Brainscape's Knowledge GenomeTM

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


See full index

CPT > Session 1 Clinical Trials > Flashcards

Session 1 Clinical Trials Flashcards

You may prefer our related Brainscape-certified flashcards:
NASM ® CPT flashcards
1
Q

Definition of a clinical trial

A

Any form of PLANNED experiment that involves PATIENTS
Is designed to explain/clarify what the most appropriate method of treatment would be for FUTURE patients with a given medical condition

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

Purpose of a clinical trial

A

To provide reliable evidence of treatment efficacy and safety

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

Define efficacy (clinical)

A

The ability of a health care intervention to IMPROVE the HEALTH of a defined group under specific conditions

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

Define safety (clinical)

A

The ability of a health care intervention NOT TO HARM a defined group under specific conditions

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

In order to be able to give a fair comparison of effect and safety, what 3 things does a clinical trial need to be?

A

Reproducible (in experimental conditions)
Controlled (comparison of interventions)
Fair (unbiased and without confounding)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the difference between efficacy and effectiveness?

A 
Efficacy = ideal clinical conditions (e.g. subjects will be taking the correct amount of medication at a very specific time etc) 
Effectiveness = real world clinical experience
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what estimates are more realistic? Efficacy or effectiveness?

A

Effectiveness = real world clinical experience

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

What are the stages in drug development and monitoring?

A 
Pre-clinical phase
Phase I 
Phase II
Phase III
Phase IV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q
  1. What type of study is the pre clinical phase?
  2. What is the main focus?
  3. Subjects looked at?
A
  1. Laboratory studies
  2. Pharmacology and animal toxicology
  3. Cell cultures and animals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Phase I

  1. Type of study
  2. Main focus
  3. Number of volunteers
A
  1. Volunteer study
  2. Pharmacodynamics, pharmacokinetics and MAJOR side effects
  3. <100 HEALTHY volunteers (normally get paid)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Phase II

  1. Type
  2. Main focus
  3. Volunteers
A
  1. Treatment study
  2. effects and dosage and COMMON side effects
  3. <1,000 PATIENTS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Phase III

  1. Type
  2. Main focus
  3. Volunteers
A
  1. Clinical trials
  2. Comparison with standard treatments
  3. <10,000 PATIENTS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Phase IV

  1. Type
  2. Main focus
  3. Volunteers
A
  1. Post-marketing surveillance (so when the drug has passed and is given to the general public - this phase can last years)
  2. Monitoring for adverse reactions and looking for potential new uses
  3. Whole population
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What do non-randomised clinical trials involve?

Disadvantages?

A

Involve the allocation of patients receiving a new treatment to compare with a group of patients receiving the standard treatment

  • allocation bias - by patient, clinician or investigator
  • confounding - known and unknown
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What does comparison with historical controls involve?

disadvantages for the standard treatment group?

A

Involves the comparison of a group of patients who had the standard treatment with a group of patients receiving a new treatment

  • selection is often less well defined (less rigorous)
  • they are treated differently from the ‘new treatment’ group
  • less information about potential bias/confounders
  • unable to control for confounders
  • it’s a different time period so there will be so many differences in health care etc
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the steps involved in a randomised controlled trial?

Conduct of the trial (7 points)

A
  1. Identify a source of eligible patients
  2. Invite eligible patients to be in the trial
  3. Consent patients willing to be in the trial
  4. Allocate participants to the treatments fairly (so without confounding or bias)
  5. follow-up participants in identical ways
  6. Minimise losses to follow-up
  7. Maximise adherence to treatments
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Steps involved in a randomised control trial?

Comparison of outcomes fairly to see what? 4 points

A

Need to compare the outcomes fairly to see:

  1. Is there an observe difference in outcome between the treatment groups?
  2. Could the observed difference have arisen by chance? (is it statistically significant?)
  3. How big is the observed difference between the treatment groups? (Is it clinically important)
  4. Is the observed difference attributable to the treatments compared in the trial? (Was the design and conduct of the trial good?)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the meaning of the 95% confidence interval?

A

It is a range of values that you can be 95% certain contains the true mean of the population

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

If the null hypothesis value is within the 95% CI, what does this tell you?

A

P = >0.05
* if the null hypothesis value is consistent with the observed data, then any observed difference from the null hypothesis may be due to chance

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

In regards to CI’s, where is the observed value?

A

Always within the CI - in the middle!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Is the null hypothesis value is outside the 95% CI, what does this tell you?

A

P <0.05 (is statistically significant!)

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

What are the reasons for pre-defining outcomes?

As in why do we do it before the start of a clinical trial?

A

So we need to define the what, when and how we’re going to measure the outcomes before we start the trial because:

  • it prevents ‘data dredging’ and ‘repeat analyses’ (misusing data to find patterns that are statistically significant)
  • allows us to have a protocol for data collection
  • can agree on criteria for measurement and assessment of outcomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the basics of having primary outcomes?

A
  • should only have one primary outcome ideally

* used in the sample size calculation

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

What are the basics of having secondary outcomes / what are they?

A

These are the other outcomes of interest and often includes occurrence of side effects

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

What are the three types of outcomes? Give an example for each

A
  1. Pathophysiological (tumour size, thyroxine level, ECG changes)
  2. Clinically defined (mortality/death, morbidity/disease, disability)
  3. Patient-focused (QoL, psychological well-being, social well-being and satisfaction)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the 6 features of an IDEAL outcome?

A+R
V+A
S+S
R+R
S+S
C+T
A
  1. appropriate and relevant - to patient, clinician, society etc
  2. Valid and attributable - any observed effect can be reasonable linked to the treatments being compared
  3. Sensitive and specific - chosen method of measurement can detect changes accurately
  4. Reliable and Robust - outcomes measurable by different people in various settings (to get a similar result!)
  5. Simple and sustainable - method of measurement is easily carried out repeatedly
  6. Cheap and timely - not excessively expensive to measure nor has a long lag time
27
Q

Outline the timing of measurements

Baseline
During
Final

WHY?

A

baseline measurement first of the relevant factors
WHY? - monitoring for inadvertent differences in groups

Then - monitor outcomes DURING the trial
WHY? - looking for possible effect to see if one group is being disadvantaged AND looking for any adverse effects to see if any individuals are being harmed

Final measurement
WHY? Comparing final effect of treatments in trial

28
Q

What is non-random allocation and what are it’s disadvantages?

A

= allocation of participants to treatments by a person, historical basis, geographical location, convenience, numerical order etc

Bad because it leads to the potential for:

  • allocation bias (selection bias)
  • confounding factors - will cause unidentified differences between the treatment groups being compared
29
Q

What is random allocation and why is it good?

A

= fair allocation of participants to the treatments

Good because:
* there is minimal allocation (selection) bias: it gives each participant an equal chance of being allocated to each of the treatments in the trial
* there is minimal confounding: in the long run, it leads to treatment groups that are likely to be similar in size and characteristics by chance
(This applies to both known and unknown confounder factors)

30
Q

What do the best trials use to perform randomisation?

A

They use an external unit to create a computer generated random number that is accessed remotely either by phone or a secure website

31
Q

What is a confounder?

Give an example

A

A factor associated with the exposure and is independently a risk factor for the disease

‘does smoking affect the effect of alcohol on the risk for MI’
* smoking is a positive influencer of alcohol and MI so it is a confounder

32
Q

What are the disadvantages of actually knowing the treatment allocation? This is also referred to as ‘Open label’

Give examples regarding the patient, clinician and the investigator and give the names of the type of the effects

A

May bias the results of a clinical trial for example:

  • patient may alter their behaviour, other treatment or even experience the expectation of outcome = behaviour effect
  • clinician may alter their treatment, care and interest in the patient = non-treatment effect
  • Investigator may alter their approach when making measurements and assessing outcomes = measurement bias
33
Q

How can we minimise allocation (selection) bias?

A

By blinding!

34
Q

What are the types of blinding?

A

Single blind = one of the patient (usually), assessor or clinician doesn’t know the treatment allocation
Double blind = usually patient + clinician/assessor doesn’t know
Triple blind = rarely used but all do not know but double blind can also mean this!

35
Q

How could you perform blinding?

A
  • could aim to make the treatments appear identical in every way - appearance, taste, texture, dosage regime and warnings
36
Q

In what situations would blinding be difficult to perform?

A 
Surgical procedures 
Psychotherapy vs anti-depressant 
Alternative medicine (acupuncture) vs western medicine (drug) 
Lifestyle interventions 
Prevention programmes
37
Q

What is the effect of comparing with ‘no treatment’?

A

The effect of comparing a ‘new treatment’ group with a group receiving no treatment is to leave one unsure as to whether any observed difference was due to the ‘new treatment’ or to the fact that the group was receiving care

38
Q

What is the definition of the placebo effect?

A

Even if the therapy is irrelevant to the patient’s condition, the patient’s attitude to his or her illness, and indeed the illness itself, may be improved by a feeling that something is being done about it

39
Q

What is a ‘placebo’?

A

An inert substance made to appear identical in every way to the active formulation with which it is to be compared

E.g. appearance, taste, texture, dosage regime, warnings etc

40
Q

What is the aim of a placebo?

A

To cancel out any placebo effect that may exist in the active treatment

41
Q

What are the ethical implication of placebo?

A
  • placebo should only be used when no standard treatment is available
  • the use of a placebo is a form of deception
  • THEREFORE, it is essential that participants in a placebo-controlled trial are informed that they may receive a placebo
42
Q

What are losses to follow-up and why does it happen?

A

When not everyone remains in the trial
Due to:
* their clinical condition may necessitate their removal from the trial (appropriate)
* they may choose to withdraw from the trial (unfortunate)

43
Q

How do you minimise losses to follow-up?

A
  • make the follow-up practical and minimise inconvenience
  • be honest about the commitment required from participants
  • avoid coercion or inducements
  • maintain contact with participants
44
Q

What are the reasons for non-compliance with treatment?

A

Participants..

  • misunderstanding the instructions
  • not like taking it
  • think it’s not working
  • prefer to take something else
  • can’t be bothered
45
Q

How would you maximise compliance?

A
  • simplify the instructions
  • ask about compliance
  • ask about side effects and effects
  • monitor compliance - tablet count, urine level or blood level
46
Q

What should analysis of outcomes always take into account?

A

Follow-up and compliance because in practice, these are never 100%

47
Q

How could you interpret wether the new treatment is better than the standard treatment?

A
  • look at the physiological action
    E.g. does drug B lower blood pressure more than drug A?
  • look at wether the new treatment is better than the standard treatment in routine clinical practice
    E.g. if you prescribe drug A, is it better at lowering blood pressure than drug B (will patients take it?)
48
Q

Explanatory trial: ‘as-treated’ analysis

What does it analyse?
What does it compare?
What is bad about it?

A
  • analyses only those who completed follow-up and complied with treatments
  • compares the physiological effects of the treatments

BUT loses effects of randomisation

  • non-compilers are likely to be systematically different from compilers
  • you would get selection bias and confounding
49
Q

Pragmatic trial: ‘intention-to-treat’ analysis

What does it analyse?
what does it compare?
Why is it good?

A
  • analyses according to the original allocation to treatment groups (regardless of wether they completed follow-up or complied with treatment)
  • compares the likely effects of using the treatment in routine clinical practice
  • good because preserves the effects of randomisation
  • would get minimal selection bias and confounding
50
Q

Difference between ‘as-treated’ and ‘intention-to-treat’

A 
As-treated = analyses tend to give larger sizes of effect 
Intention-to-treat = analyses tend to give smaller and more realistic sizes of effect
51
Q

What should clinical trials normally be analysed on?

A

Intention-to-treat basis

52
Q

Basics of the deceleration of helsinki? (Regarding clinical trials involving human subjects)

A

‘The health of my patient will be try first consideration’

‘A physician shall act only in the patients interest when providing medical care’

53
Q

Collective ethic (what)

A

All patients should have treatments that are properly tested for efficacy and safety

54
Q

Individual ethic?4 principles and meaning

A

Principle of;

  1. Beneficence = doctor seeks to do good
  2. Non-maleficence = doctor avoids doing bad
  3. Autonomy = patient controls right to body and future
  4. Justice = doctor treats patient equally
55
Q

Collective vs individual ethics in regards to RCT?

A 
Collective = RCTs aim to properly test treatments for efficacy and safety
Individual 
* do not guarantee benefit 
* may result in harm 
* allocate treatment by chance 
* place burgers and confer benefits
56
Q

What are the 5 issues to consider for a clinical trial to be ethical?

A
  1. Clinical equipoise
  2. Scientifically robust
  3. Ethical recruitment
  4. Valid consent
  5. Voluntariness

All these lead to approval by research ethics committee

57
Q

What is clinical equipoise?

What are the issues?

A

= when there is reasonable uncertainty or genuine ignorance about the better treatment or intervention (including non-intervention)

Issues:

  • is the uncertainty or ignorance by the individual clinician or the scientific community as a whole?
  • what constitutes reasonable uncertainty?
  • how is ‘better’ defined for the individual patient or for society as a whole?
58
Q

What does ‘scientifically robust’ entail?

A

Addresses a relevant or important question that is valid

Has an appropriate study design and protocol (addresses potential biases and confounding)

Has the potential to reach sound conclusions
(Minimises inability to find a clinically important effect using a sample size calculation)

Can justify he use of the comparator treatment or placebo (ref. Helsinki)

Has acceptable risks of possible harm compared to anticipated benefits

Has provision for monitoring the safety and well-being do participants
(Data and patient monitoring)

Has arrangements for appropriate reporting and publication

59
Q

What are the issues of ethical recruitment? I.e…

Inappropriate inclusion of what?
Inappropriate exclusion of what?

A

Inclusion
* participants from communities that are unlikely to benefit
(E.g. aids drug trials in developing world countries)
* participants with a high risk of harm with respect to potential benefits
(Pregnant women)
* participants likely to be excluded from analysis
(A small sub-group of Chinese)

Exclusion
* people who differ from an ideal homogenous group
(Non-white, women, co-morbidities)
* people who are difficulty to get valid consent from
(Immigrants, mentally ill, children and prisoners)

60
Q

How would you get a signed consent form as evidence as valid consent? (This does not necessarily equate to valid consent!)

A 
Knowledgable informant 
Appropriate information 
* verbal and written 
* cooling off period
* freedom to opt out
Informed participant who is a competent decision maker and a legitimate authoriser
61
Q

What is voluntariness?

Example of manipulation and coercion

A

A pre-requisite for consent to be valid

I.e.the decision should be free from coercion or manipulation or the perception that coercion or manipulation may take place

Perceived coercion or manipulation = invalidates consent just as much as actual
Example of coercion = non-access to ‘best treatment’, lower quality of care, disinterest in children
Examples of manipulation = exploitation of emotional state, distortion of information, financial inducements

62
Q

Role of NHS trust/PCT R&D office

A
  • research governance
  • financial management
  • resource implications
63
Q

Role of research ethics committee?

What do they particularly focus on?

A

The dignity, rights, safety and well-being of participants must be the primary consideration in any research study

Focus on:

  • scientific design and study conduct
  • recruitment of research participants
  • care and protection of the RP’s
  • protection of RP’s confidentially
  • informed consent process
  • community considerations

CPT (23 decks)

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