Randomised Control Trials: Vaccines Flashcards
(85 cards)
1
Q
MMR vaccine report
- “Intestinal and behavioural pathologies may have occurred together by chance, reflecting a selection bias in a self-referred group; however, the uniformity of the intestinal pathological changes and the fact that previous studies have intestinal dysfunction in children with autistic-spectrum disorders, suggests that the connection is real and reflects a unique disease process.”
- Report suggested causal link between autism and MMR, wakefield said to stop in favour of MMR - still causes issues today
- What has happened since? - what is the issue with this?
A
- Was retracted
- Confounding !!
2
Q
Confounding – when we mix up causes
- What is missing?
A
ANOTHER FACTOR
3
Q
Confounding
- Additional issues in the Wakefield study:-
- Children selected because their mothers believed they had …-related health problems
- Two of the children:
- were …
- with long-standing recognised histories of … and bowel problems
- the mother was a member of an anti-vaxxers group
- A further child was put forward by the brothers’ mother and this child’s mother encouraged to participate
- Issues with the diagnosis of ‘inflammatory bowel disease’
A
- Additional issues in the Wakefield study:-
- Children selected because their mothers believed they had vaccine-related health problems
- Two of the children:
- were brothers
- with long-standing recognised histories of autism and bowel problems
- the mother was a member of an anti-vaxxers group
- A further child was put forward by the brothers’ mother and this child’s mother encouraged to participate
- Issues with the diagnosis of ‘inflammatory bowel disease’
4
Q
Confounding
- Additional issues in the … study:-
- Children selected because their mothers believed they had vaccine-related health problems
- Two of the children:
- were brothers
- with long-standing recognised histories of autism and bowel problems
- the mother was a member of an … group
- A further child was put forward by the brothers’ mother and this child’s mother encouraged to participate
- Issues with the diagnosis of ‘inflammatory bowel disease’
A
- Additional issues in the Wakefield study:-
- Children selected because their mothers believed they had vaccine-related health problems
- Two of the children:
- were brothers
- with long-standing recognised histories of autism and bowel problems
- the mother was a member of an anti-vaxxers group
- A further child was put forward by the brothers’ mother and this child’s mother encouraged to participate
- Issues with the diagnosis of ‘inflammatory bowel disease’
5
Q
Confounding
- Additional issues in the Wakefield study:-
- Children selected because their mothers believed they had vaccine-related health problems
- Two of the children:
- were …
- with …-standing recognised histories of autism and … problems
- the mother was a member of an anti-vaxxers group
- A further child was put forward by the brothers’ mother and this child’s mother encouraged to participate
- Issues with the diagnosis of ‘inflammatory bowel disease’
A
- Additional issues in the Wakefield study:-
- Children selected because their mothers believed they had vaccine-related health problems
- Two of the children:
- were brothers
- with long-standing recognised histories of autism and bowel problems
- the mother was a member of an anti-vaxxers group
- A further child was put forward by the brothers’ mother and this child’s mother encouraged to participate
- Issues with the diagnosis of ‘inflammatory bowel disease’
6
Q
Confounding
- Additional issues in the Wakefield study:-
- Children selected because their mothers believed they had vaccine-related health problems
- Two of the children:
- were brothers
- with long-standing recognised histories of autism and bowel problems
- the mother was a member of an anti-vaxxers group
- A further child was put forward by the brothers’ mother and this child’s mother encouraged to participate
- Issues with the diagnosis of ‘inflammatory bowel disease’
A
- Additional issues in the Wakefield study:-
- Children selected because their mothers believed they had vaccine-related health problems
- Two of the children:
- were brothers
- with long-standing recognised histories of autism and bowel problems
- the mother was a member of an anti-vaxxers group
- A further child was put forward by the brothers’ mother and this child’s mother encouraged to participate
- Issues with the diagnosis of ‘inflammatory bowel disease’
7
Q
Confounding in vaccine research
- Observational studies tend to
- Identify … and … people in the population and
- compare their … outcomes
- Or compare health outcomes of population before and after … of … programme
- But people who have vaccines tend to differ from those who don’t
- People with chronic diseases are more likely to be vaccinated than people
- without chronic diseases
- People with vaccines more likely to have had previous vaccines
- Same risk factors may affect vaccine uptake and disease/adverse reaction incidence
- e.g parentaleducation,smokinginpregnancy,lowbirthweight,familyhistoryof disease, healthcare access and uptake
- Placebo / nocebo effects
A
- Observational studies tend to
- Identify vaccinated and non-vaccinated people in the population and
- compare their health outcomes
- Or compare health outcomes of population before and after implementation of vaccine programme
- But people who have vaccines tend to differ from those who don’t
- People with chronic diseases are more likely to be vaccinated than people
- without chronic diseases
- People with vaccines more likely to have had previous vaccines
- Same risk factors may affect vaccine uptake and disease/adverse reaction incidence
- e.g parentaleducation,smokinginpregnancy,lowbirthweight,familyhistoryof disease, healthcare access and uptake
- Placebo / nocebo effects
8
Q
Confounding in vaccine research
- Observational studies tend to
- Identify vaccinated and non-vaccinated people in the population and
- compare their health outcomes
- Or compare health outcomes of population before and after implementation of vaccine programme
- But people who have … tend to … from those who don’t
- People with chronic diseases are … likely to be vaccinated than people
- without chronic diseases
- People with vaccines … likely to have had previous vaccines
- Same risk factors may affect vaccine uptake and disease/adverse reaction incidence
- e.g parentaleducation,smokinginpregnancy,lowbirthweight,familyhistoryof disease, healthcare access and uptake
- Placebo / nocebo effects
A
- Observational studies tend to
- Identify vaccinated and non-vaccinated people in the population and
- compare their health outcomes
- Or compare health outcomes of population before and after implementation of vaccine programme
- But people who have vaccines tend to differ from those who don’t
- People with chronic diseases are more likely to be vaccinated than people
- without chronic diseases
- People with vaccines more likely to have had previous vaccines
- Same risk factors may affect vaccine uptake and disease/adverse reaction incidence
- e.g parentaleducation,smokinginpregnancy,lowbirthweight,familyhistoryof disease, healthcare access and uptake
- Placebo / nocebo effects
9
Q
Confounding in vaccine research
- Observational studies tend to
- Identify vaccinated and non-vaccinated people in the population and
- compare their health outcomes
- Or compare health outcomes of population before and after implementation of vaccine programme
- But people who have vaccines tend to differ from those who don’t
- People with chronic diseases are more likely to be vaccinated than people
- without chronic diseases
- People with vaccines more likely to have had previous vaccines
- Same … factors may affect … uptake and …/… reaction incidence
- e.g parentaleducation,smokinginpregnancy,lowbirthweight,familyhistoryof disease, healthcare access and uptake
- Placebo / nocebo effects
A
- Observational studies tend to
- Identify vaccinated and non-vaccinated people in the population and
- compare their health outcomes
- Or compare health outcomes of population before and after implementation of vaccine programme
- But people who have vaccines tend to differ from those who don’t
- People with chronic diseases are more likely to be vaccinated than people
- without chronic diseases
- People with vaccines more likely to have had previous vaccines
- Same risk factors may affect vaccine uptake and disease/adverse reaction incidence
- e.g parentaleducation,smokinginpregnancy,lowbirthweight,familyhistoryof disease, healthcare access and uptake
- Placebo / nocebo effects
10
Q
Confounding in vaccine research
- Observational studies tend to
- Identify vaccinated and non-vaccinated people in the population and
- compare their … outcomes
- Or compare … outcomes of population before and after implementation of vaccine programme
- But people who have vaccines tend to differ from those who don’t
- People with chronic diseases are more likely to be vaccinated than people
- without chronic diseases
- People with vaccines more likely to have had previous vaccines
- Same risk factors may affect vaccine uptake and disease/adverse reaction incidence
- e.g parentaleducation,smokinginpregnancy,lowbirthweight,familyhistoryof disease, healthcare access and uptake
- … / … effects
A
- Observational studies tend to
- Identify vaccinated and non-vaccinated people in the population and
- compare their health outcomes
- Or compare health outcomes of population before and after implementation of vaccine programme
- But people who have vaccines tend to differ from those who don’t
- People with chronic diseases are more likely to be vaccinated than people
- without chronic diseases
- People with vaccines more likely to have had previous vaccines
- Same risk factors may affect vaccine uptake and disease/adverse reaction incidence
- e.g parentaleducation,smokinginpregnancy,lowbirthweight,familyhistoryof disease, healthcare access and uptake
- Placebo / nocebo effects
11
Q
Confounding across study designs
A
12
Q
Confounding across study designs
A
13
Q
Confounding across study designs
A
14
Q
Confounding across study designs
A
15
Q
Randomisation
- If random, the probability of any individual receiving one intervention or the other is decided solely by chance
- So people of different levels of a confounder are just as likely to be allocated to each group within the study
- If sample size is sufficient, all the factors influential in the outcome are distributed equally between the groups
- Any effect of these confounders on the outcome of interest is then happening equally within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the intervention rather than any other factors
A
- If random, the probability of any individual receiving one intervention or the other is decided solely by chance
- So people of different levels of a confounder are just as likely to be allocated to each group within the study
- If sample size is sufficient, all the factors influential in the outcome are distributed equally between the groups
- Any effect of these confounders on the outcome of interest is then happening equally within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the intervention rather than any other factors
16
Q
Because cohort studies can be prospective, we can establish …
A
Because cohort studies can be prospective, we can establish temporality
17
Q
Randomisation
- If random, the probability of any individual receiving one intervention or the other is decided solely by …
- So people of different levels of a … are just as likely to be allocated to each group within the study
- If sample size is sufficient, all the factors influential in the outcome are distributed equally between the groups
- Any effect of these confounders on the outcome of interest is then happening equally within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the intervention rather than any other factors
A
- If random, the probability of any individual receiving one intervention or the other is decided solely by chance
- So people of different levels of a confounder are just as likely to be allocated to each group within the study
- If sample size is sufficient, all the factors influential in the outcome are distributed equally between the groups
- Any effect of these confounders on the outcome of interest is then happening equally within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the intervention rather than any other factors
18
Q
Randomisation
- If random, the probability of any individual receiving one intervention or the other is decided solely by chance
- So people of different levels of a confounder are just as likely to be allocated to each group within the study
- If … … is sufficient, all the … influential in the outcome are distributed equally between the groups
- Any effect of these confounders on the outcome of interest is then happening equally within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the intervention rather than any other factors
A
- If random, the probability of any individual receiving one intervention or the other is decided solely by chance
- So people of different levels of a confounder are just as likely to be allocated to each group within the study
- If sample size is sufficient, all the factors influential in the outcome are distributed equally between the groups
- Any effect of these confounders on the outcome of interest is then happening equally within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the intervention rather than any other factors
19
Q
Randomisation
- If random, the probability of any individual receiving one intervention or the other is decided solely by chance
- So people of different levels of a confounder are just as likely to be allocated to each group within the study
- If sample size is sufficient, all the factors influential in the outcome are distributed equally between the groups
- Any effect of these … on the outcome of interest is then happening … within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the intervention rather than any other factors
A
- If random, the probability of any individual receiving one intervention or the other is decided solely by chance
- So people of different levels of a confounder are just as likely to be allocated to each group within the study
- If sample size is sufficient, all the factors influential in the outcome are distributed equally between the groups
- Any effect of these confounders on the outcome of interest is then happening equally within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the intervention rather than any other factors
20
Q
Randomisation
- If random, the probability of any individual receiving one intervention or the other is decided solely by chance
- So people of different levels of a confounder are just as likely to be allocated to each group within the study
- If sample size is sufficient, all the factors influential in the outcome are distributed equally between the groups
- Any effect of these confounders on the outcome of interest is then happening equally within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the … rather than any other …
A
- If random, the probability of any individual receiving one intervention or the other is decided solely by chance
- So people of different levels of a confounder are just as likely to be allocated to each group within the study
- If sample size is sufficient, all the factors influential in the outcome are distributed equally between the groups
- Any effect of these confounders on the outcome of interest is then happening equally within each of the groups
- Therefore, any observed difference in the observed outcome between the groups is likely to be due to the intervention rather than any other factors
21
Q
Confounding in vaccine research
A
22
Q
Study - confounding
- Crude results suggest vaccine is … and … complications
- … (for confounding variables) - e.g. age, number of GP visits etc
- age, disease and GP visits make a massive difference = adjustments - vaccine … from these health outcomes
A
- Crude results suggest vaccine is ineffective and increase complications
- Adjustments (for confounding variables) - e.g. age, number of GP visits etc
- age, disease and GP visits make a massive difference = adjustments - vaccine protects from these health outcomes
23
Q
Randomised controlled trial
A
24
Q
Ethical and political issues in randomisation
- Ethical
- … = ethical basis for medical research that involves assigning patients to different treatments
- Clinical … = genuine uncertainty in the expert medical community over whether one treatment will be more beneficial
- It is not ethically acceptable to randomise patients to a treatment known to be inferior
- Political
- Even when there is genuine uncertainty, new intervention believed superior = non-randomised studies, waitlist controls more attractive
- Policy makers, commissioners, service leads can be unwilling to admit uncertainty
- Broader political reasons for preferring one treatment type over another
A
- Ethical
- Equipoise = ethical basis for medical research that involves assigning patients to different treatments
- Clinical equipoise = genuine uncertainty in the expert medical community over whether one treatment will be more beneficial
- It is not ethically acceptable to randomise patients to a treatment known to be inferior
- Political
- Even when there is genuine uncertainty, new intervention believed superior = non-randomised studies, waitlist controls more attractive
- Policy makers, commissioners, service leads can be unwilling to admit uncertainty
- Broader political reasons for preferring one treatment type over another
25
_Ethical and political issues in randomisation_
* Ethical
* Equipoise = ethical basis for medical research that involves assigning patients to different treatments
* Clinical equipoise = genuine uncertainty in the expert medical community over whether one treatment will be more beneficial
* It is not ethically ... to randomise patients to a treatment known to be inferior
* Political
* Even when there is genuine uncertainty, new intervention ... superior = non-randomised studies, waitlist controls more ...
* Policy makers, commissioners, service leads can be unwilling to admit uncertainty
* Broader political reasons for preferring one treatment type over another
* Ethical
* Equipoise = ethical basis for medical research that involves assigning patients to different treatments
* Clinical equipoise = genuine uncertainty in the expert medical community over whether one treatment will be more beneficial
* It is not ethically **acceptable** to randomise patients to a treatment known to be inferior
* Political
* Even when there is genuine uncertainty, new intervention believed **superior** = non-randomised studies, waitlist controls more **attractive**
* Policy makers, commissioners, service leads can be unwilling to admit uncertainty
* Broader political reasons for preferring one treatment type over another
26
_Ethical and political issues in randomisation_
* Ethical
* Equipoise = ethical basis for medical research that involves assigning patients to different treatments
* Clinical equipoise = genuine uncertainty in the expert medical community over whether one treatment will be more beneficial
* It is not ethically acceptable to randomise patients to a treatment known to be inferior
* Political
* Even when there is genuine uncertainty, new intervention believed superior = non-randomised studies, waitlist controls more attractive
* Policy makers, commissioners, service leads can be unwilling to admit ...
* Broader political reasons for ... one treatment type over another
* Ethical
* Equipoise = ethical basis for medical research that involves assigning patients to different treatments
* Clinical equipoise = genuine uncertainty in the expert medical community over whether one treatment will be more beneficial
* It is not ethically acceptable to randomise patients to a treatment known to be inferior
* Political
* Even when there is genuine uncertainty, new intervention believed superior = non-randomised studies, waitlist controls more attractive
* Policy makers, commissioners, service leads can be unwilling to admit **uncertainty**
* Broader political reasons for **preferring** one treatment type over another
27
Equipoise = ethical basis for medical ... that involves assigning ... to different ...
Equipoise = ethical basis for medical **research** that involves assigning **patients** to different **treatments**
28
Clinical ... = genuine uncertainty in the expert medical community over whether one treatment will be more beneficial
Clinical **equipoise** = genuine uncertainty in the expert medical community over whether one treatment will be more beneficial
29
_Practical issues in randomisation_
* Practical:-
* ... and ...
* ... randomisation needed for some scenarios; cluster-based
* There may be no research evidence suggesting a difference in efficacy between two arms of a trial but that does not stop participants from having a preference.
* Strong preferences between trial treatments may make it harder to recruit patients
* They don’t want to be randomised
* “Watch and wait” or “treatment as usual” may be seen as inferior
* Practical:-
* **Money and resources**
* **Complex** randomisation needed for some scenarios; cluster-based
* There may be no research evidence suggesting a difference in efficacy between two arms of a trial but that does not stop participants from having a preference.
* Strong preferences between trial treatments may make it harder to recruit patients
* They don’t want to be randomised
* “Watch and wait” or “treatment as usual” may be seen as inferior
30
_Practical issues in randomisation_
* Practical:-
* Money and resources
* Complex randomisation needed for some scenarios; cluster-based
* There may be no research evidence suggesting a difference in efficacy between two arms of a trial but that does not stop participants from ... ... ...
* ... preferences between trial treatments may make it ... to recruit patients
* They don’t want to be ...
* “Watch and wait” or “treatment as usual” may be seen as ...
* Practical:-
* Money and resources
* Complex randomisation needed for some scenarios; cluster-based
* There may be no research evidence suggesting a difference in efficacy between two arms of a trial but that does not stop participants from **having a preference.**
* **Strong** preferences between trial treatments may make it **harder** to recruit patients
* They don’t want to be **randomised**
* “Watch and wait” or “treatment as usual” may be seen as **inferior**
31
_BIAS_
* Generally - ‘a partiality that prevents ... ... of an issue or situation’
* In ... - ‘a tendency of an estimate to deviate in one direction from a true value’
* Bias is any departure of results from the truth
* Bias in RCTs occurs when systematic error is introduced into sampling or testing by selecting or encouraging one outcome or answer over others
* Bias is independent of both sample size and statistical significance (sometimes greater samples increase present bias)
* Generally - ‘a partiality that prevents **objective consideration** of an issue or situation’
* In **statistics** - ‘a tendency of an estimate to deviate in one direction from a true value’
* Bias is any departure of results from the truth
* Bias in RCTs occurs when systematic error is introduced into sampling or testing by selecting or encouraging one outcome or answer over others
* Bias is independent of both sample size and statistical significance (sometimes greater samples increase present bias)
32
_BIAS_
* Generally - ‘a partiality that prevents objective consideration of an issue or situation’
* In statistics - ‘a tendency of an estimate to deviate in one direction from a true value’
* Bias is any departure of ... from the truth
* Bias in RCTs occurs when ... error is introduced into sampling or testing by selecting or encouraging one ... or answer over others
* Bias is independent of both sample size and statistical significance (sometimes greater samples increase present bias)
* Generally - ‘a partiality that prevents objective consideration of an issue or situation’
* In statistics - ‘a tendency of an estimate to deviate in one direction from a true value’
* Bias is any departure of **results** from the truth
* Bias in RCTs occurs when **systematic** error is introduced into sampling or testing by selecting or encouraging one **outcome** or answer over others
* Bias is independent of both sample size and statistical significance (sometimes greater samples increase present bias)
33
_BIAS_
* Generally - ‘a partiality that prevents objective consideration of an issue or situation’
* In statistics - ‘a tendency of an estimate to ... in one direction from a true value’
* Bias is any departure of results from the ...
* Bias in ... occurs when systematic error is introduced into sampling or testing by selecting or encouraging one outcome or answer over others
* Bias is independent of both sample size and statistical significance (sometimes greater samples increase present bias)
* Generally - ‘a partiality that prevents objective consideration of an issue or situation’
* In statistics - ‘a tendency of an estimate to **deviate** in one direction from a true value’
* Bias is any departure of results from the **truth**
* Bias in **RCTs** occurs when systematic error is introduced into sampling or testing by selecting or encouraging one outcome or answer over others
* Bias is independent of both sample size and statistical significance (sometimes greater samples increase present bias)
34
_BIAS_
* Generally - ‘a partiality that prevents objective consideration of an issue or situation’
* In statistics - ‘a tendency of an estimate to deviate in one direction from a true value’
* Bias is any departure of results from the truth
* Bias in RCTs occurs when systematic error is introduced into sampling or testing by selecting or encouraging one outcome or answer over others
* Bias is independent of both ... ... and ... ... (sometimes greater samples increase present bias)
* Generally - ‘a partiality that prevents objective consideration of an issue or situation’
* In statistics - ‘a tendency of an estimate to deviate in one direction from a true value’
* Bias is any departure of results from the truth
* Bias in RCTs occurs when systematic error is introduced into sampling or testing by selecting or encouraging one outcome or answer over others
* Bias is independent of both **sample size and statistical significance** (sometimes greater samples increase present bias)
35
Bias in RCTs occurs when ... error is introduced into ... or ... by selecting or encouraging one outcome or answer over others
Bias in RCTs occurs when **systematic** error is introduced into **sampling** or **testing** by selecting or encouraging one outcome or answer over others
36
_Types of bias_
* ... bias
* Representativeness of sample to wider population
* Systematic differences between baseline characteristics of groups that are compared
* .../ ... bias
* Outcome measure does not adequately capture outcome of interest
* Systematic differences between groups in how outcomes are determined
* **Selection** bias
* Representativeness of sample to wider population
* Systematic differences between baseline characteristics of groups that are compared
* **Observer/ Detection** bias
* Outcome measure does not adequately capture outcome of interest
* Systematic differences between groups in how outcomes are determined
37
_Types of bias_
* Selection bias
* Representativeness of sample to ... population
* Systematic differences between baseline ... of groups that are compared
* Observer/ Detection bias
* Outcome measure does not adequately capture outcome of interest
* Systematic differences between groups in how outcomes are determined
* Selection bias
* Representativeness of sample to **wider** population
* Systematic differences between baseline **characteristics** of groups that are compared
* Observer/ Detection bias
* Outcome measure does not adequately capture outcome of interest
* Systematic differences between groups in how outcomes are determined
38
_Types of bias_
* Selection bias
* Representativeness of sample to wider population
* Systematic differences between baseline characteristics of groups that are compared
* Observer/ Detection bias
* Outcome measure does not adequately capture outcome of ...
* Systematic differences between groups in how outcomes are ...
* Selection bias
* Representativeness of sample to wider population
* Systematic differences between baseline characteristics of groups that are compared
* Observer/ Detection bias
* Outcome measure does not adequately capture outcome of **interest**
* Systematic differences between groups in how outcomes are **determined**
39
_Types of bias_
* ... bias
* Representativeness of sample to wider population
* Systematic differences between baseline characteristics of groups that are compared
* ... bias
* Outcome measure does not adequately capture outcome of interest
* Systematic differences between groups in how outcomes are determined
* **Selection** bias
* Representativeness of sample to wider population
* Systematic differences between baseline characteristics of groups that are compared
* **Observer/ Detection** bias
* Outcome measure does not adequately capture outcome of interest
* Systematic differences between groups in how outcomes are determined
40
_Selection bias_
* Allocated groups were ... at outset
* Study sample does not ... ... population
* Solutions:
* Inclusion/exclusion criteria – reflect target population
* Randomisation and sample size– effective randomisation and sampling methods
* Retention to follow-up– remaining participants in both groups at end of study reflect target population
* Allocated groups were **different** at outset
* Study sample does not **represent** **target** population
* Solutions:
* Inclusion/exclusion criteria – reflect target population
* Randomisation and sample size– effective randomisation and sampling methods
* Retention to follow-up– remaining participants in both groups at end of study reflect target population
41
_Selection bias_
* Allocated groups were different at outset
* Study sample does not represent target population
* Solutions:
* .../... criteria – reflect target population
* Randomisation and ... size– effective randomisation and sampling methods
* Retention to follow-up– remaining participants in both groups at end of study reflect target population
* Allocated groups were different at outset
* Study sample does not represent target population
* Solutions:
* **Inclusion/exclusion** criteria – reflect target population
* Randomisation and **sample** size– effective randomisation and sampling methods
* Retention to follow-up– remaining participants in both groups at end of study reflect target population
42
_Selection bias_
* Allocated groups were different at outset
* Study sample does not represent target population
* Solutions:
* Inclusion/exclusion criteria – reflect target population
* ... and sample size– effective ... and sampling methods
* Retention to ...-...– remaining participants in both groups at end of study reflect target population
* Allocated groups were different at outset
* Study sample does not represent target population
* Solutions:
* Inclusion/exclusion criteria – reflect target population
* **Randomisation** and sample size– effective **randomisation** and sampling methods
* Retention to **follow-up**– remaining participants in both groups at end of study reflect target population
43
_Observer Bias_
* Information collected does not adequately capture ... of ...
* ... differences in the way information is collected for the groups being studied
* Self-report of symptoms experienced
* Why might participants report things differently?
* Why might physician or researcher report things differently?
* Solution: Blinding – to exposure, intervention, disease status or hypothesis
* Information collected does not adequately capture **outcome** of **interest**
* **Systematic** differences in the way information is collected for the groups being studied
* Self-report of symptoms experienced
* Why might participants report things differently?
* Why might physician or researcher report things differently?
* Solution: Blinding – to exposure, intervention, disease status or hypothesis
44
_Observer Bias_
* Information collected does not adequately capture outcome of interest
* Systematic differences in the way information is collected for the groups being studied
* ...-report of symptoms experienced
* Why might participants report things ...?
* Why might physician or researcher report things ...?
* Solution: Blinding – to exposure, intervention, disease status or hypothesis
* Information collected does not adequately capture outcome of interest
* Systematic differences in the way information is collected for the groups being studied
* **Self**-report of symptoms experienced
* Why might participants report things **differently**?
* Why might physician or researcher report things **differently**?
* Solution: Blinding – to exposure, intervention, disease status or hypothesis
45
_Observer Bias_
* Information collected does not adequately capture outcome of interest
* Systematic differences in the way information is collected for the groups being studied
* Self-report of symptoms experienced
* Why might participants report things differently?
* Why might physician or researcher report things differently?
* Solution: ... – to exposure, intervention, disease status or hypothesis
* Information collected does not adequately capture outcome of interest
* Systematic differences in the way information is collected for the groups being studied
* Self-report of symptoms experienced
* Why might participants report things differently?
* Why might physician or researcher report things differently?
* Solution: **Blinding** – to exposure, intervention, disease status or hypothesis
46
_Blinding - RCT_
* Blinding – to exposure, intervention, disease status or hypothesis - prevents ... bias
* Blinding – to exposure, intervention, disease status or hypothesis - prevents **observer** bias
47
_Blinding - RCT_
* Blinding – to exposure, intervention, disease status or hypothesis - prevents ... bias
* Blinding – to exposure, intervention, disease status or hypothesis - prevents **observer** bias
48
... is a measure in randomized controlled trials (RCT) to reduce detection and performance bias.
**Blinding** is a measure in randomized controlled trials (RCT) to reduce detection and performance bias.
49
_Data Analysis considerations_
* A...
* In an RCT of a long-term tablet treatment you might see:
* “At the end of the first year, the proportion who reported taking study medication was 82% in the hormone group and 91% in the placebo group.
* By the end of the third year, these proportions had declined to 75% and 81%.
* Pill counts revealed 79% of the women in the hormone group to be taking at least 80% of their study medication at the end of year 1 and 70% to be doing so at the end of year 3.
* **Adherence**
* In an RCT of a long-term tablet treatment you might see:
* “At the end of the first year, the proportion who reported taking study medication was 82% in the hormone group and 91% in the placebo group.
* By the end of the third year, these proportions had declined to 75% and 81%.
* Pill counts revealed 79% of the women in the hormone group to be taking at least 80% of their study medication at the end of year 1 and 70% to be doing so at the end of year 3.
50
_Data Analysis considerations_
* Adherence
* In an RCT of a long-term tablet treatment you might see:
* “At the end of the ... ..., the proportion who reported taking study medication was 82% in the hormone group and 91% in the placebo group.
* By the end of the third year, these proportions had ... to 75% and 81%.
* Pill counts revealed 79% of the women in the hormone group to be taking at least 80% of their study medication at the end of year 1 and 70% to be doing so at the end of year 3.
* Adherence
* In an RCT of a long-term tablet treatment you might see:
* “At the end of the **first year**, the proportion who reported taking study medication was 82% in the hormone group and 91% in the placebo group.
* By the end of the third year, these proportions had **declined** to 75% and 81%.
* Pill counts revealed 79% of the women in the hormone group to be taking at least 80% of their study medication at the end of year 1 and 70% to be doing so at the end of year 3.
51
_Data Analysis considerations_
* ...
* In an RCT of a long-term tablet treatment you might see:
* “At the end of the first year, the proportion who reported taking study medication was 82% in the hormone group and 91% in the placebo group.
* By the end of the third year, these proportions had declined to 75% and 81%.
* Pill counts revealed 79% of the women in the hormone group to be taking at least 80% of their study medication at the end of year 1 and 70% to be doing so at the end of year 3.
* **Adherence**
* In an RCT of a long-term tablet treatment you might see:
* “At the end of the first year, the proportion who reported taking study medication was 82% in the hormone group and 91% in the placebo group.
* By the end of the third year, these proportions had declined to 75% and 81%.
* Pill counts revealed 79% of the women in the hormone group to be taking at least 80% of their study medication at the end of year 1 and 70% to be doing so at the end of year 3.
52
_Data Analysis considerations_
* Adherence
* In an RCT of a long-term tablet treatment you might see:
* “At the end of the first year, the proportion who reported taking study medication was 82% in the hormone group and 91% in the placebo group.
* By the end of the third year, these proportions had declined to 75% and 81%.
* Pill counts revealed 79% of the women in the hormone group to be taking at least 80% of their study medication at the end of year 1 and 70% to be doing so at the end of year 3.
* Adherence
* In an RCT of a long-term tablet treatment you might see:
* “At the end of the first year, the proportion who reported taking study medication was 82% in the hormone group and 91% in the placebo group.
* By the end of the third year, these proportions had declined to 75% and 81%.
* Pill counts revealed 79% of the women in the hormone group to be taking at least 80% of their study medication at the end of year 1 and 70% to be doing so at the end of year 3.
53
_Data Analysis considerations_
* Adherence
* In a ... study, adherence is slightly different
* Some vaccines may have a ... e.g. top-ups, multiple injections
* Many vaccines are a ...-off event
* So adherence is often categorical i.e. had vaccine or did not have vaccine
* Why is adherence important to measure and report? - non-...
* Adherence
* In a **vaccine** study, adherence is slightly different
* Some vaccines may have a **schedule** e.g. top-ups, multiple injections
* Many vaccines are a **one**-off event
* So adherence is often categorical i.e. had vaccine or did not have vaccine
* Why is adherence important to measure and report? - non-**compliance**
54
_Data Analysis considerations_
* Adherence
* In a vaccine study, adherence is slightly different
* Some vaccines may have a schedule e.g. top-ups, multiple injections
* Many vaccines are a one-off event
* So adherence is often ... i.e. had vaccine or did not have vaccine
* Why is adherence important to measure and report? - non-compliance (may have bad outcomes)
* Adherence
* In a vaccine study, adherence is slightly different
* Some vaccines may have a schedule e.g. top-ups, multiple injections
* Many vaccines are a one-off event
* So adherence is often **categorical** i.e. had vaccine or did not have vaccine
* Why is adherence important to measure and report?
55
_Analysis strategies_
* 4th participant with bad outcome, non-compliant
* What do we do with data?
* Per ... (remove the person entirely - only examine data of compliant people)
* As ... (examines participants in group they actually conformed to)
* ... to treat (all participants in group they were randomly assigned to)
* Results are shown
* 4th participant with bad outcome, non-compliant
* What do we do with data?
* Per **protocol** (remove the person entirely - only examine data of compliant people)
* As **treated** (examines participants in group they actually conformed to)
* **Intention** to treat (all participants in group they were randomly assigned to)
56
_Analysis strategies_
* 4th participant with bad outcome, non-...
* What do we do with data?
* Per protocol (... the person entirely - only examine data of compliant people)
* As treated (examines participants in group they actually ... to)
* Intention to treat (all participants in group they were randomly assigned to)
* Results are shown
* 4th participant with bad outcome, non-**compliant**
* What do we do with data?
* Per protocol (**remove** the person entirely - only examine data of compliant people)
* As treated (examines participants in group they actually **conformed** to)
* Intention to treat (all participants in group they were randomly assigned to)
57
_Analysis strategies_
* 4th participant with bad outcome, non-compliant
* What do we do with data?
* ... protocol (remove the person entirely - only examine data of compliant people)
* As ... (examines participants in group they actually conformed to)
* Intention to ... (all participants in group they were ... ... to)
* Results are shown
* 4th participant with bad outcome, non-compliant
* What do we do with data?
* **Per** protocol (remove the person entirely - only examine data of compliant people)
* As **treated** (examines participants in group they actually conformed to)
* Intention to **treat** (all participants in group they were **randomly assigned** to)
58
_Analysis strategies_
* 4th participant with bad outcome, non-compliant
* What do we do with data?
* Per protocol (remove the person entirely - only examine data of compliant people)
* As treated (examines participants in group they actually conformed to)
* Intention to treat (all participants in group they were randomly assigned to)
* Which is the best way to minimise bias?
* 4th participant with bad outcome, non-compliant
* What do we do with data?
* Per protocol (remove the person entirely - only examine data of compliant people)
* As treated (examines participants in group they actually conformed to)
* **Intention to treat** (all participants in group they were randomly assigned to) - superior to minimise bias
59
... diagrams are good when conducting a RCT - analysis section, detail whether any exclusions (per protocol, intention to treat) - intention to treat is best
**Consort** diagrams are good when conducting a RCT - analysis section, detail whether any exclusions (per protocol, intention to treat) - intention to treat is best
60
_Patient perspective on research priorities_
* The traditional role of patients in research is
* As participants
* As funder/fundraisers
* More recently, patients are being recognised in more ... roles in research
* All major research councils/funders in health and medical research mandate the ... of patients and the public in the ... process
* Organisations such as INVOLVE and the James Lind Alliance are driving the public and patient involvement agenda
* Without such involvement, the priorities of funders and researchers may not match patients’ needs and preferences, may be less effective and may be less likely to be implemented
* The traditional role of patients in research is
* As participants
* As funder/fundraisers
* More recently, patients are being recognised in more **active** roles in research
* All major research councils/funders in health and medical research mandate the **involvement** of patients and the public in the **research** process
* Organisations such as INVOLVE and the James Lind Alliance are driving the public and patient involvement agenda
* Without such involvement, the priorities of funders and researchers may not match patients’ needs and preferences, may be less effective and may be less likely to be implemented
61
_Patient perspective on research priorities_
* The traditional role of patients in research is
* As participants
* As funder/fundraisers
* More recently, patients are being recognised in more active roles in research
* All major research councils/funders in health and medical research mandate the involvement of patients and the public in the research process
* Organisations such as INVOLVE and the James Lind Alliance are driving the public and patient involvement agenda
* Without such involvement, the priorities of funders and researchers may not match patients’ needs and preferences, may be less ... and may be less likely to be ...
* The traditional role of patients in research is
* As participants
* As funder/fundraisers
* More recently, patients are being recognised in more active roles in research
* All major research councils/funders in health and medical research mandate the involvement of patients and the public in the research process
* Organisations such as INVOLVE and the James Lind Alliance are driving the public and patient involvement agenda
* Without such involvement, the priorities of funders and researchers may not match patients’ needs and preferences, may be less **effective** and may be less likely to be **implemented**
62
_Patient perspective on research priorities_
* Priorities on-
* ... questions / focus
* ... / settings /services
* Research design and delivery
* Findings and interpretation
* Next steps
* Priorities on-
* **Research** questions / focus
* **Populations** / settings /services
* Research design and delivery
* Findings and interpretation
* Next steps
63
_Patient perspective on research priorities_
* Priorities on-
* Research questions / focus
* Populations / settings /services
* Research ... and delivery
* Findings and ...
* Next steps
* Priorities on-
* Research questions / focus
* Populations / settings /services
* Research **design** and delivery
* Findings and **interpretation**
* Next steps
64
_Patient perspective on research priorities_
* Priorities on-
* ... questions / focus
* ... / settings /services
* Research design and delivery
* Findings and interpretation
* ... steps
* Priorities on-
* **Research** questions / focus
* **Populations** / settings /services
* Research design and delivery
* Findings and interpretation
* **Next** steps
65
_Patient perspective on research priorities_
* Priorities on-
* ... questions / focus
* ... / settings /services
* Research design and ...
* ... and interpretation
* Next steps
* Priorities on-
* **Research** questions / focus
* **Populations** / settings /services
* Research design and **delivery**
* **Findings** and interpretation
* Next steps
66
_Patient perspective on research priorities_
* How to capture:
* Setting priorities
* Setting focus of funding
* Sitting on funding panels
* As ...
* Within individual research ... steering committees
* On ethical ... panels
* How to capture:
* Setting priorities
* Setting focus of funding
* Sitting on funding panels
* As **researchers**
* Within individual research **project** steering committees
* On ethical **review** panels
67
_Patient perspective on research priorities_
* How to capture:
* Setting ...
* Setting ... of funding
* Sitting on ... panels
* As researchers
* Within individual research project steering committees
* On ethical review panels
* How to capture:
* Setting **priorities**
* Setting **focus** of funding
* Sitting on **funding** panels
* As researchers
* Within individual research project steering committees
* On ethical review panels
68
_The role of qualitative research in health and medicine_
* Sets a patient-centred ...- challenges received wisdom and can generate new theory new ...
* Exploratory looking at the ‘...’, ‘...’ & ...’ questions rather than ‘ how many’, ‘how much’ or how frequently’
* Increasing awareness of social, cultural and environmental characteristics in outcomes
* Many of the most important issues faced by RCT participants—their feelings, hopes, and beliefs, for example—cannot be meaningfully reduced to numbers or adequately understood without reference to the Immediate context in which they live
* Sets a patient-centred **agenda**- challenges received wisdom and can generate new theory new **hypotheses**
* Exploratory looking at the **‘what’, ‘how’ & why’** questions rather than ‘ how many’, ‘how much’ or how frequently’
* Increasing awareness of social, cultural and environmental characteristics in outcomes
* Many of the most important issues faced by RCT participants—their feelings, hopes, and beliefs, for example—cannot be meaningfully reduced to numbers or adequately understood without reference to the Immediate context in which they live
69
_The role of qualitative research in health and medicine_
* Sets a patient-centred agenda- challenges received wisdom and can generate new theory new hypotheses
* Exploratory looking at the ‘what’, ‘how’ & why’ questions rather than ‘ how many’, ‘how much’ or how frequently’
* Increasing awareness of ..., cultural and ... characteristics in outcomes
* Many of the most important issues faced by ... ... —their feelings, hopes, and beliefs, for example—cannot be meaningfully reduced to numbers or adequately understood without reference to the Immediate ... in which they live
* Sets a patient-centred agenda- challenges received wisdom and can generate new theory new hypotheses
* Exploratory looking at the ‘what’, ‘how’ & why’ questions rather than ‘ how many’, ‘how much’ or how frequently’
* Increasing awareness of **social**, cultural and **environmental** characteristics in outcomes
* Many of the most important issues faced by **RCT participants**—their feelings, hopes, and beliefs, for example—cannot be meaningfully reduced to numbers or adequately understood without reference to the Immediate **context** in which they live
70
_The role of qualitative research in designing and conducting RCTs_
71
_The role of qualitative research in designing and conducting RCTs_
72
_The role of qualitative research in designing and conducting RCTs_
73
_Qualitative research in vaccine RCTs_
* Before an RCT: Park et al. (2012)
* Qualitative assessment of ... to participate in future HPV vaccine trials
* Most common motivator was ..., followed by potential health benefits
* Most common barriers were concerns about vaccine safety, mistrust of biomedical research, fear of acquiring HPV from the vaccine
* Outcomes:
* impact on future trial recruitment and consent processes,
* development of brief intervention to improve clinical trial literacy and ensure ethical participation
* Before an RCT: Park et al. (2012)
* Qualitative assessment of **willingness** to participate in future HPV vaccine trials
* Most common motivator was **altruism**, followed by potential health benefits
* Most common barriers were concerns about vaccine safety, mistrust of biomedical research, fear of acquiring HPV from the vaccine
* Outcomes:
* impact on future trial recruitment and consent processes,
* development of brief intervention to improve clinical trial literacy and ensure ethical participation
74
_Qualitative research in vaccine RCTs_
* Before an RCT: Park et al. (2012)
* Qualitative assessment of willingness to participate in future HPV vaccine trials
* Most common motivator was altruism, followed by potential health benefits
* Most common barriers were concerns about vaccine ..., ... of biomedical research, fear of ... HPV from the vaccine
* Outcomes:
* impact on future trial recruitment and consent processes,
* development of brief intervention to improve clinical trial literacy and ensure ethical participation
* Before an RCT: Park et al. (2012)
* Qualitative assessment of willingness to participate in future HPV vaccine trials
* Most common motivator was altruism, followed by potential health benefits
* Most common barriers were concerns about vaccine **safety**, **mistrust** of biomedical research, fear of **acquiring** HPV from the vaccine
* Outcomes:
* impact on future trial recruitment and consent processes,
* development of brief intervention to improve clinical trial literacy and ensure ethical participation
75
_Qualitative research in vaccine RCTs_
* Before an RCT: Park et al. (2012)
* Qualitative assessment of willingness to participate in future HPV vaccine trials
* Most common motivator was altruism, followed by potential health benefits
* Most common barriers were concerns about vaccine safety, mistrust of biomedical research, fear of acquiring HPV from the vaccine
* Outcomes:
* impact on future trial ... and ... processes,
* development of brief ... to improve clinical trial literacy and ensure ... participation
* Before an RCT: Park et al. (2012)
* Qualitative assessment of willingness to participate in future HPV vaccine trials
* Most common motivator was altruism, followed by potential health benefits
* Most common barriers were concerns about vaccine safety, mistrust of biomedical research, fear of acquiring HPV from the vaccine
* Outcomes:
* impact on future trial **recruitment** and consent **processes**,
* development of brief **intervention** to improve clinical trial literacy and ensure **ethical** participation
76
_Qualitative research in vaccine RCTs_
* After RCT: Masaryk & Hatoková (2016)
* Investigation why parenting ... appear to fail/sometimes increase vaccine ...
* Qualitative focus group asking female students and mothers about four pro-vaccine interventions; autism corrected information, disease risk information, disease narrative story intervention, disease image intervention
* Results-
* participants wanted more information and to understand different ...,
* participants were conscious that interventions might be trying to ... or emotionally blackmail them,
* participants felt that the information was too simplistic or not connected enough to topic of vaccinations, information might be about one case rather than general facts and evidence
* After RCT: Masaryk & Hatoková (2016)
* Investigation why parenting **interventions** appear to fail/sometimes increase vaccine **refusal**
* Qualitative focus group asking female students and mothers about four pro-vaccine interventions; autism corrected information, disease risk information, disease narrative story intervention, disease image intervention
* Results-
* participants wanted more information and to understand different **perspectives**,
* participants were conscious that interventions might be trying to **manipulate** or emotionally blackmail them,
* participants felt that the information was too simplistic or not connected enough to topic of vaccinations, information might be about one case rather than general facts and evidence
77
_Qualitative research in vaccine RCTs_
* After RCT: Masaryk & Hatoková (2016)
* Investigation why parenting interventions appear to fail/sometimes increase vaccine refusal
* Qualitative focus group asking female students and mothers about four pro-vaccine interventions; ... corrected information, ... risk information, disease ... story intervention, disease image intervention
* Results-
* participants wanted more information and to understand different perspectives,
* participants were conscious that interventions might be trying to manipulate or emotionally blackmail them,
* participants felt that the information was too simplistic or not connected enough to topic of vaccinations, information might be about one case rather than general facts and evidence
* After RCT: Masaryk & Hatoková (2016)
* Investigation why parenting interventions appear to fail/sometimes increase vaccine refusal
* Qualitative focus group asking female students and mothers about four pro-vaccine interventions; **autism** corrected information, **disease** risk information, disease **narrative** story intervention, disease image intervention
* Results-
* participants wanted more information and to understand different perspectives,
* participants were conscious that interventions might be trying to manipulate or emotionally blackmail them,
* participants felt that the information was too simplistic or not connected enough to topic of vaccinations, information might be about one case rather than general facts and evidence
78
_Qualitative research in vaccine RCTs_
* After RCT: Masaryk & Hatoková (2016)
* Investigation why parenting interventions appear to fail/sometimes increase vaccine refusal
* Qualitative focus group asking female students and mothers about four pro-vaccine interventions; autism corrected information, disease risk information, disease narrative story intervention, disease ... intervention
* Results-
* participants wanted more information and to understand different perspectives,
* participants were conscious that interventions might be trying to manipulate or emotionally blackmail them,
* participants felt that the information was too ... or not connected enough to topic of ..., information might be about one case rather than general facts and evidence
* After RCT: Masaryk & Hatoková (2016)
* Investigation why parenting interventions appear to fail/sometimes increase vaccine refusal
* Qualitative focus group asking female students and mothers about four pro-vaccine interventions; autism corrected information, disease risk information, disease narrative story intervention, disease **image** intervention
* Results-
* participants wanted more information and to understand different perspectives,
* participants were conscious that interventions might be trying to manipulate or emotionally blackmail them,
* participants felt that the information was too **simplistic** or not connected enough to topic of **vaccinations**, information might be about one case rather than general facts and evidence
79
_Qualitative research in vaccine RCTs_
* After RCT: Masaryk & Hatoková (2016)
* Investigation why parenting interventions appear to fail/sometimes increase vaccine refusal
* Qualitative focus group asking female students and mothers about four pro-vaccine interventions; autism corrected information, disease risk information, disease narrative story intervention, disease image intervention
* Results-
* participants wanted more information and to understand different perspectives,
* participants were conscious that interventions might be trying to manipulate or emotionally blackmail them,
* participants felt that the information was too simplistic or not connected enough to topic of vaccinations, information might be about one case rather than general facts and evidence
* After RCT: Masaryk & Hatoková (2016)
* Investigation why parenting interventions appear to fail/sometimes increase vaccine refusal
* Qualitative focus group asking female students and mothers about four pro-vaccine interventions; autism corrected information, disease risk information, disease narrative story intervention, disease image intervention
* Results-
* participants wanted more information and to understand different perspectives,
* participants were conscious that interventions might be trying to manipulate or emotionally blackmail them,
* participants felt that the information was too simplistic or not connected enough to topic of vaccinations, information might be about one case rather than general facts and evidence
80
_Summary - RCTs: Vaccines_
* ... = third variable causes a spurious association between two other variables
* Best defence against ... is an RCT
* Randomisation should balance known and unknown ... across groups
* RCTs are complex studies with many design features
* Many remaining sources of bias in RCTs even with randomisation
* Selection bias
* Participants don’t match target population / participants not identical at start of trial
* Recruitment, retention, randomisation and sampling procedures against selection bias
* Observer/detection bias
* Outcomes don’t capture those of interest / outcomes measured differently in different groups
* Blinding and analytic techniques (e.g. intention-to-treat) guard against observer/ detection bias
* The patient perspective on research priorities is an important feature before, during and after RCTs
* Qualitative research is one way of trying to capture patient perspectives across RCTs
* **Confounding** = third variable causes a spurious association between two other variables
* Best defence against **confounding** is an RCT
* Randomisation should balance known and unknown **confounder** across groups
* RCTs are complex studies with many design features
* Many remaining sources of bias in RCTs even with randomisation
* Selection bias
* Participants don’t match target population / participants not identical at start of trial
* Recruitment, retention, randomisation and sampling procedures against selection bias
* Observer/detection bias
* Outcomes don’t capture those of interest / outcomes measured differently in different groups
* Blinding and analytic techniques (e.g. intention-to-treat) guard against observer/ detection bias
* The patient perspective on research priorities is an important feature before, during and after RCTs
* Qualitative research is one way of trying to capture patient perspectives across RCTs
81
_Summary - RCTs: Vaccines_
* Confounding = third variable causes a spurious association between two other variables
* Best defence against confounding is an RCT
* Randomisation should balance known and unknown confounder across groups
* RCTs are complex studies with many design features
* Many remaining sources of bias in RCTs even with randomisation
* ... bias
* Participants don’t match target population / participants not identical at start of trial
* Recruitment, retention, randomisation and sampling procedures against this bias
* .../... bias
* Outcomes don’t capture those of interest / outcomes measured differently in different groups
* Blinding and analytic techniques (e.g. intention-to-treat) guard against this bias
* The patient perspective on research priorities is an important feature before, during and after RCTs
* Qualitative research is one way of trying to capture patient perspectives across RCTs
* Confounding = third variable causes a spurious association between two other variables
* Best defence against confounding is an RCT
* Randomisation should balance known and unknown confounder across groups
* RCTs are complex studies with many design features
* Many remaining sources of bias in RCTs even with randomisation
* **Selection** bias
* Participants don’t match target population / participants not identical at start of trial
* Recruitment, retention, randomisation and sampling procedures against selection bias
* **Observer/detection** bias
* Outcomes don’t capture those of interest / outcomes measured differently in different groups
* Blinding and analytic techniques (e.g. intention-to-treat) guard against observer/ detection bias
* The patient perspective on research priorities is an important feature before, during and after RCTs
* Qualitative research is one way of trying to capture patient perspectives across RCTs
82
_Summary - RCTs: Vaccines_
* Confounding = third variable causes a spurious association between two other variables
* Best defence against confounding is an RCT
* Randomisation should balance known and unknown confounder across groups
* RCTs are complex studies with many design features
* Many remaining sources of bias in RCTs even with randomisation
* Selection bias
* Participants don’t match target population / participants not identical at start of trial
* ..., retention, ... and sampling procedures against selection bias
* Observer/detection bias
* Outcomes don’t capture those of interest / outcomes measured differently in different groups
* ... and analytic techniques (e.g. ...-to-treat) guard against observer/ detection bias
* The patient ... on research priorities is an important feature before, during and after RCTs
* Qualitative research is one way of trying to capture patient perspectives across RCTs
* Confounding = third variable causes a spurious association between two other variables
* Best defence against confounding is an RCT
* Randomisation should balance known and unknown confounder across groups
* RCTs are complex studies with many design features
* Many remaining sources of bias in RCTs even with randomisation
* Selection bias
* Participants don’t match target population / participants not identical at start of trial
* **Recruitment**, retention, **randomisation** and sampling procedures against selection bias
* Observer/detection bias
* Outcomes don’t capture those of interest / outcomes measured differently in different groups
* **Blinding** and analytic techniques (e.g. **intention**-to-treat) guard against observer/ detection bias
* The patient **perspective** on research priorities is an important feature before, during and after RCTs
* Qualitative research is one way of trying to capture patient perspectives across RCTs
83
_Summary - RCTs: Vaccines_
* Confounding = third variable causes a spurious association between two other variables
* Best defence against confounding is an RCT
* Randomisation should balance known and unknown confounder across groups
* RCTs are complex studies with many design features
* Many remaining sources of bias in RCTs even with randomisation
* Selection bias
* Participants don’t match target population / participants not identical at start of trial
* Recruitment, retention, randomisation and sampling procedures against selection bias
* Observer/detection bias
* Outcomes don’t capture those of interest / outcomes measured differently in different groups
* Blinding and analytic techniques (e.g. intention-to-treat) guard against observer/ detection bias
* The patient perspective on research priorities is an important feature ..., ... and ... RCTs
* ... research is one way of trying to capture patient perspectives across RCTs
* Confounding = third variable causes a spurious association between two other variables
* Best defence against confounding is an RCT
* Randomisation should balance known and unknown confounder across groups
* RCTs are complex studies with many design features
* Many remaining sources of bias in RCTs even with randomisation
* Selection bias
* Participants don’t match target population / participants not identical at start of trial
* Recruitment, retention, randomisation and sampling procedures against selection bias
* Observer/detection bias
* Outcomes don’t capture those of interest / outcomes measured differently in different groups
* Blinding and analytic techniques (e.g. intention-to-treat) guard against observer/ detection bias
* The patient perspective on research priorities is an important feature **before, during and after RCTs**
* **Qualitative** research is one way of trying to capture patient perspectives across RCTs
84
The ... ... on research priorities is an important feature before, during and after RCTs
The **patient perspective** on research priorities is an important feature before, during and after RCTs
85
... research is one way of trying to capture patient perspectives across RCTs
**Qualitative** research is one way of trying to capture patient perspectives across RCTs
