S1 - Safe Prescribing And Medicine Errors

Question 1

What are some patient - related prescribing problems ?

Answer 1

Drug interactions
Increased drug use
Sicker/older patients vulnerable to side effects

Question 2

What are some population prescribing problems ?

Answer 2

Increasing numbers

Elderly patients with co-morbidities

Question 3

What are some pharmaceutical prescribing problems ?

Answer 3

New drugs

Side effects only seen later as trails usually on healthy patients

Question 4

What are some doctor related prescribing problems ?

Answer 4

On call/junior doctors can be sleep deprived and not know patients very well
Bad handwriting on prescriptions

Question 5

What do you need to confirm before writing a prescription ?

Answer 5

Drug name 
Dose 
Strength 
Frequency 
Allergies 
Adherence(more likely to adhere to fewer drugs)

Question 6

What are the legal prescription requirements ?

Answer 6

Black ink
Patients and DRS name and address
DOB
Signed and dated

Question 7

What are black triangle drugs

Answer 7

Intensively monitored drug which may be newly released or have changed formulas

Question 8

Basic checklist for Drugs:

Answer 8

The right drug
Drug distribution/elimination
Alternatives
Non- prescription medications
The route 
The dose
The frequency
Duration
SE
Monitoring 
Infromation
Special requirements

Question 9

How long does it take to develop a medicine ?

Answer 9

12 years

Question 10

What are the first 4 years of development for ?

Answer 10

Discovery research (medicinal chemistry , pharmacology and toxicology )
There are patent regulations
>5000 compounds used

Question 11

What are the stages of drug development ?

Answer 11

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

Question 12

What does the Research stage comprise of ?

Answer 12

Idea
Feasibility
Target validation (screening)
Identification of potential compounds (PK and potency optimised)
Selection of candidate drug (toxicology studies)

Question 13

What screening is used in the research stage ?

Answer 13

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

Question 14

What is lead identification ?

Answer 14

Allows us to identify candidate drug
Drug tested on smaller animals
Measure ADME

Question 15

What are the aims of lead identification ?

Answer 15

Increase potency
Optimise selectivity and pharmacokinetics
Ensure efficacy

Question 16

What do phase 1 studies comprise of ?

Answer 16

First administered to humans - single or multiple ascending doses
Small number of healthy volunteers
Requires MHRA ethical and regulatory approval
1 year

Question 17

What are the 4 principles of ethics ?

Answer 17

Justice : being fair
Beneficence : doing good
Non- maleficence : not doing harm
Autonomy : allowing individual to determine what happens to them

Question 18

What do phase 2 studies comprise of ?

Answer 18

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

Question 19

What do phase 3 studies comprise of ?

Answer 19

Targets patient with disease
Large randomised controlled trial
Determines efficacy against placebo
4 years

Question 20

What occurs after Phase 3 ?

Answer 20

Regulatory review (1 year )- submitted to national body (MHRA), if it is to be marketed , a product license is required

Question 21

What does MHRA do ?

Answer 21

Give approval for clinical trials and issues licenses, can also remove products from the market

Question 22

What does phase 4 studies comprise of ?

Answer 22

Seeks new indications ( valid reason to use the drug )

Outcome - based

Question 23

What is a clinical trial ?

Answer 23

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

Question 24

What is its purpose ?

Answer 24

To provide reliable evidence of treatment efficacy and safety

Question 25

What is efficacy ?

Answer 25

The ability of healthcare to improve the health of a defined group

Question 26

What is safety ?

Answer 26

The ability of a healthcare to not harm a defined group

Question 27

Explain the significance of the 95% confidence interval

Answer 27

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

Question 28

What are disadvantages of non- randomised clinical trials ?

Answer 28

Allocation bias | Confounding variables

Question 29

What are disadvantages of using historical controls ?

Answer 29

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

Question 30

What are steps involved in a RCT ?

Answer 30

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 ?

Question 31

What are some suitable outcomes for clinical trials ?

Answer 31

Pathophysiological - tumour size Clinically defined - death ( mortality ), disease Patient - focussed - quality of life

Question 32

What does the benefits of random allocation ?

Answer 32

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

Question 33

Methods of random allocation

Answer 33

Coin toss | Computer generated

Question 34

What are disadvantages of open label allocation ?

Answer 34

Behaviour effect and non- treatment effect

Question 35

Purpose of blinding ?

Answer 35

Don’t know the treatment allocation to prevent bias

Question 36

What is a placebo ?

Answer 36

A placebo is an inert substance made to appear identical to the active formulation which it is meant to be

Question 37

What is the aim of a placebo ?

Answer 37

Cancel out any placebo effect that may exist in the active treatment

Question 38

What are the ethical implications of a placebo ?

Answer 38

Should only be used where no standard treatment is available | Participants should be informed that they may receive a placebo

Question 39

How do you deal with losses to follow up and non compliance ?

Answer 39

Some participants need/are made to withdraw | Maintain contact with patients and simplify instructions

Question 40

What is explanatory trial ?

Answer 40

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

Question 41

What is a pragmatic trial ?

Answer 41

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.

Question 42

What are the ethical principles involved in medical research involving human subjects ?

Answer 42

Declaration of Helsinki Collective ethic Individual ethic

Question 43

What issues should be considered for a clinical trail to be regarded as ethical ?

Answer 43

Clinical equipoise : where there is uncertainty about the better treatment Scientifically robust Ethical recruitment : no inappropriate exclusion or inclusion Valid consent : written

Question 44

What is the purpose of a research ethics committee ?

Answer 44

Conduct of study Recruitment and protection of participants Informed consent