1
Q
Definition of incidence of a disease
A
- The rate at which new cases occur in a population at risk during a specific time period
- The measure of the populations average risk of disease
2
Q
Definition of prevalence
A
The proportion of a population who have a disease at a specific moment of time
(Lowered by death and cure)
3
Q
Define the relationship between incidence and prevalence
A
Prevalence = incidence x mean duration of disease
4
Q
How do you compare the incidence in two different groups?
A
Incidence rate ratio
5
Q
How do you interpret the incidence rate ratio?
A
IRR = (8/40000) / (3/30000) = 2
Therefore, you are 2 times as likely to die in an exposed region than in the unexposed region
6
Q
What is a confounding factor?
A
A factor which is linked to both the outcome and the exposure but is not on the causal pathway
7
Q
How do you deal with confounding from age and sex?
A
Use a standardised mortality ratio or standardises morbidity ratio
8
Q
Define variation
A
Difference between the observed value and the actual value
9
Q
What allows for variations?
A
Error factors
10
Q
What are confidence intervals?
A
The values between which we are 95% confident that our actual value lies between
11
Q
How do you obtain confidence intervals?
A
- Calculate incidence rate/incidence rate ratio/SMR
- Calculate error factors
- Calculate confidence intervals
- Interpret confidence intervals
12
Q
How do you calculate confidence intervals?
A
Upper bound value = value x error factor
Lower bound value = value/error factor
13
Q
Interpreting a 95% confidence interval when null lies within values
A
- is null hypothesis within CI (Yes)
- are 95% confident that the true value lies within values as it includes the null hypothesis
- p>0.05
- cannot reject the null hypothesis
- results are not statistically significant
14
Q
Interpreting a value that lies outside the CI
A
- null hypothesis within CI (no)
- 95% certain that true value lies within CI which does not contain hull hypothesis value
- p< 0.05
- can reject the null hypothesis
- results are statistically significant, unlikely to have occurred due to chance
15
Q
What does the rate measure?
A
Absolute risk
16
Q
What does a ratio measure?
A
Relative risk
17
Q
What does a p value < 0.05 signify?
A
Data is not due to chance
Substantial evidence against null hypothesis
Should reject null hypothesis
Observations are statistically significant
17
Q
What does a p-value > 0.05 signify?
A
Data is due to chance
No evidence to reject null hypothesis (can’t accept though)
Results are due to chance
Observations are not statistically significant
18
Q
What is bias?
A
The deviations of results from the truth via certain processes
19
Q
What is selection bias?
A
Error due to systematic differences in the way that the data was collected
- allocation bias
- healthy worker effect
- non-random sample of the population
20
Q
What is information bias?
A
Bias due to measurement errors
- recall bias
- publication bias
21
Q
What are cohort studies?
A
Recruit disease-free individuals and classify based on their exposure.
Follow up for extended periods
Calculate incidence rates
22
Q
Advantages of cohort studies
A
- Compares outcomes based on one exposure
- Can study a range of outcomes for each exposure
- Limits bias
- Measures incidence directly
- Establishes that exposure precedes the outcome
- Good for rare exposures
23
Q
What are the types of cohort studies?
A
Prospective – recruit disease free individuals then follow up
Retrospective – calculate exposure status from historical records then follow up
24
Disadvantages of cohort studies
1. Expensive -- large sample sizes
2. Not good for rare diseases
3. Time consuming
4. Prone to losses to follow up
25
What are the benefits and disadvantages of retrospective studies?
Are quicker
| More likely to be affected by confounding
26
What type of comparisons can you have with cohort studies?
Internal and external
27
What are the differences between internal and external cohort studies?
Internal has sub-cohorts within the original cohort and you compare an exposed group with an unexposed group e.g. Gulf war syndrome in army vets
External compares the cohort with the rest of the population -- uses SMR to remove co founders
28
What is a case control study?
Identify cohort on basis of disease (cases)
Identify a cohort of controls who do not have the disease (controls)
Compare the exposure status of both the cases and the controls
29
How do you analyse case control studies and how do you increase the precision of it?
Odds ratio
| -- increase the number of controls up to five per case
30
Advantages for case control studies
1. Good for rare disease but not rare exposures
2. Quicker to perform so are cheaper
3. Can study multiple exposure for one disease
4. Can do nested case control studies (case control within cohort)
31
How do you calculate the odds ratio?
Exposed cases X unexposed control/ exposed control X unexposed cases
A x D/ B x C
32
What is a nested case control?
A case control study within a cohort study -- calculate incidence rate
33
What is the definition of Bradford Hill's Criteria?
Minimum conditions needed to establish a causal relationship between two items
34
What are the nine Bradford Hill's Criteria?
1. Strength of association - stronger association = more likely
2. Specificity of association - only with specific factor
3. Consistency of association - observed in different studies
4. Temporal sequence - exposure proceeds outcome
5. Dose response - different levels of exposure lead to different risk of getting outcome
6. Reversibility - removing exposure reduced risk of outcome
7. Coherence of theory - association conforms with current knowledge
8. Biological plausibility - biologically plausible mechanism is demonstrated
9. Analogy - analogy exist with other disease (similar disease has similar outcome)
35
Define clinical trial
Planned experience involving patients to find the most appropriate method of treatment for future patients with a given medical condition
36
What is the difference between controlled trial and cohort study?
Controlled trial -- investigator does something
| Cohort study -- investigator observes only
37
Purpose of a clinical trial
Provide reliable evidence of treatment efficacy and safety
38
What are the requirements of a clinical trial?
Must be fair, controlled and reproducible
| -- gives a fair comparison of safety and efficacy
39
How can two factors be linked?
Due to:
1. Unknown confounders
2. Common cause
3. Reverse causality (think X causes Y but really Y causes X)
4. True causal association
40
What is the definition of epidemiology?
The study of the distribution and determinants of health-related states or events in specified populations and the application of this study to the control of health problems.
41
What are the items in a hierarchy of evidence?
1. Systematic reviews of meta-analysis
2. Randomised control trials
3. Cohort studies
4. Case-control studies
5. Cross-sectional surveys
6. Case reports
42
What do you compare your new treatment with in a RCT?
If there is an existing treatment, compare it with that.
| If there is no treatment, use a placebo.
43
What are the steps involved in a randomised controlled trial?
1. Identify a source of eligible patients
2. Invite patients and gain consent
3. Allocate to group -- new or standard/placebe treatment randomly
4. Follow-up each group equally
5. Try to keep all the patients in the trial
6. Assess treatments using same criteria
7. Compare results:
- - how big is the difference in outcomes
- - is difference attributable to treatment?
44
What can non-random allocation of patients in a RCT lead to?
Confounding factors cause difference in the groups compared
45
What does random allocation in RCTs give?
Minimal allocation bias -- equal likelihood of being in each group
Minimal confounding -- groups have same size and characteristics
46
What can you use to randomly allocate people into groups?
Random number tables, computer generated random number
47
What types of blinding can you have and when is blinding difficult?
Single, double and triple
| -- in surgery vs. non-surgery or in changes in lifestyle
48
How can knowledge of the treatment confound results in an RCT?
Patient alters own behaviour
Clinician alters treatment or care to suit the treatment
Investigator may alter approach when making comparisons
49
Describe the placebo effect
The patient may feel an improvement in their health if they feel that someone is doing something to help them even if the therapy is irrelevant to the patients condition
50
What is a placebo?
An inert substance that has the same characteristics as the treatment
51
What are the two types of losses?
Unfortunate -- patient chooses not to continue
| Appropriate -- clinical condition, requires the removal from trial
52
How can you avoid losses to follow up?
Clear explanation of requirements, treatment and time commitments.
Don't offer rewards etc.
Make follow up as quick and simple as possible
Give patient to opportunity to ask questions
Maintain contact with patients
53
What are the ethical implications of using a placebo?
1. Should only be used when there is no standard treatment
2. Use of placebo is a form of deception
3. Patient must be informed that they may receive a placebo
54
Why may differences in outcomes between treatment groups occur?
1. By chance
2. Patient may know what treatment they are on - altered behaviour
3. Clinician knows treatment & changes secondary treatment
4. Assessor knows the treatment & investigates differently for each group
5. One treatment is better than the other
55
What twelve characteristics must outcome measures have?
Appropriate and relevant
Valid and attributable -- effect is linked to treatments
Sensitive and specific -- changes are detected accurately
Reliable and robust -- outcome is messed by diff people in diff places
Simple and sustainable -- method of measurement is carried out easily
Cheap and timely
56
When does non-compliance occur?
Occurs when patients do not adhere to treatment as prescribed or they may not take it at all.
57
Hw can non-compliance be reduced?
Clear instructions for treatment
Checks on compliance e.g urine and blood test and table counts
Ask about side-effects and effects
58
What are the two types of randomised trial?
Explanatory and pragmatic
59
Define an explanatory trial
'As-treated' analysis
- - is the physiological action of the drug better than the new drug?
- - non-compilers are excluded
- - trial is affected by confounding as groups are no longer allocated randomly
60
Define a pragmatic trial
'Intention-to-treat' analysis
- - would replacing the standard drug with the new drug benefit patients in clinical practice?
- - see real world effect of the treatment
- - should analyse the whole group regardless of whether they took the drugs or not
- - randomisation is preserved
61
What analysis should be used for RCTs?
Intention-to-treat analysis
- - randomisation is preserved
- - confounding does not affect results
- - represents standard clinical practice
62
What are the three ways that you can define outcomes?
1. PATHO-PHYSIOLOGICAL e.g. Tumour size, thyroxin levels
2. CLINICALLY DEFINED e.g. Mortality, morality, disability
3. PATIENT FOCUSSED e.g. Quality of life (included in all cancer trials), psychological and social well-being, satisfaction
63
When do you measure outcomes in a RCT?
Beginning -- baseline measurement
Throughout trial -- possible and adverse effects (is one group disadvantaged, are individuals being harmed?)
End of trial -- final measurement of outcomes
64
Why does non-compliance occur?
```
Misunderstood instructions
Don't like taking treatment
Think treatment isn't working
Prefer another treatment
Can't be bothered to take treatment
```
65
Describe the differences between as-treated vs. intention-to-treat analysis
As-treated give larger sizes of effect
| Intention-to-treat gives smaller, more realistic sizes of effect
66
What are the four ethical principles that govern individual care?
Principal of beneficence -- do good
Principal of non-maleficence -- do no harm
Principal of autonomy -- let the patient decide
Principal of justice -- be fair
67
What issues should be considered to have an ethical clinical trial?
```
Clinical equipoise
Scientifically robust
Ethical recruitment
Valid consent
Voluntariness
```
68
What is clinical equipoise?
Reasonable uncertainty into which drug is better for the patient
- - not subjecting patients to a treatment that is less effective or harmful
- - includes non-intervention
69
Describe 'scientifically robust'
The pursuit of knowledge for the good of the general population
- - address relevant and important issue
- - ask a valid question
- - appropriate design and protocol
- - have potential to reach sound conclusions
- - justify use of comparative treatment
- - have acceptable risks of harm compared to future benefits
- - have provisions to monitor patient safety & well-being
- - have arrangements for appropriate reporting and publication
70
What are the two main issues involved in ethical recruitment
Inappropriate inclusion and inappropriate exclusion
71
Give example of inappropriate inclusion in RCTs
1. Participants who are unlikely to benefit e.g. AIDS treatment in Africa
2. Participant with a high risk of harm compared to potential benefits e.g. Pregnant women
3. Participants likely to be excluded from analysis e.g. Small sub-groups of the population
72
Give examples of inappropriate exclusions in RCTs
1. People who differ from ideal homogenous group e.g. Non-white people, women, elderly (co-morbidities so hard to isolate disease)
2. People who are difficult to obtain valid consent from e.g. Immigrants (language issues), children, mentally ill, prisoners
73
Describe valid consent
Patients must have sufficient knowledge given by a knowledgeable informant and have been given a cooling-off period.
Must be able to ask questions and know they can opt out at any point.
Must get written and verbal consent.
74
What do you need in order to gain consent?
Informed participant
Competent decision maker
Legitimate authoriser
-- usually the same person unless child, elderly, mentally ill when you can have different people in each role
75
What is signed consent evidence of?
Evidence of valid consent but it is not valid consent in its own right.
Consent must be both written and verbal.
76
Define voluntariness
For consent to be valid, the decision should be free from coercion and manipulation as well as the perception that coercion and manipulation took place.
77
What are examples of coercion?
Non-access to best treatment
Lower quality of care
Disinterest of clinician
78
Examples of manipulation
Exploitation of emotional state
Distortion of information
Financial inducements
79
What is the main responsibility of a research ethics committee?
The ensure that research respects the dignity, well-being safety and rights of participants
80
What factors do research ethics committees focus on?
1. Scientific design and conduct of study
2. Recruitment of participants
3. Care and protection of participants
4. Protection of the confidentiality of participants
5. Informed consent process
6. Community consideration (must be able to use treatment in the future)
81
Why do we have a moral obligation to participate in clinical trials?
We have benefitted from previous studies so we have an obligation to take part to benefit the patients of the future
82
What is a systematic review?
Secondary research that is an overview of primary studies that used explicit and reproducible methods
-- large no. of studies identified then narrowed down to most relevant and credible
83
Define meta-analysis
A quantitative synthesis of results of two or more primary studies that addressed the hypothesis in the same way
-- provides an overall, combined value for all the primary studies with confidence intervals
84
What type of studies do systematic reviews usually combine?
Cohort studies, randomised control trial and case-control studies
85
Give the advantages of systematic reviews
- - explicit methods reduce bias and exclusion of poor quality studies
- - large amount of info is assimilated quickly
- - reduction in time between research discovery end implementation in clinical practice
- - used in evidence based practice guidelines
86
What are the key aspects of a systematic review?
It is:
Transparent
Reproducible
Explicit
87
Describe the characteristics of a systematic review
Has a clearly focussed question
Explicit statements about: type of study, participants, interventions and outcome measures
Systematic search for literature
Appraisal of trials
Synthesis of conclusion and outcomes, sometimes with meta-analysis
88
What is the purpose of a meta-analysis?
- - allows synthesis of large number of study results
- - systematically collate study results
- - reduce problems of interpretation due to variation in sampling
- - quantify effect sizes and uncertainty as pooled estimate
89
What does weighting do in meta-analysis?
Allows to to compare sizes of studies, how uncertain reviewers are about odds ratio and how important they are
E.g. Smaller error factor = greater weight to result
90
Why are systematic reviews important?
Are crucial in evidence based medicine
91
How is the data from a meta-analysis collated?
In a forest plot
92
How do you interpret a forest plot?
- - odds ratios and CIs are given for each study (square with line)
- - size of square equates to weight given to study
- - diamond is pooled estimate (centre is OR, width is CI)
- - solid line is null hypothesis
93
What causes heterogeneity between studies?
Studies are not identical and are usually have variation within the data
94
What are the two models you can use in meta-analysis?
Fixed effects model
| Random effects model
95
What is the fixed effects model?
Assumes studies are homogenous and variation is due to within study variation
-- assumes studies are estimating exactly the same effect size
96
What is the random effects model?
Assume studies are heterogenous and and variation is due to within-study and between-study variation.
-- assumes studies are investigating similar effect size
97
How can the quality of studies used for systematic review be affected?
Poor study design
Poor design protocol
Poor protocol implementation
98
How can you determine publication bias?
Using a funnel plot for studies used in a systematic review
Well-balanced review (published and unpublished) will show a balanced funnel shape
A biased review will vary in shape
99
How do you ensure that your systematic review is of a high quality?
Include studies above a quality standard
| Assess impact of quality on pooled effect
100
Disadvantages for case control studies?
Does not establish that ensure precedes outcome
Bad for rare exposures
Prone to selection and information bias
Relative risk only
