Clinical Trials Flashcards
What is the purpose of a clinical trial?
To provide reliable evidence of treatment efficacy + safety
Define clinical trial
Any form of planned experiment which involves patients and is designed to elucidate the most appropriate method of treatment for further patients with a given medical condition
What are the stages in drug development?
What are they testing
- pre-clincal phase: lab studies on cultures + animals | toxicity
- phase 1: volunteer studies | major side effects, pharmacodynamics + pharmacokinetics| < 100 healthy volunteers
- phase 2: treatment studies | dosage + common side effects <1,000 patients
- phase 3: clinical trials | comparison | <10,000 patients
- phase 4: post marketing surveillance | monitor for adverse reactions + new uses
Describe key ethical considerations in trial design + conduct
- trials of new drugs may do harm
- patient must give informed consent
- trial must only be conducted if in clinical equipoise
Advantages of using random allocation to minimise confounding
Randomisation leads to treatment groups that are likely to be similar in size + characteristics
What is clinical equipoise?
The assumption that there is not one better intervention present during design of randomised controlled trial
Disadvantages of using historical control group in non randomised trial
- selection often less well defined
- treated differently from new group
- may be less information about possible bias
- unable to control for confounders
What is a confounder?
A third factor that is associated with the exposure + the outcome which distorts the relationship between them
Factors need of a clinical trial to give a fair comparison
Reproducible
Controlled
Fair
What does randomisation mean?
Whether a participant ends up in the treatment or comparison group is due to chance alone
What is single blind?
One of patient, clinician, assessor does not know which group the patient is in
What is double bind?
Two of patient, clinician, assessor does not know which group the patient is in
What is triple blind?
Everyone does not know which group a patient is in
Examples where blinding is difficult
- surgical procedures
- psychotherapy vs anti depressant
- alternative medicine
- lifestyle interventions
- prevention programmes
Why is allocation concealment important in a randomised controlled trail?
- Without it the recruiter may unconsciously affect who gets enrolled in the trail
- prevents allocation bias (type of selection bias)
What is the purpose of allocation concealment
To hide the randomisation sequence from those recruiting people into the trail
Purpose of randomisation
Distributes confounders equally between groups
What does randomisation prevent?
Confounding
What is the purpose of blinding?
Makes patient, clinical and/or assessor unaware of treatment received
What does blinding prevent?
Bias in how patients act, clinical treat patients or assessors measure outcomes
What are the types of outcome?
Patho-physiological
Clinically defined
Patient-focused
Features of an ideal outcome
- appropriate + relevant
- valid + attributable
- sensitive + specific
- reliable + robust
- simple + sustainable
- cheap + timely
Reasons for pre-defining outcomes
- prevent data dredging, repeated analyses
- have a clear protocol for data collection
- agreed criteria for measurement + assessment of outcomes
What are pre defining outcomes?
Need to define what, when and how outcomes are to be measured before start of clinical trial
What are primary outcomes?
Normally only one thing that you want to find out from the trial
What are secondary outcomes?
Other outcomes of interest that are not your main point
e.g side effects
What is the placebo effect?
Even if the therapy is irrelevant to the patients condition, the patients attitudes towards their illness + the illness itself may be improved by a feeling that something is being done
What is a placebo?
An inert substance made to appear identical in every way to the active drug it’’s being compared to
What are the ethical implications for placebo?
- only used when no standard treatment is available
- use of placebo is a form of deception
- therefore, participants must be told that they may receive a placebo
Why may not every patient remain in the trial?
- clinical condition may necessitate their removal
- choose to withdraw from trail
How do you minimise losses to follow up?
- make follow up practical + minimise inconvenience
- be honest about commitment needed
- avoid coercion
- maintain contact with participant
Why may participants not adhere to treatments?
- misunderstanding instruction
- not bothered to take treatment
- may not like taking treatment
- may not think it is working
- may rather another treatment
How can you maximise adherence to treatment?
- simple instructions
- ask about adherence
- ask about side effects
- monitor adherence
- understand that you will never achieve 100* adherence
What is the aim of a placebo?
To cancel out any placebo effect that may exist in the active treatment
What type of analysis is an explanatory trial?
Per protocol analysis
What type of analysis is a pragmatic trail?
Intention to treat
Explain an explanatory trial
- ‘per-protocol analysis’
- analyse only those who completed follow up + adhered to treatments
- compares physiological effects
- but loses effects of randomisation > may introduce confounding
Explain a pragmatic trail
- ‘intention to treat’ analysis
- analyses according to original allocation regardless of completion of follow up or adherence
- compares likely effects of using treatments
- AND preserves randomisation > minimise confounding + bias due to loss of follow up
Key design features in clinical trails + purpose
- should be reproducible, comparative + fair
- randomisation: minimise confounding
- concealing allocation sequence: minimise allocation bias
- blinding: minimise performance + detection bias
- *suitable outcome measures
- minimise losses to follow up
- maximise adherence
- use intention to treat analysis
Should you use per-protocol or intention to treat analysis in a RCT?
Why?
Intention to treat
Preserves randomisation > minimises confounding + bias sue to loss to follow up
