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Flashcards in 1-Clincial Trials Deck (26):

Define clinical trial

A planned experiment involving patients and designed to explain the most appropriate treatment for future patients with a given medical condition


What is the purpose of a clinical trial?

Provide reliable evidence of treatment efficacy and safety


Define efficacy

Ability of a health care intervention to improve the health of a defined group under specific conditions


Define safety

Ability of a health care intervention not to harm a defined group under specific conditions


What are the disadvantages of comparison with historical controls?

Less information about potential bias
Unable to control for confounders
Selection less rigorous


What needs to be defined before a trial starts?

Disease of interest
Treatments to be compared
Outcomes to be measured
Possible bias and confounders
Eligible patients
Patients who need to be excluded


What are the steps of conducting a trial?

Identify source of eligible patients
Invite them to trial
Consent willing patients
Allocate patients to treatment
Follow up patients identically
Minimise losses to follow up
Maximise compliance


What questions are asked when comparing results of a trial?

Is there an observable difference between treatment?
Could the difference have arisen by chance - statically significant?
How big is the difference between treatments - clinically important?
Is the observed difference attributable to the treatment?


What are the types of outcome in a trial?

Patho-physiological (tumour size/ECG change)
Clinically defined (mortality/morbidity)
Patient focused (quality of life/satisfaction)


When are outcomes measured in a trial?

Baseline - for inadvertent differences in groups
During trial - side effects, is one group being disadvantaged
Final - effects of treatment


What does random allocation lead to?

Minimal allocation bias - each patient has equal chance of being allocated to each treatment
Minimal confounding - groups likely to be similar in size and characteristic due to chance


What are the potential consequences of open label treatment?

Behavioural effects - patient
Non treatment effects - clinician
Measurement bias - investigator


Define the placebo effect

Patients attitude/illness improves as they feel something is being done


Define a placebo

Inert substance appearing identical in every way to active form it is being compared to, aiming to cancel out placebo effect


How can compliance be maximised?

Simplify instructions
Ask about side effects
Measure compliance (urine/blood levels, tablet counts)


Define as treated analysis

Only including patients who have complied in any analysis


What are the disadvantages of as treated analysis?

Loses randomisation (and therefore minimal allocation bias)
Won’t address if there is a reason for low compliance such as negative side effects


What is intention to treat analysis?

Analysis according to original allocation of treatment groups regardless of whether they complied or completed follow up


What are the advantages of intention to treat analysis?

Compares likely effect of using treatment in routine clinical practice
Preserves effects of randomisation - minimal selection bias and confoundings


What is the collective ethic surrounding human clinical trials?

Patients should have treatments properly tested for safety and efficacy


What are the individual ethics in relation to human clinical trials?

Non maleficence


What issues must be considered for a trial to be considered ethical?

Clinical equipoise
Scientifically robust
Ethical recruitment
Valid consent


What governs the ethics of clinical trials in the uk?

NHS trust and PCT R and D office


What are the roles of clinical trials?

Testing the safety of drug
Phase I - proof of principle
Phase II - Proof of concept and dose range finding
Phase III - pharmoeconomics


Describe the regulatory process of clinical trials

MHRA give approval for human clinical trials
Phase III data given to MHRA to be granted a product licence
Wording of packaging and marketing regulated by MHRA, can remove product from market


What are the differences in phases I, II and III?

Phase I - first into man study, single/multiple ascending dose on small number of healthy volunteers to evaluate safety
Phase II - Patients with disease but no co-morbidities to determine dose for therapeutic action
Phase III - Large number of patients with disease and co-morbidities to determine efficacy against standard treatment/placebo