Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Principles of Disease-Megan > Clinical Trial Design > Flashcards

Clinical Trial Design Flashcards

1
Q

Why are clinical trials important

A

They provide evidence and most medical practice is evidence based

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name some drug treatments which are based on clinical trial evidence

A 
Treatment of:
Myocardial infarction
Stroke
Many cancers
Rheumatoid arthritis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What type of questions should be asked when developing a new drug/clinical trial

A 
Does it work?
What dose is therapeutic?
What dose is toxic?
Is it safe?
Is it necessary?
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name some drugs used today that were developed before clinical trials

A

Digoxin

Warfarin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Name some false positives which have occurred with observational studies

A 
High cholesterol diet and rectal cancer
Smoking and breast cancer
Vasectomy and prostate cancer
Red meat and colon cancer
Red meat and breast cancer
Drinking water frequently and bladder cancer
Not consuming olive oil (reduces bp in women) and breast cancer
HRT and cardiovascular risk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are observational studies difficult to replicate

A

Due to bias/different criteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why should robust clinical trials be conducted

A

What works in theory may not be best in practice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Give some examples of treatments which have changed due to robust clinical trials

A

Intermittent positive pressure ventilation (IPPV) - reduced use as no benefit
Tonsillectomy -
unnecessary in most cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What acts and regulations are in place for clinical trials

A

UK Medicines Act 1968

The Medicines for Human Use (Clinical Trials) Regulations 2004

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What should clinical trials test

A

Efficacy

Saftey

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What should the drug efficacy be compared with in clinical trials

A

Placebo

Another drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the stages in development

A

Drug discovery
Pre-clinical development
Clinical development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Name some drugs and how they were discovered

A

Fox gloves and digoxin
Poppies and morphine
Dogs and insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is done in pre-clinical development

A

Animal pharmacology
Animal toxicology
Tissue culture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does animal pharmacology test

A

Dose

Adverse effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does animal toxicology test

A

Teratogenicity
Fertility
Mutagenicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How many phases are there in clinical trials

A

4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does phase 1 (volunteer studies) in clinical development involve

A

Clinical pharmacology in normal volunteers generating pharmacokinetic, metabolic and pharmacodynamic data.
Usually involves around 100 subjects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What type of drugs can bypass phase 1

A

Cytotoxics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Give an example of a phase 1 trial

A 
Tegenero drug which used 8 volunteers
Six given active drug intravenously
Two given placebo
Given in regulated environment
According to the protocol approved by MHRA
Volunteers got paid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What does phase 2 clinical trials involve

A

About 500 PATIENTS

Clinical investigation to confirm kinetics and dynamics in patients
Provides some evidence of efficacy and identifies a likely dosage range

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are phase 3 clinical trials

A

Formal therapeutic trials where efficacy will be established and evidence of safety obtained (so does it work for the condition we are testing)
Involves 1000-3000 patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What happens at the end of phase 3 clinical trials

A

All data (pre-clinical, pharmaceutical and clinical data) is submitted as an application to the regulatory authority for a license to sell the drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What occurs in a phase 4 clinical trial

A

Post-marketing surveillance to produce evidence of long term safety (can involve tens or hundreds of thousands of patients)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are pilot studies for

A

To test study design not estimate outcome

26
Q

What can trials be

A

Double blind
Single blind
Prospective
Retrospective

27
Q

What does a placebo controlled study compare

A

Compare the outcome in two groups (one given active drug and other given placebo)

28
Q

What does an other therapy study compare

A

Compare the end points with the use of two different drugs

29
Q

What is a cross over design

A

When one group of patients start of with the study drug and the other with the compared therapy for a certain amount of time then they have a wash out period and swap drugs

30
Q

What is a randomised control clinical trial (RCCT)

A

When patients are assigned at random to either treatment(s) or control
This is the gold standard

31
Q

What are the disadvantages of randomised control clinical trials

A

Results may not be generalisable
Recruitment of patients
Acceptability of randomisation process
Administrative complexity (randomisation methods)

32
Q

Why is the fact that results may not be generalisable a disadvantage in RCCT

A

The subjects may not represent general patient population

Tend to be better at complying

33
Q

Why is recruitment a disadvantage of RCCT

A

Twice as many new patients needed for the study

34
Q

Why is the acceptability of the randomization process in RCCT a disadvantage

A

Some physicians will refuse (PFO closure)

Some patients will refuse (want treatment)

35
Q

What are commonly used phase 3 designs

A 
Parallel
Withdrawal
Group/Cluster
Randomized Consent
Cross Over
Factorial
Large Simple
Equivalence/Non-inferiority
Sequential
36
Q

What is a superiority design

A

To show that new treatment is better than the control or standard (maybe a placebo)

37
Q

What is a non-inferiority design

A

To show that the new treatment:

  • Is not worse that the standard by more than some margin
  • Would have beaten placebo if a placebo arm had been included (regulatory)
38
Q

When designing a study what should the end points be

A 
Simple as possible:
Death
No of hospital admissions
Lowering of blood pressure
Compare with pain control or change in mood
39
Q

What needs to be considered when designing a study

A

Hypothesis
Endpoints
Number of subjects
Safety endpoints

40
Q

What needs to be thought of when choosing subjects

A

Need enough to be able to detect or reject a difference between the groups
Statistical design is very important

41
Q

What does the number of patients depend on

A

Frequency of outcome measurement
e.g. Smarties vs atenolol in mild hypertensives
BP reduction: 200 patients over 12 weeks
Stroke reduction: thousands of patients over five years

42
Q

How should a control drug be chosen

A

Placebo (50% effective in anxiety)

Drug of known efficacy (e.g. atenolol)

43
Q

What should be considered when choosing patients

A

Age and sex matched
Race
Other diseases and drugs
Are they going to comply?

44
Q

What should be part of the exclusion/selection criteria

A 
Exclude pregnant women
Children
Seriously ill patients
Elderly patients
Patients at risk of side effects
45
Q

Why should elderly people be excluded

A

Declining renal function

46
Q

How is analysis and interpretation done

A

Choice a statistical test

Are differences due to chance?

47
Q

What is normally taken as significance

A

p<0.05

48
Q

How can an insignificant finding be interpretated

A

No difference or just that the study hasn’t found one?

Two treatments may be clinically equivalent

49
Q

What needs to be considered in regards to ethics

A 
Consent
Ethics committee
Placebos
Children
Study design
‘Policing’ studies
MHRA/CSM/EU
Insurance
The Law
50
Q

How long does pharmaceutical produce development tend to take

A

About 10 years

Goes through reasearch, decision for development and development

51
Q

How many trials tend to drop out in phase 1

A

70%

52
Q

How many trials tend to drop out in phase 2

A

20%

53
Q

How many trials tend to drop out in phase 3

A

5-8%

54
Q

Where must all pre-clinical and clinical trial evidence be submitted

A

To the regulatory authority

55
Q

Who is the MHRA

A

Medicines and Healthcare devices Regulatory Authority - A committee on safety of medicines

56
Q

Where can the yellow card system be found

A

GPs
Hospital doctors
Pharmacists

57
Q

Name some important clinical trials

A

4S Scandinavian Simvastatin Survival Trial

Cholesterol and Recurrent Events Trial (CARE)

58
Q

What were the results of the 4S and CARE trial

A

4S - 37% reduction in revascularisation

CARE - stroke reduced by 31% (p=0.03)

59
Q

Why are good clinical trials necessary

A

Protect the public

Provide evidence to help rational prescribing

60
Q

Who regulates clinical trials in the UK

A

MHRA

Medicines and Healthcare products Regulatory Agency

61
Q

What is the best type of clinical trial

A

Prospective randomized double blind

Principles of Disease-Megan (41 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions