The Concept of Quality in Clinical Research. Dorota Śwituła Senior Clinical Quality Assurance Advisor

Transcription

1 The Concept of Quality in Clinical Research Dorota Śwituła Senior Clinical Quality Assurance Advisor 1

2 Agenda What is quality? How we define quality in clinical research? The standard components of a Quality Management System in clinical research Its practical application in clinical trials Conclusion 2

3 Quality as defined by ISO 9000 A quality is a set of characteristics that a product or service must have to satisfy needs and expectations of the customer requirements 3

4 The end product of clinical research A product is an output from a process The output from the clinical research process is information trial protocol collection of data pooling of data in the database analysis trial report 4

5 Quality in clinical research may be defined as... Reliability and credibility of information providing an answer to a scientific question Compliance of the trial process with defined requirements A question Collection & analysis of data An answer 5

6 Customers of clinical research Society/consumers Research subjects Sponsors Regulatory authorities worldwide Hospitals/institutions IECs 6

7 Clinical research customers requirements budget timelines law & regulations ethical standards trial protocol good practice standards GXPs 7

8 Clinical research customers requirements ethical standards: Declaration of Helsinki law & regulations: EU Directives US CFR local legislation good practice standards: GXPs: ICH GCP, ICH GMP, OECD GLP 8

9 Quality Management System, definition based on ISO 9000 A set of interacting elements established to direct and control an organisation with regards to quality QMS is a tool to establish and continuously & consistently achieve quality objectives based on customers requirements. In clinical research these objectives are: - Compliance with ethical, regulatory and GXP standards - Credibility and reliability of clinical data 9

10 The standard components of QMS in clinical research Quality Assurance Quality Control Trial protocol Collection & analysis of data Trial report Training Procedures 10

11 Procedures, Sponsor High level documents, e.g. Policies & Guidelines describe standards/customer requirements that the sponsor is going to comply with SOPs & Working Instructions detail how these standards/requirements will be implemented in core activities within the clinical research process the every day work 11

12 Procedures, Investigator Trial-related instructions, protocol, CRFs, etc. usually provided by the Sponsor Investigator / Research Site may have own internal procedures: e.g. procedures for financial agreements, trial management, investigational medicinal product handling IEC procedures Laboratory procedures 12

13 Procedures, benefits Clear instructions on what should be done, when and by whom, plus specification of required inputs & outputs Training tool Maintain consistency of work and consistency in achieving quality objectives Facilitate change management (may be easily updated & reviewed when requirements change) 13

14 Training Sponsor s staff must be trained before being delegated any tasks Sponsor is responsible for providing trial-related training to investigators: Investigator s Meetings, initiation visits, GCP courses Investigator is responsible for training his personnel Training records, CVs are required as evidence of training & qualifications 14

15 Quality Control ISO: activities & techniques applied to ensure that products consistently fulfil requirements Clinical Research: systematic checks on the compliance of the trial process & reliability and credibility of data - performed at every step of the clinical trial process - applied to each stage of data handling. 15

16 Quality Control Sponsor approval & sign off monitoring of investi- -gational sites proof-reading, validation, generation of queries identification of non-ppt cases trial protocol collection of data pooling of data in the database analysis trial report IEC approval 16 analysis of outlier data variability & trends approval & sign-off

17 17 QC: analysis of variability & trends

18 QC: analysis of variability & trends 18

19 Quality Assurance ISO: a set of activities to provide confidence that quality requirements will be fulfilled Clinical Research: independent audits of all trial-related processess & functions - performed by QA function not involved in the research process (no conflict of interests) - assess efficiency of sponsors QC processes. 19

20 Quality Assurance audits Trial / project specific audits Systems audits System: A selected process plus all related activities, resources, organisation, documents (including SOPs & records), facilities and equipment e.g.: Pharmacovigilance, Data Management 20

21 QA, trial specific audits audit of the study protocol audits at trial sites audit of trial database audit of trial report trial protocol collection of data pooling of data in the database analysis trial report 21 audit of CRF, IB audit of graphs, tables & stats

22 QA, systems audits audits of computerised data collection sytems (validation audits) audit of monitoring system audit of IP management & distribution system audit of document management & archiving collection & handling of data 22 audits of central lab & other service providers audit of sponsor s pharmacovigilance system

23 Benefit of QMS It supports continuous quality improvement implement recommendations development of trial protocol & instructions training, QA audits QC activities clinical trial process in line with SOPs 23

24 Conclusions Quality of clinical research may be defined as compliance with requirements and credibility & reliability of data obtained Sponsors apply several preventive measures and controls to ensure quality A Quality Management System is a set of tools to ensure, control, maintain and improve quality Standard QMS applied by clinical research sponsors are / may be based on ISO