SPMM - Study Designs Flashcards
What is ecological fallacy?
Ascribing the characteristics of a group to all individuals in the group –> thus drawing subject level conclusions based on group observations
Name some study designs that belong to:
- Descriptive research
- Analytical research
- Experimental research
Descriptive (describe and do not test causal relationships)
- Case reports/series
- Cross sectional studies
- Prospective longitudinal studies
Analytical:
- Case control studies
- Cohort studies
- Ecological studies
Experimental
- controlled trials
- uncontrolled trials
Name some pros and cons of Case-Control studies?
Pros:
- Cheaper
- Less time consuming
- No exposure to new risks
- Can assess different exposures at once
- Good for rare cases where exposure may be common but chance of disease occuring following exposure is not certain
- No attrition problems
Cons:
- Difficulties with selection and recall bias
- Selecting controls is difficult
- Establishing temporality is challenging
- Incidence cannot be assessed - odds ratio provided rather than relative risk
- Cannot prove causality
Name some important features to adhere to for a well designed case-control study?
- Strict diagnostic criteria to identify cases
- Appropriately matched controls (for sex, age and other characteristics). Can be done group wise/pair wise. Note overmatching may actually reduce risk by controlling for factors related to the exposure/causal factors. Overmatching also makes it difficult to recruit controls
- Not necessary to increases ratio from 4 controls : 1 case - increases above this do not increase statistical power
When may a cohort study be appropriate? (in terms of exposure frequency & chance of disease after)
For rarer exposures but ones where chance of disease after is high
What does an internal control mean in a cohort study?
Where control is still exposed but exposure is under a threshold dose (i.e. 1 pack a day vs. 2 packs a day)
Can cohort studies calculate relative risk?
Yes
What are the pros and cons of cohort studies?
Pros:
- Less selection and recall bias compared to case-controls
- Good for studying multiple effects of one exposure
- Temporality can be established more accurately
- Better assessment of causal relationship than case-controls
- Can calculate incidence and relative risk
- Dose response relationship of exposure can be assessed
- Can assess natural disease progression
Cons:
- Expensive and time consuming
- Not good for rare diseases (need to recruit significant numbers)
- Cannot calculate incidence
- Drop out and attrition
- Can only assess one etiological factor at a time
What is a nested cohort study?
One which cases and controls are recruited from within one existing defined cohort (i.e. blood results)
They are cheaper and easier conduct but can still be precise
Describe verification (work up bias)
A type of bias whereby the decision to perform a gold-standard diagnostic (reference) test is influenced by the results of the initial assessed test
Commonly negative results of the initial test may mean the gold-standard test is not performed (Negative d-dimer - no CTPA)
Thereby more false negatives may not be detected
For biological efficacy what analysis may be best conducted?
Per protocol analysis - to see the biological efficacy need to analyse those who took the drug
Note this does not relate to clinical efficacy where ITT analysis would be best conducted
What do secondary outcomes test?
An additional hypothesis
What is a minimisation allocation scheme?
Matching candidates based on the criteria of those already allocated
What is best case/worst case scenario?
Sensitivity analysis conducted for when patients are lost to follow up
Firstly all patients who are lost are assumed to have good outcomes (best case) then assumed to have bad outcomes (worst case). Each analysis is run - if positive results persist after worst case we can be reassured trial results favoured
Attrition bias is when those lost to follow up differ from those left in the trial (migration bias also termed)
Outline the different types of randomisation?
- Simple - i.e. computer generated list
- Block - randomisation occurs in groups of certain number (larger the block size the harder to predict assignment)
- Stratified - baseline characteristics are stratified to ensure an equal spread in intervention/control groups. Larger the sample size the less gain in precision through stratification
- Cluster - units of randomisation are treatment centres/catchment zones. As patients in each cluster are not independent of each and thus more likely to respond to a treatment there is loss of statistical power. To try and resolve this effective sample size is used > actual sample size. This is calculated using the degree of similarity between participants in each cluster on an outcome measure.
Quasi-randomisation - date of birth, alternate numbers etc
When is minimisation used?
- Wanting to do stratified randomisation but small sample size and worried about mismatch of confounders across treatment groups
- Cluster randomisation
Minimisation is not true randomisation - computerised schemes can reduce bias
Why is randomisation used?
- Allows us to use probability theory
- Allows blinding
- Random distribution of baseline characteristics
- Eliminates effect bias
Name some features of sound randomisation
- Future sequences not predictable from past
- Reproducible
- Allocation is concealed
- Can detect departures from documented procedures
- Can document assignment processes
What is a patient preference trial?
Patients get to choose which group randomised to, if no preference they get randomised. Analysis should be limited to those randomised however data obtained from both wider observational groups. Can analyse the impact of motivation for a certain treatment on outcome
Can help recruitment however complex to conduct the trial
Describe when informed consent is done in Zelen’s modified RCT?
Following randomisation - normally consent done before for ethical reasons however participants may drop out if they feel they are not going to get their preferred treatment.
MRC does not accept Zelen modified RCT designs
Are larger or smaller sample sizes required for non-inferiority RCTs?
Larger - since the alternative hypothesis is no difference between groups, effect size of 0 (in theory sample should be infinity).
In these trials it is best to report per-protocol analysis and intention to treat as ITT may blur actual differences between groups
What do pragmatic RCTs assess for?
Effectiveness of a drug - how it works in the real world (not efficacy how it works in ideal circumstances)
Name some features of pragmatic RCTs?
(1) Select clinically relevant alternative interventions to compare,
(2) Include a diverse population of study participants,
(3) Recruit participants from heterogeneous practice settings
(4) Collect data on a broad range of health outcomes.
(5) They do not tell how well a drug works (EFFICACY) – they inform how EFFECTIVE is the intervention in the real world.
(6) Recruit based on presentation > diagnosis
Name the 6 conditions of causality as proposed by Bradford and Hill
- Temporal association
- Dose response relationship
- Specificity of association - of order
- Consistency of association
- Biological plausibility
- Strength of association
- Absence of reverse causality
What does the mantel-haenszel method aim to do?
Adjust for confounding when analysing the relationship between a dichotomous risk factor and dichotomous outcome variable
When is matching required?
Case control studies and small studies
Not for RCTs (randomisation aimed to reduce need), extremely hard for large cohort studies and not possible for ecological studies or cross-sectional surveys
Describe Koch’s criteria for causality?
Consistency
Specificity - agent not found in other diseases
Biological coherence
Predictive or experimental performance
-> These were designed for infectious diseases following a causal germ
Name Melvyn Susser’s criteria of causality?
Criteria:
- Association
- Directionality
- Time-order (reversal gets rid of putative effect)
The 5 categories are strength, specificity (both in the cause and in the effect); consistency (measured using replicability); predictive performance; and coherence or plausibility (with theoretical; factual; biological; statistical coherence as subcategories)
Outline the characteristics of a confounder?
Related to exposure
Related to outcome in - susceptibility or prognosis
Not on the causal pathway
Different distribution in groups analysed can be central tendency (mean) or variation (standard deviation)
Methods to control for confounders?
- Randomisation controls for known/unknown
- Matching
- Stratification
- Multivariate analysis (post-hoc)
What is the Pygmalion effect?
The pygmalion effect is the also known as the experimenter expectancy effect. This refers to through the subjects awareness of the experimenters hypothesis she may change her behaviour in a way closer to the hypothesis
What is detection bias?
Also known as surveillance bias is when a group is followed up more closely than another group therefore more detections may be made
What is Neyman bias?
Incidence-prevalence bias - a form of selection bias
When studying risk factors and causation we need to look at incidence > prevalence. If we look at prevalent cases the risk factor may be under-represented if it contributes to death
How may selection bias be reduced?
Can be by randomisation processes or more even diagnostic detection methods
Name a couple of analysis bias
Contamination bias - when participants change groups during a study
Attrition bias - minimised by doing ITT analysis
What is reporting bias?
A type of measurement bias where cases or controls are less likely to report exposure due to attitudes/perceptions
What is observer bias?
If the researcher knows the participant is a certain group he may come to a different judgement (i.e. depression higher if knows in the placebo group)
Describe the steps in grounded theory?
- Data is collected and constantly compared
- From the comparisons new categories are created until no more can be made “theoretical saturation”
- New data is collected using the new categories “theoretical sampling” and this data tests the categories
Grounded theory is a method of generating theories/using qualitative methods
What is action research?
PAR or action research involves a blurring of the lines between researchers and the researched.
Here the researcher and groups explore their own personal belongings and socio-cultural experiences
Compare structured, semi and unstructured interviews?
Structured - tight schedule of questions
Semi-structured - the interviewer will have a list of topics but can modify the order and how they are phrased - the questions are open ended
Unstructured (in-depth) only a limited number of topics and how these are asked are formed by the participants responses to previous questions
How can reliability be improved in qualitative studies?
By triangulation and member checking e.g. using more than one researcher to code the findings
How can saturation influence the sample size needed for qualitative research?
Saturation indicates maximum data has been collected and no further participants are required
Whats the difference between emic and etic perspectives in ethnography?
emic - perspective of individual from cultural group about the cultural group
etic - perspective of an individual outside of the cultural group about the group
Name some factors that contribute to the weighting of individual studies in a meta-analysis
- Sample size
- Impact factor of journal
- Precision of results
- Methodological rigour of studies
Describe the difference between fixed effects and random effect analysis in meta-analysis?
Fixed effects assumes that all studies show a common effect and any variation between them is due to random error in the studies. It can therefore only be used if heterogeneity is excluded between by testing for it
Random effects assumes that different studies show different effects that are normally distributed around the mean while helpful a a random effects gives proportionally more weight to smaller studies with wider confidence intervals and increased risk of publication bias
What is a cost benefit analysis?
When two or more different interventions with different outcomes are compared - converted into monetary purposes
What are the differences between average cost effectiveness ratio and incremental cost effectiveness ratio?
Average cost effectiveness ratio is just for the intervention of interest = cost of the intevention/effect
Incremental cost effectiveness ratio
= cost of intervention - cost of control / effect of intervention - effect of control
Name some sensitivity analyses conducted in economic analysis?
One way analysis
Bootstrapping
Monte carlo simulations
Time trade off measures
An economic analysis makes several assumptions inc. standard inflation, discount rates for money and sensitivity analyses tests these
Which is the most cost effective quadrant on an incremental cost effectiveness plane?
Southeast
What is a standard gamble measurement?
Method of establishing the utility of a specified health state
For chronic health states individuals have to choose between the certainty of the health state for a period of time vs a gamble that is the probability of a return to full health and the probability of (1 - p) of immediate death
What are implicit costs?
The indirect costs of using the next best alternative that could have been put in place with the same resources
- method of estimating opportunity costs
- opportunity costs are the differences in costs of using the treatment of choice
What are intangible costs?
Costs that cannot be quantified in monetary terms (separate from indirect costs which can be quantified)
How do lifetime prevalence and lifetime morbid risk differ from each other?
Lifetime prevalence - proportion of individuals at a current time that have ever manifested the disease
Lifetime morbid risk - probability of developing the disorder during the entire period (specified normally by life expectancy)
What do population pyramids show?
Good graphical depictions of age and sex distribution of a population
The Jarmen index is a measure of?
Social deprivation - generally only valid in the UK
Attack rate refers to?
Incidence rate at point of exposure
What are the differences between QI and research projects?
Interventions tested in QI projects are not novel as they are within existing clinical practice
Pareto charts are based upon what management principle?
80/20
- That 80% of the resources go to 20% of the population whereas 20% of the resources go to 80%
- Focussing on 20% of high impact circumstances increases efficiency
On a pareto chart more frequent events are listed on the left of the chart whereas less frequent events are on the right
PDSA stands for?
Plan-Do-Study-Act
In cases when checking for clinical error > QI PDCA is sometimes used instead (Plan-Do-Check-Act)
What is intensity sampling in qualitative research?
Intensity sampling is where a subject who is the expert in the topic of a study provides expert information on a specialised subject
You want to assess IQ and cognitive functioning before onset of illness what type of participants may be recruited?
Army recruits - at conscription IQ and cognition are often assessed
