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.
21 CFR 312 mandatory toxicology, PK, mechanism data before human exposure. Typically 2–5 years pre-clinical → clinical transition. CMC ready in parallel.
IND / CTA submission.
FDA IND (30-day safe-to-proceed). EMA CTR Part I + II via CTIS. CDSCO NDCT. PMDA CTN. ANVISA via VICTOR. 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). Source data verification (proportionate, not universal). 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.