RANDOMIZED CLINICAL TRIALS

What is a randomized clinical trial?

Scientific investigations: examine and evaluate the safety and efficacy of new drugs on human volunteers.

Compare a new drug vs. existing drugs or placebo.

designed in an ethical: voluntary consent.

The results: the most valued data in the era of evidence-based medicine.

Classification of clinical trialsPhases:

Phase I, safety – tolerability – pharmacokinetic/dynamics – dose/ response.

Phase II, Dosing – Efficacy

Phase III, Effcacy compared to gold standard treatment.

Phase IV, post-marketing - pharmacovigilance.

Phase I

Phase II

Phase III

Phase IV

Classification of clinical trialsTrial design:

Parallel-group, followed-up to determine the effect of each treatment in parallel groups.

Crossover, patients to different sequences of treatments.

Factorial, assign patients to more than one treatment-comparison group.

Cluster randomized, larger groups are randomized instead of individual patients.

Classification of clinical trialsNumber of centres:

Single-center.

Multicenter.

What the study was designed to prove:

Superiority study, new drug is more effective than placebo.

Equivalence study, how that two drugs have the same clinical benefit.

No inferiority study, new treatment cannot be said to be significantly weaker.

Erroneous results

Bias/Systematic errors

Design, conduct, analysis, and the results associate the occurrence of systematic errors for influenced by bias.

The bias can also make the trial-derived estimate of a treatment effect deviate from its true value.

Types of bias in clinical trials: Related to subject selection.outcome measurement.estimate bias.

Erroneous resultsRandom error

The sampling error is produced because the sample might yet show a chance false result.

Reduced: choosing a very large group of patients. special analytic techniques (meta-analysis).

Statistical testing involves an evolution of the probability of obtaining the observed treatment difference.

Erroneous resultsConfounding

Distortion of the real relationship: treatment and outcome by another factor.

Eliminate bias: the solution is randomization in conjunction.

Before start the trial delete the bias of confounding across randomization techniques: stratified randomization confounding. regression analysis.

How develop a randomized clinical trial?1) Objectives and endpoints

Clear objectives that are measured by endpoints.

2) Study design

Type of trial design

Minimize bias

3) Patient population

Define number of patients.

Exclude some patients.

Informed consent.

How develop a randomized clinical trial?

4) Sample size calculation

used for minimize random error.

For calculate: statistical models that take account of the recruitment of patients into the trial and the type of statistical test to be used.

5) Conduct of the trial

Define the initial dose used of the study drug.

the investigators recruit patients for the trial.

Management, and coordination.

Visits will scheduled every for X time.

How develop a randomized clinical trial?6) Interim monitoring

Randomly assign patients: an independent statistician centre (DSMB).

DSMB has to make sure that the new drug that patients are taking is not damaging.

7) Final data analysis

All endpoints can analyse: the log-rank test, stratified and displayed on Kaplan–Meier plots.

Statistical analyses are usually stipulated in the trial protocol.

8) Trial reporting

Results publish different reports, which follow the CONSORT (Consolidated Standards of Reporting Trials).