of Quality Control (QC) and QA events in order to ensure the integrity of the data before it is sent out to the client/customer. StudyDoc has several features to help ensure the integrity of the data is maintained. Lock Sections Field Code Table creation field codes can be preceded and followed by the field codes [LOCKSECTION] and [UNLOCKSECTION], respectively. The portion of the document enclosed by these field codes are then locked using Word s Restrict Editing feature. A random password (unknown to anyone) is created and applied to the section. Graphical Tables Users can configure tables to created, then converted to a figure, ensuring that table data cannot be modified. Table Date/Time Stamp Users can configure tables to include a date/time stamp. Watson Check When a study is opened in StudyDoc, StudyDoc checks to ensure that any reported concentrations have not been changed since the last time a Final Report has been generated in StudyDoc. If a concentration is found to have been changed, StudyDoc displays a constant warning message with a blinking red dot: The specific concentration that has been changed can be viewed by clicking View Report History View Underlying Data : 2016 LabIntegrity Inc. 15

16 5 Method Validation Tables 2016 LabIntegrity Inc. 16

17 Built-in Tables Method Validation Tables The following are examples of StudyDoc built-in Method Validation tables 1. Summary of Interpolated QC Std Conc Intra- and Inter-Run Precision 2. Summary of Interpolated Dilution QC Concentrations 3. Summary of Combined Recovery 4. Summary of True Recovery 5. Summary of Suppression/Enhancement 6. Summary of Matrix Factor 7. Summary of Interpolated Unique QC Low for Matrix Effects on Quantitation Assessments 8. Summary of [Period Temp] Stability in Matrix 9. Summary of Freeze/Thaw [#Cycles] Stability in Matrix 10. [Period Temp] Final Extract Stability of Interpolated QC Std Concentrations 11. [Period Temp] Stock Solution Stability Assessment 12. [Period Temp] Spiking Solution Stability Assessment 13. [Period Temp] Long-Term QC Std Storage Stability 14. Hemolysis Sample Summary 15. Carryover Table 16. Ad Hoc Stability 17. Ad Hoc Stability Comparison 2016 LabIntegrity Inc. 17

18 Summary of Interpolated QC Std Conc Intra- and Inter-Run Precision 2016 LabIntegrity Inc. 18

19 Summary of Interpolated QC Std Conc Intra- and Inter-Run Precision Statistics and ANOVA Section Summary of Interpolated Dilution QC Concentrations 2016 LabIntegrity Inc. 19

20 Summary of Combined Recovery 2016 LabIntegrity Inc. 20

21 Summary of True Recovery 2016 LabIntegrity Inc. 21

22 Summary of Suppression/Enhancement 2016 LabIntegrity Inc. 22

23 Summary of Matrix Factor 2016 LabIntegrity Inc. 23

24 Summary of Interpolated Unique QC Low for Matrix Effects on Quantitation Assessments 2016 LabIntegrity Inc. 24

25 Summary of [Period Temp] Stability in Matrix Summary of Freeze/Thaw [#Cycles] Stability in Matrix 2016 LabIntegrity Inc. 25

26 [Period Temp] Final Extract Stability of Interpolated QC Std Concentrations 2016 LabIntegrity Inc. 26

27 [Period Temp] Stock Solution Stability Assessment 2016 LabIntegrity Inc. 27

28 [Period Temp] Spiking Solution Stability Assessment 2016 LabIntegrity Inc. 28

29 [Period Temp] Long-Term QC Std Storage Stability 2016 LabIntegrity Inc. 29

30 Hemolysis Sample Summary 2016 LabIntegrity Inc. 30

31 Carryover Table Ad Hoc Stability Table The Ad Hoc Stability table is a table that can be used to create a custom stability QC table LabIntegrity Inc. 31

32 Ad Hoc Stability Comparison Table The Ad Hoc Stability Comparison table is a table that can be used to create a custom stability comparison QC table LabIntegrity Inc. 32

33 6 Sample Analysis Tables 2016 LabIntegrity Inc. 33

34 Built-in Tables Sample Analysis Tables The following are examples of StudyDoc built-in Sample Analysis tables 1. Summary of Analytical Runs 2. Summary of Regression Constants 3. Summary of Back-Calculated Calibration Std Concentrations 4. Summary of Interpolated QC Std Concentrations 5. Summary of Samples 6. Summary of Reassayed Samples 7. Summary of Repeat Samples 8. Incurred Sample Reanlysis Samples 2016 LabIntegrity Inc. 34

35 Summary of Analytical Runs Summary of Regression Constants Note that Regression Constants can also be displayed in the Back Calculated Calibration Standard Table LabIntegrity Inc. 35

36 Summary of Back-Calculated Calibration Std Concentrations Calibration Standard Table with Regression Constants 2016 LabIntegrity Inc. 36

37 Summary of Interpolated QC Std Concentrations Note that Result 33.5 is not outside of acceptance criteria, but excluded in the Watson data to demonstrate Summary Statistics functionality 2016 LabIntegrity Inc. 37

38 Summary of Samples 2016 LabIntegrity Inc. 38

39 Summary of Reassayed Samples Summary of Repeat Samples Incurred Sample Reanalysis Samples 2016 LabIntegrity Inc. 39

40 7 Tox and Custom Tables 2016 LabIntegrity Inc. 40

41 Toxicokinetic Parameter and Custom Tables It is recognized that study managers vary widely in how they wish to have toxicokinetic (tox) and pharmacokinetic (PK) data displayed. If users intend on creating reports with tox and PK tables, table requirements may be described during the purchasing negotiating stage. Tox and PK tables will then be generated using the StudyDoc Custom Tables feature. The code for creating the custom tables is embedded in the Visual Basic for Applications (VBA) module of the Microsoft Word report template. The VBA module is password protected. Using this technique, all custom code is separated from StudyDoc core code, Future modifications then will require a minimal amount of validation testing without affecting StudyDoc core code LabIntegrity Inc. 41

42 8 Report Tables Configuration 2016 LabIntegrity Inc. 42

43 Report Tables Configuration In this module, the tables needed for the study are shown (configured from the Study Template applied when the study was initially opened in StudyDoc). Users may change the tables if the study has additional table needs. For example, it may be that two Dilution QC tables are required. In this scenario, users would click choose the Dilution QC table and click the Create a Replicate Table button to create a second Dilution QC table LabIntegrity Inc. 43

44 Advanced Table Configuration Window Statistics Section Configuration The Statistics section of each table is configured in this window, in addition to any other table-specific items required for the correct generation of the table LabIntegrity Inc. 44

45 Advanced Table Configuration Window Auto-Assign Samples Configuration StudyDoc allows users may assign and/or exclude Sample Name and Analytical Run Description text fragments to specific tables, which allows StudyDoc to automatically assign samples to specific assay tables LabIntegrity Inc. 45

46 Advanced Table Configuration Window Copy/Paste from Excel Often times Advanced Table Configuration parameters are easily managed within an Excel workbook. StudyDoc includes a feature that allows the user to retrieve this information from an appropriately formatted Excel file LabIntegrity Inc. 46

47 9 Report Features 2016 LabIntegrity Inc. 47

48 Report Writer Aids LABIntegrity Report Features After the generation of a StudyDoc, it is sometimes possible that a field code has not been configure (e.g. a missing table, a missing Study Data item, a missing custom field code entry, etc.), StudyDoc notifies the user that StudyDoc needs additional attention: In addition, the place in the document where the field code occurred is shown as a ref [NA]. Automated Formatting StudyDoc automatically hyperlinks table/appendix/figure references in the report body section. StudyDoc automatically replaces spaces with non-breaking spaces in such items as Compound Name. In addition, there is a Non-Breaking Space field code to hard code needed formatting 2016 LabIntegrity Inc. 48

49 10 Field Codes 2016 LabIntegrity Inc. 49

50 Field Codes StudyDoc has over 1,000 available Study- and Table-specific field codes. Every QC table statistics section parameter (mean, SD, Precision, Accuracy and [n]) are available to be reported in the Report Body section of the report. In addition, all temperature and time parameters for stability QC tables are available for reporting. Study-Specific Field Code Examples Report Template: Samples in this project were analyzed for [ANALYTE] according to [SUBMITTEDBY] Laboratory Method (LM) [LABMETHODNAME], [LABMETHODNUMBER]. This method employs [METHODASSAYPROCEDUREDESCRIPTION]. This method was validated for the analysis of [ANALYTE] in [SAMPLESIZE] [SAMPLESIZEUNITS] [ANTICOAGULANT] buffered [SPECIES] [MATRIX] over a concentration range of [LLOQ] [LLOQUNITS] to [ULOQ][ULOQUNITS] Final Report: Samples in this project were analyzed for Verapamil and Reserpine according to acro Division, Inc. Laboratory Method (LM) Standard Study, 7201B. This method employs protein precipitation. This method was validated for the analysis of Verapamil and Reserpine in 20 µl K2-EDTA buffered rat plasma over a concentration range of 1.00 ng/ml to 1000 ng/ml 2016 LabIntegrity Inc. 50

51 Table-Specific Field Code Examples Report Template Accuracy and Precision: Intra-day [RPTS][ANALYT E_1][RPTE] Intra-day accuracy and precision is considered acceptable if at least 67% of all the calculated concentrations for all QC sample levels are within 15% of the theoretical value ( 20% at the LLOQ) and a minimum of 50% of the calculated concentrations at each QC sample level are within 15% of the theoretical value ( 20% at the LLOQ). At least 75% of all calibration standards for the analytical run must be acceptable, with an acceptable standard at both the LLOQ and upper limit of quantitation (ULOQ). Coefficient of variation (CV) 15% ( 20% at the LLOQ) for the mean calculated concentrations at each QC sample level within one analytical run containing a minimum of six QC sample replicates at each concentration. [RPTS][ANALYTE_1] [SummaryInterRun[n]ForAnalyte_1_Tabl e_qccore] of 60 (75.0%) acceptable QC samples at QC-LLOQ, QC-Low, QC- Mid, and QC-High. CV ranged from [IntraRunPrecisionMinForAnalyte_1_Tabl e_qccore]% to [IntraRunPrecisionMax ForAnalyte_1_Table_QCCORE]%, for N = 6.[RPTE] Acceptance criteria were met. Accuracy and Precision: Inter-day [RPTS][ANALYT E_1][RPTE] For a minimum of three analytical runs with acceptable standard curves, at least 67% of the mean calculated concentrations for all QC sample levels are within 15% of the theoretical value (±20% at the LLOQ) and the CV is 15% ( 20% at the LLOQ). In addition, at least 50% of the calculated concentrations at each QC sample level must be within 15% of the theoretical value (±20% at the LLOQ). [RPTS][ANALYTE_1] RE of mean calculated QC samples ranged from [SummaryInterRunAccuracyMinForAnalyt e_1_table_qccore]% to [SummaryInt errunaccuracymaxforanalyte_1_table_ QCCORE]% for 3 runs. CV ranged from [SummaryInterRunPrecisionMinForAnalyt e_1_table_qccore]% to [SummaryInt errunprecisionmaxforanalyte_1_table_ QCCORE]% for 3 runs.[rpte] Acceptance criteria were met LabIntegrity Inc. 51

52 Table-Specific Field Code Examples Final Report Results Accuracy and Precision: Intra-day Cmpd 1 Cmpd 2 Intra-day accuracy and precision is considered acceptable if at least 67% of all the calculated concentrations for all QC sample levels are within 15% of the theoretical value ( 20% at the LLOQ) and a minimum of 50% of the calculated concentrations at each QC sample level are within 15% of the theoretical value ( 20% at the LLOQ). At least 75% of all calibration standards for the analytical run must be acceptable, with an acceptable standard at both the LLOQ and upper limit of quantitation (ULOQ). Cmpd 1 59 of 60 (75.0%) acceptable QC samples at QC-LLOQ, QC-Low, QC-Mid, and QC-High. CV ranged from 3.1% to 12.9%, for N = 6. Cmpd 2 59 of 60 (75.0%) acceptable QC samples at QC-LLOQ, QC-Low, QC-Mid, and QC-High. CV ranged from 5.2% to 11.9%, for N = 6. Acceptance criteria were met. Coefficient of variation (CV) 15% ( 20% at the LLOQ) for the mean calculated concentrations at each QC sample level within one analytical run containing a minimum of six QC sample replicates at each concentration. Accuracy and Precision: Inter-day Cmpd 1 Cmpd 2 For a minimum of three analytical runs with acceptable standard curves, at least 67% of the mean calculated concentrations for all QC sample levels are within 15% of the theoretical value (±20% at the LLOQ) and the CV is 15% ( 20% at the LLOQ). In addition, at least 50% of the calculated concentrations at each QC sample level must be within 15% of the theoretical value (±20% at the LLOQ). Cmpd 1 RE of mean calculated QC samples ranged from 2.9% to 7.6% for 3 runs. CV ranged from 6.4% to 10.2% for 3 runs. Cmpd 2 RE of mean calculated QC samples ranged from 1.2% to 4.8% for 3 runs. CV ranged from 7.2% to 11.8% for 3 runs. Acceptance criteria were met LabIntegrity Inc. 52

53 Table-Specific Field Code Examples Report Template 1 Accuracy and Precision, Inter-Day Inter-day assay accuracy and precision statistics were compiled from the results of the first three acceptable validation runs for each analyte. For each of these runs, a minimum of six QC samples at four different concentration levels were extracted and analyzed. Inter-day accuracy and precision are summarized in [TableREFTable_QCCORE] for [ANALYTERESP]. For a minimum of three analytical runs with acceptable standard curves, at least 67% of the calculated concentrations for all QC samples, and at least 50% of QC samples at each concentration level, must be within 15% of the theoretical value (±20% at the LLOQ). In addition, the mean calculated concentration at each QC sample concentration level must be within 15% of the theoretical value (±20% at the LLOQ) with a CV 15% ( 20% at the LLOQ). [RPTS]For [ANALYTE_1], [SummaryInterRun[n]ForAnalyte_1_Table_QCCORE] of 60 (100.0%) of QC samples were acceptable. The relative error (%bias) of the mean QC sample concentrations was demonstrated to be between [SummaryInterRunAccuracyMinForAnalyte_1_Table_QCCORE]% and [SummaryInterRunAccuracyMaxForAnalyte_1_Table_QCCORE]%, with a CV of not more than [SummaryInterRunPrecisionMaxForAnalyte_1_Table_QCCORE]%, demonstrating good precision as well as accuracy for the assay.[rpte] 2 Sensitivity (LLOQ) The LLOQ is defined as the lowest concentration demonstrated to be within the limits of CV 20% and mean relative error (RE) within ±20%. The inter-day accuracy and precision at the LLOQ concentration level are presented in [TableREFTable_LLOQ] for [ANALYTERESP]. [RPTS]For [ANALYTE_1], the relative error (%bias) of the mean value for the LLOQ was [AccuracyForAnalyte_1_QCLevel_1_Table_LLOQ]% with a CV of [PrecisionForAnalyte_1_QCLevel_1_Table_LLOQ]% (N=[(n)ForAnalyte_1_QCLevel_1_Table_LLOQ]). Therefore, the LLOQ for [ANALYTE_1] in [SPECIES] [ANTICOAGULANT] [MATRIX] was determined to be [NomConcForAnalyte_1_QCLevel_1_Table_LLOQ] [LLOQUNITS], indicating that the method demonstrated acceptable sensitivity.[rpte] 2016 LabIntegrity Inc. 53

54 Table-Specific Field Code Examples Final Report Results 1 Accuracy and Precision, Inter-Day Inter-day assay accuracy and precision statistics were compiled from the results of the first three acceptable validation runs for each analyte. For each of these runs, a minimum of six QC samples at four different concentration levels were extracted and analyzed. Inter-day accuracy and precision are summarized in Table 13 and Table 14for Cmpd 1 and Cmpd 2, respectively. For a minimum of three analytical runs with acceptable standard curves, at least 67% of the calculated concentrations for all QC samples, and at least 50% of QC samples at each concentration level, must be within 15% of the theoretical value (±20% at the LLOQ). In addition, the mean calculated concentration at each QC sample concentration level must be within 15% of the theoretical value (±20% at the LLOQ) with a CV 15% ( 20% at the LLOQ). For Cmpd 1, 59 of 60 (100.0%) of QC samples were acceptable. The relative error (%bias) of the mean QC sample concentrations was demonstrated to be between 2.9% and 7.6%, with a CV of not more than 10.2%, demonstrating good precision as well as accuracy for the assay. For Cmpd 2, 59 of 60 (100.0%) of QC samples were acceptable. The relative error (%bias) of the mean QC sample concentrations was demonstrated to be between 1.2% and 4.8%, with a CV of not more than 11.8%, demonstrating good precision as well as accuracy for the assay. 2 Sensitivity (LLOQ) The LLOQ is defined as the lowest concentration demonstrated to be within the limits of CV 20% and mean relative error (RE) within ±20%. The inter-day accuracy and precision at the LLOQ concentration level are presented in Table 15 and Table 16 for Cmpd 1 and Cmpd 2, respectively. For Cmpd 1, the relative error (%bias) of the mean value for the LLOQ was 7.6% with a CV of 6.4% (N=6). Therefore, the LLOQ for Cmpd 1 in human K3EDTA blood was determined to be ng/ml, indicating that the method demonstrated acceptable sensitivity. For Cmpd 2, the relative error (%bias) of the mean value for the LLOQ was 1.2% with a CV of 10.0% (N=5). Therefore, the LLOQ for Cmpd 2 in rat K3EDTA plasma was determined to be ng/ml, indicating that the method demonstrated acceptable sensitivity LabIntegrity Inc. 54

55 11 Appendices and Figures 2016 LabIntegrity Inc. 55

56 Appendices and Figures Report appendices and figures are configured in the Appendices & Figures window. Appendices and figures may be maintained as common graphics files (e.g..jpg,.bmp,.png, etc.) or as Microsoft Word documents. Each appendix and figure is placed in the report via its own Field Code based on the user-configurable entry in the Field Code ID column LabIntegrity Inc. 56

57 Gubbs Inc ChromReporter ChromReporter allows users to quickly and create Microsoft Word or PDF documents of selected Sciex Analyst chromatograms (Figure 6) A tedious step in creating Analyst chromatograms is the need to optimize font size of the header and sidebar (if included) and sidebar composition. ChromReporter allows users to quickly and easily investigate font sizes and choose sidebar components(figure 8). ChromReporter allows users to configure Figure captions (Figure 7) to include in the Word/PDF output as well as offering six different output formats (Figure 9). StudyDoc integrates with ChromReporter to generate Analyst chromatograms to be included in the StudyDoc final report. Figure 6: ChromReporter LabIntegrity Inc. 57

58 Figure 7: ChromReporter Heading Configuration Figure 8: ChromReporter Sidebar Configuration Figure 9: ChromReporter Output Configuration 2016 LabIntegrity Inc. 58

59 Figure 10: ChromReporter Output (as Word document) 2016 LabIntegrity Inc. 59

60 12 Additional Modules 2016 LabIntegrity Inc. 60

61 Additional Modules Outlier Evaluator The Evaluate Outliers function will evaluate all QC samples in the study and display any values that may be considered an outlier based on a user-chose statistical method. The information may be printed and is intended to be used to make a decision on the status of the sample. The Evaluate Outliers function does not do any actual sample exclusion. The samples may be excluded in Watson, or the samples may be excluded in StudyDoc in the Assigned Samples window LabIntegrity Inc. 61

62 Review Analytical Runs Scientists and managers may monitor study progress by viewing the Analytical Run Summary tab LabIntegrity Inc. 62

63 Review Validated Method The Method Validation study(s) performed to validate the analytical method used to analyze samples in a Sample Analysis study may be linked to the Sample Analysis study in the Review Validated Method window. If linked, the Method Validation parameters shown in the table will be populated with the information from the Method Validation study. This information may be used to automatically create a Method Validation Summary Table (as an Appendix) to be included in the Sample Analysis Final Report (see next section for additional Method Validation Summary Table information) LabIntegrity Inc. 63

64 Method Validation Summary Table The Method Validation Summary Table content is configured in the Summary Table Configuration tab LabIntegrity Inc. 64

65 Report Template Configuration Microsoft Word Report Templates are configured in the Word Document window. If configured at the StudyDoc administrative level, report templates are version controlled. Users who do not have permissions cannot access this window Versions may be compared in the Document Compare window LabIntegrity Inc. 65

66 Analytical Reference Standards Table Analytical Reference Standard information may be recorded here to be used to create an Analytical Reference Standard table. StudyDoc Hooks may be used to retrieve this information from another data store if it exists (requires customer-specific customization). Note the bottom table contains Precision and Accuracy summary information for each compound LabIntegrity Inc. 66

67 Contributing Personnel Table Contributing personnel may be recorded here to create a Contributing Personnel table. The information from this table is used by the StudyDoc Signature Block field codes. Contributor names are retrieved from the StudyDoc User Account tables LabIntegrity Inc. 67

68 QA Events Table QA Event information may be recorded here to create a QA Events table LabIntegrity Inc. 68

69 Sample Receipt Record Management Sample Receipt information may be recorded here. The information is used by the Sample Receipt related field codes. If the Watson Sample Receipt functionality is used, StudyDoc retrieves that information and shows it in the bottom table. Hooks to additional data stores Information needed in the report may already reside in existing company or 3 rd party software data stores (e.g. in a laboratory notebook data store or a well-defined Excel system). StudyDoc may be configured to retrieve this information from the additional data stores (requires company-specific StudyDoc customization) LabIntegrity Inc. 69