Standard Operating Procedures for Clinical Research Personnel Part 16 Wendy Bohaychuk and Graham Ball GCRP Consultants, Lakehurst General Delivery, Ontario, Canada KOL 2JO Summary This is the 16th in a series of articles containing proposals for wording and content of Standard Operating Procedures (SOPs) for clinical research activities conducted by sponsors and Contract Research Organisations (CROs). The procedures include those required by the International Conference on Harmonisation (ICH), the Food and Drug Administration (FDA), many other guidelines and regulations, and best practice observed by the authors. The model forms require modification for actual use. In this article, SOPs are presented for internal review of case report forms and data: initial internal CRF review (after retrieval to sponsor/cro) (SOP 405); data correction after retrieval from study sites (SOP 406); database development, review and lock (SOP 407); and statistical review (SOP 408). SOPs are also presented for management of CROs (SOP 409) and clinical laboratories during studies (SOP 410). (The full text of all 101 SOPs is available from the authors.) Copyright 2003 John Wiley & Sons, Ltd. Key Words GCP; SOP; data tracking; data query SOP 405. Initial Internal CRF Review (After Retrieval to Sponsor/CRO) Policy Immediately upon retrieval of CRFs to the sponsor/cro premises, the CRFs must be reviewed Correspondence to: Wendy Bohaychuk, GCRP Consultants, Lakehurst General Delivery, Ontario, Canada KOL 2JO E-mail: wbohaychuk@gcrpc.com internally to determine any further clarification and resolution of data which might be necessary. (This SOP includes procedures which require the involvement of clinical research personnel. It must not supersede SOPs developed by personnel in the data management department.) Procedures 405.1. Sponsor/CRO personnel must not make any entries on original top white copies of CRFs retrieved to the sponsor/cro site (or on copies of CRFs at the investigator site) except on designated areas. 405.2. Upon retrieval to the sponsor/cro premises, the top white copy of the CRF will immediately be sent to the archives by the [Monitor]. Thereafter, all personnel will only work with the middle working copy of the CRF. 405.3. The [Monitor] will maintain a record of distribution of all CRFs on the CRF tracking form (Form 405-1). 405.4. The CRFs will first be reviewed by another [Monitor] (ie secondary monitoring) using the CRF internal review form (Form 405-2) which will initially be completed by the primary [Monitor]. 405.5. The CRF internal review form must accompany the CRF during all subsequent review. 405.6. If AEs are observed on retrieved CRFs, the CRFs must be sent to the [Medical Safety Advisor] of the sponsor/cro within two working days. [The [Medical Safety Advisor] will then be responsible for further distribution of the CRF with the attached internal CRF review form.] DOI: 10.1002/qaj.222
Standard operating procedures for clinical research personnel 101 405.7. If serious AEs are observed on retrieved CRFs, the CRFs must immediately (within 24 hours) be sent for review by the [Medical Safety Advisor]. (The [Medical Safety Advisor] will then be responsible for further distribution of the CRF and attached internal CRF review form.) 405.8. Questions about eligibility and evaluability which might affect the statistical analysis require further review by the [Biostatistician] which should also be documented on Form 405-2. 405.9. CRFs must be reviewed by all responsible reviewers in the clinical research department within three working days of retrieval from the investigator site. [This time period may vary, of course. Again, the objective is to review data as promptly as possible.] 405.10. After review by clinical research personnel, the CRFs and the completed attached Form 405-1 will be transmitted to the data processing department by the [Monitor]. 405.11. Data recorded on CRFs will be entered into the computer within ten working days of being received by the data processing group. [Again, this time period may vary. There should be separate data management SOPs to deal with this requirement in more detail.] 405.12. After the data are entered into the computer, any questions concerning the data should be sent to the [Monitor] who will, if necessary, contact the investigator for correction of the data, according to the procedures described in SOP 406. 405.13. The [Monitor] must inform the [Title] of all relevant information (eg CRFs undergoing review) that must be entered into the clinical study tracking schedule in accordance with SOP 109. 405.14. Forms 405-1 and 405-2 will be filed by the [Monitor] in the sponsor/cro study site archives. [Depending on how the database is being handled, it might also be wise to file these forms in the sponsor/ CRO study archives.] Related SOPs: SOP 401. Monitoring Visits, SOP 403. Source Documents versus Case Report Forms, SOP 404. Source Data Verification and CRF Review at Study Sites, SOP 406. Data Correction After Retrieval from Study Sites, SOP 407. Database Development, Review and Lock, SOP 408. Statistical Review SOP 602. Recording and Reporting Adverse Events. Suggestions for Forms: Documentation of Internal Safety Review of CRFs, List of Protocol Violations. Form 405-1. CRF Tracking Please complete a separate form for each CRF. Please provide a comment for all NO and NA (Not Applicable) responses. Please attach a copy of the form to the CRF. Sponsor/CRO name: Study medication/device name: Project name/code number: Study/protocol number: Study/protocol version number and date: (dd/mmm/yy) Study/protocol title:
102 W. Bohaychuk and G. Ball (Form designer: prepare the following items in a column format.) Study subject s initials: Study subject s number/code: CRF number: Study visit days/numbers: Study visit dates: (dd/mmm/yy) Date CRF received by sponsor/cro: (dd/mmm/yy) Date CRF sent to data processing group: (dd/mmm/yy) Original top (white) copy sent to archives: Secondary monitoring review undertaken: Safety review undertaken: Biostatistician review undertaken: DQF required: DQF issued: Responsibility for completion of form: name, title, signature, date (dd/mmm/yyyy) Distribution: Medical Safety Advisor, Data Management Department Archiving: Sponsor/CRO Study Site Archives Form 405-2. Internal CRF Review Please complete a separate form for each CRF. Please provide a comment for all NO and NA (Not Applicable) responses. Please attach a copy of this form to the CRF. Sponsor/CRO name: Study medication/device name: Project name/code number: Study/protocol number: Study/protocol version number and date: (dd/mmm/yy) Study/protocol title: Study subject s initials: Study subject s number/code: CRF number: Study visit days/numbers: Study visit dates: (dd/mmm/yy) This form should initially be completed by the [Monitor]. Other reviewers may comment on the initial entries in the space provided below. Is study subject eligible? Specify protocol violations affecting eligibility: Other reviewer comments: Is study subject evaluable for safety? Specify protocol violations affecting safety evaluability: Other reviewer comments:
Standard operating procedures for clinical research personnel 103 Is study subject evaluable for effectiveness? Specify protocol violations affecting effectiveness evaluability: Other reviewer comments: Did the study subject complete the study? If not, specify the reasons for premature termination: Other reviewer comments: Were AEs noted? If yes, notify the [Medical Safety Advisor] within two working days. Specify the AEs: Other reviewer comments: Were SAEs noted? If yes, notify the [Medical Safety Advisor] immediately. Specify the SAEs: Other reviewer comments: Did the study subject withdraw due to AEs? Specify the AEs resulting in withdrawal: Other reviewer comments: Did the study subjects withdraw due to ineffectiveness of the study medication/device? Specify: Other reviewer comments: Is the study subject a dropout? Other reviewer comments: Is data resolution requested? If yes, attach DQF. (Specify DQF numbers.) Other reviewer comments: Primary [Monitor] review: name, title, signature, date (dd/mmm/yyyy) Secondary [Monitor] review: name, title, signature, date (dd/mmm/yyyy) [Medical Safety Advisor] review: name, title, signature, date (dd/mmm/yyyy) Biostatistician review: name, title, signature, date (dd/mmm/yyyy) Data management review: name, title, signature, date (dd/mmm/yyyy) Responsibility for completion of form: name, title, signature, date (dd/mmm/yyyy) Supervisor review: name, title, signature, date (dd/mmm/yyyy) Supervisor comments if there are disagreements between reviewers: Distribution: Medical Safety Advisor, Data Management Department, Statistics Department Archiving: Sponsor/CRO Study Site Archives SOP 406. Data Correction After Retrieval from Study Sites Policy To ensure that the integrity of clinical research data is maintained and that there is total agreement between the data recorded on CRFs (and data query forms [DQFs]), the data entered on the computer, the data recorded in data listings and cross tabulations, the data entered into statistical and clinical study reports, and finally the data in the sponsor/cro and investigator archives, it is essential that the data must only be changed by following a formal procedure. Sponsor/CRO personnel may not make any unauthorised changes to data: all data changes must be authorised by the investigator. After the CRFs have been reviewed at the investigator site, and signed and dated by the investigator, and returned to the sponsor/cro, the data contained within these CRFs will not be changed except by means of a documented data correction
104 W. Bohaychuk and G. Ball procedure. [This SOP includes procedures which require the involvement of clinical research personnel. It must not supersede SOPs developed by personnel in the data management department.] [The correction procedure described in this SOP is followed by many companies. However, there are other ways of achieving the same goal.] Procedures 406.1 Requests for data clarification and resolution must be documented on a DQF, Form 406-1, which will be issued by the [Monitor] within five working days of retrieval of the CRFs to the sponsor/cro premises or issued by the data processing personnel within eight working days of receipt of the CRFs from the clinical research personnel. [These time periods may vary within a specific organisation: however, data must always be processed promptly.] 406.2 The DQF will be printed on three-part NCR paper, with completed copies ultimately designated for: [Some companies use four-part forms to save on extra photocopying and to provide a working copy for the monitors.] Sponsor/CRO study site archives (original copy); Investigator study site archives (bottom copy); Data processing personnel (middle copy). 406.3. The DQF must be taken by the [Monitor] to the study site for completion and signature by the investigator. (If sent by post, the [Monitor] must subsequently visit the study site to verify the data resolution. Verification by the [Monitor] will be confirmed on the DQF.) The [Monitor] will use a DQF tracking form (Form 406-2) to document movement of the DQF. 406.4. After completion and signature by the investigator, the bottom copy of the DQF should be retained with the investigator copy of the CRF at the study site. 406.5. The (top) white original and second copies must be returned to the sponsor/cro. The (top) white original copy will immediately be archived, with the original relevant CRF pages. 406.6. The second copy of the DQF will be forwarded for use by data entry and data processing personnel immediately after secondary review by the [Title]. 406.7. Data entry can occur before an investigator signature is obtained on the DQF. However, the database cannot be locked until all signed and dated DQFs are received and verified. 406.8. The [Monitor] must inform the [Title] of all relevant information (e.g. data queries issued, reviewed) that must be entered into the clinical study tracking schedule in accordance with SOP 109. 406.9. The [Monitor] is responsible for filing Forms 406-1 and 406-2 in the sponsor/ CRO study archives. Related SOPs: SOP 401. Monitoring Visits, SOP 404. Source Data Verification and CRF Review at Study Sites, SOP 405. Initial Internal CRF Review (After Retrieval to Sponsor/CRO), SOP 407. Database Development, Review and Lock, SOP 408. Statistical Review Suggestions for Forms: Documentation of Secondary Review of DQFs. Form 406-1. Data Query Forms (DQFs) Sponsor/CRO name: Study medication/device name: Project name/code number:
Standard operating procedures for clinical research personnel 105 Study/protocol number: Study/protocol version number and date: (dd/mmm/yy) Study/protocol title: DQF number: Date of issue of DQF to study site: (dd/mmm/yy) CRF number: Study subject number/code: Randomisation number: Study subject initials: Study site number: Investigator name: Monitor name: Originator of DQF: name, title, signature, date (dd/mmm/yyyy) (Form designer: prepare the following items in a column format.) CRF page: Item requiring clarification: Correction: (To be completed by study site personnel) Reason for correction: (To be completed by study site personnel) I have reviewed and approved all the queries noted above: name, title, signature, date (dd/mmm/yyyy) Source data verification conducted by: name, title, signature, date (dd/mmm/yyyy) Responsibility for completion of form: name, title, signature, date (dd/mmm/yyyy) Supervisor review: name, title, signature, date (dd/mmm/yyyy) Distribution: Data Management Department Archiving: Sponsor/CRO Study Site Archives, Investigator Study Site Archives Form 406-2. DQF Tracking Please provide a comment for all NO and NA (Not Applicable) responses. Sponsor/CRO name: Study medication/device name: Project name/code number: Study/protocol number: Study/protocol version number and date: (dd/mmm/yy) Study/protocol title: (Form designer: prepare the following items in a column format.) Study subject number/code: DQF number: Date of issue of DQF to study site: (dd/mmm/yy) DQF issued by: (initials) Date completed DQF received by sponsor/cro: (dd/mmm/yy) Date completed DQF sent to data processing group: (dd/mmm/yy)
106 W. Bohaychuk and G. Ball Original top (white) copy sent to archives: Secondary monitoring review undertaken: Safety review undertaken: Biostatistician review undertaken: Further query required: [If further query is required, the same process noted in this SOP must be repeated.] New DQF issued: Responsibility for completion of form: name, title, signature, date (dd/mmm/yyyy) Supervisor review: name, title, signature, date (dd/mmm/yyyy) Distribution: Medical Safety Advisor, Data Management Department Archiving: Sponsor/CRO Study Site Archives SOP 407. Database Development, Review and Lock Policy Data recorded on computer databases must accurately reflect data contained in the CRFs. Clinical research personnel must co-operate with the data management group to ensure that this is achieved. [This SOP includes procedures which require the involvement of clinical research personnel. It must not supersede SOPs developed by personnel in the data management group.] Procedures 407.1. Prior to study subject enrolment, the following activities should be undertaken: The [Title] in the clinical research department will be provided with the opportunity to review and comment upon the data management plan, the data management manuals, and the proposed structure of the database. A copy of the final protocol with attachments (e.g. CRF, diary cards, psychological tests, quality of life forms, etc.) will be sent to the data processing personnel, by the [Title] in the clinical research department, to facilitate the preparation of data entry screens. Data entry screens will be tested by the [Title] in the clinical research department and by the data processing personnel by entry of data from a test set. This process will also help the development of any particular instructions that must be given to the data processing personnel by the [Title] in the clinical research department, and vice versa. 407.2. After data entry has begun, verification of the data listings (compared to the data in the CRF) will require review by the [Title] in the clinical research department. Any new queries or errors detected during review of the listings must be sent to the data entry personnel. 407.3. If, as a result of the review of the data listings, the [Title] in the clinical research department or data processing personnel determine that further data queries must be issued to the investigator, this procedure must be undertaken in accordance with SOP 406. 407.4. The data conventions (e.g. the variations to protocol requirements which will be permitted for statistical analysis) will normally be determined during the development of the protocol. Further refinement of the definitions of data conventions may arise during the performance of the study.
Standard operating procedures for clinical research personnel 107 407.5. All proposed data conventions, with reasons, are to be discussed and agreed in a formal meeting which should be documented. A [Biostatistician] must also approve all final decisions. 407.6. Final data conventions will be established and documented in Form 407-1 before the statistical analysis of the study. 407.7. Study subject classification (e.g. the final determination of eligibility and evaluability within the limits of the data conventions) will be determined and documented after clinical completion of the study, but prior to unmasking (in the case of a double-masked study). The following must be considered in determining study subject classifications: After data correction procedures have been completed, and just prior to statistical analysis, all issues relating to inclusion/exclusion of study subjects for analysis must be resolved to enable formal study subject classification to be achieved. Data listings (masked) to treatment allocation, of all protocol violations and copies of the final agreed data conventions form (Form 407-1) will be issued to all individuals responsible for determining final study subject classifications. If a protocol violation falls within the limits of the data conventions, the study subjects may be considered to be eligible and/or evaluable (whichever is being assessed). If a protocol violation falls outside the limits of the data conventions, the study subjects will be assessed on a subject-by-subject basis for eligibility and evaluability. 407.8. All study subject classifications, with reasons, are to be discussed and agreed in a formal meeting which should be documented. A [Biostatistician] must also approve all final decisions. 407.9. A final masked study subject classification document which lists acceptability for safety and effectiveness analyses will be prepared and documented in a study subject classification form (Form 407-2), after all questions regarding protocol violations have been resolved. 407.10. When the database has been declared to be clean (i.e. all data corrections have been completed and authorised) by the data processing group and has been formally locked, the database will be released to the [Biostatistician] for the final statistical analysis (SOP 408). The clinical research personnel must be informed of the locking procedure. 407.11. After locking, further access to the data in the database will be denied, unless a formal authorization is documented by the [Title]. 407.12. The [Monitor] must inform the [Title] of all relevant information (e.g. CRFs entered on the database, number of clean CRFs) that must be entered into the clinical study tracking schedule in accordance with SOP 109. 407.13. The [Title] must inform the [Title] of all relevant information (e.g. data conventions and subject classification agreed, database clean, database locked, database released for analysis and display) that must be entered into the clinical study tracking schedule in accordance with SOP 109. 407.14. The [Monitor] will ensure that Forms 407-1 and 407-2 are filed in the sponsor/cro study archives. Form 407-2 must also be filed in the sponsor/cro study site archives. Related SOPs: SOP 401. Monitoring Visits, SOP 404. Source Data Verification and Review at Study Sites, SOP 405. Initial Internal CRF Review (After Retrieval to Sponsor/CRO), SOP 406. Data Correction after Retrieval from Study Sites, SOP 408. Statistical Review.
108 W. Bohaychuk and G. Ball Suggestions for Forms: Data Management Plan Review, Data Management Manual Review, Data Entry Screen Review, Data Entry Procedures Review, Verification of Data Listings, Documentation of Data Conventions Meeting, Documentation of Study Subject Classification Meeting, Authorization to Lock Database, Notification of Locked Database, Request to Change (Unlock) Database, List of Changes to Database, Authorization of Final Approved Database, Authorization for Database Release for Biometrical Evaluation [Most of these forms should probably be developed by personnel in the data management department with appropriate expertise. Clinical research personnel may provide some input to development of the forms.] Form 407-1. Data Conventions Sponsor/CRO name: Study medication/device name: Project name/code number: Study/protocol number: Study/protocol version number and date: (dd/mmm/yy) Study/protocol title: Date of data conventions meeting: (dd/mmm/yy) (Form designer: prepare the following items in a column format.) Data item/variable: Protocol limits: Acceptable extension to protocol limits: Reason: Authorization of data conventions: Clinical research department: name, title, signature, date (dd/mmm/yyyy) Data management department: name, title, signature, date (dd/mmm/yyyy) Biostatistician: name, title, signature, date (dd/mmm/yyyy) Archiving: Sponsor/CRO Study Archives Form 407-2. Study Subject Classification Sponsor/CRO name: Study medication/device name: Project name/code number: Study/protocol number: Study/protocol version number and date: (dd/mmm/yy) Study/protocol title: Study site number: Investigator name: Date of study subject classification meeting: (dd/mmm/yy) (Form designer: prepare the following items in a column format.)
Standard operating procedures for clinical research personnel 109 Study subject number: Data item/variable: Description of variation: Violation of protocol limits: Within data conventions: Eligible: Reason: Evaluable: Reason: Authorization of study subject classifications: Clinical research department: name, title, signature, date (dd/mmm/yyyy) Data management department: name, title, signature, date (dd/mmm/yyyy) Biostatistician: name, title, signature, date (dd/mmm/yyyy) Archiving: Sponsor/CRO Study Archives, Sponsor/CRO Study Site Archives SOP 408. Statistical Review Policy Statistical review and analysis of all clinical study data must be undertaken in conjunction with preparation of a final clinical report. Clinical research personnel must co-operate with the data management and statistics department to ensure that this is achieved. [This SOP includes procedures which require the involvement of clinical research personnel. It must not supersede SOPs developed by personnel in the data management department and the statistics department.] Procedures 408.1. The statistical analysis plan for a clinical study will be written by the [Biostatistician] responsible for the analysis of the study in consultation with the clinical team, prior to the issue of the final approved protocol. 408.2. The [Title] in the clinical research department must review and approve the statistical analysis plan. 408.3. A synopsis of the statistical analysis plan should be included in the protocol. 408.4. The statistical analysis of a study may only commence after the study has been completed and the data are clean (SOP 407). Any exceptions (i.e. interim analyses) must be documented with reasons. 408.5 The [Title] in the clinical research department must provide the [Biostatistician] with a subject-by-subject listing of evaluability to specify in which forms of analyses each subject may be included (eg intent-to-treat, valid case, per protocol, special case, etc). 408.6. In the case of masked studies, the randomisation schedule will be released to the [Biostatistician] after the statistical analyses of masked groups have been completed in order that assignment of treatments to the study populations can be completed. 408.7. After the statistical analysis report has been completed, it will be issued with the signed and dated approval of the [Biostatistician]. The approval of the [Biostatistician] implies that: all data have been included in the analysis and any exclusions have been clearly stated in the report; data have been accurately tabulated and summarised; all listings, tables and graphs in the report are correct; and the statistical methodology is correct. 408.8. The [Title] in the clinical research department must review and approve the statistical analysis report which may then be released for preparation of the final clinical report (SOP 703).
110 W. Bohaychuk and G. Ball 408.9. The [Title, statistics department] must inform the [Title] of all relevant information (e.g. interim analysis conducted, statistical analysis plan prepared and agreed, statistical analysis undertaken, statistical report prepared, reviewed and agreed) that must be entered into the clinical study tracking schedule in accordance with SOP 109. 408.10. The statistical analysis plan and the statistical analysis report must be archived by the [Title] in the sponsor/cro study archives. Related SOPs: SOP 304. Preparation of Protocols, SOP 405. Initial Internal CRF Review (After Retrieval to Sponsor/CRO), SOP 406. Data Correction after Retrieval from Study Sites, SOP 407. Database Development, Review and Lock, SOP 513. Revealing Randomisation Code Assignments After Study Completion, SOP 703. Preparation of Clinical Study Reports. Suggestions for Forms: Format of Statistical Analysis Plans, Statistical Analysis Plan Review, Statistical Analysis Plan Approval, Recipients of Statistical Analysis Plans, Eligibility Listing of Study Subjects, Format of Statistical Analysis Reports, Statistical Analysis Report Review, Statistical Analysis Report Approval, List of Recipients of Statistical Analysis Reports [Most of these forms should probably be developed by personnel in the statistics department with appropriate expertise. Clinical research personnel may provide some input to development of the forms.] SOP 409. Management of Contract Research Organisations During Studies Policy During a clinical study, further management of the CRO (including Phase I facilities) is necessary to ensure the progress of the study in a timely and efficient manner. Procedures 409.1. It is the responsibility of the assigned [Title] to maintain contact with the CRO on a regular and frequent basis (at least weekly) to ensure that the study is being conducted in accordance with the contract. 409.2. Contacts will involve visits to the CRO and randomly selected investigator sites. Telephone contact reports and all other correspondence will also be archived. 409.3. The [Title] will record observations about the conduct of the CRO during the study, and will particularly address the following items: Changes, if any, in personnel, and additional training of personnel; Changes, if any, in equipment; Promptness of distribution of progress reports and CRO visit reports to study sites; Promptness of reporting of significant events to sponsor, study sites, ethics committees and regulatory authorities (e.g. adverse events, protocol amendments); Maintenance of quality control systems. 409.4. Any deficiencies observed in the conduct of the study will be reported immediately in writing to the [Title] who will determine the corrective action required. 409.5. The [Title] must inform the [Title] of all relevant information (e.g. significant event or changes) that must be entered into the clinical study tracking schedule in accordance with SOP 109. 409.6. All correspondence and documentation of review of CRO activities will be filed by the [Title] in the sponsor study archives. (The CRO should also archive the same documentation.) Related SOPs: SOP 326. Selection of Contract Research Organisations.
Standard operating procedures for clinical research personnel 111 Suggestions for Forms: List of Items Provided to CROs Prior to Study Initiation, Initiation Visits to CROs, Monitoring Visits to CROs During Studies, Documentation of CRO Telephone Contacts, Assessment of CRO Compliance with Contracts. SOP 410. Management of Clinical Laboratories During Studies Policy During a clinical study, further management of the clinical laboratory is necessary to ensure the progress of the study in a timely and efficient manner. Procedures 410.1 It is the responsibility of the assigned [Title] to maintain contact with the clinical laboratory on a regular and frequent basis (at least once a month) to ensure that the study is being conducted in accordance with the contract. 410.2. Contacts will involve visits to the clinical laboratory. Telephone contact reports and all other correspondence will also be archived. 410.3. The [Title] must provide the clinical laboratory with: name, address, telephone and fax number of each investigator and study site; and name, address, telephone and fax number of the sponsor/cro monitor. Contact numbers provided must be available on a 24-hour basis. 410.4. The [Monitor] must arrange for attendance of clinical laboratory personnel at startup meetings (or individual site initiation visits) to demonstrate use of all items for the collection, storage and shipment of samples, and the management of clinical laboratory reports. 410.5. The [Monitor] must work with the clinical laboratory to provide appropriate information to investigators such as: Routine and special procedures or equipment for collecting, handling, storing, packaging and shipping clinical samples; Sample request forms with instructions for completion; Labels with instructions for use; Procedures to report test results; Procedures for clinically significant results; Contact names and addresses. 410.6. The [Title] will record observations about the conduct of the clinical laboratory during the study, and will particularly address the following items: Changes, if any, in the clinical laboratory protocol; Changes, if any, in reference ranges; Changes, if any, in personnel; Changes, if any, in equipment; Promptness of sample management, with regard to: Receipt; Analysis; Issue of laboratory report; Promptness of reporting significant out-of-range values to sponsor/ CRO; Promptness of reporting significant out-of-range values to investigators; Maintenance of quality control systems; Maintenance of accreditation and certification. 410.7 Any deficiencies observed in the conduct of the study will be reported immediately in writing to the [Title], who will determine the corrective action required. 410.8. The [Monitor] must inform the [Title] of all relevant information (e.g. collection of samples, changes in procedures) that must be entered into the clinical study tracking schedule in accordance with SOP 109.
112 W. Bohaychuk and G. Ball 410.9. The [Monitor] is responsible for ensuring that all correspondence and documentation of review of the clinical laboratory will be filed in the sponsor/cro study archives. (The clinical laboratory should also archive the same documentation.) Related SOPs: SOP 327. Selection of Clinical Laboratories, SOP 328. Study Site Initiation Visits, SOP 329. Study Startup Meetings for Multicentre Studies, SOP 514. Management of Clinical Laboratory Samples. Suggestions for SOPs: Clinical Laboratory Protocols Suggestions for Forms: List of Items Provided to Clinical Laboratories Prior to Study Initiation, Initiation Visits to Clinical Laboratories, Monitoring Visits to Clinical Laboratories During Study, Documentation of Clinical Laboratory Telephone Contacts.