RANDOMIZED

CLINICAL TRIALS
Erika Chua
Medical Oncology Fellow
ELEMENTS OF AN
RCT
 Effectiveness Randomization
New Intervention Examine cause-effect
VS relationships
Control

Randomized
Clinical Trials

Low risk of High quality of evidence

bias
 Pros and Cons
Strength Limitation

Ability to evaluate causal relationships High costs

Minimized bias within the study Concerns for external

resulting in high internal validity validity and generalizability

Investigator control over patient exposure Ethical considerations

Concerns regarding
Prospective data collection
duration of follow-up

Inefficiency of detection
Randomization
of rare or delated outcomes
 Types of Randomized Clinical Trials

Preventive Intervention Therapeutic

To cure a disease
To avert To reduce risk of
To relieve symptoms
disease development disease development
To prolong survival
 Spectrum of Disease

Preventive Intervention Therapeutic

The Design of an RCT
 Outline for a Research Protocol

● Rationale and background for study

● Specific objectives of study
● Concise statement of the study design
● Criteria for including and excluding subjects
● Outline of treatment procedures
● Definition of all clinical, laboratory, and other methods
● Methods of assuring the integrity of the data
● Major and minor outcomes
 Outline for a Research Protocol

● Provisions for observing and recording side-effects

● Procedures for handling problem case
● Procedures for obtaining the informed consent of the subjects
● Procedures for periodic review of the trial
● Procedures of analyzing results
● Procedures for termination of trial
● Procedures for communicating results of trial to study subjects and other
interested person
● Appendices
Cross-Over RCT

Parallel RCT
Sampling Size
The only way to simultaneously DECREASE
both Type I and Type II Errors are:
1. Increase the Sample Size
2. Increase the Size of the Minimum Effect that the Trial will
Detect
Sample Size Estimation

1. Difference in response rates to be detected

2. Estimate of the response rate in one of the groups
3. Level of statistical significance (alpha)
4. Power desired (1-beta)
5. One-sided or two-sided test
 Statistical Significance Testing

One-sided Two-sided

Directional Non-directional

Region of rejection either left or right Region of rejection both left and
right
RCT CONDUCTION
Conducting an RCT

Randomization Allocation
■ Treatment and
comparison groups ■ Random assignment
should be to either treatment or
comparable in all comparison groups
aspects except the one
being studied ■ Stratification: use
of factors known to
■ Ensure that the influence the disease
distribution of these being studied to
factors is based on structure allocation
chance and not on
factors that may lead
to bias
Benefits of Randomization

1.Eliminates selection bias.

2.Balances arms with respect to prognostic variables (known and
unknown).
3.Forms basis for statistical tests, a basis for an assumption-free
statistical test of the equality of treatments.
Methods of Randomization: Simple
Methods of Randomization: Block
Methods of Randomization: Stratified
INTERPRETATION OF
RESULTS
Ways of Expressing Results of a Clinical Trial
Ways of Expressing Results of a Clinical Trial
Ways of Expressing Results of a Clinical Trial
RCT Results
RCT Results
Expressing Dichotomous Data
Expressing Continuous Data
Relative Risk Reduction
Relative Risk
Absolute Risk Reduction
Numbers Needed to Treat
Survival Curves
Thank you!