DR TAMSIN NEWLOVE-DELGADODOCTORAL RESEARCH FELLOW

UNIVERSITY OF EXETER

STUDY DESIGNS:case control, cohort and

qualitative

Aims and objectives

To outline and revise:Causation

Case control study design, advantages and disadvantages The odds ratio Cohort study design, advantages and disadvantages Relative risk

To summarize some key points about qualitative study design: Use Methods Advantages and disadvantages

Relevant Paper 3 Syllabus

3.1.10. Knows the benefits and weaknesses of different quantitative study designs to address different clinical questions: Case-control Cohort

3.6 Critically appraises cohort and case control studies

Relevant Paper 3 Syllabus

3.4. Qualitative Methods Knows when to apply qualitative research methodologies Additional approaches to sampling in qualitative studies Different approaches to data gathering in qualitative

studies The role of qualitative methodologies in instrument (i.e.

screening, diagnostic, outcome measure) development Methods for validating qualitative data Methods for minimising bias Methods of analyzing data Data saturation

3.6 – Critically appraises qualitative research

Plan of afternoon

1pm-2.30pm – Case control and cohort studies: including coffee break and exam questions

2.30pm – 3.30pm – Qualitative studies

1. Causation and study designs

Example MCQ

Which of the following is not one of the Bradford-Hill criteria?

a)Temporalityb)Biological gradientc)Plausibilityd)Residual confoundinge)Strength of association

http://www.youtube.com/watch?v=fFfWykH05Gw

The Daily Mail List of Things That Give You Cancer

AGE: http://www.dailymail.co.uk/news/arti...st-cancer.htmlAIR POLLUTION: http://www.dailymail.co.uk/health/ar...ld-cancer.htmlAIR TRAVEL: http://www.dailymail.co.uk/health/ar...ncer-risk.html andhttp://www.dailymail.co.uk/travel/ar...nt-fliers.htmlALCOHOL: http://www.dailymail.co.uk/news/arti...ncer-risk.html andhttp://www.dailymail.co.uk/health/ar...-wine-day.htmlALLERGIES: http://www.dailymail.co.uk/health/ar...ncer-risk.html ARTIFICIAL FLAVOURS: http://www.dailymail.co.uk/news/arti...soy-sauce.html ARTIFICIAL LIGHT: http://www.dailymail.co.uk/health/ar...ncer-risk.html ASBESTOS: (as if it wasnt bad enough already) http://www.dailymail.co.uk/news/arti...ng-cancer.html ASPIRIN: http://www.dailymail.co.uk/health/ar...ncer-risk.html BABIES: http://www.dailymail.co.uk/news/arti...st-cancer.html BABY BOTTLES: http://www.dailymail.co.uk/health/ar...fertility.htmlBABY FOOD: http://www.dailymail.co.uk/health/ar...cer-alert.htmlBACON: http://www.dailymail.co.uk/health/ar...cers-grow.html BARBEQUES: http://www.dailymail.co.uk/news/arti...ncer-risk.htmlBEEF: http://www.dailymail.co.uk/news/arti...st-cancer.html BEER: http://www.dailymail.co.uk/health/ar...te-cancer.htmlBEING A BLACK PERSON: http://www.dailymail.co.uk/health/ar...cancer.htmlandhttp://www.dailymail.co.uk/health/ar...ite-women.htmlBEING A WOMAN: http://www.dailymail.co.uk/health/ar...n-smokers.html BEING A MAN: http://www.dailymail.co.uk/health/ar...cer-women.html BEING SOUTHERN: http://www.dailymail.co.uk/health/ar...st-cancer.htmlBISCUITS: http://www.dailymail.co.uk/femail/ar...ods-avoid.html 

BRAS: http://www.dailymail.co.uk/news/arti...a-bad-you.html BREAD: http://www.dailymail.co.uk/health/ar...ncer-risk.html

RCT: not always the answer1

UnnecessaryImpractical/UnethicalInappropriate

Prognosis Diagnosis Quality issues And more

Study designs2

Objective Common design

Prevalence Cross-sectional

Incidence Cohort

Cause Cohort, case-control, cross-sectional (in order of reliability)

Prognosis Cohort

Treatment effect Controlled trial

Issues of how, why etc as opposed to what or how much

Qualitative design

Investigating aetiology

Epidemiological studies of aetiology are usually observational not experimental

An observed association may be due to: True cause Reverse causation Chance (random error) Bias (systematic error) Confounding

Investigating aetiology

Assessing causation

Criteria?

Questions of causation

The Bradford-Hill criteria (J Roy Soc Med 1965:58:295-300)

1. Strength of the association.2. Consistency of findings.3. Specificity of the association.4. Temporal sequence of association.5. Biological gradient.6. Biological plausibility.7. Coherence.8. Experiment.

Can you think of examples where this doesn’t work?

2. Case control designs

The Case Control Study: Design

The case control study: design3

Advantages

Efficient for studies of rare diseases and diseases with long latent periods

Cheap, simple, quick (in comparison to cohorts)

Can examine multiple exposures – generate hypotheses

Sometimes the only practical option (e.g. where long latent period between exposure and disease)

Disadvantages

There are many!Can study only one outcomeNotorious for being prone to bias:

Sampling/selection bias – selection of cases and controls

Observation and recall bias

Not good for rare exposuresThe temporal sequence between exposure

and disease may be difficult to determine.As with all studies, confounding

Selecting cases

Need a clear case definition and source Cases selected for a study should be

representative of all cases of the disease in the population. 

This is difficult!: many cases not diagnosed or misdiagnosed

A hospital sample in some diseases may be very different from a community sample

Selecting controls

 Controls are used to estimate the prevalence of exposure in the population which gave rise to the cases.

The ideal control group would comprise a random sample from the general population that gave rise to the cases. 

 Controls should meet all the criteria for cases, apart from having the disease itself; but they should have the potential to develop it

Methods of selecting controls

Convenience sampleMatched sampleUsing two or more control groupsUsing population base sample e.g. from

registers

Recruiting more than one control per case may improve the statistical power of the study (up to 4 controls per case)

Selecting controls: matching

Matching – Some studies are matched to select cases/controls who are as similar as possible e.g on age, ethnicity etc

Can be useful in small samples – as we might not have sufficient subjects to adjust for several variables at once.

Difficult/complicated to match on too many factors

Important not to match on basis of risk factor of interest / too many factors – ‘overmatching’ may make the controls unrepresentative and underestimate the true difference

Example of selection bias

• Bias introduced through poor selection of controls

• Case control studies of NSAIDS (exposure) in colorectal cancer3

Case control studies in psychiatry

Suicide a popular subject……. Barraclough, B., Bunch, J., Nelson, B., et al

(1974) A hundred cases of suicide: clinical aspects. British Journal of Psychiatry, 125, 355-373.

More modern examples: Fuller Torrey E, Rawlings R, Yolken RH. The

antecedents ofpsychoses: a case-control study of selected risk factors.

Schizophr Res2000; 46: 17–23.

Case control studies and the odds ratio

Estimates the strength of association between an exposure and an outcome

Does not calculate relative risk as retrospective

Does not give incidence/prevalence – unless all cases in a population are included

The odds ratio is a measure of the odds of exposure in the cases, compared to the odds of exposure in the control group. 

OR: 2 by 2 table

Cases Controls Total

Exposed a b A + b

Unexposed c d C + d

Total A + c B +d

OR = (a/c)/(b/d)

Imaginary worked example – Cats and schizophrenia

Schizophrenia Controls

Owned cat as child 80 100

Did not own cat as child

20 300

Total 100 400

Imaginary example– are cats associated with schizophrenia?

Odds of exposure in the cases: 80/20 = 4Odds of exposure in the controls: 100/300 = 0.33Odds ratio: 4/0.33 = 12.12So……the odds of having had a cat as a child in the

group with schizophrenia were over 12 times the odds of having had a cat as a child in the control group –

Or those with schizophrenia were over 12 times more likely to have had a cat as a child….

Why might we get this result?

Feline bias

Selection bias Cases recruited through a charity that runs ‘pet

experiences’ for people with mental illness Controls were a hospital sample recruited from an

allergy clinic Both of these would spuriously increase estimate of

effect

Recall bias Are those with schizophrenia more likely to

remember/report having had a cat – particularly if aware of hypothesis in question

3. Cohort study designs

Cohort study design

Usually prospective; but can be retrospective

A prospective cohort

Prospective and retrospective cohort

Cohort studies may be prospective or retrospective, but both types define the cohort on the basis of exposure, not outcome.

Prospective and retrospective cohorts

Advantages

Can investigate risk factors impossible to study in controlled trials - e.g. smoking or asbestos

Describe incidence and natural historyMultiple outcomes can be measured for any one

exposure.Exposure is measured before the onset of disease

(in prospective cohort studies).Good for measuring rare exposures, for example

among different occupations.Demonstrate direction of causality.Can calculate relative risk

Disadvantages

Expensive, time consumingLoss to follow up can introduce biasNeed a large sample size – especially for less

common outcomesNot good for rare outcomes or long latency

periodsNeed to maintain consistency of follow up

over timeSystematic misclassification of exposure or

outcome status – information bias

Sources of bias in cohort studies

Differential misclassification: can lead to an over- or underestimate of the effect between exposure and outcome.

 Losses to follow up : degree to which losses to follow up are related to either exposure or outcome can lead to serious bias in the measurement of effect of exposure and outcome.2

Cohort studies in psychiatry

Andreasson et al:  cannabis consumption and development of schizophrenia in a cohort of 45,570 Swedish conscripts4.

Relative risk in cohort studies

Analysis Riskexp = a / (a+c) (divide by total exposed)

Riskunexp = b / (b+d) (divide by total unexposed)

Estimate relative risk = Riskexp / Riskunexp

Indicates increased/decreased risk of disease assoc with exp: RR = 1 – risk is same in exposed and unexposed groups RR > 1 – risk is greater in exposed group RR < 1 – reduction in risk in exposed group Exposed to factor:

Yes No Total

Disease of interest:

Yes a b a+b

No c d c+d

Total a+c b+d N = a+b+c+d

Example: relative risk from Swedish conscript cohort study4

Cannabis exposure

None Low Medium High

Schizophrenia

197 18 10 21

No schizophrenia

41083 2818 692 731

Total 41280 2836 702 752

Exam questions – example EMIs

4. Qualitative studies

Qualitative studies

Answers questions such as: What is X & how does X vary in diff circumstances & why? Not ‘how big is X or how many X’s are there?

Concerned with meanings people attach to their experience & how they make sense of world

Some features of qualitative research

Uses of qualitative research

Preliminary to quantitative research Helps ensure validity of data obtained E.g. interviews to inform a survey Generate theory

To validate quantitative research or provide a diff perspective on same phenomena. Mixed methods

Used independently to uncover processes or practice not amenable to quantitative research

Address the 'gap' between evidence based approaches and practice

Example: Owens et al 20115

Objective To shed light on the difficulties faced by relatives, friends, and colleagues in interpreting signs of suicidality and deciding whether and how to intervene.

Design Qualitative study of completed suicides, based on in-depth interviews with multiple informants.

Setting London, southwest England, and south Wales. Participants 31 lay informants (one to five for each case),

including parents, partners, siblings, friends, and colleagues of 14 cases of suicide in which the deceased was aged 18-34 and was not in contact with secondary mental health services

Quotes5

Friend: “He’s a bloke, isn’t he? We don’t do emotion.”

Sibling: “I’d try and get things out of him about how he felt, especially when he’d had a few drinks, but he never ever opened up . . . He was a typical bloke in that respect . . . So I never really pushed it. I didn’t want to make him feel uncomfortable.”

Interpretation/themes arising

‘‘Informants also mentioned the strong social pressures, especially among young men, to hide distress and keep up a pretence of coping. The social contexts in which young men meet, such as pubs and clubs, may not be conducive to “troubles telling,”26 and lack of emotional literacy may mean that they do not have the vocabulary or skills to do so.

These quotations betray a tacit acceptance of this situation on the part of significant others, and even an expectation that boys will not talk about emotions, which may have served to reinforce inhibitions and close down opportunities to confide.’’(Owens et al 2011)

Qualitative vs. quantitative

Quantitative Qualitative

Type of reasoning Deduction Induction

Objectivity Subjectivity

Causation Meaning

Type of question Pre-specified Open-ended

Outcome orientated Process orientated

Type of analysis Numerical estimation Narrative description

Example MCQs

In qualitative research, which of the following refers to modifying the research methods and hypothesis as and while one conducts the research?

A. TriangulationB. Iterative approachC. Theoretical samplingD. Content analysisE. Deductive approach

Example MCQs

In qualitative research, which of the following terms does not refer to a method of selecting a sample:

A.SnowballingB.PurposiveC.ConvenienceD.Framework approachE.Theoretical sampling

Example MCQs

In qualitative research, the inclusion of which of the following may be an indicator of the quality of a study? Sensitivity analysis Reflexivity Bootstrapping Snowballing Blinding

Broad methodologies

Grounded Theory (Glaser and Strauss) Social and psychological processes – may generate

theory/models Key concepts: theoretical sampling and constant

comparison

Phenomenology Lived experience rather than theory generation

Ethnography Learning about a culture from the people that live in it

Data collection

InterviewsFocus groupsObservational approaches

Participant observation Ethnographic Discourse/conversational analysis

Documentary analysis

Qualitative vs quantitative approaches to sampling

Often a smaller sample size – but rich in detail

Quantitative research uses probability sampling

Qualitative research uses non-probability sampling   not representative samples  findings cannot be generalised to the whole study

population from which the sample was taken.   the people in the study population do not each have

an equal chance of being selected.

Concepts in qualitative sampling

Some sampling approaches

Process of analysing qualitative data

Data preparation Nature and scale of qualitative data Transcription

Relationship between data and analysis Transcripts provide descriptive record Analytical process begins during data collection as data

already gathered are analysed and feed into/shape ongoing data collection

QUANT QUAL

CollectAnalyse

CollectAnalyse

Analysing qualitative data

Goal To develop analytic categories to describe & explain May be

derived inductively (from the data) or deductively (predefined themes drawn from schedule & research Qs)

Broad approaches Thematic analysis Grounded theory Framework approach

Initial steps Manage & make sense of data Reading & re-reading to identify initial set of themes Coding, label themes, use their language Organising, grouping & refining of themes/categories

Specific methods of analysis

Quality in qualitative research

Summary – Qualitative research

Some key words/concepts to be familiar with - see syllabus

Cannot apply same rigid concepts re appraisal etc as for quantitative research

However, there are ways of considering the quality of a piece of qualitative research

Also a CASP critical appraisal tool available: http://www.casp-uk.net/

References

1. Greenhalgh T. How to Read a Paper2. Mann CJ. Observational Research methods: Research

design 2: cohort, cross-sectional and case-control studies. Emerg Med 2003 20: 54-60

3. Schulz KF and Grimes DA. Case Control Studies: research in reverse. The Lancet doi:10.1016/S0140-6736(02)07605-5

4. Andreasson S., Engstrom A., Allebeck P., Rydberg U. Cannabis and schizophrenia. A longitudinal study of Swedish conscripts (1987) Lancet, 2 (8574), pp. 1483-1485+1486.

5. Owens, C., Owen, G., Belam, J., Lloyd, K., Rapport, F., Donovan, J., & Lambert, H. (2011). Recognising and responding to suicidal crisis within family and social networks: qualitative study. BMJ, 343(oct18 1), d5801–d5801. doi:10.1136/bmj.d5801