CAT

Question 1

Concealment of allocation

Answer 1

In an RCT it is critical there is no opportunity for selection bias in allocation to treatment. To do this we need make sure allocation of treatment can’t be predicted when deciding whether or not recruit a patient.

Question 2

Intention to treat (ITT) analysis

Answer 2

This means keeping individuals in the group they were allocated to when analysing – even if they don’t in the end get that treatment. This is important as only at randomisation is selection bias not an issue. It also provides a pragmatic estimate of treatment effect.

Intention to treat analysis is a method of analysis for randomized controlled trials in which all patients randomly assigned to one of the treatments are analysed together, regardless of whether or not they completed or received that treatment

Intention to treat analysis is done to avoid the effects of crossover and drop-out, which may affect the randomization to the treatment groups

Question 3

Completeness of follow-up

Answer 3

Any loss of follow-up results in a loss of statistical power in the study. Some loss is almost inevitable – the importance of any loss is a matter of judgement. Loss to follow-up introduces a possibility of bias if there is differential follow-up in different groups.

Question 4

Blinding (or masking)

Answer 4

Keeping participants and particularly outcome assessors unaware of allocation prevents any conscious or unconscious bias in estimating effect on basis of expectations.

Question 5

Clinical heterogeneity in a SR

Answer 5

means that the forms of treatment being compared in the individual studies varied.

Question 6

Statistical heterogeneity in a SR

Answer 6

means that estimates of how effective the treatment was differed between individual studies.

Question 7

Meta-analysis (plain english)

Answer 7

means that the results of more than one study are combined (or pooled) together to create an overall average estimate of the effectiveness of a treatment. Done appropriately this can give a more precise estimate of how well a treatment works

Question 8

2 instances where meta-analyses could not be used

Answer 8

Only one study measured the outcome (e.g. return to physical exercise), so there were no data to pool.

High level of statistical heterogeneity (e.g. pain scores), so meta-analysis would have produced a result that was unreliable.

Question 9

What is selection bias?

Answer 9

Error in the process of selecting participants for the study and assigning them to particular arms of the study.

**Bias introduced by the selection of individuals, groups or data for analysis in such a way that proper randomization is not achieved, thereby ensuring that the sample obtained is not representative of the population intended to be analyzed

Question 10

What is attrition bias?

Answer 10

Occurs when those patients who are lost to follow-up differ in a systematic way to those who did return for assessment or clinic.

**Bias that arises from systematic differences in the way participants are lost from a study.

Question 11

What is measurement bias?

Answer 11

Measurement bias refers to any systematic or non-random error that occurs in the collection of data in a study.

**when information is recorded in a distorted manner (e.g. an inaccurate measurement tool).

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Question 12

What is observer bias?

Answer 12

Occurs when variables are reported differently between assessors.

Question 13

What is procedure bias?

Answer 13

Occurs when subjects in different arms of the study are treated differently (other than the exposure or intervention).

Question 14

What is misclassification bias?

Answer 14

Occurs when a study participant is categorised into an incorrect category altering the observed association or research outcome of interest.

**Basically occurs when a variable is classified incorrectly.

Question 15

What is information bias?

Answer 15

Information bias is any systematic difference from the truth that arises in the collection, recall, recording and handling of information in a study, including how missing data is dealt with.

**Happens when key information is either measured, collected, or interpreted inaccurately.

Question 16

What are the 4 major types of information bias?

Answer 16

Misclassification bias
Observer bias

Recall bias
Reporting bias

Question 17

What is confounding?

Answer 17

Happens when a relationship between an exposure and an outcome is distorted by their shared relationship with another variable.

Question 18

Name 4 ways in which confounding can be addressed in study design and/or analysis.

Answer 18

1) Restriction
2) Matching

3) Stratification
4) Mutliple variable regression

Question 19

How is restriction carried out in terms of addressing confounding variables?

Answer 19

• exclusion of participants with the identified confounding factor
• means that you will have less data
• difficult to implement when there are multiple confounding factors.

Question 20

How is matching carried out in terms of addressing confounding variables?

Answer 20

• equal distribution among exposed and unexposed groups of the variables believed to be confounding variable.
• used commonly in case-control studies
• used for strong confounders like age and sex
• not the most effective answer to most confounding variables

Question 21

How is stratification carried out in terms of addressing confounding variables?

Answer 21

• an analytical approach where exposure: outcome associations are categorised into different subgroups of the confounder.
• different subgroups are known as different strata.

Question 22

How is multiple variable regression carried out in terms of addressing confounding variables?

Answer 22

Allows us to estimate the association between a given independent variable and the outcome holding all other variables constant.

It provides a way of adjusting for (or accounting for) potentially confounding variables that have been included in the model.

Question 23

What is evidence based decision making?

Answer 23

The process for identifying and using the most up to date and relevant evidence to inform decisions for individual patient problems.

Question 24

What does critical appraisal assess a research study for?

Answer 24

Bias, applicability and value.

CA identifies whether the evidence a study provides is useful for patient care.

Question 25

What does phase III of a clinical trial often involve?

Answer 25

RCTs with one or more experimental treatments being compared against control/ standard treatments. Attempts are made to draw a definite conclusion regarding benefit or otherwise.

Question 26

What is the best method of allocation in an RCT?

Answer 26

An independent organisation who centrally organise randomised allocation via a computer programme. This is designed to be unpredictable and is the least subject to potential subversion of the allocation process.

Question 27

What are the advantages of a systematic review?

Answer 27

- All available evidence - Published/Unpublished research - Increased total sample size = certainty and precision - Indicated heterogeneity - Subgroup and sensitivity analyses

Question 28

What are the disadvantages of a systematic review?

Answer 28

- Researcher can only use published or readily available studies - Conclusions may be unreliable - Unpublished studies may be hard to find - Results that are negative or inconclusive may remain unpublished

Question 29

What are the advantages of an RCT?

Answer 29

- Causal inferences - Randomisation minimises bias -Tailored to a specific research question

Question 30

What are the disadvantages of an RCT?

Answer 30

Not always ethical -High dropout when intervention has undesirable effects -Expensive

Question 31

What are the advantages of cohort studies?

Answer 31

-Measurement of exposure to risk factor(s) not biased by the presence or absence of outcome - Can provide data on time course of development of an outcome - More than one outcome can be examined at once - Useful for investigating rare exposures

Question 32

What are the disadvantages of cohort studies?

Answer 32

- Potential for bias due to selection of subjects - Danger of losses to follow-up OR historical studies dependent on accuracy of records/ family/ patient recall - Exposure to risk factors/existence of prognostic factors may change over course of study - Can be timely and costly to carry out (e.g. some cohort studies can last for 20 years or more)

Question 33

What are the advantages of case-control studies?

Answer 33

- Rare disease, long latency - Less costly and time consuming -Studying dynamic populations in which follow up is difficult

Question 34

What are the disadvantages of case-control studies?

Answer 34

- Subject to selection bias - Inefficient for rare exposures - Subject to observation bias - Hard to calculate incidence - Bias and confounding. - Recall bias

Question 35

Recall bias

Answer 35

Difference in the accuracy of the recollections retrieved by study participants, possibly due to whether they have disorder or not.

Question 36

Publication bias

Answer 36

Failure to publish results from valid studies, often as they showed a negative or uninteresting result. Important in meta-analyses where studies showing negative results may be excluded.

Question 37

Expectation bias

Answer 37

Only a problem in non-blinded trials. Observers may subconsciously measure or report data in a way that favours the expected study outcome.

Question 38

Late-look bias

Answer 38

Gathering information at an inappropriate time e.g. studying a fatal disease many years later when some of the patients may have died already

Question 39

Procedure bias

Answer 39

Occurs when subjects in different groups receive different treatment

Question 40

confidence interval

Answer 40

a range of values for a variable of interest constructed so that this range has a specified probability of including the true value of the variable. The specified probability is called the confidence level, and the end points of the confidence interval are called the confidence limits

Question 41

Describe structure of a forest plot

Answer 41

The name of the trials is listed down the left hand side, usually in chronological order. On the right hand side the results of the studies are shown as squares centred on the point estimate of the result of each trial. The size of the square is proportional to the weight of the study in the meta-analysis. The line running through the square shows the confidence interval, usually at 95%.

Question 42

Cohort study

Answer 42

Observational and prospective. Two (or more) are selected according to their exposure to a particular agent (e.g. medicine, toxin) and followed up to see how many develop a disease or other outcome. The usual outcome measure is the relative risk.

Question 43

Case control study

Answer 43

Observational and retrospective. Patients with a particular condition (cases) are identified and matched with controls. Data is then collected on past exposure to a possible causal agent for the condition. The usual outcome measure is the odds ratio.

Question 44

Internal validity

Answer 44

Internal validity is the confidence that we can place in the cause and effect relationship in a study. It is the confidence that we have that the change in the independent variable caused the observed change in the dependent variable (rather than due to poor control of extraneous variables)

Question 45

Threats to internal validity:

Answer 45

Reliability of measurement instruments Regression towards the mean (subjects selected based on extreme scores will tend to regress spontaneously towards the mean on subsequent tests) Sampling Experimental mortality (loss of participants over time may result in unequal characteristics in two groups) Instrument obtrusiveness (the instrument should not affect the data collection e.g. poorly designed questionnaires) Manipulation effectiveness (the independent variable must be manipulated enough so that the effect can be seen, ideally the degree of manipulation should be measured) History (where two measurements of the dependent variable occur that are separated in time, there is the potential for various other influences to get introduced) Maturation (people mature over time and this may in itself explain the change of a dependent variable) Measurement sensitisation (the instrument may affect the way the subject see's the world and so may bias future measures) Measurement instrument learning (people may get used to the measurement instrument, a good example is the increasing performance on repeated use of the WAIS for estimation of IQ)

Question 46

External validity

Answer 46

External validity is the degree to which the conclusions in a study would hold for other persons in other places and at other times, i.e. its ability to generalise.

Question 47

Threats to external validity:

Answer 47

Representativeness of the sample Reactive effects of setting (is the research setting artificial) Effect of testing (if a pre-test was used in the study that will not be used in the real world this may affect outcomes) Multiple treatment inference (this refers to study's in which subject receive more than one treatment, the effects of multiple treatments may interact)

Question 48

What should a good study have in regard to loss to follow up

Answer 48

Both intention to treat analysis and per protocol analysis