Flow of a trial.
The lifecycle below is the operational pipeline that sits beneath the four-phase architecture. Each step has a regulator-facing artefact; each is a place where studies most often slip schedule or trigger inspection findings.
Flow of a trial.
Concept → submission · 12 stepsThe lifecycle below is the operational pipeline that sits beneath the four-phase architecture. Each step has a regulator-facing artefact; each is a place where studies most often slip schedule or trigger inspection findings.
Concept · target product profile.
Sponsor defines indication, mechanism, comparator landscape, target label. Strategy precedes protocol. Decision: pursue or not.
IND-enabling · preclinical package.
IND-enabling packages generally require nonclinical safety, PK, mechanism, and CMC readiness before human exposure. Timelines vary by modality, programme maturity, and prior evidence.
IND / CTA submission.
FDA IND, EMA CTR/CTIS, CDSCO NDCT, PMDA CTN, and ANVISA pathways should be mapped from current official requirements. Ethics committee submission parallel or sequenced.
Protocol · ICH M11 structured.
Quality-by-design from inception (E6(R3) requirement). Estimands per E9(R1). Statistical analysis plan locked. Investigator brochure, ICF, CRF triad finalised.
Site selection · feasibility.
Therapeutic-area fit, PI track record, recruitment realism, system readiness (EDC, eTMF, IRT). DCT components feasibility assessed at site level.
Site initiation · SIV.
Contracts and budgets executed. Site-level EC/IRB approvals confirmed. Investigator and staff trained on protocol, ICF, e-systems. Drug supply at site. Green-to-enrol.
Recruitment · screening · randomisation.
Patient identification, informed consent, screening assessments, inclusion/exclusion check, IRT randomisation. Diversity Action Plan operational measures live (FDA Phase 3 pivotal).
Dosing · visit conduct.
IMP administration, scheduled visits, sample collection, PRO and ePRO capture. Telemedicine and home-nursing for hybrid DCT. Source data captured at site / direct-to-participant.
Monitoring · SDV · safety surveillance.
Risk-based monitoring per E6(R3) direction. Source data verification should be proportionate and justified. AE reporting. Independent DSMB review for blinded interim analyses. CAPA for deviations.
Database lock · DBL.
All data queries resolved. CRF finalised. Coding (MedDRA, WHODrug) reconciled. Statistician and DM sign-off. Database frozen.
Statistical analysis · CSR.
Pre-specified analysis per SAP. Estimand-aligned outputs. Clinical Study Report (ICH E3) drafted. TMF closure parallel.
Submission · NDA / MAA / NDS.
FDA NDA / EMA MAA / CDSCO NDA / PMDA J-NDA / ANVISA Registro. Module 5 CSRs anchor; ISS/ISE integrate across studies. Inspection-readiness file maintained.
Official source register.
GCP / trial conduct anchorsGood Clinical Practice Step 4.
Official ICH E6(R3) Step 4 guideline. Use as the primary GCP anchor for participant protection, quality-by-design, sponsor oversight, and proportionality.
General considerations for clinical studies.
Official ICH E8(R1) guideline. Use for quality-by-design and critical-to-quality thinking before trial execution begins.
Estimands and sensitivity analysis.
Official ICH E9(R1) addendum. Use for aligning trial objectives, intercurrent events, estimands, and statistical interpretation.
Clinical electronic structured harmonised protocol.
Official FDA-hosted ICH M11 page. Use for structured protocol thinking and protocol information that can become more reusable across systems.
Clinical trials with decentralized elements.
FDA guidance page for decentralized trial elements. Use for remote visits, local healthcare providers, direct-to-participant processes, and oversight expectations.
Diversity Action Plans for clinical studies.
FDA guidance page for Diversity Action Plan expectations. Use for enrolment goals, rationale, and operational measures where applicable.
Regulation (EU) 536/2014 on clinical trials.
Official EUR-Lex anchor for the EU Clinical Trials Regulation. Use for EU authorisation, transparency, reporting, and trial-conduct context.
WHO guidance for best practices for clinical trials.
WHO 2024 clinical-trials best-practice guidance. Use for quality, relevance, ethics, and operational credibility across resource settings.