European Patients’ Academy on Therapeutic Innovation Clinical Trial Designs

European Patients’ Academy on Therapeutic Innovation  There are several types of trial designs:  Non-randomised controlled trial  Randomised controlled trial -Parallel group -Cross-over  Single or double blind  Superiority or non-inferiority trial 2 Trial design types

European Patients’ Academy on Therapeutic Innovation  In a clinical trial design, there are a number of different types of comparisons that can be included:  Superiority comparison trials demonstrate that the investigational medicine is better than the control.  Equivalence comparison trials demonstrate that the endpoint measure is similar (no worse, no better) to the control.  Non-inferiority comparison trials demonstrate that the investigational medicine is not worse than the control.  Dose-response relationship trials demonstrate various dose parameters including starting dose and maximum dos. 3 Comparisons

European Patients’ Academy on Therapeutic Innovation  Randomisation is the process of assigning a trial participant randomly (by chance) to treatment or control groups.  Different tools are used to randomise (closed envelopes, computer sequences, random numbers).  There are two components to randomisation: a)the generation of a random sequence b)Implementation of the random sequence, ideally in a way so that participants are not aware of the sequence. 4 Randomisation in clinical trials

European Patients’ Academy on Therapeutic Innovation  Participants are allocated into treatment and control groups by the investigator.  Controls used in non-randomised trials:  Concurrent controls: participants matched according to demographics.  Historical controls: all participants receive the medicine being studied; the results are either compared to the patient's history (for example a patient living with a chronic illness) or a previous study control group. 5 Non-randomised controlled trials

European Patients’ Academy on Therapeutic Innovation  Participants are randomly allocated between treatment and control groups.  Randomisation removes potential for bias.  There are different types of randomised trial designs: 1.Factorial design trials 2.Withdrawal trials 3.Parallel group trials 4.Cross-over trials 6 Randomised controlled trials

European Patients’ Academy on Therapeutic Innovation 7 Parallel groups design

European Patients’ Academy on Therapeutic Innovation 8 Evaluation of the parallel groups design

European Patients’ Academy on Therapeutic Innovation 9 Cross-over design (2 x 2)

European Patients’ Academy on Therapeutic Innovation 10 Evaluation of the cross-over design

European Patients’ Academy on Therapeutic Innovation 11 Matched-pair design

European Patients’ Academy on Therapeutic Innovation  Stratification ensures balanced allocation within each combination.  Studies can be stratified for more than one factor, for example, age and gender.  Common stratification factors include by site, age groups, previous exposure, gender, and lifestyle factors. 12 Randomisation using stratification

European Patients’ Academy on Therapeutic Innovation  Find suitable geographical areas (e.g. catchment area, city, country, etc.).  Randomly choose a number of these geographical areas  For each of these chosen geographical areas, choose a proportional subsample from the members of the study population in that area.  Combine these subsamples to get a sample group. 13 Randomisation using cluster sampling