QC & QA in Clinical Trials- An Overview
An Overview
Quality Management System ( QMS)- A brief description QC Definitions Role of QC in clinical trials Difference b/w QC and QA Importance of QC QA: Definitions Audits Type and reasons for audit
Module of process-based quality management system Management responsibility
Measurement, analysis and improvement
Resource Management
Quality realization
Documentation of Quality Systems
Quality manual: States company policy and objectives of an organization Quality procedures Work Instructions Documents approval
Basic Quality System Structure Quality Manual
Policy
Procedures Manual
Methods
Work Instructions Details
Forms, Files & Records
Quality Control (QC) ď Ź
ď Ź
Periodic functional checks to verify that clinical data are generated , collected, handled, analysed and reported according to protocol, SOPs and GCP. Internal operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of trial related activities
Role of QC in Clinical Research The sponsor is responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data are generated, documented ( recorded) and reported in compliance with the protocol, GCP and the applicable regulatory requirements
ICH GCP 5.1.1.
Difference b/w QC & QA QC: Ongoing checks QA: Periodic checks QC: Can be carried out by functional personnel QA: Should be carried out by an independent person/ team QC: Subpart of Quality Assurance System
Operational QC
Develop a QC plan for each operational Step of the clinical study. A QC plan should define standards against which QC will be conducted including: Purpose of QC Scope Responsibilities Sampling plan to be used( if applicable) Procedure of QC Generation of report and its distribution Corrective Actions Proposed
During the Data collection and pooling stage
Periodic Quality checks shall be performed to review of data entry errors and data management procedures and Data entry vs. original paper CRFs.
Also a detailed QC review of
Data Listings, tables, graphs database update
clinical trial report etc shall be carried out.
During the Data entry process in the Database at the sponsor’s end ideally, 100% QC of the database with the CRFs should be done.
Critical Items to be verified: Demographic and Medical History Selection Criteria Physical Examination Vital Signs Efficacy Assessment Laboratory values Concomitant Medication Adverse Events/ Serious Adverse Events
Define a error rate For any sponsor, better the quality systems, lesser the error rate. For minimizing the error rate,
impart training to the clinical team (Inhouse and / or site), Present the findings to the team on regular basis Suggest corrective actions and implement.
Quality Assurance ( QA) in clinical Trials
Definition as per GCP
Quality System Audit
Main Stages of an audit are a follows:
Planning- 40% Performing: 40% Reporting: 10% Follow up: 10%
Depth of Quality System Audits
System Audits
Compliance Audits
Types of Audits
Types of Audits ( Contd..) Investigator
Database
site audit
audit
Off
site archiving
Laboratory
Clinical
study report audit
Clinical
supplies
System
audit
Clinical
Research Organisation (CRO)
Protocol,
protocol amend., consent forms, patient/volunteer information leaflet and CRFs Master
file audit
QA, Trial Specific Audits
QA, Systems Audits
What gets audited?
The auditor will interview the investigator and staff to obtain information on
How they are recruiting subjects, Obtaining informed consent, Implementing the protocol and Documenting the results.
The investigator's site files will be reviewed and a sample of subjects will be selected for source data verification. The storage, documentation and management of the investigational products would be reviewed routinely. The auditor will conduct a tour of the facilities and check documentation for equipment being used in the study.
End of an Audit ď Ź
At the end of the audit, a post-audit meeting will be held to feed-back on findings to the investigator, study staff and monitor.
Any misunderstandings are usually resolved at this point in the audit.
Audit tools and Techniques
Four Key tools and techniques used are:
Audit planning: Schedules, Audit personnel, agenda, checklist Audit Performance: Entry Meetings, Audit Questions, How u do an audit? Audit Reporting: CARs, Audit Summaries, Audit reports Audit Follow Up: Audit Close Up
For Cause Audits
Allegation/Suspicion of non-compliance.
Safety or efficacy data is inconsistent with other study sites.
PI conducting research outside area of specialty.
Accrual is abnormally high for geographical or ethnicity/race location.
Audit Findings Everything’s perfect, no problems at all PROBLEMS WITH:
Protocol compliance
Record keeping
AE reporting/subject’s complaint
Drug accountability
Consent process
Deficiency Statistics 27% - Protocol noncompliance 20% - Poor record keeping, inadequate source documents, CRF’s, and/or IRB forms 15% - Poor AE reporting 9% - Poor drug accountability 8 % - Informed consent problems
QC and QA are Inevitable As Clinical Research Professionals, we all are bound to be
Audited
Scrutinized and Checked upon
Audit is not policing
Audit is a positive, learning tool
Audit prepare you for an Inspection