Clinical Trials Flashcards
(24 cards)
What is a clinical trial?
An investigation in human subjects intended to discover or verify the clinical pharmacological and/or pharmacodynamic effects of an investigational product
To identify any adverse effects to investigational products
To study ADMA of an investigational product with the object of ascertaining its supply and/or efficacy
Why do we do Clinical Trials?
To investigate new drugs
To investigate different indications for existing drugs
For new surgical techniques
To improve current treatments
What happens in Phase I of clinical trials?
Small number of healthy volunteers
Research ADME
Pharmacokinetics and Pharmacodynamics
What happens in Phase II of clinical trials?
Therapeutic exploration
Patients in clearly defined inclusion and exclusion criteria
Trial medication in the same dosage form as intended for market
What happens in Phase III of clinical trials?
Therapeutic Conformation
Build upon evidence from Phase III
Patients with a range of severities of the indication
Multi-centre and multi-national
Must be blinded
Comparator or placebo
Modifications to marketable medication only for blinding purposes
What happens in Phase IV of clinical trials?
Post marketing surveillance
Additional patient groups or indications
Actual marketed product used
What is randomisation?
Assigning trial subjects to treatment or control groups using an element of chance to determine the assignment on order to reduce bias
What is single blinding?
The trial subject is unaware of which treatment group they have been assigned to
What is double blinding?
Neither the investigator or the trial subject are aware of which group they have been assigned to
What is a placebo?
Using an inactive replica of the trial drug to enable blinding
What is a Gold Standard comparator?
Using the current best treatment for the condition as the control. Requires modification of appreance to remove potenital bias
What are the legal ethics of clinical trials?
Numberg Code of 1947
Declaration of Helsinki
What is the Declaration of Helsinki?
Protects the rights of human subjects
Ensures informed consent
Reviewed on a regular basis
What is an ethics committee?
Panel of volunteers
Experts in the field and lay people
Check prospective studies for ethical compliance
Must give approval before CT starts
What is over-encapsulating?
Placing tablets or capsules into a larger opaque capsule and over filling with inert filler
Must use filler that will not react or affect rate or extent of absorption
Must ensure tablet or capsule is not too large
What is film coating?
Application of a thin coating to the original tablet
Can only be used when test product can be made identical to placebo or comparator
Opacifying agents such as titanium oxide can be used to cover colour and printing
3-5% increase in weight with film coating
What is sugar coating?
Used when IMPs are slightly different shapes or have debossed details and/or are too big to fit into a capsule
Longer process with many steps
Coating uses sugars, titanium oxide and waxes
What are important factors in blinding liquids?
Must look, smell and taste the same
Appearance is modified by opacifying agents and colours
Talc may be used to give the impression of settling
What are challenges with CT packaging?
Hand Assembly
Blinding so that contents cannot be identified
Zero tolerance to errors
What is crossover?
Switching regimen with a washout period
Previous medication cannot affect the next lot of results
Used for conditions with a limited pool of patients
What are extra risks with CT packaging?
Multiple products with the same appearance
Lacks identification on packaging
Labels identical except for subject number
What are reasons for patient non-compliance?
Complex instructions
Forgetfulness
Physical difficulties
Complex regimens
What are CT packaging considerations?
Primary pack design
Label content
Tamper evidence
Climactic zone
Childproof packaging
Reconciliation
When can unblinding occur?
Inadvertently - poor blinding
For emergencies
- scratch and see labels
- encrypted bar codes
