Clinical Trials Flashcards
The pre-clinical phase of drug development involves what?
Laboratory studies
Pharmacology
Animal toxicology
Cell cultures
Phase I of drug development involves what?
Volunteer studies Pharmacodynamics Pharmacokinetics Major side-effects In <100 healthy volunteers
Phase II of drug development involves what?
Treatment studies
Effects and dosages
Common side-effects
In <1000 patients
Phase III of drug development involves what?
Clinical trials
Comparison with standard treatments
In <10000 patients
What does phase IV of drug development involve?
Post-marketing surveillance
Monitoring ADRs
In the whole population
What is an orphan drug?
A synthetic pharmaceutical that remains commercially unavailable, for economic reasons for e.g.
“Scientifically proven to work” means what in terms of the benefit of taking the drug?
Is this the absolute or relative risk?
You are not necessarily more likely to benefit than not… BUT it is better than the other treatment.
Relative risk
What is the definition of a clinical trial?
Any form of planned experiment which involves patients and is designed to elucidate the most appropriate method of treatment for future patients with a given medical condition.
What is the purpose of performing clinical trials?
To provide reliable evidence of treatment efficacy and safety.
In order to be able to give a fair comparison of effect and safety, a clinical trial needs to be….
Reproducible
Controlled
Fair (unbiased, no confounding)
What are some disadvantages of non-randomised clinical trials?
Allocation bias
-by patient, clinician, investigator
Confounding
-known, unknown
What are the disadvantages of comparison with historical controls?
For the ‘standard treatment’ group:
- selection often less well defined
- treated differently from ‘new treatment group’
- less information about potential bias/confounders
- unable to control for confounders
Outline the three steps involved in RCT.
- Definition of factors
- Conduct of the trial
- Comparison of outcomes
RCT: “Definition of factors” involves defining what?
- The disease of interest
- The treatments to be compared
- The outcomes to be measured
- Possible bias and confounders
- The patients eligible for the trial
- The patients to be excluded from the trial
RCT: “Conduct of the Trial” involves what steps?
- Identify a source of eligible patients
- Invite eligible patients in the trial
- Consent patients willing to be in the trial
- Allocate participants to the treatments fairly
- Follow-up participants in identical ways
- Minimise losses to follow-up
- Maximise compliance to treatments
During RCT: “Comparison of Outcomes” what questions are we hoping to answer?
Is there an observed difference in outcome between the treatment groups?
Could the observed difference have arisen by chance i.e. is it statistically significant?
How big is the observed difference between the treatment groups i.e. is it clinically important?
Is the observed difference attributable to the treatments compared in the trial?
Why do we set pre-defined outcomes before clinical trials?
Prevent data dredging & repeated analysis
Protocol for data collection
Agreed criteria for measurement and assessment of outcomes
Name three types of outcome and give examples of each.
Patho-physiological
e.g. tumour size, thyroxine level, ECH changes
Clinically defined e.g. mortality, morbidity, disability
Patient-focussed e.g. QoL, psychological well-being, social well-being, satisfaction
What do we mean by monitoring for possible effect?
Seeing if one group is being disadvantaged.
What do we mean by monitoring for adverse effect?
Seeing if patients are being harmed.
What is non-random allocation?
Allocation of [articipants to treatments by a person, historical basis, geographical location etc.
What can non-random allocation lead to that might be detrimental to the validity of the clinical trial?
Allocation bias
Confounding factors
How can we achieve minimal allocation bias?
Ensuring that randomisation gives each participant an equal chance of being allocated to each pf the treatments in the trial.
What is the difference between single, double and triple blind?
Single- one (usually patient) does not know the treatment allocation
Double- two of patient, clinician, assessor does not know the treatment allocation
Triple- all do not know the allocation including analysis
What examples can you give where blinding may be difficult?
Surgical procedures
Psychotherapy vs. antidepressants
Lifestyle interventions
Prevention programmes
Define what is meant by the placebo effect.
Even if the therapy is irrelevant to the patient’s condition, the patient’s attitude to their illness and indeed the illness itself may be improved by feeling that something is being done about it.
What is a placebo?
An inert substance made to appear identical in every way to the active formulation with which it is to be compared.
What are the two types of losses to follow up for clinical trials?
Appropriate- their clinical condition necessitates their removal
Unfortunate- they choose to remove themselves from the trial
How can we maximise compliance with treatments?
Simplify instructions
Ask about compliance
Ask about effects/side-effects
Monitor compliance
What is the difference between “explanatory” and “pragmatic” trials?
Explanatory trials ignore those who didn’t take the treatment
“As-treated”
Pragmatic trials analyses all regardless of whether they completed follow-up or treatment
“Intention-to-treat”
Should clinical trials be analysed on an explanatory or pragmatic basis?
Why?
Pragmatic (intention-to-treat)
Because they tend to give smaller and more realistic sizes of effect and preserves effects of randomisation
