Types of study design

Epidemiology is the study of the distribution of disease in populations and the factors that
determine those distributions. The aim is to try and understand what is causing disease or
outcomes so you can eventually come up with a preventative measure.
Two types of study designs: descriptive and analytic
Descriptive

 Include case reports, case series, cross-sectional studies and ecologic studies.
 Descriptive studies are used to describe patterns in a population. These patterns can be
related to prevalence or incidence or trends.
Case-reports
 A case-report is normally a study of a single patient or the report of something that has
occurred, such as an unusual case of a disease which is generally reported or observed by
a physician.
 A case-report usually focuses on the clinical course, prognosis or outcome of a particular
patient.
 Case-reports can help us identify novel issues and can lead to new hypotheses and
avenues for research.
 However, case-reports are often subject to bias and suffer from low scientific rigour.
Case-series
 Case-series is a consecutive set of cases of a disease identified usually by healthcare
professionals or within a healthcare setting such as a hospital.
 Similar to case-reports, they can identify potential hypotheses for testing in analytical studies.
 Case-series are also subject to bias, as physicians or clinicians may self-select the cases.
Cross-sectional studies
 Cross-sectional studies are snapshots of the population of interest, at a specific point in time.
We use the word snapshot, because we assess both the exposure and the outcome at the
same moment in time.
 The same moment in time, may last for days or weeks, if you're collecting data from large
numbers of people.
 The point here, is that each individual is only assessed once, and there is no follow up.
 As a result, you can assess the prevalence of a disease or condition with a cross-sectional
study, but not the incidence rate or risk, both of which require follow-up period.
 While the most frequent method of data collection in cross-sectional studies is through
questionnaires, you could collect blood samples, use diagnostic tests or do physical
measurements. As long as participants are only assessed once, it will still be a cross-sectional
study.
 Overall cross-sectional studies despite all their limitations, still play a key role in epidemiology
and public health, and provide valuable data for both researchers and policy makers.
Where descriptive studies describe the occurrence of disease or its determinants within a
population analytic studies are concerned with how the determinant may influence the
occurrence of disease among individuals.
Analytical
Case control study (retrospective)
  A case control study involves comparing individuals with a particular condition or disease,
known as the cases, to a group of individuals with the same general characteristics but
without the condition or disease of interest known as controls.
 The starting point of most case control studies is the identification of cases, however prior
to selecting cases clear eligibility criteria should be defined, based on the objectives of your
study. This is referred to as the case definition
 Cases can be sourced from a variety of places such as hospitals, clinics or the community
setting. Control should come from the same study population as the cases and should be
representative of the population at risk and exposures within controls should be
measurable with similar accuracy in the cases.
 Assessing exposure in cases and controls has to be carefully considered.
 Another important factor is how many cases and controls are required.
 In the case control study you begin with the outcome of interest and then estimate
exposure.
 We calculate the odds ratio, or the likelihood of having the exposure if you have the
disease, relative to if you do not have the disease.
 The odds ratio can be defined as the odds of exposure among the cases over the odds of
exposure among the controls.
 If the odds ratio equals 1, this means there is no association. If the odds ratio is greater than
one, this indicates a positive association between the exposure and disease. That is that the
exposure is associated with an increased risk of disease. On the other hand if the odds ratio
is less than one there is an inverse association between the exposure and the disease, and
the exposure reduces the risk of disease.

Cohort studies
The cohort study typically involves a group of people without disease who are observed over a
period of time to see what happens to them. This is also known as a longitudinal study.
As a result, the first step in conducting a cohort study is to select your target population and assess
their exposure status.

Observational studies are studies in which the investigator only observes populations or individuals,
and does not interfere or manipulate the exposure. We will now discuss the strengths and
limitations of two most commonly used observational study designs: cohort studies and case-
control studies.

Cohort studies

In cohort studies, a group of individuals without the disease are followed-up over a period of time
to observe what happens to them. Cohort studies try to find associations between previously
defined characteristics of a cohort and the development of disease.

Advantages of cohort studies include:

 They enable researchers to investigate multiple outcomes simultaneously.

 The temporal relationship between exposure and disease can be explored. In other words, we
can be certain that the exposure preceded the disease.
  Cohort studies can allow researchers to calculate incidence rates as well as risks (and the
respective ratios).
 Cohort studies suffer from fewer ethical concerns as researchers are not assigning exposures
or intervening with participants.

On the other hand, there are also limitations of cohort studies which should be acknowledged.

 One weakness of cohort studies is that they usually have a long duration which also implies
larger costs.

 Cohort studies are not useful for studying rare diseases.

 Loss to follow-up which is likely to occur when running cohort studies can introduce bias.
 In occupational cohorts, the healthy worker effect may introduce bias. The healthy worker
effect refers to the low mortality or disease incidence in healthy populations or industrial
cohorts compared to the general population.

Cohort studies are warranted when the time between exposure and disease is relatively short, the
occurrence of the disease is not rare, and when adequate funding is available.

Case-control studies

Case-control studies are another type of observational study where the investigator does not
interfere or manipulate the exposure. In case-control studies, individuals with a particular disease
are compared with individuals without the disease with regard to their exposure status.

Advantages of case-control studies include:

 One of the major strengths of a case-control study is that it is good for studying rare diseases.
 Compared to cohort studies, it is also relatively inexpensive and has a shorter duration,
reducing the time required to acquire results.

On the other hand, like all study designs, case-control studies have limitations.

 Case-control studies are prone to selection bias. Selection bias can occur as a result of how the
participants are recruited into the study; this bias can be related to the case-control status of
the participant or the exposure status.
 Case-control studies do not allow the investigation of multiple outcomes.

Nested case-control and case-cohort studies are studies nested within cohort studies.

 One of the major strengths of nested case-control and case-cohort studies is that the data or
biospecimen is collected prior to the disease, ensuring that the exposure preceded the
disease. This also means there is less chance of bias when assessing the exposure. Finally,
nested studies also reduce selection bias.
 When dealing with valuable biological samples it may be too costly to analyse all biological
samples or researchers may want to use samples for investigating multiple research questions.
In that case, it is more advantageous to use nested case-control or case-cohort studies than full
cohort analyses. Similarly, costs to data entry can be high and it may be more cost-effective to
only analyse data from those who become cases and a sub cohort of non-cases.
  Overall, they allow for the most efficient use of resources.
 Nested studies are useful for studying rare outcomes.
 Specific to case-cohort studies, one of its strengths is that it allows for the estimation of risk
factor distributions and prevalence rates as well as unbiased assessment of correlations among
variables, and can also include person-time in the analyses.

Nested case-control and case-cohort studies have limitations as well. For example, nested case-
control studies can suffer from reduced precision and power as a result of the sampling of controls.

Randomized controlled trials

 Considered the gold standard in analytic epidemiology.

 Randomised controlled trials are experimental studies which compare and assess the
effectiveness of two or more treatments, to see if one treatment is better than another.
 The treatment being tested could be a drug or some method of care, but there must
always be a comparator group which acts as the control.
 Before a prescribed treatment can be used to treat any given condition, it should always be
rigorously tested using clinical trials. Treatments being tested could be compared with no
treatment, ideally using a placebo as the control.
 Randomised control trials simply involve the random allocation of individuals to receive one
of two or more interventions.
 Random allocation means that all participants have an equal chance of assignment to each
of the available interventions.
 Allocation is not determined by the investigator, clinicians, or participants and allocation is
not predictable. The key to randomised controlled trials lies in the random allocation
process.
 Randomisation involves two steps: first, generation of the allocation sequence and second,
implementation of the allocation, which requires allocation concealment to be effective.
 First, you need to generate the allocation sequence. Good methods of generating a
random allocation sequence include using a random numbers table, or a computer
software program, that generates the random sequence.
 The next step is allocation concealment. This is required to ensure that implementation of
the random allocation sequence occurs without anyone knowing which patient will
receive which treatment, as knowledge of the next assignment could influence whether a
patient is included, or excluded, based on perceived prognosis. One commonly used
method is sequentially numbered opaque envelopes.
 Blinding is a procedure whereby one or more parties in a trial are kept unaware of which
treatment arm participants have been assigned to. It's an important aspect of any trial, and
is performed to avoid or prevent conscious, or unconscious bias in the design and delivery
of a clinical trial.
 The different parties involved in a clinical trial are all possible sources of bias, including the
patient being treated, the clinical staff administering the treatment, the physician assessing
the treatment, and the team interpreting the results. Wherever possible, blinding should be
performed in trials.
 There are essentially two types of blinding: single and double. Single blinding occurs when
only one party is blinded, usually the participants. If both the participants and study staff are
blinded, it's called a double blind study.
 Detection bias refers to systematic differences between groups in how outcomes
determined.
Randomised Controlled Trials

Randomised Controlled Trials (RCTs) is often considered the optimal study design for a number of
reasons

 Randomisation substantially reduces the risk of bias in the study

 RCTs are also relevant to actual interventions in populations and settings of interest
 They can provide precise measures of efficacy which we can use to evaluate interventions

However, RCTs are also subject to certain limitations, including:

 The results may not be generalisable to populations that are different than the sample used in
the study
 They can be quite complex and costly to conduct
 Due to cost and practical considerations, they often rely on surrogate endpoints. For example,
a biomarker is measured instead of a health outcome which might require a long time to
develop
 They are experimental studies, which raises ethical issues. Some exposures (e.g. smoking or
radiation) cannot be studied with RCTs because it is unethical to intentionally expose people
to them

The validity of a study may be considered to have two dimensions.

 The first dimension is whether the study is asking an appropriate research question. This is
often described as ‘external validity’, and its assessment depends on the purpose for which
the study is to be used.
 The second dimension of a study’s validity relates to whether it answers its research
question ‘correctly’, that is, in a manner free from bias. This is often described as ‘internal
validity’
‘Bias’ and ‘risk of bias’
 A bias is a systematic error, or deviation from the truth, in results or inferences.
 Biases can operate in either direction: different biases can lead to underestimation or
overestimation of the true intervention effect.
 Bias should not be confused with imprecision. Bias refers to systematic error, meaning that
multiple replications of the same study would reach the wrong answer on average.
 Imprecision refers to random error, meaning that multiple replications of the same study
will produce different effect estimates because of sampling variation even if they would
give the right answer on average.
Types of bias

 Selection bias: Systematic differences between baseline characteristics of the groups that
are compared. E.g: Sequence generation and Allocation concealment.
 Performance bias: Systematic differences between groups in the care that is provided, or in
exposure to factors other than the interventions of interest. Blinding of participants,
personnel and outcome assessors. Other potential threats to validity.
 Attrition bias: Systematic differences between groups in withdrawals from a study.
Incomplete outcome data. Blinding of participants, personnel and outcome assessors.
 Detection bias: Systematic differences between groups in how outcomes are determined.
Blinding of participants, personnel and outcome assessors. Other potential threats to
validity.
 Reporting bias: Systematic differences between reported and unreported findings. Selective
outcome reporting