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The Concept of Quality in Clinical Research

Dorota ŚwitułaSenior Clinical Quality Assurance Advisor

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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

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Quality as defined by ISO 9000

• A quality is a set of characteristics that a product or service must have to satisfyneeds and expectations of the customer

requirements

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The end product of clinical research

• A product is an output from a process• The output from the clinical research

process is information

collectionof data

poolingof data in the

database

analysis trialreport

trialprotocol

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Quality in clinical research maybe defined as...• Reliability and credibility of information

providing an answer to a scientific question• Compliance of the trial process with defined

requirements

Aquestion Collection & analysis of data An

answer

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Customers of clinical research

• Society/consumers• Research subjects• Sponsors• Regulatory authorities worldwide• Hospitals/institutions• IECs

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ethical standards

Clinical research customers’ requirements

budget timelines

good practice standardsGXPs

law & regulations

trialprotocol

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Clinical research customers’ requirements

good practice standards:GXPs:

ICH GCP, ICH GMP, OECD GLP

ethical standards:Declaration of Helsinki

law & regulations:EU Directives

US CFRlocal legislation

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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

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The standard components ofQMS in clinical research

Training Procedures

Trialprotocol Collection & analysis of data

Quality Control

Quality Assurance

Trialreport

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Procedures, Sponsor

• High level documents, e.g. Policies & Guidelinesdescribe standards/customer requirements that thesponsor is going to comply with

• SOPs & Working Instructions detail how thesestandards/requirements will be implemented in core activities within the clinical research process– the ‘every day work’

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Procedures, Investigator

• Trial-related instructions, protocol, CRFs, etc. – usually provided by the Sponsor

• Investigator / Research Site may have owninternal procedures: e.g. procedures for financial agreements, trial management, investigational medicinal product handling

• IEC procedures• Laboratory procedures

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Procedures, benefits

• Clear instructions on what should be done, whenand 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)

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Training

• Sponsor’s staff must be trained before beingdelegated any tasks

• Sponsor is responsible for providing trial-relatedtraining to investigators: Investigator’s Meetings, initiation visits, GCP courses

• Investigator is responsible for training hispersonnel

• Training records, CVs – are required as evidenceof training & qualifications

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Quality Control

• ISO: activities & techniques applied to ensure thatproducts consistently fulfil requirements

• Clinical Research: systematic checks on thecompliance 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.

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Quality Control

collectionof data

poolingof data in the

database

analysis trialreporttrial

protocol

Sponsor approval &

sign off

IEC approval

monitoringof investi--gational

sites

analysis ofoutlier data

proof-reading,validation,

generation ofqueries

variability &trends

approval & sign-off

identificationof non-PPT

cases

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QC: analysis of variability & trends

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QC: analysis of variability & trends

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Quality Assurance

• ISO: a set of activities to provideconfidence that quality requirements will be fulfilled

• Clinical Research: independent audits of alltrial-related processess & functions- performed by QA function not involved in the

research process (no conflict of interests)- assess efficiency of sponsors’ QC processes.

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Quality Assurance audits

• Trial / project specific audits• Systems auditsSystem: A selected process plus all related

activities, resources, organisation, documents (including SOPs & records), facilities and equipment

e.g.: Pharmacovigilance, Data Management

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QA, trial specific audits

collectionof data

poolingof data in the

database

analysis trialreporttrial

protocol

audit of thestudy

protocol

audits attrial sites

audit of trialdatabase

audit of graphs, tables & stats

audit oftrial report

audit of CRF, IB

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QA, systems auditsaudit of

monitoringsystem

audits ofcomputerised data collection sytems(validation audits)

audits of central lab &other service providers

audit of IP management &

distributionsystem

audit ofdocument

management& archiving

audit of sponsor’spharmacovigilance system

collection & handling of data

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Benefit of QMS

development oftrial protocol &

instructionstraining,

clinical trial process

QC activities

QA audits

implementrecommendations

implementrecommendations

It supports continuous quality improvement

in line with SOPs

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Conclusions

• Quality of clinical research may be defined as compliance with requirements and credibility & reliability of data obtained

• Sponsors apply several preventive measures andcontrols to ensure quality

• Standard QMS applied by clinical researchsponsors are / may be based on ISO 9000

• A Quality Management System is a set of tools to ensure, control, maintain and improve quality