Types of study design

Question 1

Cohort studies

Answer 1

select disease-free individuals

classify the individuals by their exposure

follow-up and measure number of people with disease and extent of exposure.

calculate incidence rates for each exposure group

Tells you about disease aetiology and disese prognosis

Question 2

Types of comparison in cohort studies

Answer 2

Internal: Individuals split into sub-cohorts based on exposure and compared using Incidence Rate Ratio (IRR). Requires large cohort study, prone to greater random variation

External: comparison of exposed cohort with an external reference population normally using Standardised Mortality Ratio (SMR). Prone to inadvertent selection bias and unmeasured confounders

Question 3

Case control studies

Answer 3

Aim to identify whether an exposure is associated with a disease

Cases are identified as a group of people who have the disease

Controls are identified who do not have the disease

Cases and controls interviewed to compare exposure frequency in two groups. Enquires about exposures that happened before the event.

Analysed using Odds ratio

Question 4

Advantages of case control studies

Answer 4

Suitable for rare diseases (start with cases, no need for follow up)

Can look at multiple exposures at once.

Quick and cheap

Question 5

Disadvantages of case control studies

Answer 5

Not suitable for rare exposures

Only possible to estimate relative risk, not incidence rates.

Does not tell you about the prevalence or incidence of disease

Prone to selection bias

Prone to recall bias

Confounding

Question 6

Outline the steps involved in an RCT

Answer 6

Identify, recruit, consent and maintain two comparable groups of participants

Randomise: one group to be given a new treatment and the other the standard treatment

Follow-up: two groups followed up equally an aim to maintain all participants

Assess: using same criteria of outcome in both groups

Compare: outcomes in the two groups to see how big the difference is and whether this difference is attributable to the intervention

Question 7

Explanatory trial

Answer 7

Uses As-treated analysis

Used to establish the physiological potency of the drug in comparison with standard drug.

Non-compliers are excluded and assessed with the control group

Problem: two groups no longer randomised. Non-compliers are likely to be different to compliers which would be related to their response. Leaves study open to confounding

Question 8

Pragmatic trial

Answer 8

uses intention-to-treat analysis

Gives a more realistic indication of the likely impact of routine clincal use of the drug. Doctors cannot control if a patient will take the drug or not

Allows randomisation to be preserved, problems due to confounding are avoided.

Question 9

Clinical equipoise

Answer 9

For a treatment to be considered for clinical trial, there must be reasonable uncertainty or genuine ignorance about whether it or the comparator is better.

To do otherwise would be unethical

Question 10

Blind trials

Answer 10

Attempts to remove placebo effect

Single blind trials: either the patient, clinician or assessor does not know the treatment allocation

Double blind: two or more of the patient, clinician or assessor does not know the treatment allocation

Question 11

Explain the disadvantages of non-randomised control trials and the use of historical controls

Answer 11

Historical controls: all patients in trial receive new treatment and compared with patients who previously received the standard treatment. Historical group may be less well defined in selection, differ in prognosis or standard treatment and have poor information on confounders. New treatment group may be subject to selection bias and reporting bias

Non-randomised control trials are where patients are selected to receive the new or standard treatment. Subject to selection bias, reporting bias and confounding.

Question 12

What is a prevalence survey

Answer 12

Survey where people in a population are examined for the presence of a condition of interest. The proportion of the population that has the condition tells you the prevalence of the disease Also known as cross-sectional studies

Question 13

Things to consider when designing a prevalence survey

Answer 13

Defining a case

Defining the whole population

Defining your sample

Choice of examination

Response rates

Question 14

Give 4 reasons why differences may exist between different prevalence surveys

(e.g. HSE, QoF)

Answer 14

Difference in case definition

Time-point of survey

Proportion of the population sampled (sampling frame)

Difference in sampling technique

Differences in the sample populations (age, ethnicity)

Difference in response rate

Question 15

Analysis of case control studies

Answer 15

Odds Ratio

Odds of exposure in cases/odds of exposure in controls

axd/bxc

Question 16

Nested Case Control Studies

Answer 16

Combines both cohort studies and case control studies

Cases are selected from participants in a cohort that have experienced a certain event and the controls are selected from participants in the cohort who have not experienced that event.

Question 17

Advantages of nested case control studies

Answer 17

Can calculate incidence rate

Population that the controls should be selected from is already defined

Eliminates recall bias associated with conventional case control studies.

More detailed information can be collected on the smaller group of participants compared to in a cohort study.

Cost-effective alternative to a full cohort study

Question 18

Definition of a clinical trial

Answer 18

Planned experiment involving patients which id designed to determine the most appropriate method of treatment of future patients with a given medical condition.

Allows new treatments to be evaluated scientifically and safely

Question 19

Difference between observational and intervention studies

Answer 19

Observational studies:
Patients receive normal medical care and then patient outcomes are observed and relationships to risk factors are assessed

Intervention studies:
Patients receive treatment in a designed experiment and the effect of the clinical intervention is assessed.

Question 20

What are the advantages of random allocation in clinical trials?

Answer 20

Gives patients equal chance of receiving each treatment

leads to groups that are likely to have similar characteristics by chance (minimises known and unknown confounders)

reduces selection bias if patients enter a trial before randomisation

non-randomisation may result in selection bias, reporting bias and confounding between treatment groups.

Question 21

What is the placebo effect?

Answer 21

The psychological benefit that arises from being looked after or cared for more carefully or differently, or from receiving a ‘new’ treatment’. This effect can result in an improved clinical condition and a better outcome even if the new treatment is ineffective.

Question 22

How does blinding eliminate the placebo effect?

Answer 22

Blinding in a study means that a group of people involved in the study are prevented from knowing information which could introduce bias

Clinical trials can be single or double blinded.

Reduces placebo effect and assessor/interviewer bias

Question 23

What are placebos and why are they used?

Answer 23

A placebo is an inert treatment which looks identical to the drug under study but has no biological effect.

Used to remove the ‘placebo effect’ i.e. the psychological benefit from being looked after better or being on a ‘new’ treatment. Also help maintain blinding and acts as a blank control tto compare an active drug vs. no drug.

Question 24

Systematic Review

Answer 24

Assembles and critically appraises all the available data on a particular subject.

Studies are included systematically using predefined methods (inclusion and exclusion criteria) which appraise the quality of that data and help minimise bias.

Resuts from similar studies (normally RCTs) are pooled, which incrases the sample size and power of the study. Statistical analysis is then carried out on the data. (Meta analysis)

Question 25

Benefits of using systematic reviews

Answer 25

Data from RCTs cant always be used in clinical practice because they are very restricted

Systematic reviews are rigorous, objective and reproducible

Pooling data increases the statistical power

Enables more actionable conclusions on the benefits of an intervention

Allows clinicians to make evidence-based judicious descisions

Question 26

How is data synthesised in a meta analysis?

Answer 26

Continuous data - weighted mean difference

Continuous data from standardised scales - standardised mean difference (gives you an effect size)

Dichotomous data: relative risk

Question 27

How are effect sizes interpreted?

Answer 27

0. 2 - small effect size
1. 5 - medium
2. 8 - large effect size

Question 28

Limitations of systematic reviews

Answer 28

Synthesis of the data may oversimplify important distinctions between primary studies regarding inclusion and exclusion criteria or the nature of an intervention

Reviews of similar topics may appear to reach different conclusions depending on the precise form of the review question

Systematic reviews dependent on the data currently available

Findings from systematic reviews are not always consistent with the finding of large scale RCTs

Question 29

What are funnel plots?

Answer 29

Way of assessing whether the results of a review have been influenced by publication bias.

Trial specific effect (OR, RR) is plotted against a measure of prescision (standard error).

If the plot is symmetric, this means that there is probable no publication bias, whereas asymmetric plots suggest there is.

Question 30

What is a forest plot?

Answer 30

A plot of the quantitative results of each study with the results of the meta analysis shown. Results of the trial are given with 95% CI

Question 31

What is a regression analysis?

Answer 31

AIms to isolate the effect of a single determinant or causal factor on a single disease from a number of factors associated with a disease.

Eliminates the effect of cnfounding factors

Assumed that the factor most strongly related statistically is the key factor.

Not suitable for estimating effect in complex causal pathways, multifactorial diseases and assesting holistic effects.

Question 32

Define number needed to treat

Answer 32

The average number of patients who need to be treated to prevent one additional bad outcome

The ideal NNT is 1, where everyone improves with treatment and no one improves with control. The higher the NNT, the less effective is the treatment