L19. Drug development and clinical trial Flashcards
What are the 6 steps of drug development process - sequential process and objectives of each stage - including times of regulatory approval (2)
- Drug discovery
- Preclinical development
A: Regulatory approval for proposed clinical trials
- Phase 1 trials: dose finding for further clinical evaluation
- Phase 2 trials: Protocol development- defines the treatment and type of patients, other medicines that could be used, generate clinical data that the medicine is doing what it is expected to do.
- Phase 3 trials: definitive test to prove safety and effectiveness comparison to standard care
B: Approval for marketing/selling the drug in the jurisdiction.
- Phase 4 trials: Observational studies post marketing for the confirmation of safety and effectiveness in the general population during routine care.
What is the role of ethical committee in drug development
Ethical committee reviews: Trial protocol, patient information sheet and informed consent form, and conduct of the study
Makes sure that
- Participants need to be fully informed, give consent and can change their mind
- Clinical trials are testing interventions not known to be inferior to each other.
What are the 3 processes in Drug discovery
- Target identification: New candidate medicines are discovered by identifying biological targets for new medicines
- Lead finding: finding compounds with desired pharmacological activity
- Lead optimisation: Improving dose potency, selectivity and pharmacokinetic properties
What is done in the preclinical development
Establishing the basic pharmacology, and human starting dose of drug including Clinical dose form and manufacturing processes.
using animal studies-
(pharmacokinetics, toxicology profile)
and in vitro studies -(mainly for metabolism and mutagenicity).
What are the Participants, Treatment and Design of Phase 1 Clinical trials
P: Normal healthy volunteers - (20-50 ppl)
T: Dose ranging
D: Prospective - sequential cohort studies to limit the number of people exposed to the new medicine, giving ascending dose per cohort or individuals.
What are the Participants, Treatment and Design of Phase 2 Clinical trials
P: Homogenous Patients (30-300)
T: Standardised dose, treatment schedule w/out other concomitant medicines
P: Prospective; single group; open-label
What are the Participants, Treatment and Design of Phase 3 Clinical trials
P: Homogenous patients (300-3000)
T: Standardised dose, treatment schedule w/wout other concomitant medicines
P: Prospective; parallel group; randomised; double blind, initial to treat analysis
What are the Participants, Treatment and Design of Phase 4 Clinical trials
P: Patients treated in the setting of routine care
T: Not under control of the researchers
D: Retrospective; observational; cohort study
What is a controlled trial
Where group receiving the study treatment is compared to a control group receiving standard treatment, or where there is none, placebo. Retrospective studies can use historical treatments as a control as well.
Define Randomisation and what are the good things about it?
Random allocation to treatment groups avoiding selection bias.
Good bc it controls confounding variables - (other factors not the treatment that can affect the study outcome - eg age) by equal distribution between study groups. Don’t even need to know what the confounding variables are.
Compare Parallel group trial and Cross-over trial and what is the good/bad things
Parallel:
Two or more groups compared simultaneously. Each subject is assigned to one treatment for the duration of the study.
Crossover: Each subject receives all treatments in random sequence after a washout period, acting as their own control:
Good that fewer patients needed, and statistically powerful but prone to carry over time dependent effects- first treatment can affect the second.
Define the terms open label, single blind, double blind and the advantage.
OL: both researcher and subject know the assigned treatment
SB: only researcher knows
DB: both don’t know: controls for placebo effects and observer expectations of the treatment that the patient is getting
What regulations are there around clinical trials during drug development and which medicines are getting regulated
Regulations for clinical trial of unregistered medicines and new indications of registered medicines
-Investigators brochure review trial protocol and preclinical/ clinical data from applicants to make a reccomendation to the MoH for approval
Clinical trials have to meet Good Clinical Practice quality standards
Clinical trials are required to gain approval for marketing
What are some Statistical factors that impact clinical trial design and analysis. (2)
- Sample size required to achieve the trial objective is calculated before the study starts, as it is an investment.
This depends on the magnitude of effect to be detected, confidence intervals and probabilities of false +/- trial results. - Analysis: statistical procedures for determining study results.
eg. Intention to treat analysis : all patients remain in assigned group regardless of their actual treatment- whether they followed it or not
How do clinical trials help to contribute to knowledge required by prescribers of the medicine
Information about side effects, tolerability of drug, dosing ranges, therapeutic window, what dose of medicine you would need to prescribe a patient
