Overview
This lecture covers the end-to-end clinical trial process and the specific workflow, roles, and responsibilities of Clinical Data Management (CDM) in ensuring data quality, from pre-clinical studies to post-marketing surveillance.
Clinical Trial Process Overview
- Clinical trials test new drugs, devices, vaccines, or procedures, starting with animal testing (pre-clinical) and progressing to human trials.
- Pre-clinical studies assess pharmacology and toxicology on animals to determine safety for human testing.
- Approval from regulatory bodies (e.g., FDA via IND application) is needed before starting human trials.
- Human trials have three main phases: Phase I (safety, healthy volunteers), Phase II (safety & efficacy, patients), Phase III (confirm efficacy, large group).
- After Phase III, marketing approval is needed (NDA application); drug is then released to market.
- Phase IV (post-marketing surveillance) monitors long-term or rare adverse effects in a larger population.
The Role & Workflow of Clinical Data Management (CDM)
- CDM ensures clinical trial data is clean, complete, consistent, and accurate before submission to regulatory agencies.
- CDM activities are grouped in three main phases: Study Startup, Study Conduct, and Study Closeout.
- Data is collected via Case Report Forms (CRFs), either paper or electronic (eCRFs), often directly by site staff into electronic systems (EDC).
- Raw data often contains discrepancies (invalid, incomplete, inconsistent, or illogical entries) that must be identified and resolved.
- CDM uses validation checks (edit checks), derivation checks, and manages discrepancies through queries and resolutions.
CDM Workflow & Key Activities
Study Startup (Setup)
- Design the study in the database, including naming, visits, sites, investigators, and patient assignments.
- Design eCRFs and plan their layout based on the study protocol and source documents.
- Create validation and derivation checks as per data requirements.
- Conduct User Acceptance Testing (UAT) to ensure system setup is correct before live data entry.
Study Conduct
- Data is entered into databases, mostly directly by sites via EDC; paper-based trials require CDM staff data entry.
- Validation checks catch discrepancies; batch validations run checks at scheduled intervals.
- CDM manages discrepancies, resolves queries, and ensures data coding using standard medical dictionaries (e.g., MedDRA).
- Reconciliations are performed to match key fields between clinical data and external/vendor (lab) data or pharmacovigilance (safety) databases.
Study Closeout
- Conduct pre-closeout checks to confirm all discrepancies and queries are resolved and coding/reconciliation is complete.
- Data is locked and extracted for statistical analysis and regulatory submission.
Clinical Trial Types & Designs
- Trial types: Screening, Diagnostic, Treatment, Prevention.
- Study designs: Active-controlled vs. placebo-controlled, single/double/triple-blinded, randomized vs. non-randomized, factorial/crossover/parallel assignments.
Key Contents of Case Report Forms (CRF)
- Header (study ID, subject ID, site, visit details)
- Inclusion/Exclusion criteria
- Demographics, medical history, vital signs, physical examinations
- Study drug/exposure, concomitant medications
- Adverse events (AEs), serious adverse events (SAEs)
- Lab exams, questionnaires, protocol deviations, study completion
Key Terms & Definitions
- CDM (Clinical Data Management) — Processes ensuring the quality and integrity of clinical trial data.
- CRF (Case Report Form) — Document (paper or electronic) to collect clinical trial data from participants.
- EDC (Electronic Data Capture) — Software systems for direct electronic entry of clinical trial data.
- IND (Investigational New Drug application) — Application for FDA approval to start human trials.
- NDA (New Drug Application) — Application for FDA approval to market a drug.
- Discrepancy — Any data entry error, inconsistency, or missing data in clinical trial records.
- Validation (Edit) Check — Automated or manual rule to detect data discrepancies.
- Derivation Check — Automated calculation or transformation of data from existing entries.
- SAE (Serious Adverse Event) — Life-threatening, fatal, or hospitalization-requiring event during a trial.
- DMP (Data Management Plan) — Document outlining comprehensive CDM processes for a study.
Action Items / Next Steps
- Review CRF examples and identify data collected in each section.
- Study phases and designs of clinical trials for deeper understanding.
- Read provided protocol/sample documents.
- Prepare for hands-on practice with Oracle RDC or other EDC systems as instructed.