MP4. Clinical trials

Question 1

purposes of clinical trials (each phase description)?

Answer 1

ONE NOTE

Question 2

Give an overview of phase 1 clinical trials?

Answer 2

-‘First in Humans’ trials
-In 50-200 healthy volunteers* (remunerated)
-In a clinical setting (‘Clinical Research Unit’)
-IND by injection or orally as a liquid or capsules
-Strict monitoring (during and after time spent in CRU)
-Typical duration of Phase I -Trials: 12-18 months
-Success rate: around 70%

Question 3

what is monitored during phase 1 clinical trials?

Answer 3

-Blood/urine samples: PK profile + Biochemical profile
(liver/kidney functions, blood count, inflammation, etc..) -Physical examination (blood pressure, heart rate, etc..)
-Record of side effects experienced by volunteers

Question 4

How are volunteers recruited for phase 1 clinical trials?

Answer 4

-Must be able to give informed consent
-Must meet strict pre-defined inclusion criteria Free from the disease and in general good health!
-Typical exclusion criteria

Question 5

what is the typical exclusion criteria of phase 1 clinical trials?

Answer 5

<18 or >55-60 year old
-Women of child bearing age
-Recent participation in another trial (NHS Over- volunteering Prevention Scheme)
-Smoking, taking OTC or herbal medicines

Question 6

Describe the typical protocol of phase 1 clinical trials?

Answer 6

-Computer generated randomisation of volunteers into groups of three
-Blinded administration and placebo-controlled

Question 7

Describe the first step of the typical protocol in phase 1 clinical trials

Answer 7

First step: single ascending doses:
-Initial dose lower than predicted minimum effective dose
-Dose escalation if no serious adverse effects and PK is as expected
-Trial is stopped when maximum pre-determined dose is reached or serious adverse effects occurred

Question 8

Describe the second step of the typical protocol in phase 1 clinical trials

Answer 8

Second step: multiple ascending doses:
-Several doses given at pre-determined time intervals
-In the same group of volunteers or a different group
- ‘Cross-over’ if same group

Question 9

Describe the optional third step of the typical protocol in phase 1 clinical trials

Answer 9

‘Safe doses’ taken with high fat content meal

Question 10

Describe phase 2 clinical trials

Answer 10

-In 100-300 patients with the disease
-High homogeneity in patients recruited
-Different doses and dosing regimens tested
-Pre-determined efficacy measure
-Monitoring of side effects
-Aim: to determine effective dosing regimens for Phase III trials
-Typical duration: 2 years
-Success rate: < 50% which passed Phase I trials

Question 11

Describe the phase 3 clinical trials

Answer 11

-In a broad patient’s population with the disease (1000-3000 subjects)
-Several hospitals involved (two studies are required by regulatory bodies, usually three are performed)
-Very expensive! ( 90% of development costs!)
-Comparison with current treatment or placebo if
no treatment available
-Aim: prove IND is ‘better’ (more effective or safer or more convenient) than current treatment or placebo

Question 12

What is the typical protocol for phase 3 clinical trials?

Answer 12

-Cross-over
-Double blinded
-Typical duration: 3-5 years
-Success rate: around 60% which passed Phase II trials
ONE NOTE

Question 13

Describe the new drug application (NDA)

Answer 13

-If Phase III trials shows significant statistical improvement on placebo or current treatment
-Submission of a long dossier to government agencies (in every single country!)
-Detailed information about the drug and medicine
-Pre-clinical and clinical data
-Packaging, labelling, information leaflets (for patients and prescribers), etc…
-Post-marketing surveillance plans (Phase IV trials)
-When satisfied, the government agency will issue a Marketing Authorisation (MA)

Question 14

Describe phase 4 clinical trials

Answer 14

-Also called post-marketing surveillance or ‘Pharmacovigilance’
-Take place AFTER the product has been approved
-AIM: monitoring of the new medicine in practice
-‘Yellow card’ scheme in the UK
Medicine can be withdrawn from the market if not
effective or causes serious adverse effects
ONE NOTE

Question 15

Describe how to new drug is promoted and marketed

Answer 15

-Essential to recover the development costs and make profits
-Very different strategy from other industries (POM can’t be advertised to the general public in the UK and EU)
AIMS:
-Make the medical and scientific communities aware
of the new drug
-Convince healthcare systems to adopt the new drug

Question 16

pharmacist roles in clinical trials?

Answer 16

-Dispensing medicines for trials
-Safeguarding trial volunteers/patients
-Ensuring medicine is used as per protocol and following guidelines/regulations
-Ensuring adequate storage of medicines for trials
-Ensuring proper storage and management of study
files
-Data analysis