Clinical Trials 101
Under scientific review
This introductory page is under scientific review. Use it for orientation, not clinical decision-making.
Clinical trials are the gold standard for evaluating new cancer treatments. Understanding their design, phases, and regulatory requirements is essential for anyone involved in cancer research or treatment.
Skeptic's corner: Not all clinical trials are created equal. The key is understanding study design, endpoints, and potential biases. Many trials fail, and success rates are low.
Source Guardrail
Last source guard review: 2026-05-22.
Clinical-trial numbers drift by disease area, drug class, sponsor, trial design, endpoint, and calendar period. Use this page for vocabulary. For any public claim about approval probability, timelines, costs, trial status, or accelerated approval, cite a specific source and date it.
| Claim | Minimum source |
|---|---|
| Trial status and phase | ClinicalTrials.gov, EU CTR, ReBEC, WHO ICTRP, or protocol paper |
| Trial phase definitions | NCI or regulator education pages |
| Accelerated approval | FDA program page and current product label |
| Approval probability or development timeline | Peer-reviewed attrition study with field and date range |
What Are Clinical Trials?
Definition
- Clinical trial: Research study involving human participants
- Purpose: Evaluate safety and efficacy of interventions
- Types: Drugs, devices, procedures, behavioral interventions
- Regulatory: FDA, EMA, and other health authorities
Why Are They Important?
- Evidence-based medicine: Rigorous evaluation of treatments
- Patient safety: Systematic assessment of risks
- Regulatory approval: Required for market authorization
- Clinical practice: Inform treatment guidelines
Phases of Clinical Trials
Phase 0 (Exploratory)
- Purpose: Pharmacokinetics and pharmacodynamics
- Participants: 10-15 patients
- Duration: variable; protocol- and endpoint-dependent
- Endpoints: Drug levels, target engagement
- Success rate: source-dependent; do not quote a fixed percentage without a dated attrition source
Phase I (Safety)
- Purpose: Safety, tolerability, and dose finding
- Participants: 20-100 patients
- Duration: variable; accrual- and endpoint-dependent
- Endpoints: Maximum tolerated dose, safety
- Success rate: source-dependent; varies by modality and indication
Phase II (Efficacy)
- Purpose: Preliminary efficacy and safety
- Participants: 100-300 patients
- Duration: variable; accrual- and endpoint-dependent
- Endpoints: Response rate, progression-free survival
- Success rate: source-dependent; oncology attrition is high and heterogeneous
Phase III (Confirmation)
- Purpose: Confirm efficacy and safety
- Participants: 300-3000+ patients
- Duration: variable; often longer when survival or late safety follow-up is required
- Endpoints: Overall survival, quality of life
- Success rate: source-dependent; must be tied to disease area and endpoint
Phase IV (Post-marketing)
- Purpose: Long-term safety and effectiveness
- Participants: Thousands of patients
- Duration: Ongoing
- Endpoints: Real-world outcomes
- Success rate: Variable
Study Design
Randomized Controlled Trials (RCTs)
- Randomization: Random assignment to treatment groups
- Control group: Standard treatment or placebo
- Blinding: Single, double, or triple blind
- Bias reduction: Minimize confounding factors
Study Endpoints
In oncology clinical trials (and in the use of Real-World Evidence - RWE), endpoints are not a simple "cured/didn't cure" rate. They deal with the time factor (survival analysis).
- Overall Survival (OS): The time from randomization to death from any cause. It is the "gold standard" for efficacy, but takes years to measure.
- Progression-Free Survival (PFS): The time from randomization to tumor progression or death. It is a "surrogate endpoint" that can be measured more quickly.
- Objective Response Rate (ORR): The proportion of patients whose tumor shrank a predefined amount (usually via RECIST criteria).
Survival Analysis and Statistics
Technologists working with clinical data must master the following mathematical concepts:
- Censoring: A patient is "censored" in the data if the study ends before the event occurs, or if they drop out. You know they survived at least $X$ months, but you don't know the final value. The mathematical model must accommodate this.
- Kaplan-Meier Curves: A non-parametric estimator used to estimate the survival probability over time in the presence of censored data. It's the ubiquitous "staircase" graph in oncology.
- Hazard Ratio (HR): The ratio between the hazard rate in the treatment group versus the control group. An HR of 0.60 means the treatment reduces the risk of progression or death by 40% at any point in time, compared to the control.
- Log-Rank Test: The statistical test (p-value) used to prove whether the visual difference between two Kaplan-Meier curves is statistically significant.
Primary vs Secondary Endpoints
- Primary: Main outcome measure
- Secondary: Additional outcomes
- Exploratory: Hypothesis generating
- Safety: Adverse events, toxicity
Regulatory Requirements
FDA Requirements
- IND: Investigational New Drug application
- NDA: New Drug Application
- BLA: Biologics License Application
- Fast Track: Accelerated approval
- Breakthrough: Significant improvement
EMA Requirements
- MAA: Marketing Authorization Application
- PRIME: Priority Medicines
- Orphan: Rare disease designation
- Conditional: Conditional approval
Statistical Considerations
Sample Size Calculation
- Power: Probability of detecting true effect
- Alpha: Type I error rate (usually 0.05)
- Beta: Type II error rate (usually 0.20)
- Effect size: Clinically meaningful difference
- Dropout rate: Expected patient loss
Interim Analysis
- Purpose: Early stopping for efficacy or futility
- Alpha spending: Adjust for multiple looks
- Data monitoring: Independent committee
- Stopping rules: Predefined criteria
Clinical Trial Databases
ClinicalTrials.gov
- Purpose: Public registry of clinical trials
- Scope: Worldwide trials
- Updates: Regular status updates
- Search: Advanced search capabilities
Other Registries
- EU Clinical Trials Database: European trials
- WHO ICTRP: International registry
- National registries: Country-specific
- Industry registries: Company-specific
Research Applications
Drug Development
- Target identification: Biomarker discovery
- Patient stratification: Biomarker-guided trials
- Response prediction: Treatment selection
- Resistance mechanisms: Biomarker evolution
Precision Medicine
- Molecular profiling: Comprehensive characterization
- Targeted therapy: Biomarker-guided treatment
- Clinical trials: Biomarker-driven studies
- Real-world evidence: Post-market surveillance
Practical Considerations
Patient Recruitment
- Eligibility criteria: Inclusion/exclusion
- Informed consent: Patient understanding
- Randomization: Fair assignment
- Retention: Patient adherence
Data Management
- Case report forms: Data collection
- Electronic data capture: EDC systems
- Quality control: Data validation
- Regulatory compliance: FDA/EMA requirements
FAQ
Q: How long do clinical trials take? A: There is no safe single answer. Duration depends on trial phase, accrual speed, endpoint timing, follow-up, regulatory pathway, manufacturing, and whether confirmatory studies are required.
Q: What percentage of clinical trials succeed? A: Success rates vary substantially by disease area, drug class, biomarker strategy, trial design, and date range. Quote a specific attrition study rather than a generic percentage.
Q: Can patients participate in multiple trials? A: Generally no, as it can confound results and increase risks.
References
National Cancer Institute. Clinical trial phases. https://www.cancer.gov/about-cancer/treatment/clinical-trials/what-are-trials/phases
ClinicalTrials.gov. Learn About the API. https://clinicaltrials.gov/data-about-studies/learn-about-api
U.S. Food and Drug Administration. Accelerated Approval Program. https://www.fda.gov/drugs/nda-and-bla-approvals/accelerated-approval-program
Friedman, L. M., Furberg, C. D., & DeMets, D. L. (2015). Fundamentals of clinical trials. Springer.
Pocock, S. J. (2013). Clinical trials: A practical approach. John Wiley & Sons.
Contributing
- Review existing content for accuracy
- Add missing trial types or regulatory requirements
- Create practical examples and code snippets
- Cite recent research and regulatory updates
This article provides the foundation for understanding clinical trials in cancer research. Master these concepts to understand drug development and evidence-based medicine.