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Chapter 26: Study CloseoutChapter 26: Study Closeout

As a protocol finishes data collection and comes to a close, steps must be taken to ensure that the data are complete and accurate. This process requires a lot of communication between the sites and the Data Coordinating Center (DCC) to clarify outstanding issues and finalize the study database. A. Purpose

To establish procedures to ensure that the data collected during the protocol is compiled, finalized, and locked at the end of the protocol in a consistent manner across study sites.

B. Personnel

Study Coordinator

Principal Investigator

Data Manager

Technical Director

Project ManagerBiostatisticianC. Protocol CloseoutDuring this phase of the study, the DCC actively queries the data and the sites to resolve anomalies and oddities identified in the database. This may include posting of data queries, posting of study queries, or other means of communication regarding the anomalies. Only once all data queries have been resolved or adequately explained, can the database be considered final.C.1 Cleaning and Querying Phase Data cleaning will begin prior to the end of the study. Once data collection is completed at a given site, the DCC will begin the final cleaning and querying process for that site. At this time, the site Study Coordinator should also begin to review and complete the items listed on the Site Study Closeout Checklist (Appendix A).The final cleaning process can take up to three months to complete (refer to the DCC Data Cleaning timeline in Appendix B for more timeline information). During this three-month period, the DCC will review the sites study data to identify anomalies and oddities. This may include writing new data queries on the back-end, writing new reports or working with the study Biostatistician to calculate new variables.The DCC will communicate all queries to the sites through the DEMS or X-ACT study website. All resolutions and responses to the queries should be documented as instructed by the DCC.C.2 Closeout Site VisitsAfter a site has completed their last study visit, but prior to finalizing the data for the site, DCC staff will make their final visit to the site. During this visit, the DCC monitors will review the paper research and consent charts and study documentation. A study closeout visit agenda is included as Appendix C.The DCC will post the final site visit monitoring report within two weeks of the visit. The site must review and respond to all issues identified within one month of the report posting date. All reports and responses will be posted to the X-ACT study website. Refer to XACT MOP Chapter 14: Quality Assurance for additional information on site visits.C.3 Mint Destruction

After all study visits are completed, the Study Coordinator should complete the mint destruction process. All mints must be destroyed according to study-wide and site-specific procedures. The study-wide mint destruction procedure is detailed in Chapter 25 of the X-ACT MOP.D. Database LockDatabase lock occurs once all data points are considered to be finalized, and no further changes to the database are expected. This usually occurs once all data cleaning is completed and all anomalies and oddities have been fully documented.D.1 Completing Site Study Closeout Checklist The Site Study Closeout Checklist is included as Appendix A of this document. Beginning during the querying phase of the closeout process, the site Study Coordinator will begin to complete this checklist. The checklist must be finalized prior to database lock. Each item listed on the checklist must be checked as either Complete or Not Applicable (N/A). All N/A responses must be explained in the notes section. In addition, the notes section should be used to explain any anomalies or oddities that are identified during the data cleaning process. The notes section can also be used to document the location of information relevant to the study (i.e. the location where research charts will be stored after the study is complete, the dates of mint transfer for destruction, etc.).

The site should keep the original, signed version of the completed checklist on file. They must also either upload a copy of the signed checklist to the XACT website (in .pdf format) or mail a copy of the signed checklist to the DCC for their records. If uploaded to the website, post the checklist to the Documents/Clinical Sites/your site name/Closeout folder and send an email to the Data Manager detailing the completion of the checklist. The DCC stores the completed and signed Closeout Checklist with all of the other protocol database documentation and binders.

D.2 Locking the DatabaseOnce each site has sent a signed copy of the Site Study Closeout Checklist to the DCC, the DCC will complete the DCC Closeout Checklist (Appendix D). The Data Manager, DCC PI, and DCC Biostatistician must all sign off on the DCC Closeout Checklist. Once all sign-offs are complete, the DCC Data Manager will lock the raw database. The final raw database includes only those data collected on the CRFs and as specified by the data dictionaries. The database does not include recoded or transformed variables or scales created using the raw data. Locking does not include data that are changed in some way based on decisions that are made in the analysis of the data such as omitting subjects, collapsing variables, truncating distributions, data transformations, and outlier exclusions.Only once the raw final database has been locked, will the DCC proceed with creating the final analytic database. The analytic database is the database that is used for the study analyses. The analytic database contains variables that are derived and/or computed from the raw data on the CRFs, including subscales and total scores. The analytic database contains the transformed values of raw variables if data needs to be transformed prior to analysis; summarized variables (e.g., if a weekly mean is being used in analyses, but there are 3 measurements per week, then the weekly mean would be in the analytic database); and imputed variables.D.3 Database UnlockingShould the DCC find any database issue that requires the database to be unlocked, the DCC Data Manager will immediately notify the site PI, DCC PI, DCC Biostatistician and DCC Technical Director. Conversely, if a site finds any database issue that requires the database to be unlocked, they should notify the DCC Data Manager immediately. The DCC Data Manager will specify the database issue and the plan to rectify the database issue. Once the issue has been resolved, the database will be relocked and the Database Relock Form will be completed (see Appendix E).Appendix ASite Study Closeout ChecklistTo be completed by the Site PI and Study Coordinator

Site: Protocol:

Marking Complete means that all versions of the following essential documents are present and up-to-date or items are completed as stated

Marking N/A means that the listed item is Not Applicable for the Protocol (if marked, explain why in the Notes section)

CompleteN/ANotes

I CRF/DATA Completeness

A. All data collection is completed through the last participants last follow-up. FORMCHECKBOX

FORMCHECKBOX

B. All CRFs are complete, including data that requires transcription from source materials. FORMCHECKBOX

FORMCHECKBOX

C. All study data has been entered into the DEMS. FORMCHECKBOX

FORMCHECKBOX

D. All SAEs have been followed until conclusion or acceptable resolution. FORMCHECKBOX

FORMCHECKBOX

E. All Oral Examination forms were double key entered as required by study procedures. FORMCHECKBOX

FORMCHECKBOX

II CRF/DATA Queries

A. All data queries have been resolved or explained in the dataset (this includes full explanation of all true data anomalies that cannot be corrected in the database). FORMCHECKBOX

FORMCHECKBOX

B. All Closeout Site Visit issues have resolved and/or documented and the final response(s) posted to the XACT website . FORMCHECKBOX

FORMCHECKBOX

III. Reports

A. Final Trial Monitoring Reports have been stored with the sites study documentation (either paper or electronic version). FORMCHECKBOX

FORMCHECKBOX

B. All site visit reports and site responses to reports are completed and stored with the sites study documentation (either paper or electronic). FORMCHECKBOX

FORMCHECKBOX

C. Plans have been made for submitting ongoing IRB submissions until the final IRB report can be filed. FORMCHECKBOX

FORMCHECKBOX

D. All documentation relating to protocol violations (from both the site and the DCC) are stored with the sites study documentation. FORMCHECKBOX

FORMCHECKBOX

E. A list of site specific anomalies that occurred that may have interfered with normal study flow (e.g. earthquake, strike). FORMCHECKBOX

FORMCHECKBOX

IV. Mint Destruction

A. All mints and mint containers have been destroyed in compliance with study-wide and site-specific procedures.

B. All completed Mint Destruction Logs have been sent to the DCC (either uploaded to XACT website or mailed/faxed).

C. All documents related to Mint Destruction are stored with the sites study documentation.

V. Document Storage

A. Arrangements for storage of all hard copy study related documentation have been made.

B. Arrangements for storage of all electronic study related documentation have been made.

Summary or other Comments:

The sites Principal Investigator confirms the above checklist is complete and the sites files are ready for data lock-down.

Site PI Name

Site Study Coordinator Name

Signature(s)//

//

Appendix BXACT DCC Closeout Time Line

Appendix CX-ACT Final Monitoring Site Visit Agenda1. Meet with Study Coordinator: This is just a brief discussion to get oriented and determine if the site has any issues or questions that need to be addressed. It is optional for other staff (PI, examiners, hygienists, data entry staff, etc) to be present for this first discussion.

Overview of todays site visit plan

Discussion of current issues/concerns

Final visits

Study procedures

Staffing concerns

Adverse Events

Drug Accountability and treatment application

2. Review Final Regulatory Documentation

IRB materials and documentation

Protocol documentation

Forms and MOP binders

Training documentation

3. Review Participant charts

Review newly collected data for charts that were reviewed at previous visits Finish reviewing all consent charts, if not already complete

4. Review mint accountability records

5. Review supplies

Storage of supplies

Final record keeping related to supplies and destruction6. Debriefing session with PI and Study Coordinator

During the visit: The DCC monitors will want to meet briefly with the Study Coordinator to go over any current issues or concerns. The majority of the visit will be spent reviewing the regulatory documentation and both the consent and research charts. The DCC monitor will need a private area with a table and seating for two monitors. A debriefing meeting with the Study Coordinator, at a minimum, will be held at the end of the visit to go over any issues or concerns that the monitor may have.

Following the visit: The DCC monitors will complete a detailed monitoring visit report within two weeks of the site visit. The report is due within one month of the monitoring visit. Copies of the monitoring visit report will be distributed via the secure XACT website. Copies will be made available to relevant site staff, the XACT administrative chair, the DCC, and the XACT Project Officer. The site PI or designee must respond to the monitoring report, showing resolution of all issues, within one month of receipt.

Appendix DDCC Closeout Checklist

To be completed by DCC Data Manager

Protocol Title:

Study Type: FORMCHECKBOX Behavioral FORMCHECKBOX Medication FORMCHECKBOX Combination FORMCHECKBOX Other

Marking Complete means that all versions of the following essential documents are present and up-to-date or items are completed as stated

Marking N/A means that the listed item is Not Applicable for the Protocol (if marked, explain why in the Notes section)CompleteN/ANotes

I CRF/DATA Completeness

A. All data collection is completed through the last participants last follow-up. FORMCHECKBOX

FORMCHECKBOX

B. All CRFs are complete, including data that requires transcription from source materials. FORMCHECKBOX

FORMCHECKBOX

C. All data has been entered into the DEMS or sent to the DCC (including any site data that is analyzed off-site, e.g. urine data files). FORMCHECKBOX

FORMCHECKBOX

D. All collected data are entered in one or more data files (including screen fail data where collected, baseline records, in treatment records, final visit/tx-end records, and all follow-up points). FORMCHECKBOX

FORMCHECKBOX

E. All missing records (CRFs) have been verified as truly missing (e.g. not collected). FORMCHECKBOX

FORMCHECKBOX

F. Missing values with forms (e.g. missing items on a CRF that is otherwise complete) have been verified as truly missing (e.g. not collected). FORMCHECKBOX

FORMCHECKBOX

G. Primary Key fields do not contain any missing data. FORMCHECKBOX

FORMCHECKBOX

H. All AE/SAE CRFs are complete. FORMCHECKBOX

FORMCHECKBOX

II CRF/DATA Accuracy

A. There are no duplicate records in the data files. FORMCHECKBOX

FORMCHECKBOX

B. All range checks were performed (as specified in the Data Dictionaries). FORMCHECKBOX

FORMCHECKBOX

C. All within-form consistency checks between items were performed (as specified in the Data Dictionaries). FORMCHECKBOX

FORMCHECKBOX

D. All cross-form consistency checks for critical and repeated items were performed (as specified in the Data Dictionaries). FORMCHECKBOX

FORMCHECKBOX

E. All outside data files (e.g. urinalysis results files) have been checked for accuracy and consistency. FORMCHECKBOX

FORMCHECKBOX

FORMCHECKBOX

FORMCHECKBOX

III CRF/DATA Queries FORMCHECKBOX

FORMCHECKBOX

A. All queries have been resolved or explained in the data set. FORMCHECKBOX

FORMCHECKBOX

B. All DCC Closeout visits have been completed. FORMCHECKBOX

FORMCHECKBOX

IV. Reports

A. Summarized or Aggregated Report of Participant Recruitment, Progress, and Retention. FORMCHECKBOX

FORMCHECKBOX

B. A list by follow-up point of all participants that did not complete each follow-up visit with a reason why (e.g. Never Showed, In Jail, Asked never to be contacted again, etc.). FORMCHECKBOX

FORMCHECKBOX

F. Summarized or Aggregated Report of the CRF Completeness. FORMCHECKBOX

FORMCHECKBOX

G. Include a list, by CRF, of all participants missing the CRF with a reason why (e.g. Participant Never Showed for appointment, Participant left early, etc.). FORMCHECKBOX

FORMCHECKBOX

H. Summarized or Aggregated Report of the errors triggered during chart review, at time of entry and nightly. FORMCHECKBOX

FORMCHECKBOX

I. Summarized or Aggregated Report of the Data Audit Reports by CRF. FORMCHECKBOX

FORMCHECKBOX

J. A Report of Protocol Violations This report would summarize each violation and describe the process for resolution, if necessary. FORMCHECKBOX

FORMCHECKBOX

K. A Summarized Report of any data anomalies that exist in the clean database. The report must include information that would uniquely identify the record or records affected. FORMCHECKBOX

FORMCHECKBOX

L. A list of site specific anomalies that occurred that may have interfered with normal study flow (e.g. earthquake, strike). FORMCHECKBOX

FORMCHECKBOX

M. A report listing the final timelines of data entry for all forms. FORMCHECKBOX

FORMCHECKBOX

N. Final adverse events reports to summarize serious and non-serious adverse events. FORMCHECKBOX

FORMCHECKBOX

O. An electronic copy of the CRFs and Data Dictionaries. FORMCHECKBOX

FORMCHECKBOX

V. Mint Destruction

A. All mints and mint containers have been destroyed in compliance with study-wide and site-specific procedures. FORMCHECKBOX

FORMCHECKBOX

B. All completed Mint Destruction Logs from the sites and DCC are on file at the DCC. FORMCHECKBOX

FORMCHECKBOX

Summary or other Comments:

The Data Coordinating Center Data Management team confirms the above checklist is complete and the data files are ready for data lock-down.

DCC PIs Name

DCC Biostatisticians name

Technical Directors

Data Managers Name

Signature(s)//

//

//

//

Appendix EX-ACT Database ReLocking Form

Date of UnlockSiteReason for UnlockDate of RelockSignatures

Site PI:

DCC PI:

DCC Data Manager:

DCC Biostatistician:

Site PI:

DCC PI:

DCC Data Manager:

DCC Biostatistician:

Site PI:

DCC PI:

DCC Data Manager:

DCC Biostatistician::

Site sends completed Site Closeout Checklist to DCC

Site works on completing Site Closeout Checklist

4+ months later

DCC and site work together to clean the database and resolve all queries

3 months later

2 months later

1 month later

A site collects its last data point

DCC Closeout checklist completed & DCC locks the raw database

DCC creates analytic database

Chapter 26: Study Closeout Version 1.0 01/12/2011 Page 26-5