Pharmaceutical Roadshow

Question 1

How does a drug drug interaction show on a graph

Answer 1

Two lines are apart so you must adjust the dose or avoid if there is a safety concern

Question 2

What is the victim

Answer 2

CYP P-450 substrate

Question 3

What is an aggressor

Answer 3

CYP P-450 inducer/inhibitor

Question 4

CYP P-450 induces do what

Answer 4

Speed up drug metabolism so plasma levels decrease

Question 5

CYP P-450 inhibitors do what

Answer 5

Slowdown drug metabolism so plasma levels increase

Question 6

When consider risks and benefits of medication you must consider

Answer 6

Disease, alternative treatment, patients preference, evidence, informed consent, patient (genes, family history, lifestyle etc), potential to Give a test dose and increase, case of managing side-effects, compliance

Question 7

What does generics do

Answer 7

Promote drug innovation, protect/information so company can make money

Question 8

Generics laws

Answer 8

Data exclusivity for eight years after license, market exclusivity for two years after data exclusivity, patent for 20 years for molecule or formulation

Question 9

What is nonbiological generic

Answer 9

They do not need to repeat nonclinical and clinical studies but need to show PK bioequivalence

Question 10

PK bioequivalence values

Answer 10

90% confidence interval within 80 to 125%

Question 11

Biological generic must show

Answer 11

Efficacy in safety in phase 3 in most sensitive patience

Question 12

Don’t continue drug/ research if

Answer 12

PK concerns, those care response is U shaped in animal studies, polymorphism of targets, evidence of toxicity, of target affects, effects in human but not seen in animals so non-clinical data not appropriate – change animal subject

Question 13

Drugs must be developed for use in

Answer 13

Paediatrics as well unless they have a waiver

Question 14

What is the null hypothesis

Answer 14

Treatments are equal- you would reject the null hypothesis if your drug is more effective

Question 15

Informed consent in drug development

Answer 15

Provide patient information sheet, involve ethics committee

Question 16

In drug development you must report all

Answer 16

Side-effects, unexpected efficacy, pregnancy prescribing and breastfeeding prescribing, overdoses/misuse, medication errors, withdrawal symptoms

Question 17

Major drug therapy achievements

Answer 17

Type one diabetes was a killer before insulin, antibiotics, vaccines e.g. smallpox, heart disease decreased, two out of three people with cancer survived 5+ years, antivirals e.g. HIV and Hepatitis C (chronic/curable)

Question 18

Many drugs won’t recoup their

Answer 18

Investment even if they make it to market

Question 19

What is the cost to develop a drug

Answer 19

In 2000 it was $403 million, in 2016 it was $1395 million

Question 20

Drug development stages

Answer 20

Find potential new target medicine, nonclinical studies, phase 1 clinical studies, phase 2 clinical studies, phase 3 clinical studies, regulatory submission and pricing, launch a new medicine, post-launch R&D, patent expiry and genetic entry

Question 21

What are the discovery and development phases that take 10 to 15 years

Answer 21

Find potential new target medicine, non-clinical studies, phase 1 clinical studies, phase 2 clinical studies, phase 3 clinical studies and regulatory submission and pricing

Question 22

What is the launch stages which takes 5 to 10 years

Answer 22

Launch a new medicine and post-launch R&D

Question 23

How long is patent expiry and genetic entry for

Answer 23

20 years

Question 24

What happens if there is a food drug interaction

Answer 24

Suggest taking the medicine with no food e.g. four hours after eatint

Question 25

On a graph how can you tell if there is a food drug interaction

Answer 25

The fed and fasted Lines on the drug plasma concentration are not close to each other

Question 26

What are the non-clinical testing requirements

Answer 26

Two species toxicology – one rodent and one non-rodent, 14 day exposure for two week use in humans, ideally by the same route e.g. IV, histological examinations of all major organs, PK to say no adverse side-effects and ADME, Check local tolerance, phototoxicity, immuno toxicity and genotoxicity

Question 27

Non-clinical testing during clinical development

Answer 27

Long-term mammalian studies, reproductive toxicity studies, specific studies on safety findings in humans, carcogenicity studies

Question 28

Phase 1 trials

Answer 28

Test safety and tolerability using labs, ECG, vitals and monitoring adverse side-effects
Look at PharmaKinetics eg cmax, tmax and t1/2 and oharmodynamics
Look at special populations e.g. with kidneys/liver impairment
Therapeutic dose guide
Drug drug and drug-food interactions
Usually use healthy patients except for cancer drugs


Question 29

What do you consider when choosing your trial population

Answer 29

Age, gender, other medication and disease, lifestyle and genetics

Question 30

Things to consider with your trial design

Answer 30

Parallel verse crossover groups, single/multiple doses, starting dose and escalate slowly, use a placebo group/control group, endpoints, location– needs 24/7 emergency cover and staff

Question 31

Phase 2

Answer 31

Randomised clinical trial, uses patients, enables dose selection, check safety/tolerability/PK/efficacious dose

Question 32

Phase 3

Answer 32

Registration
2 randomise controlled trials, International data monitoring, uses patients, endpoints – regulatory acceptance, safety essential and patient reported outcomes and needs to be approved by MHRA which can take up to 210 days

Question 33

Phase 3B

Answer 33

Further scientific data is collected for efficacy and safety, it uses real world evidence