Clinical Research: The Randomized Clinical Trial — The Methodological Gold Standard

Research Methodology · Clinical Bases

How it begins

An exhaustive and detailed analysis of the epistemological, bioethical, mathematical and operational foundations of experimental design in human beings. The supreme methodological standard for establishing therapeutic causal links.

What it covers

1. The Randomized Clinical Trial
2. Epistemology and Historical Evolution of the Clinical Trial
3. · The Bradford Hill Causality Criteria and Experimental Design
4. · Historical Evolution: From Observational Empiricism to MRC
5. Bioethical Principles and International Regulatory Framework
6. · The Historical Evolution of the Codes of Medical Ethics
7. · The Thirteen Principles of Good Clinical Practice (ICH-GCP)
8. · Informed Consent: Foundation and Dynamic Process
9. Formulation of the Scientific Hypothesis and Architecture of the Protocol
10. · The PICOT Structure in the Formulation of the Research Question
11. · Primary, Secondary and Exploratory Assessment Variables
12. · Surrogate Variables (Surrogate Endpoints) versus Hard Clinical Outcomes
13. Clinical Trial Designs according to their Methodological Architecture
14. · 1. Design in Parallel Groups
15. · 2. Crossover Design
16. · 3. Factorial Design (Example: 2x2 Design)
17. · 4. Design by Conglomerates (Cluster Randomized Trials)
18. · 5. Adaptive Designs and Platform Testing
19. The Art and Science of Randomization
20. · Methodological Randomization Techniques
21. · Concealment of the Allocation Concealment
22. Blinding and Bias Control
23. · Classification of Masking Levels
24. · Sham Procedures in Surgical Trials
25. · Critical Bias Analysis according to the Cochrane Manual
26. Pharmacokinetics, Pharmacodynamics and Phases of Clinical Development
27. · The Phases of Clinical Research in Humans
28. · Dose Escalation Methodology in Phase I Trials: The 3+3 Design
29. Mathematical Determination of Sample Size
30. · Fundamental Statistical Parameters
31. Statistical Analysis Strategies: ITT versus PP
32. · The Comparison of Analysis Strategies
33. · Statistical Treatment of Missing Data (Missing Data)
34. Tests of Superiority, Equivalence and Non-Inferiority
35. · 1. Superiority Tests
36. · 2. Non-Inferiority Tests
37. Survival Analysis and Time to Event Models
38. · The Cardinal Concept of Censorship (Censoring)
39. · Curve Comparison: The Log-Rank Test
40. · The Cox Proportional Hazards Model (Cox Regression)
41. Data Monitoring, Security and Committees (DSMB)
42. · The Independent Data and Safety Monitoring Board (DSMB)
43. · Preventing Type I Error Inflation: The Alpha Spending Rules
44. · Mandatory Notification of Adverse Events in Clinical Trials
45. Subgroup Analysis and Heterogeneity of Effect
46. · Pre-specification vs. Post-Hoc Analysis
47. · The Danger of the Multiplicity of Hypothesis Tests
48. Publication, Transparency and Impact on Clinical Practice Guidelines
49. · The CONSORT Statement (Consolidated Standards of Reporting Trials)
50. · Translation into Clinical Practice: The GRADE System