S1 - Safe Prescribing And Medicine Errors Flashcards
What are some patient - related prescribing problems ?
Drug interactions
Increased drug use
Sicker/older patients vulnerable to side effects
What are some population prescribing problems ?
Increasing numbers
Elderly patients with co-morbidities
What are some pharmaceutical prescribing problems ?
New drugs
Side effects only seen later as trails usually on healthy patients
What are some doctor related prescribing problems ?
On call/junior doctors can be sleep deprived and not know patients very well
Bad handwriting on prescriptions
What do you need to confirm before writing a prescription ?
Drug name Dose Strength Frequency Allergies Adherence(more likely to adhere to fewer drugs)
What are the legal prescription requirements ?
Black ink
Patients and DRS name and address
DOB
Signed and dated
What are black triangle drugs
Intensively monitored drug which may be newly released or have changed formulas
Basic checklist for Drugs:
The right drug Drug distribution/elimination Alternatives Non- prescription medications The route The dose The frequency Duration SE Monitoring Infromation Special requirements
How long does it take to develop a medicine ?
12 years
What are the first 4 years of development for ?
Discovery research (medicinal chemistry , pharmacology and toxicology )
There are patent regulations
>5000 compounds used
What are the stages of drug development ?
Research Healthy volunteers Patients Testing efficacy and safety Testing different formulas H/e, throughout each stage, the number of drugs eventually decrease to only 1
What does the Research stage comprise of ?
Idea
Feasibility
Target validation (screening)
Identification of potential compounds (PK and potency optimised)
Selection of candidate drug (toxicology studies)
What screening is used in the research stage ?
High through-put screening - helps to identify compounds that may work as the drug and it is usually automated
Identifies if compound has correct structure, is chemically stable and is selective for the target
What is lead identification ?
Allows us to identify candidate drug
Drug tested on smaller animals
Measure ADME
What are the aims of lead identification ?
Increase potency
Optimise selectivity and pharmacokinetics
Ensure efficacy
What do phase 1 studies comprise of ?
First administered to humans - single or multiple ascending doses
Small number of healthy volunteers
Requires MHRA ethical and regulatory approval
1 year
What are the 4 principles of ethics ?
Justice : being fair
Beneficence : doing good
Non- maleficence : not doing harm
Autonomy : allowing individual to determine what happens to them
What do phase 2 studies comprise of ?
Targets patient with disease but few other complications - 200 - 400 patients
2 years
Evaluates pharmacology in disease
Phase 2a : pilot study to find the correct dose
Phase 2b : measures therapeutic action and determines dose for phase 3
Proof of concept/principle
What do phase 3 studies comprise of ?
Targets patient with disease
Large randomised controlled trial
Determines efficacy against placebo
4 years
What occurs after Phase 3 ?
Regulatory review (1 year )- submitted to national body (MHRA), if it is to be marketed , a product license is required
What does MHRA do ?
Give approval for clinical trials and issues licenses, can also remove products from the market
What does phase 4 studies comprise of ?
Seeks new indications ( valid reason to use the drug )
Outcome - based
What is a clinical trial ?
Any form of planned experiment which involves patients and is designed to find the most appropriate method of treatment for future patients with a given medical condition
What is its purpose ?
To provide reliable evidence of treatment efficacy and safety
What is efficacy ?
The ability of healthcare to improve the health of a defined group
What is safety ?
The ability of a healthcare to not harm a defined group
Explain the significance of the 95% confidence interval
If the null hypothesis value is consistent with the observed data, then any observed difference from the null hypothesis may be due to chance. The observed value is always within the 95% confidence interval. Null hypo inside 95% CL - p>0.05, Null hypo outside 95% CL - p<0.05
What are disadvantages of non- randomised clinical trials ?
Allocation bias
Confounding variables
What are disadvantages of using historical controls ?
Comparison with historical control involves the comparison of a group of patients who had the standard treatment with a group receiving a new treatment but this is often flawed for the standard treatment group as :
Selection process is less rigorous
Treated differently to a new treatment group
Unable to control confounders
What are steps involved in a RCT ?
Definition of factors- disease of interest, treatments to be compared, outcomes to be measured
Conduct of trial - identify source of eligible patients , gain consent
Allocate participants to the treatment fairly
Follow up in identical ways
Minimise losses to follow up
Maximise compliance with treatments
Comparison of outcomes - is there an observed difference ? How big is it ?
What are some suitable outcomes for clinical trials ?
Pathophysiological - tumour size
Clinically defined - death ( mortality ), disease
Patient - focussed - quality of life
What does the benefits of random allocation ?
Minimal allocation bias : equal chance of being allocated to each of the treatments
Minimal confounders : treatments groups likely to be similar in size and characteristics
Applies to both known and unknown confounder factors
Methods of random allocation
Coin toss
Computer generated
What are disadvantages of open label allocation ?
Behaviour effect and non- treatment effect
Purpose of blinding ?
Don’t know the treatment allocation to prevent bias
What is a placebo ?
A placebo is an inert substance made to appear identical to the active formulation which it is meant to be
What is the aim of a placebo ?
Cancel out any placebo effect that may exist in the active treatment
What are the ethical implications of a placebo ?
Should only be used where no standard treatment is available
Participants should be informed that they may receive a placebo
How do you deal with losses to follow up and non compliance ?
Some participants need/are made to withdraw
Maintain contact with patients and simplify instructions
What is explanatory trial ?
As treated analysis
Analyses only those who completed follow up and complied with treatment which allows comparison of psychological effects of treatment but loses effects of randomisation
What is a pragmatic trial ?
Intention to treat analysis
Analyses according to original allocation regardless of whether they completed follow up or complied with treatment. This preserves the effects of randomisation.
What are the ethical principles involved in medical research involving human subjects ?
Declaration of Helsinki
Collective ethic
Individual ethic
What issues should be considered for a clinical trail to be regarded as ethical ?
Clinical equipoise : where there is uncertainty about the better treatment
Scientifically robust
Ethical recruitment : no inappropriate exclusion or inclusion
Valid consent : written
What is the purpose of a research ethics committee ?
Conduct of study
Recruitment and protection of participants
Informed consent
