Lecture 19: Drug development and clinical trial Flashcards
What are the three steps to drug discovery?
1) Target identification
- > Molecular target for drug
2) Lead finding
- > Find compounds with desired pharmacological activity
3) Lead optimisation
- > Improve dose potency, selectivity and pharmacokinetic properties.
What is the goal of preclinical development?
Establish basic pharmacology, Pk, toxicological profile and human starting dose of drug using animal and in vitro systems
Establish clinical dose form and manufacturing processess
What are the phases of clinical trials?
Phase 1 - Finding doses for clinical testing Phase 2 - Establish treatment protocols Phase 3 - Definitive comparison to standard care Phase 4 - Post marketing confirmation of safety and efficacy
What is the objective, participants, treatment and design of phase 1 clinical trials?
Know really well
Objective: - Find doses for further clinical evaluation based on safety, tolerability and pharmacology Participants: - Normal healthy (20-50) Treatment: - Dose ranging Design: - Prospective, sequential cohort, ascending dose
What is the objective, participants, treatment and design of phase 2 clinical trials?
Know really well
Objective:
- Therapeutic exploration to establish treatment protocol
Participants:
- Patients (Homogenous group; 30-300 subjects)
Treatment:
- Standard dose, treatment schedule concomitant medicines
Design:
- Prospective, single group, open-label
What is the objective, participants, treatment and design of phase 3 clinical trials?
Know really well
Objective:
- Definitive confirmation of efficacy and safety compared to standard care
Participants:
- Patients (homogenous; 300-3k)
Treatment:
- Standard dose, treatment schedule concomitant medicines
Design:
- Prospective; parallel group, randomised, double blind, initial-to-treat analysis
What is the objective, participants, treatment and design of phase 4 clinical trials?
Know really well
Objective:
- Confirmation of safety and effectiveness in the general population
Participants:
- Patients treated in the setting of routine care
Treatment:
- Not under the control of the researcher
Design:
- Retrospective; Observational; cohort study
What is a prospective study design?
Study groups, participants, interventions, endpoints and procedures are defined before the study is done
What is a retrospective study?
- Endpoints reached before the study questions are defined
- Study groups defined after data collection
- More prone to bias and confounding than prospective studies
What is a controlled trial?
- Study treatment is compared to something else i.e control group receives standard treatment, placebo
What is randomisation?
- Unbiased method of allocation
- Done by chance
- Avoids selection bias
- Controls confounding variables
= Achieves equal distribution of potential confounding variables between different study groups.
What is a parallel group trial?
- Two or more groups compared simultaneously
- Each subject is assigned to one treatment group for duration of study
What is a cross over trial?
- Each subject receives all treatments in random sequence, acting as their own control
- Statistically powerful but prone to carry over and time dependent effects
What are the types of blinding?
- Open label
- Single blind (researcher)
- Double blind
-> Controls for placebo effects and observer expectations
What are the ethical aspects?
- Ethical committees review the trial protocol, patient information sheet and informed consent form, and over see the conduct of the study.
- Participant consent
- Ethical trials only answer important clinical questions and test interventions not known to be inferior to each other.
