Study Design

Question 1

what is evidence based medicine?

Answer 1

The conscientious, judicious and explicit use of current best evidence when making decisions about the care of individual patients

Question 2

what are the three components to EBM?

Answer 2

• Gathering best evidence available
• Using your clinical expertise
• Acknowledging patient values and expectations

Taking all these factors into account allows you to decide the best course of management for a patient.

Question 3

what is the evaluation bypass?

Answer 3

We want to ensure all procedures are first evaluated so only useful procedure are taken up into health services.
We also want to ensure unevaluated procedures (e.g. treatments or diagnostic tests etc.) are not introduced into health services.
Often unevaluated procedures can arrive into health services due to enthusiasms, convictions and commercial pressure rather than because there is evidence that they are useful.

Question 4

give an example of harm caused by lack of evidence

Answer 4

Sudden Infant death syndrome
UK clinicians started to recommend infants sleep on their front to prevent cot death in the 1970s.
However, this advice was not based on any evidence (based on rational that by sleeping on front, infant unlikely to choke on vomit when sleeping).
It was later discovered that placing infants to sleep on their front was harmful - it caused increased risk of Sudden infant death syndrome.

-Two case control studies were published in UK in 1965 and 1970 which showed no evidence of benefit.
-When combined these studies gave evidence that front sleeping was harmful.

image: between 1974 and 1991: an estimated 11,000 excess deaths in
England & Wales (12 babies per week) due to front sleeping position

Question 5

give another example of harm caused by lack of evidence

Answer 5

Thalidomide was marketed as a sleeping pill in the 1950s and was claimed to be safe even in pregnancy. By the late 50s and early 60s it was also being used in the UK to combat morning sickness.
- 1961: Lenz in Germany and McBride in Australia made the connection between thalidomide and an epidemic of congenital defects.
- Early mortality rate 40% in affected babies
- Sales of thalidomaide in the UK stopped in late 1961.
- UK: 5070 babies born; 455 survivors today

Question 6

what is the AAAA framework?

Answer 6

Assess: what type of healthcare question do you have? what type of study would best answer your question?
Access: finding the ‘best’ evidence (validity and relevance)
Appraise: evaluating the quality of the evidence and interpreting the results
Act: is this evidence relevant to my clinical practice. Should this evidence change my practice?

Question 7

why is the AAAA framework
important?

Answer 7

An essential professional and academic skill
Medical knowledge is continually evolving.
The medical profession frequently fails to use effective treatments.
Keeping up to date is a lifelong commitment for every doctor
You need to develop and use the skills to: find, appraise and act on research evidence.

Question 8

what are the different types of healthcare questions about frequency, cause and effect?

Answer 8

Question 9

what are other types of healthcare questions?

Answer 9

Question 10

what questions would you ask when matching healthcare questions to study designs to do with frequency, cause and effect?

Answer 10

The type of healthcare question will determine the type of study design that will be used to answer it.

Question 11

what questions would you ask when matching healthcare questions to study designs for any other types of healthcare questions?

Answer 11

Question 12

what are epidemiological studies: descriptive?

Answer 12

Descriptive studies are observational (not analytical)
They are used to learn about patterns of disease:
Frequency of disease
Distribution of disease:
who gets it?
where it geographically occurs?
when do people get disease e.g. when in life?
Descriptive studies are used for hypothesis generation.
They therefore often precede more expensive analytic studies which investigate cause and effect.

Question 13

what are the different ways that descriptive studies are carried out?

Answer 13

Descriptive studies can be done at a population level -ecological studies
They can also be done at an individual level:
Cross sectional studies (survey and questionnaires)
case series and case reports.
Case report: a detailed report of an unusual ‘condition’ or ‘occurrence’ in a single patient.
Case series: a detailed report of an unusual ‘condition’ or ‘occurrence’ in several patients.

Question 14

explain a cross-sectional descriptive study
give example

Answer 14

Cross sectional study: a study in which information is collected in a planned way from individuals in a defined population at one point in time.
All information for this type of study is gathered at one single point of time.

Example of cross-sectional study:
Office for National Statistics perform People, Population and community surveys
Census is example of a cross sectional study.
Information from cross sectional studies can be used to plan health care services
Example of cross-sectional study: Survey for weekly alcohol consumption by age. Individuals were asked about their drinking behaviour

Question 15

explain descriptive studies: ecological
study

Answer 15

A study in which information is collected from population groups to compare disease frequencies
Information might be collected:
in the same population at different points in time (population defined temporally)
between different populations (population defined geographically) at the same period in time
Key difference: information collected on population level – individuals are not asked for this data.
Example: see image

Question 16

explain analytical studies: cause and effect, as a branch of epidemiological studies

Answer 16

Analytical studies are used to investigate whether an exposure causes an outcome (cause and effect relationship)
Key feature: they make explicit comparison between two or more groups of individuals
Exposure may be harmful (eg smoking) or beneficial (nicotine replacement for smoking cessation)

Question 17

what are the 2 types of analytical studies?

Answer 17

Observational: researcher is an observer of exposures and outcomes
- Cohort
- Case control

Interventional / Experimental: researcher allocates exposure and observes outcomes
- Clinical Trials

Question 18

what are the 2 types of observational studies?

Answer 18

In observational studies the exposure is not under the control of the researcher because of ethical or logistical constraints,
For example, if you are investigating whether an exposure causes harm/causes a disease it not ethical to allocate people to be exposed to harmful factor or not.
Types:
Case control: study starts with identification of the outcome (e.g disease) one it has occurred.
Cohort: study starts with identification of the exposure (e.g. risk factor) to causal factor.

Question 19

Case control vs Cohort Study - Example: Does smoking cause lung cancer?

Answer 19

Smoking is the exposure
Lung cancer is the outcome
Cause and effect question: does smoking cause lung cancer?

Question 20

how do you carry out an analytic observational study: case control study?

Answer 20

Starting point is outcome (condition)
A case-control study compares those with a condition (cases) to those without the condition (controls).
Subjects are grouped for comparison according to the outcome of study.
The level of “exposure” to one or more factors is measured and compared between the two groups (cases and controls).
If the level of exposure is higher in the cases than in the controls the exposure might be a risk factor.
So, if we were to do a case-control study to see if smoking causes lung cancer our cases would be those with lung cancer and our control would be those without.

Question 21

explain how you would carry out a case control study: smoking and lung cancer

Answer 21

In 1950 lung cancer patients were identified across 20 London hospitals. For every patient with Lung cancer (case) a patient with another disease was identified as a control (no lung cancer)
Smoking history was compared in lung cancer cases with controls.
The risk of developing lung cancer in smokers was 14 X that of non-smokers

Question 22

how do you carry out an analytic observational study: cohort study?

Answer 22

• A cohort study compares those exposed to a factor of interest (exposed) to those not exposed to a factor of interest (non exposed). Subjects are grouped for comparison according to whether they have been exposed or not
• The two groups are followed up over time and the amount of disease developing over a specified time period (incidence) is compared between the two groups (exposed and unexposed).
• If the incidence of the outcome is higher in the exposed compared to the unexposed the exposure might be a risk factor.

Question 23

explain how you would carry out a cohort study: smoking and lung cancer

Answer 23

if we were to do a cohort study to see if smoking causes lung cancer we would start off identifying individuals who smoked and those who did not smoke and we would follow them up over period of time to see what proportion of those who smoked developed lung cancer and what proportion who did not smoke developed lung cancer.

Question 24

explain the Doll & Hill British Doctors Cohort study

Answer 24

Doll & Hill British Doctors Cohort
In 1951, a questionnaire was sent to 59,600 British doctors asking about their smoking habits (ever smoked versus never smoked).
Deaths over the next 10 years were recorded (death certificates).
Higher proportion of lung cancer deaths in those who had smoked.

Question 25

which to choose: case control or cohort study?

Answer 25

Consider:
How many exposures do you want to capture?
If you want to look at more than 1 exposure 🡪 case control study
How many outcomes do you want to measure?
If you want to look at more than one outcome 🡪 cohort study
How long between exposure and development of outcome?
If long period a cohort study would take a long time. So, a case control study is better
Is the outcome rare or common?
Case control study are usually preferred as our study population is based on finding cases – we do not wait for rare cases to happen.

Question 26

give a summary of case control study vs cohort study

Answer 26

Case Control Study
Can investigate multiple exposures
Can only investigate one outcome
Recruitment is based on presence or absence of outcome, so do not have to wait for this to occur
Groups for comparison are based on the presence of the outcome: active case finding overcomes the problem of rare outcomes

Cohort Study
Can only investigate one exposure
Can investigate multiple outcomes
You have to wait for the outcome to occur after recruiting on the basis of exposure –so loss to follow up is a problem for diseases with long latency periods
For rare outcomes a lot of exposed individuals would need to be recruited to be sure of enough outcomes occurring.

Question 27

what happens during Analytic Intervention Studies: Clinical Trials?

Answer 27

A randomised controlled trial (RCT) is an experimental study where participants are randomised by researchers to either receive the new intervention (exposure) being tested or to receive a control treatment 🡪 usually either the standard/existing treatment or a placebo.
RCTs are used to investigate effectiveness (does a treatment cause an improvement in health)
Effectiveness is the balance between harms and benefits
Pre-requisite for an RCT (experiment) is that there is genuine uncertainty about which treatment is best (2 active treatments or active treatment and nothing) and it is believed that the new treatment will do more good than harm.
In RCT Participants consent to ‘not having a choice’ of which treatment option they receive (active vs placebo, or new-treatment vs existing treatment)

Question 28

what are specific features of a RCT?

Answer 28

In RCT Participants consent to ‘not having a choice’ of which treatment option they receive (active vs placebo, or new-treatment vs existing treatment)
RCTs have design features that enhance their validity - reduce bias.
It is for this reason that they are better quality evidence if they are well done than case control or cohort study for cause-and-effect relationship.
However, circumstances we can do RCT is restricted to exposures that most likely to cause benefit and not harm.

Question 29

explain the method for RCT

Answer 29

Start off with establishing the exposure (new treatment) and the control.
The decision about whether individual receives either the new treatment or control treatment is randomised
Individuals are then followed up in group to observe outcomes and then compare the outcomes between groups.

Question 30

give an example of an RCT

Answer 30

RCT Example: Comparison of HRT with placebo in post-menopausal women with no pre-existing coronary heart disease
Does hormone replacement therapy in post-menopausal women reduce their risk of heart disease, stroke or death?
[See Below] Risk of CHD was marginally higher.
It was also found that there was a higher incidence in breast cancer but risk of colorectal cancer and hip fractures were reduced.
RCT are special type of cohort study. See 6 different outcomes here.

Question 31

how can we ensure that we get the best evidence for cause and effect?

Answer 31

theres a heirachy of evidence (see image below)
The best evidence for cause and effect comes from RCT.
A Well-done cohort study is better than case control study as in cohort study we measure exposure before outcomes and this is a plus to prove cause and effect relationship.
Therefore, if we want to demonstrate that exposure causes an outcome a RCT is most valid evidence.
However, circumstances we can do RCT is restricted to exposures that most likely to cause benefit and not harm.

Question 32

give examples of other types of healthcare questions

Answer 32

Healthcare questions about Patient / Carer/ Health professional experiences are best addressed using qualitative research
Example Questions:
Why don’t patients adhere to weight loss programmes even though RCTs have shown they are effective?
Why do patients continue to smoke despite evidence of harm and RCT evidence that nicotine replacement therapy is effective?
Why don’t parents immunise their children even though the evidence for benefit far outweighs any harms?

Question 33

what does qualitative research entail?

Answer 33

Involves the collection of non-numerical data about people’s subjective understandings of their lives and experiences: ‘why and how’ people behave rather than ‘how often’ they behave in that way.
Characterised by In depth study of a small number of individuals in a specific setting rather than aiming for generalisability across different settings in quantitative research (which requires larger sample sizes)
Interpretation of the meaning of the data helps us understand individual’s behaviour and social phenomena
Multiple methods available for collecting data including direct observation of behaviour, individual interviews and group interviews (focus groups).

Question 34

how would you go about answering this example:
A Qualitative research study: Barriers to Cervical screening: A qualitative study among Somali women in Oslo, Norway

Answer 34

Background: Research findings suggest that immigrant women are less likely to participate in cervical cancer screening. Increased understanding of the barriers confronted and possibilities for facilitating screening participation is needed.
Methods: Individual interviews and focus group discussions conducted with 57 Somali women in Oslo to explore perceptions of cervical cancer screening.
Results: some of barriers to participating in screening
Lack of familiarity with cervical cancer
Perceived irrelevance of screening
Emotional barriers such as fear and embarrassment
Practical barriers such as childcare
Language, cultural and religious concerns related to modesty, sexuality and mistrust.
Participants suggestions for reducing barriers and facilitating screening participation included awareness creation, translated materials and female practitioners

Question 35

Lecture Summary:
Health care can cause considerable harm.
Evidence Based Medicine includes accessing and appraising clinical research which can be done using the AAAA framework
Keeping up to date (practising EBM) is a life long commitment
Different healthcare questions require different types of study designs.
Healthcare questions can be divided into 3 types: those measuring frequency, those aiming to establish cause and effect relationships and other types: diagnostic test accuracy and individual’s experiences
Questions about frequency of disease (who, where, when) are addressed by descriptive studies:
cross sectional studies (data collected at individual level)
ecological studies (data collected at population level)
Questions about cause and effect are addressed by analytic studies.
Observational analytic studies (natural experiments) include cohort and case control designs. Experimental analytic studies (where the researcher controls exposure) are limited to exposures that are believed to be beneficial
Questions about individual experiences and beliefs that may help us to understand behaviour are addressed by qualitative studies, most commonly individual or group interviews (focus groups).