Clinical trial designs

The most widely used clinical trial designs to evaluate effectiveness and safety of a drug are parallel, cross - over, and titration designs.


Parallel

In a parallel design trial, patients are randomized into cohorts who receive one of the several treatments (control, dose 1, dose 2 or dose 3). ). Such a design will offer the population, rather than the individual, PK / PD characteristics. The advantage of such a design is the lack of confounding factors such as time (carry over effects) and design dependent outcomes.


Crossover

In a crossover design, each patient receives some (incomplete block) or all (complete block) of the treatments being studied.Therefore, a cross - over design is the most powerful design if deducing the individual concentration (or dose) - response curves is the ultimate aim. In a crossover design, three types of effects are evaluated. They are period effect (Period I vs Period II), Carry over effect and sequence effect (Placebo, active treatment or active treatment , placebo).The disadvantages of this approach are that of its longer trial duration, possible carry - over effects from previous doses and the need for sophisticated data analysis (nonlinear mixed effects modeling).

Titration

The titration design ensures that the patients usually start at a relatively low dose and the dose is increased gradually until either no additional benefit is observed or dose - limiting toxicity occurs. This design closely resembles the clinical practice and the individual PK / PD characteristics can be obtained. The major disadvantage of this design is that of the possibility of an inverted U-shaped PK / PD relationship, as an artifact. The patients who are less sensitive to the drug need higher doses of the drug, making it appear as if the response decreases after a certain dose. Data analysis using conventional methods such as ANOVA fail and the use of sophisticated modeling techniques is required .