Designing Epidemiological Studies (2)

Question 1

How can it be assessed whether an exposure is associated with an outcome?

Answer 1

1. Experimental study

2. Observational study

Question 2

How is the strength of an association judged?

Answer 2

Robustness of evidence

Question 3

What are some issues with observational studies?

Answer 3

Observed groups may differ in characteristics (confounding variables)

Question 4

What are randomised control trials?

Answer 4

Experimental studies that compare and assess the effectiveness of 2 or more treatments to see if one is better than another
Comparative group acts as control

Question 5

What are placebo controlled trials?

Answer 5

Placebo (control) VS treatment

Question 6

What is intention to treat?

Answer 6

Analysing patients according to which group they were originally assigned

Question 7

What is the randomisation process?

Answer 7

1. Generation of the allocation sequence

2. Implementation of the allocation (allocation concealment - single / double blind)

Question 8

What is performance bias?

Answer 8

Systematic differences between groups in care that is provided, or in exposure to factors other than the intervention of interest

Question 9

What is detection bias?

Answer 9

Systematic differences between groups in how outcomes are determined

Question 10

What are the 2 types of literature review?

Answer 10

1. Narrative review

2. Systematic review

Question 11

What is a narrative review?

Answer 11

Brings together the published literature into a single article enabling the reader to rapidly understand the issues

AKA scoping review or non-systematic review

Question 12

What is a systematic review?

Answer 12

Sets out a highly structures approach to searching, sifting, including and summarising the literature
Often presented as the basis for meta-analysis, but also exists separately

Question 13

What are the strengths and weaknesses of narrative reviews?

Answer 13

Strengths: agile - easier and faster to write
Useful in areas with limited research or variations in research approaches
Useful when bringing together diverse ranges of opinions and disciplines

Weaknesses: Subject to potential bias (authors free to select works - unbalanced)
No search is specified - evidence may be omitted by chance

Question 14

What are the strengths and weaknesses of systematic reviews?

Answer 14

Aims to collate all available evidence that relates to a highly focused research question
Implements highly specified protocol
Includes evidence based on pre-specified criteria: inclusion and exclusion criteria

Can take many months
Bad search structure - miss out literature
Only as good as the evidence they incorporate
Dating very quickly - search date not article publication date (search date may be from 18-24mo ago)

Question 15

What is the process of a systematic review?

Answer 15

1. Research question - narrowly defined RQ
2. Structured search - series of search terms or phrases placed into search engine, reproducible approach
3. Indices - e.g. medline, specify which indices are used upfront
4. Screening / inclusion - PRISMA diagram, shows how many articles found, how many come up as duplicates, then screening of content for eligibility, then calculate how many studies are included in the final systematic review / meta-analysis
5. Reporting
6. Writing
7. Submitting, peer review, revising, publishing

Question 16

What are registries?

Why are registries used before indices?

Answer 16

Registration of research yet to be completed or published

To avoid duplication or omission of relevant studies

Question 17

What is grey information / grey literature?

Answer 17

Not everything that is known is necessarily in the published literature online e.g. gov ports, evaluations of certain programmes, etc.

Question 18

How can grey literature be examined?

Answer 18

Do not follow structured search engines - use open grey searches e.g.
Google scholar
Open grey

Question 19

Why is referencing important??

Answer 19

Can snowball out the reviews to find the individual literatures
You can look at the individual literature to see in what other publications they have been cited

Question 20

What is the Cochrane Collaboration?

Answer 20

Brings together series of systematic reviews and meta-analyses
Decisions of health and healthcare are informed by high-quality, relevant and up-to-date synthesised research evidence

Question 21

What is meta-analysis (in the context of systematic review)

Answer 21

Uses same principles as systematic review, except uses quantitative data instead of qualitative data

A quantitative, formal, epidemiological study design used to systematically assess previous research studies to derive conclusions about that body of research

Question 22

What is the process of meta-analysis?

Answer 22

Extract results (stats) from the individual literatures, compile (add up) all the results to give better results

Pool the estimate of association (i.e. add together the no. of ppts, and results)

Question 23

How are the estimates presented? (i.e. findings of meta-analysis communicated?)

Answer 23

Forest plots
Midline = line of no effect
Square = number of ppts
Horizontal lines = confidence around each of the estimates

Higher no. of ppts = shorter horizontal lines

Position of square relative to the midline indicates what is going on (i.e. to the right = positive effect, to the left = negative effect)

Diamond = pooled estimate, combined power of individual literature findings, (right and left) corners of diamond represents confidence

Question 24

How are individual literatures weighted differently in the meta-analysis?

Answer 24

Usually dependent on size of study

Question 25

What is heterogeneity in meta-analyses?

What are the 3 sorts of heterogeneity?

Answer 25

Differences between the individual studies

Clinical = patients, selection criteria
Methodological = different study designs, blinding, intervention approaches
Statistical: reporting differences in different ways

Question 26

What is publication bias?

Answer 26

Studies with positive findings are more likely to be submitted and accepted for publication

Question 27

What are the limitations of meta-analyses?

Answer 27

Limited by the quality of the studies included, stats methods employed
Need to go back to original authors of studies to ask for more data for the meta-analysis

Question 28

What is meant by endpoint in clinical trials?

Answer 28

An outcome that usually describes a clinically meaningful outcome e.g. cancer survival

Question 29

What is the difference between safety and efficacy of a therapy?

Answer 29

Efficacy – how well a therapy works in achieving a desired outcome

Safety – how well a therapy works in not causing adverse events

Question 30

What are the 2 types of efficacy endpoints?

What are they?

Answer 30

Primary endpoint – pre-specified endpoint before the study is begun

Secondary endpoint – it is common that a study will want to examine a slightly different endpoint in addition to the primary endpoint. For example, while a study seeks to examine survival (i.e. alive or dead) another – often ‘softer’ - measure such as recurrence of disease or hospital admission might also be measured. If the secondary endpoint is proven but the primary endpoint is not, then the findings of the study may still contribute to the understanding of disease.

Question 31

What are safety endpoints?

Answer 31

Major issues e.g. anaphylaxis or direct mortality associated with the therapy
Therapy stopped at this

Question 32

What are phrase composite endpoints?

Answer 32

Composite = multiple potential endpoints have been added together
Particularly common when an outcome is uncommon
E.g. combine MI and ischaemic stroke =
cardiovascular event

Question 33

What is survival analysis?

Answer 33

Follow the two conditions in an experiment for the whole duration of the primary endpoint (E.g. survival after 5 years)
Plot when each person dies
Compare curves of both conditions