Clinical Trials Flashcards
What is the role of clinical trials?
To provide reliable evidence of treatment efficacy and safety
For a clinical trial to give a fair comparison of effect and safety, what does it need to be?
Reproducible – in experimental conditions
Controlled – comparison of interventions
Fair – unbiased without confounding
What are the different types of clinical trials?
Observational = monitoring pts over time to advance the understanding of how to treat a disease
Interventional = test the safety and effectiveness of a candidate drug, therapy or experimental treatment
Explain the disadvantage of non-randomise clinical trials
Allocation bias – by patient, clinician or investigator
Confounding – known and unknown
Explain the use of historical controls
involves the comparison of a group of patients who had the standard treatment with a group of patients receiving a new treatment
Outline the steps involved in a randomised controlled trial (RCT)
1) define factors = disease, treatments compared, outcomes measured, bias, confounders, eligible pts, excluded pts
2) conduct of trial = source of eligible pts, invite, consent, allocate treatment fairly, identical follow up, minimise losses, maximise compliance
3) compare outcomes fairly = is there an observed diff, could the diff have arisen by chance, how big is the diff
Describe suitable ‘outcome measures’ for clinical trials
Appropriate + relevant – to pt, clinician, society
Valid + attributable – observed effects can be reasonably linked to treatment
Sensitive + specific – can detect changes accurately
Reliable + robust – diff people in various settings = similar result
Simple and sustainable – easily carried out and repeatable
Cheap + timely – not expensive nor has long lag time
Give examples of types of outcomes
Pathophysiological – tumour size, ECG changes
Clinical defined – death, disease, disability
Pt-focused – QoL, psychological well-being
What are the advantages of random allocation
Minimal allocation bias – equal chance of each treatment
Minima confounding – treatment groups similar in size and characteristics
What are the advantages of blinding
Minimal allocation bias – equal chance of each treatment
Single blind, double blind, triple bind
Describe the placebo effect
Even if the therapy is irrelevant to the patient’s condition, the patient’s attitude to his or her illness, and indeed the illness itself, may be improved by a feeling that something is being done about it
What is a placebo?
inert substance made to appear identical in every way to the active formulation with which it is to be compared
How should one deal with ‘losses to follow-up’?
Make the follow-up practical and minimise inconvenience
Be honest about the commitment required from participants
Avoid coercion or inducements
Maintain contact with participants
How should non-compliance be dealt with?
Simplify the instructions
Ask about compliance
Ask about effects and side-effects
Monitor compliance, e.g. tablet count, urine level, blood level
What is the difference between ‘explanatory’ and ‘pragmatic’ trials
E = analyses only those who completed follow up and complied with treatment – compares physiological effects of treatment
P = analyses regardless of whether they completed follow-up or complied with treatment – compares likely effects of using treatments
Explain the meaning of the term ‘intention-to-treat’ analysis
tend to give smaller and more realistic sizes of effect
Discuss the ethical principles involved in medical research involving human subjects
Declaration of Helsinki 2013 - the health of my pt will be my first consideration
Collective ethic - all pts should have treatments that are properly tested for efficacy and safety
Individual ethic - beneficence, non-maleficence, autonomy, justice
Describe the issues that should be considered for a clinical trial to be regarded as ethical
Clinical equipoise = reasonable uncertainty/genuine ignorance about better treatment or intervention
Scientifically robust = address relevant issues, asks valid questions, appropriate study design, sound conclusions, acceptable risks, monitory and safety, appropriate reporting
Ethical recruitment
Valid consent
Voluntariness = decision free from coercion
Describe the role and function of a Research Ethics Committee
Scientific design and conduct of the study
Recruitment of research participants
Care and protection of research participants
Protection of research participants’ confidentiality
Informed consent process
Community considerations
