[Audio] Standard operating system. Standard operating system.
[Audio] Agenda Clinical Study Documentation Setup Clinical Study SOP’s Preparations CDISC Standards.
[Audio] Clinical Study Documentation Setup Data Management Plan Document Database Structure Document Database Structure UAT Document Data Validation Plan Document Data Validation Plan UAT Document Data Entry Guidelines Document Self Evidence Correction Document.
[Audio] Clinical Study SOP’s Preparations. Clinical Study SOP’s Preparations.
[Audio] What are SOPs? International Conference on Harmonization (ICH) defines a SOP as “Detailed, written instructions to achieve uniformity of the performance of a specific function.” (ICH GCP 1.55) In simple terms a SOP is… A written process A way for the clinical site/CDM/Operation to perform a task the same way each time it is completed..
[Audio] SOPs are used to Identify the responsible person for each task. Describe actions (what is to be completed). Train staff. Monitor site/CDM/Operation performance..
[Audio] Are SOPs Required by Law/Regulations? SOPs are not specifically mentioned in the FDA regulations HOWEVER there is guidance and regulations that infer responsibility and SOPs formalize investigator responsibilities. 21 CFR 312.53 the investigator will “ensure that all associates, colleagues, and employees assisting in the conduct of the study (ies) are informed of their obligations in meeting the above commitments.” ..
[Audio] Are SOPs Required by Law/Regulations (Cont.)? Additionally, SOPs are mentioned repeatedly in the ICH GCP Guidelines. ICH GCP 2.13 -“Systems with procedures that assure the quality of every aspect of the trial should be implemented.”.
[Audio] Benefits of a SOP Ensures that all research conducted within the clinical site follows federal regulations, ICH GCP, and institutional policies to protect the rights and welfare of human study participants. Provides autonomy within the clinical site. Improves the quality of the data collected, thereby improving the science of the study. Utilized as a reference and guideline as to how research will be conducted within the clinical site/CDM/Operation. Excellent training source for new employees and/or fellows..
[Audio] SOP Topics Preparing and Submitting Initial IRB Documents. Preparing and Submitting Continuing Review IRB Documents. Preparing and Submitting Amendment IRB Documents Establishing and Training the Clinical Study Team, and Delegating Responsibilities. Establishing Study Files. Establishing Source Documents. Study Subject Recruitment Plan..
[Audio] SOP Topics Contacting and Scheduling Potential Study Subjects for an Initial Visit Obtaining Informed Consent from a Potential Study Subject Enrolling a Subject Recording Subject Data Making Corrections on Study Documents Monitoring Subject Compliance During a Study Responding to a Clinical Hold Order Receiving and Storing Investigational Drugs Drug and Study Supply Transfer Between Sites.
[Audio] SOP Topics Dispensing Study Drugs to Study Subjects Identifying and Reporting Adverse Events Packing, Labeling, and Shipping Samples Identifying and Reporting Protocol Deviations Additional Topics Contact with potential sponsors Budget review and determinations Pre-study study site visit Initiation Site Visit Monitor Visits Audits Data management Study closure Long term storage.
[Audio] Writing SOPs Develop a template for the SOP to be used throughout the document. Potential elements of the SOP Header – title, original version date, revision date, effective date, approved by Purpose – why one has the policy Responsibilities – who the policy pertains to Instruction/Procedures – how to accomplish the items of the policy References – what the policy is based on Appendix – source documents/case report.
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[Audio] Process Mapping for Writing SOPs Determine which clinical site/CDM/Operation task needs mapping. Lay out all the steps currently used to complete that task. “Mapping” involves taking each step in the task and making it more efficient and easier to follow. Once you have finished mapping, convert your process map to an outline for easy use. Once a task has been mapped, it should be tested..
[Audio] SOPs and Guidelines Some SOPs have a two-tiered system that includes both SOPs and guidelines. SOPs provide a general view of all the main steps whereas guidelines are significantly more detailed. One advantage of a two-tiered system is that SOPs will rarely need to be changed, whereas guidelines may need to be changed or updated more frequently due to changes in organizational structure or equipment..
[Audio] Tips for Writing SOPs Use clear, concise language. Use active voice. Avoid names; use titles instead..
[Audio] Implementing and Monitoring SOPs SOPs should be introduced gradually. Prioritize most relevant SOPs and present them first. Department head should approve all SOPs and designate an effective date. SOPs should be reviewed on a regular basis (usually annually) to ensure policy based regulations are up-to-date. Previous versions of SOPs should be retained..
[Audio] SOP Training All staff should have SOP training. Training should be documented. SOP should be accessible to staff..
[Audio] What is the difference between a SOP and a Manual of Procedures (MOP)/WI? These terms have been used interchangeably. Both provide a standardization of a process. SOP provides general information that is to be utilized throughout any research study. How as a clinical site/CDM/Operation we will assess delegation of duties. MOP/WI is specifically written for a particular Database which will incorporate elements of the SOP..
[Audio] MOP/WI The MOP/WI should be written so that anyone in your clinical site/CDM/Operation can follow the procedures for that study and find all relevant materials. The MOP should be extremely detailed..
[Audio] SOP or MOP Both documents are important! Start with the SOP first. Once you have written general procedures, the MOP will be easier. This process will take lots of time and patience..
[Audio] . [image] CLINICAL DATA INTERCHANGE STANDARDS CONSORTIUM.
[Audio] CDISC – Clinical Data Interchange Standards Consortium The mission of CDISC is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare. • SDTM – Study Data Tabulation Model • FDA – Food and Drug Administration • FDA desires SDTM data. Future: require SDTM.
[Audio] CDISC STANDARD MODELS SDTM - Study Data Tabulation Model ODM - Operational Data Model LAB - Laboratory Data Model SDS - Submission Data Model ADM - (Analysis Dataset Model) which are under development by CDISC are all XML based. ODM - addresses data used during trials and analyses LAB - describes ECG and other laboratory data standards SDS - emphasizes data flow from database to regulatory submission ADM - defines safety domains and efficacy variables to facilitate statistical analysis..
[Audio] WHY STANDARDS? 65% - 75% submission information is associated with safety data. A big volume of listings (e.g. for CRT dataset and patient profile, etc.) is always included even in electronic submissions. Only 30% of programming time is used to generate statistical results with SAS®, and the rest of programming time to familiarize data structure, check data accuracy, and tabulate/list raw data and statistical results into certain formats. This non-statistical programming time because of CDISC’s uniform data structure, its useful functions..
[Audio] What is SDTM: Study Data Tabulation Model This model describes the contents and structure of data collected during a clinical trial The purpose is to provide regulatory authority reviewers (FDA) a clear description of the structure, attributes and contents of each dataset and variables submitted as part of a product application SDTM Animals Humans (SEND) (SDTMIG).
[Audio] After SDTM Before SDTM • Domains = Yes • Standard Domain Names = Yes • Standard Variables = Yes • Standard Variable Names = Yes Result • Standard Domain Names = Easy to Find Data • Standard Variables/Variable Names = Immediate Familiarity with the Data • Consistency • Minimal learning curve • TIME EFFICIENT • Domains = Yes • Standard Domain Names = No • Standard Variables = No • Standard Variable Names = No Result • Reviewers had to familiarize themselves with unique domain names, variables and variable names used in an application - - TIME CONSUMING • Pooling, joining datasets awkward, difficult • Good portion of review time spent “cleaning up the data” • Inefficient, error-prone.
[Audio] Fundamentals of SDTM - Domains Domain: Collection of observations with common topic Case Report Form ---- SDTM domain---- Dataset – A domain may collect data from more than one CRF form – Generally each domain is represented by a dataset Each domain has a unique two-character domain name (e.g., AE, CM, VS) Variables in domain begin with the domain prefix: (e.g., VSTESTCD) Domain structure: vertical Two categories of domains: – CDISC Standard Domains (spelled out in detail in the Implementation Guide). – Custom Domains • Based on one of the General Observation Classes (findings, events, interventions) • Basic variables are outlined in the SDTM.
[Audio] Fundamentals of SDTM - Variables • CDISC categorizes variables as being – Required: variables need to be in the domains • Their values cannot be null – Expected: variables need to be in the domain • Some values may be null – Permissible: variables included in the domain as needed • CDISC categorizes variables into five roles – Identifier: identify the study, subject no., the sequence number – Topic: specify the focus of the observation (such as the name of the lab test) – Timing: describe the timing of the observation (Visit, Start/End date, Days, Time Points, Duration) – Qualifier: additional text or numeric values.
[Audio] Fundamentals of SDTM - Variables • Variables Attributes – Variable Name: limited to 8-chars – Variable Label: <=40 chars – Variable Type: mainly characters – Variable Length: <=200 chars • Date/time format – ISO 8601 is a text string YYYY-MM-DDT hh:mm:ss (not a SAS format) – Has ability to handle incomplete date – Example: December 15, 2003 13:14:17 ----- 2003-12-15T13:14:17 December 15, 2003 ------------------ 2003-12-15 • Controlled Terms or Format – Controlled terminology or text should be used instead of, or in addition to arbitrary Number codes (No SAS format!!) – CT (**) published externally (ex: MedDRA or follow CDISC-specific terminology) – CT (*) value from a sponsor-defined code list.
[Audio] Thank You For Listening! Reach out for any questions. [email protected] EMAIL @rigencemind SOCIAL MEDIA.