Flashcards in Clinical Studies Deck (33):

1

## P-values & Confidence intervals?

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P-value is a measure of statistical significance

Confidence intervals are made-up intervals used to show the likelihood that a certain result will fall into this range

2

## Significance and Key components in clinical trial design

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Phase 1 - test safety of treatment, small number of volunteers

Phase 2 - See if treatment works and safety; a few hundred people (efficacy)

Phase 3 - compare new with old and see which is better, see how well it works; several thousands of patients (effectiveness)

Phase 4 - once released into circulation, look for side effects

3

## Identify potential biases and limitations

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Allocation biases - Bias in which group someone is appointed; sorted by randomisation

Measurement biases - Bias in measurement, sorted by blinding

reporting bias - Positive traits published, Negative and neutral traits not

Sample size - must be large to properly represent the population

4

## How do you interpret findings from clinical trials?

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Outcomes presented in terms of efficacy or effectiveness

Outputs of trial:

Experimental event rate(EER): incidence in cases

Control even rate(CER): Incidence in control cases

Relative risk: EER/CER

Relative reduction: (CER-EER)/CER

Absolute risk reduction(ARR): CER - EER

Number needed to treat(NNT): 1/ARR

5

## Tell me strengths of case control studies

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Good for rare diseases

Quick

Cost efficient

Investigate lots of exposures at the same time

Good for long-lasting diseases

6

## Tell me weaknesses of case-control studies

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Possible bias in selection

Recall bias during investigation

Unsure of temporal relationship

Poor for rare exposure

Cannot calculate incidence

7

## Tell me about case-control studies

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It is retrospective and observational

Uses odds ratio to calculate relative risk

Only occurs post diagnosis

8

## Tell me about cohort studies

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Starts with a group of exposed or unexposed and follows up their lives

Uses Risk Ratio to calculate it

Incidence in exposed/Incidence in unexposed

9

## Advantages of cohort studies

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Able to see multiple outcomes

Follow through natural life of disease

Able to look at rare exposures

Incidence can be calculated

Minimise bias in estimating exposure if prospective

10

## Disadvantages of cohort studies

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Inefficient for rare disease

Expensive

Time consuming

Loss to follow-up may introduce bias

Healthy worker effect may cause bias in occupational population

11

## What is the healthy worker effect?

### The idea that those who are healthy enough to work are not representative of the whole population

12

## Major sources of health data in the UK

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Routine data

NHS England

Census

13

## Advantages of routine data

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Cheap

Already collected

Standardised collection procedure

Relatively comprehensive

Wide range of recorded data

Available for past years

Experience in use and interpretation

14

## Disadvantages of routine data

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May not answer the question

Incomplete ascertainment

Variable quality

Validity may vary

Disease labelling may vary over time or by area

Coding changes may create artefactual increases or decreases in rate

Need careful interpretation

15

## Purpose of systematic reviews

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It is a review of all sources using systematic and explicit methods to: Identify, Select, Critically appraise relevant research, collect data from studies, analyse data from the studies that are included in the review.

E.g. Debate on statins

16

## What is involved in a systematic review

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Efficient searching of data

Applying formal rules for critical appraisal of the sources

17

## Stages of a systematic review

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Stage 1:

Stage 2a:

Stage 2b:

Stage 2c:

Stage 3a:

18

## Stages of a systematic review

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Stage 1: Plan the review

Stage 2a: Identification of research

Stage 2b: Selection of studies

Stage 2c: Quality assessment

Stage 3a: Data analysis

Stage 3b: Data visualisation

Stage 3c: Reporting and dissemination

19

## What's happening at each stage?

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Stage 1: Planning, definition of study by PICOS (Population, interventions/comparison, outcomes, study design)

Stage 2a: Defined search criteria and a thorough research of all publicised material

Stage 2b: Eligibility and inclusion criteria based on: Study design, year of study, Publication language, Sample-size/precision, Specific exposure/intervention, Specific outcome, Completeness of information

Stage 2c: may be assessed according to recognized or user-defined criteria

Stage 3: Study details need to be abstracted from each eligible study along with the effect estimate

20

## What is a forest plot?

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Forest plot is a graphical representation of the results from each study included in the meta-analysis, combined with the meta-analysis result

Each study is shown by a box with whiskers showing confidence intervals

Overall estimate shown by diamond at bottom of forest plot, centre of diamond shows pooled point estimate, width is 95% confidence intervals

21

## What is a meta-analysis?

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The use of statistical techniques in a systematic review

to integrate the results of included studies

22

## Limitations of systematic reviews and meta-analyses?

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1. Publication Bias

2. Inconsistency of results (heterogeneity)

3. Low study quality

23

## Publication bias?

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Only the subset of the relevant data is available

Non-significant findings are less likely to be mentioned

Published studies not representative of all valid studies

24

## How is it measured?

### Publication bias measured by a funnel plot, each point meets one study and is plotted on odds ratio and sample size

25

## Heterogeneity?

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Studies differ with respect to:

Populations

Interventions/exposure

Outcomes

Study design

Clinical differences

Methodological differences

Unknown study characteristics

26

## Measurements of heterogeneity

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Tau2: estimate of between-study variance based on random-effect model

Chi2: test of statistical significance for heterogeneity (low power to detect existing inconsistency )

I2: measure or index of heterogeneity

27

## Low study quality

### Studies are of a low quality

28

## Advantages of systematic review and meta-analysis

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Generates a pooled overall estimate

Produce a more reliable and precise estimate of effect

Explore differences between published studies

Identify publication bias

29

## Critically appraising a systematic review

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Was the question addressed?

Was a comprehensive search for relevant literature carried out

Was the quality of each study assessed properly

Was heterogeneity explored?

How credible is the evidence?

Check guidelines for reporting

30

## Critically appraising a meta-analysis

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Was heterogeneity explored?

Was publication bias an issue?

Was it appropriate to pool the studies?

Was the appropriate model used to pool effect estimates? (fixed vs effect model)

Did different sub groups of study give similar results?

31

## Define: Incidence, Prevalence, Mortality and Morbidity

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Incidence: Number of new cases of a disease in a specific time interval (new cases/original population)

Prevalence: Frequency of a disease in a population at a given point in time (no. cases/population)

Mortality: Number of deaths associated with a condition in a given time period (Deaths/population)

Morbidity: Number of cases of ill health, complications, side effects attributed to a specific condition over a particular time period

32

## Fixed effects model?

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Single true underlying effect

Used when effect of exposure is not heterogeneous

33