Briefing for RCT Flashcards
Stages of drug development: Pre-clinical
- Drug discovery
* Animal testing and toxicology
Stages of drug development: Phase 1
- Few healthy volunteers, or patients with a rare or fatal condition
- Controlled clinical scrutiny
- Slow dose increase
- Used to test pharmacokinetics/pharmacodynamics
- Toxicology testing
- Generally, single-centre trials
Stages of drug development: Phase 2
- Controlled trial in a small group of patients with the condition to be treated
- Well-defined population
- Range of doses tested to confirm most effective
- Further safety evaluation in target population
- Use of ‘surrogate outcomes’ or clinical markers
- Short term
- Generally single-centre
Stages of drug development: Phase 3
- Larger RCTs or cross-over trials
- Well-defined population, specific inclusion and exclusion criteria
- Comparison with placebo or current treatment
- Efficacy and safety in larger populations
- Multi-centre studies to gain sufficient patients and be generalisable to larger populations
- Clinically relevant outcomes
Stages of drug development: Phase 4
- Open-label post-marketing studies
- RCTs or observational studies
- Risks and benefits under normal practice conditions
- Wider-ranging population
- Long term safety and efficacy
- Drug interactions
- Health economics data
Neuropathic pain -
• IASP definition:
pain caused by lesion or disease of the somatosensory nervous system
- Pain arising from damage to nerves in the central or peripheral nervous system. Examples of causes are:
o painful diabetic neuropathy
o post-herpetic neuralgia
o trigeminal neuralgia
• Clinical features: continuous or intermittent spontaneous pain, typically described as burning, aching or shooting in quality
Pharmacological treatment (NICE clinical guideline (CG173)
Non-specialist setting:
• Initial treatment: choice of amtriptyline, duloxetine, gabapentin or pregabalin
• Initial treatment not effective or tolerated: offer one of remaining 3 drugs
• Consider tramadol only if acute rescue therapy needed (potential for misuse), and in those awaiting referral to specialist services
• Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments.
Referral to specialist pain service: comprehensive assessment and multi-modal management of all types of
pain, including neuropathic pain.
• severe pain;
• pain significantly limits participation in daily activities (including self care, general tasks and demands, interpersonal interactions and relationships, mobility, and sleeping);
• or the underlying health condition that is causing neuropathic pain has deteriorated.
Key topics:
• Why randomise?
- to avoid selection bias
- to minimise the effects of known and unknown confounding factors
- to ensure an even distribution of relevant patient characteristics across treatment arms
• Methods of randomisation and allocation?
- good randomisation: computer generated codes, random number tables, coin toss
- Inadequate methods: alternative assingment, assingment by date of birth or hospital number
- Simple allocation
- patients allocated to groups regardless of where previous patient was put
- Unpredictable and can produce inequalities between groups eg in the workshop simple allocation by odd or even number gained 25 in one group and 17 in the other
• RCT designs: parallel, cross-over, cluster
Parallel where participants receive either active treatment or placebo
cross over trials where participants receive one treatment and then the other (less expensive as they use fewer participants)
cluster where randomising groups or clusters of people instead of individuals eg. implementation o a new treatment strategy in a care home or a new curriculum in a school
Balance correction
- stratified randomisation
- minimisation
- block (balance correction)
intention to treat
every patient randomised to a particular group in inc in data analysis regardless of whether or not they received treatment or remained in the trial
per protocol analysis
only those patients who participated in the trial as per the protocol and actually received treatment are analysed
• What is Good Clinical Practice?
good clinical practice is a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting clinical trials that involved the participation of human subject.
adverse event
- any untoward medical occurence which doesnt necessarily have a causal relationshop with this treatment
- adverse events are a normal occurence during the conduct of any study
