Lecture 5 on Clinical Trials PDF

Scientific research Dr\ Engy Ahmed Wahsh Head of clinical pharmacy department, Faculty of pharmacy, October 6 university  Phases of clinical trials Clinical trials are conducted in a series of steps called “phases.” Each phase has a different purpose and...

Scientific research Dr\ Engy Ahmed Wahsh Head of clinical pharmacy department, Faculty of pharmacy, October 6 university  Phases of clinical trials Clinical trials are conducted in a series of steps called “phases.” Each phase has a different purpose and helps researchers answer different questions. Clinical trial classification Based on the treatment structure, clinical trial designs are classified into Parallel, crossover, factorial design and withdrawal trials When crossover design should be considered? If you are testing treatments or conditions with short-term and reversible effects, dealing with a homogeneous and stable population of subjects, interested in within-subject variability and individual responses, wanting to reduce sample size and cost, or comparing more than two treatments or conditions When a parallel design should be considered? if you are testing treatments or conditions with long-term or irreversible effects, dealing with a heterogeneous or unstable population of subjects, interested in between-subject variability and group differences, have a large enough sample size and budget for your experiment, or wanting to avoid the complications of carryover and period effects Factorial design  a 2 × 2 factorial design with placebo, patients are randomized into four groups  In factorial design, it is assumed that there is no interaction between medicines.  Factorial design attempts to evaluate two interventions compared to a control in one trial.  Each participant receives two different treatments: x and y; x and control; y and control; control and control. Withdrawal Trials  In a randomized withdrawal trial, participants receive a test treatment to which they respond for a specified time. At the end of the specified time, participants are randomly assigned to continue treatment with the test treatment or with a placebo (i.e., withdrawal of active therapy). The objectives are:  To assess response to the dose being stopped or reduced.  To determine if treatment is still required.  To discontinue participants in a study that have not responded to the medicine being studied. The main limitations of using factorial design for clinical trials is the fact that:  ○ Increased complexity of the trial overall  ○ Makes it more difficult to meet inclusion criteria  ○ Inability to combine multiple incompatible interventions  ○ The protocols are complex  ○ High complexity of statistical analysis Types of control in clinical trials  Purpose of control group  To allow discrimination of patient outcomes.  The control group tells what would have happened to patients if they had not received the test treatment.  In most situations, a concurrent control group is needed because it is not possible to predict outcome with adequate accuracy or certainty  The test and control groups should be similar with regard to all baseline and on-treatment variables that could influence outcome, except for the study treatment.  Failure to achieve this similarity can introduce a bias into the study.  placebo no treatment The type of control different dose or regimen of the study groups treatment different active treatment External (historical ) Multiple control groups  Placebo concurrent control  Inert material that is administrated by the control group in blinded studies to overcome and eliminate the psychological effect. i.e treatment that does not contain the test drug.  seek to show a difference between treatments when they are studying effectiveness.  usually, double-blind. Placebo In in all studies; most surgery interventions cannot be blinded. Special forms of placebo Placebo in the double-dummy design  If one of the treatments is parenteral and the other is capsules, the study is called (double-dummy design); we use two placebos. One of the groups will receive (true parenteral drug + Placebo of capsule drug), and the other group will receive (Placebo of parenteral drug + true capsule drug). Sham intervention  Sham surgery is a faked surgical operation that skips the main therapeutic step in the procedure. Please, note that sham intervention is not possible in all surgical situations. The use of sham surgery is ethically controversial in some surgeries where control patients might be exposed to operative risks. Vehicle control  Vehicle control is usually used in dermatology trials. It is used when the intervention is a topical cream, saline, or mineral oil, which is used as a vehicle for a solution of the experimental drug. In this case, the vehicle without the active drug can be applied as a control.  No-treatment concurrent control  subjects are randomly assigned to test treatment or to no (i.e., absence of) study treatment.  The principal difference between this design and a placebo- controlled trial is that subjects and investigators are not blind to treatment assignment.  Because of the advantages of double-blind designs, this design is likely to be needed and suitable only when it is difficult or impossible to double-blind  Dose-response concurrent control  A randomized, fixed-dose control group where participants are randomly put into one of several fixed- dose groups. Participants either take a fixed dose or raised to that dose gradually  Dose-response trials are usually double-blind.  Carried out to establish he relationship between dose and efficacy and adverse effects.  Active (positive) concurrent control  subjects are randomly assigned to the test treatment or to an active control treatment.  Such trials are usually double-blind.  Active control trials can have two distinct objectives with respect to showing efficacy: 1. to show efficacy of the test treatment by showing it is as good as an effective treatment. 2. to show efficacy by showing superiority of the test treatment to the active control.  External control (including historical control)  compares a group of subjects receiving the test treatment with a group of patients external to the study, rather than to an internal control group consisting of patients from the same population assigned to a different treatment.  The external control can be a group of patients treated at an earlier time (historical control) or a group treated during the same time period but in another setting.  Multiple control groups ❑ Possible and advantageous to use more than one kind of control in a single study, e.g.,  use of both an active control and placebo.  trials can use several doses of test drug and several doses of an active control, with or without placebo. ❑ This design may be useful for active drug comparisons where the relative potency of the two drugs is not well established, or where the purpose of the trial is to establish relative potency.  Important Factors  There is no difference between the inclusion/exclusion criteria for the two groups (all variables must be kept as similar as possible).  Selection of experimental and control groups are random.  The results of the two groups have to be different enough to prove that the difference hasn’t occurred by chance.  The investigational treatment is compared with the standard treatment that is already proven to be effective. This determines whether the investigational treatment works better than the one already on the market.