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 trials Phases:  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 trials Trial 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 trials Number 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 results Random 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 results Confounding  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).