Understanding clinical trial designs Flashcards

1
Q

What is a clinical trial?

A
  • a type of clinical research that compares one treatment or intervention with another
  • May involve patients or healthy people or both
  • any research that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcones
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2
Q

What is bias?

A
  • aims to obtain groups where the only systematic difference are the interventions under investigation
  • Flaws in the design and conduct of a trial can introduce bias - i.e. Other systematic differences between the treatment groups
  • can severly hamper the interpretation of the results of the trial
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3
Q

What are the different types of bias?

A
  • Selection
  • Performance
  • Attrition
  • Detection
  • Reporting
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4
Q

What is selection bias?

A
  • systematic difference between groups in how participants receibe intervention/control

Methods of minimising bias:
- Randomisation allocation concealment

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5
Q

What is performance bias?

A
  • sys difference between groups in how particpants are cared for, co-interventions
  • Methods of minimising bias:
  • Blinding of participants, team and assessors
    to minimise bias
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6
Q

What is attrition bias?

A
  • Numbers of participants dropping out , non-random withdrawl
  • minimise bias: intention to treat analysis
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7
Q

What is detection bias?

A
  • How outcomes assessed
  • Objective outcome measures
  • Blinded outcome assessors
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8
Q

What is reporting bias?

A
  • Which outcomes are reported
  • minimise bias: registration of trials
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9
Q

Why should we randomise?

A
  • problems with:
  • historical controls
  • non-randomised concurrent controls
  • Factors (known and unknown) that might affect outcome similar in each arm of the trial
  • Basis of statisrical inference
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10
Q

How do we avoid performance and detection bias?

A
  • Blinding : witholding knowledge of treatment AFTER assignment
  • Trial participants
  • Healthcare providers
  • Data collectors
  • Outcome adjudicators
  • Data analysts
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11
Q

What is ITT analysis?

A
  • Exclusion of participants from the analysis can undermine randomisation
  • Any exclusion should be carefully justified
  • Where possible include all participants and “analyse as randomised - the intention to trear principle
  • This provides an unbiased estimate of the effect of being assigned to an intervention
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12
Q

What is the registration of trials?

A
  • Registration = the first step towards research transparency and future dissemination of outcomes
  • Ensures all healthcare decisions are informed by all available evidence
  • Provides opportunity for collaboration and reduces duplication of research efforts
  • Improves awareness of trials for clinicians , researchers, patients and public
  • TRIALS MUST BE REGISTERED
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13
Q

What are different trial designs?

A
  • parallel group
  • crossover
  • factorial
  • cluster
  • platform trials
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14
Q

What are parallel groups ?

A
  • groups receive different interventions in the same time period
  • all participants have the same outcome assessments
  • the groups are compared
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15
Q

What are pros and cons of parallel group trials?

A

Pros:
- simple
- robust
- both groups treated in the same time period

Cons:
- only provides differences between groups
- large studies required to study rare events

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16
Q

What are crossover trials?

A
  • Participant receives all treatments
  • Randomised to an order of treatnebt
  • can compare the responses for each subject and compare the responses between the two groups
  • Not suitable for all trials- useful for chronic conditions
  • Need to include a washout period
17
Q

What are pros of crossover trials?

A
  • smaller number of patients required
  • Each participant receives both treatments
  • Can look at responses witin each patient : each patient acts as their own control
18
Q

What are cons of crossover trials?

A
  • Not suitable in certain disease areas
  • Takes longer
  • Potential for effect of first treatment to carry over
  • Potential for a period time effect
  • Greater risk of drop out
19
Q

What is factorial design?

A
  • different type of multi-arm design where participants can receive one or a combo of treatments
  • For examole, two separate treatments and a combination of treatnents being tested together
  • Patients receive none, one or bot of the treatments
20
Q

What are pros of factorial trials?

A
  • two trials in one
  • can potentially determine if treatments work bettwe together (i.e. if there is an interaction)
21
Q

What are cons of factorial trials ?

A
  • more complicated
  • bigger sample sizes might be required depending on the strength of interaction
22
Q

What are cluster randomised trials?

A
  • Groups of participants are randomised to a treatment/intervention e.g.
  • GP surgeries
  • Communities
  • Hospitals
  • Intervention naturally applied at a cluster level
  • Convenient administration
  • Avoids potential contamination between treatments
  • Can enance recruitment
23
Q

What are pros of cluster trials?

A
  • prevents contamination between individuals assigned to different treatments
  • Useful when individual randomisation is impossible
  • May be easier to recruit to if consent is only for follow-up
24
Q

What are cons of cluster trials?

A
  • May need many participants
  • Can be less efficient than individually randomised designs
  • May be more complex to set up
25
Q

What are platform trials?

A
  • A master protocol which covers multiple research questions or comparisons
  • The flexibility to make adaptations
  • Effcient way to answer multiple questions in a short period of time
26
Q

What are pros of platform trials?

A
  • Efficient way to answer multiple research questions quickly
  • Useful when there are many untested interventions
  • Potential to greatly shorten time to patient benefit
27
Q

What are cons of platform trials?

A
  • Complex and expensive to set up and manage
  • Not necessarily always more efficient than an individual parallel group trial
28
Q

What is superiority vs non-inferiority?

A

S: Designed to show that a new treatment is better than the control
NI: Designed to show that a new treatment is not worse than te control

29
Q
A
29
Q

What is pragmatic vs explanatory?

A

-Explanatory trials : Trials which will demonstrate whether an intervention could work in idela circumstances
- Pragmatic trials
- Trials where te design mimics routine clinical practice as closely as possible with the exception that patients are randomly allocated to treatment