Table 2.

International Council for Harmonisation E6R3 critical changes

Theme	Content
Thrust on technology	Data acquisition - EHR, eCRF, source records, wearable devices, sensors, and social media
	Patient interaction – PROs and COAs
	Consent process - electronic, video
	Computer systems - validation, audit trails, metadata, user, management, backup, disaster recovery, and IT security
Quest for quality	Quality by design and fit for purpose
	Quality management system and risk management
	Quality of computer systems/technology
	QA and control of trial conduct
	QC focus - monitoring and data management
Expansion of ethics	Transparency - registration of trials and posting of results
	IC - electronic, images and video, telephonic, text in different formats, telephone, video conferencing, and remote
	Ethical review of protocol, documents, measures, and technologies to obtain and document IC if not possible in emergency research
	Process - reconsent, minor assent, and withdrawal of consent
	Conflict of interest - investigator, investigator site staff, and/or sponsor not to participate in EC review and decision
	Submission of protocol and relevant documents by sponsor
	Review of SUSARs
	Privacy, confidentiality, and data protection
Rising responsibilities-EC	Interpretation of principles to ensure ethical conduct
	Review of protocol procedures-PROs, COAs, and digital health
	Review of technology in consent documents and process
	Ensuring privacy, confidentiality, and transparency
	Review of safety information and updates
	Continuing periodic oversight
Rising responsibilities - Investigator	Oversight and quality of conduct for activities delegated to service provider/SMO
	Integrity and security of data irrespective of media used
	Transparency - sharing results and treatment with participant
	Timely access and review of data impacting participant eligibility, treatment, or safety
	Ensuring privacy, confidentiality, and transparency
	Computerized systems - quality, validity, and security
	Data governance
Rising responsibilities - Sponsor	Implement risk - proportionate processes for human protection and reliability of the trial results
	Oversight on QA/QC of the trial-related activities of investigators and service providers
	Ensuring privacy, confidentiality, and transparency
	Computerized systems - quality, validity, and security
	Data governance - data integrity, traceability, and security
	Criteria for the essentiality of records

EHR=Electronic health records, eCRF=Electronic case record form, PROs=Patient-reported outcomes, COAs=Clinical outcome assessments, IT=Information technology, QA=Quality assurance, QC=Quality control, IC=Informed consent, EC=Ethics committee, SUSARs=Suspected Unexpected Serious Adverse Reactions, SMO=Site Management Organization