5 - Clinical trials Flashcards

1
Q

Difference b/w clinical trials & controlled lab investigations

A
  • Ethics → experiment involving human subjects ?!

- Bias → “ on intelligent subjects requires new measures of control

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

What is the hierarchy of scientific evidence?

A

case reports –> case series –> ecologic studies
–> cross-sectional studies –> case-control studies –> cohort studies –> RANDOMISED CONTROLLED TRIALS

(from generating hypotheses to establishing causality)

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

How is a hypothesis formed?

A
  1. Primary Q
    Eg: “In population X, is drug A at daily dose Y more efficacious in reducing K, over a period of time T, than drug B at daily dose Z?”
  2. Secondary Q
    Study-related Qs in the whole gp or its subgroups
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which 2 groups are compared in a study?

A

Treatment gp = allocated the agent under study
Comparison gp = not allocated the agent under study
(may receive no treatment, an inactive treatment aka PLACEBO or another active treatm (e.g standard treatm))

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

Types of study designs

A
  1. Simple randomised design
  2. Stratified randomised design
  3. Crossover design
  4. Factorial design
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the basis of stratified randomised studies?

A

If prognostic factors are known & pts can be grouped into prognostic categories, comparability among treatm gps is better achieved w/ stratification
Within each gp, pts are randomly assigned to treatments

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

What is the basis of crossover studies?

A

Pts serve as their own controls

Eg: subjects may undergo therapy for 6w & then “cross over” to control therapy for another 6w

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

What is a -ve of crossover study design?

A

potential for “carryover” effects (i.e treatm given during 1st period may carry over into 2nd period)

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

What are the types & what is the basis of factorial studies?

A

Motive = ask 2 or + Qs in same clinical trial

  • 2x2 –> simplest factorial design: 2 treatments studied for their relationship to response & each is given at 2 levels (eg high dosage & low dosage or drug A & B)
  • 2x2x2 etc
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

The 5 elements of research protocol

A
  1. Sample size
  2. Funding
  3. Approval from ethics committee
  4. Eligibility criteria
  5. Signed informed consent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the main parameters of sample size estimation?

A
  • Level of significance/ α → how big a risk can be taken that the 2 treatm are incorrectly shown as statistically different?
    p Β error & 1-β (power of a trial)→ how “ “ “ as not statistically different?
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Randomisation is the preferred method of assigning pts to receive treatments being compared. True or false?

A

True

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

What are the 3 main randomisation methods?

A

Method 1: toss a coin
Method 2: use a table of random numbers
Method 3: stratified block randomisation

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

What are the +ves of randomization?

A
  • Produces study gps comparable w/ respect to known & unknown risk factors
  • Removes investigator bias in allocation of participants & guarantees results have valid significance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the purpose of a placebo?

A

match experience of comparison gp w/ that of treatm gp

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

What is blinding/masking (bias control) ?

A

= keeping identity of treatm masked for:

  • Subject → single-blind
  • Subject + investigator → double-blind
  • Triple-blind → extension of double-blind → committee monitoring response is not told identity of gps, simply given data for groups A & B
17
Q

What is the purpose of blinding/masking?

A

bias reduction

18
Q

What may adversely affect follow-ups?

A

pts dropout, or cant be located/contacted → lost to follow-up

19
Q

What are the reasons for non-compliance & the consequences?

A

Adverse reactions, waning interest, desire for other therapies

Consequences: smaller diff b/w treatm & comparison gps than truly exists → dilutes real impact of a treatm

20
Q

What can be done to prevent non-compliance?

A
  • Simple & easy-to-follow regimen
  • Present realistic pic of req tasks during consent process
  • Frequent contact w/ participants
  • Run-in period before enrollment & randomization
21
Q

What is the run-in period?

A
  • To ascertain which potential participants can comply to study regimen
  • Only compliant ppl are enrolled in trial
22
Q

What is an interim analysis?

A

Compares intervention gps at any time before formal completion of trial

23
Q

What is an ITT (intention-to-treat) analysis?

A

A specific strategy for generating results of a randomized trial
All subjects are compared in treatm gps to which they were originally randomized, regardless of any treatm they later received

(more informative & gives results closer to those that would’ve been seen if the treatm were given to the pop as a whole)

24
Q

Main advantages of ITT analysis

A

Preserves strengths of randomization, i.e minimize bias

Captures what happens in real-life

Gives a pragmatic estimate of effect of a treatm

25
Main limitations of ITT analysis
- Includes data from both compliant & non-compliant subjects + those who switch treatm gps unexpectedly - Does not determine max potential effectiveness (unlike PP analysis) - Same or less statistically significant benefit than PP - May be no more effective than placebo
26
What is a PP (Per-protocol) analysis?
- Aka efficacy analysis or analysis by treatm administered | - Exclude subjects who were not fully complaint w/ protocol
27
What are the key points concerning ITT & PP analysis?
ITT: - Provides unbiased assessment of treatm, usually preferred - Accounts for treatm effects, difficulties in administering the drug, compliance issues PP: - Evaluates max benefit from a treatm (given perfect compliance)
28
What are the 6 different types of clinical trials?
1. Prevention trials 2. Screening trials 3. Diagnostic trials 4. Treatment trials 5. Quality of life trails (supportive care trials) 6. Compassionate use (or expanded use) trials
29
What are the 4 clinical trial phases?
Phase 1: clinical pharmacology & toxicity Phase 2: initial clinical investigation for treatment effect Phase 3: full-scale evaluation of treatment (clinical trial) Phase 4: post-marketing studies
30
State the objective, design & subjects of phase 1 clinical trials.
Objective - determine a safe drug dose for further studies of therapeutic efficacy Design - dose-escalation to establish a max tolerated dose (MTD) for a new drug Subjects - 1-10 normal volunteers or pts w/ dx
31
State the objective, design & subjects of phase 2 clinical trials.
Objective - to get preliminary info on effectiveness & safety of drug Design - often single arm (no control gp) Subjects - usually 10-100 pts w/ dx
32
State the objective, design & subjects of phase 3 clinical trials.
Objective - compare efficacy of new treatm w/ standard regimen Design - randomized controlled Subjects - usually 100-1000 pts w/ dx
33
State the objective, design & subjects of phase 4 clinical trials.
After drug approved for market → monitoring of side effects & long-term + large-scale studies of morbidity & mortality (e.g thalidomide) Objective - to get more info (long-term side effects) Design - no control gp Subjects - pts w/ dx using the treatm