When planning a clinical epidemiological study, which aspect of the design should you

consider first?

a) The type of study design (prospective study, randomized controlled trial etc.)

b) The analysis plan

c) The kinds of patients who you want to include in your study

d) The size and duration of your study

e) The research question (on which the study will be based)

Correcto
The foundation of any clinical epidemiological study should be a well-defined research
question. Only after careful thought about the research question should you begin to
consider other aspects of the study (methods, analyses etc.)

Pregunta 2
Correcto
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2. Pregunta 2
Which of the following statements comparing etiologic research and diagnostic research is
correct?

a) Diagnostic research aims to identify what is causing a patient’s disease

b) Information about the etiology of a disease is generally more clinically relevant than
diagnostic information

c) Both etiologic research and diagnostic research aim to identify causal relationships
between determinants and diseases

d) As with diagnostic research, in etiologic research associations between determinants

and outcomes may need to be adjusted to account for other (confounding) factors
e) None of the above

Correcto
Diagnostic research is descriptive in nature so a), c) and d) can not be correct. In practice,
diagnostic information is generally more useful for clinical decision making. For example,
when a patient presents with a possible hip fracture, the clinician will be more interested in
whether the patient actually has a hip fracture than what factors led to the patient being
injured.

Pregunta 3
Correcto
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3. Pregunta 3
Why is it essential in a diagnostic study to have an accurate reference standard?

a) Without an accurate diagnosis, it will not be possible to get a true measure of the
accuracy of the (combination of) diagnostic tests under study.

Correcto
In diagnostic research, the predictions made by a set of new tests are compared with the
reference standard to see how accurate they are (how close they come to the truth). If the
reference standard makes errors in the diagnosis of the disease, it becomes very hard to
assess the accuracy of the tests under study. Unfortunately, in some situations, there is not
an accurate reference standard, and alternative approaches need to be taken to get around
this, such as using a panel diagnosis as the reference standard.

b) The reference standard is the new test you want to study, so ideally this should be as
accurate as possible

c) Without an accurate reference standard, the results will not be generalizable to future
patients outside of the domain

d) An accurate reference standard is necessary for the study to reflect clinical practice

e) All of the above

Pregunta 4
Correcto
 1 / 1 puntos

4. Pregunta 4
A recent diagnostic study took 2 years to complete from the recruitment of the first patient
to the final diagnosis made in a patient. Why, despite the cross-sectional nature of
diagnostic research, might the study have run over 2 years?

a) The research aim might have been to study whether patients would develop the disease
in two years time from the start of the study.

b) The reference standard as not accurate enough to confirm the diagnosis, so additional
patient follow-up was needed to truly confirm the original diagnosis.

c) The disease might be quite uncommon, and so it may have taken two years to recruit a
sufficient number of patients in the study

d) Answer a) and c) are right.

e) Answer b) and c) are right.

Correcto
Both b) and c) are correct. Sometimes, when one is concerned that the reference standard
is not sufficiently accurate, patients can be followed for a period of time to confirm whether
they really did have the original diagnosis. In addition, it can take a long period of time to
recruit a sufficient number of patients in a diagnostic study, particularly if the diagnosis is
uncommon. Option a) is not correct, as this answer describes a prognostic problem.

Pregunta 5
Correcto
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5. Pregunta 5
Blinding is not only a useful technique in intervention research, but also in diagnostic
research.Why might it be important to blind assessors to a patient’s outcome (results of the
reference standard) when taking measurements with tests that are being investigated in a
diagnostic study?

a) To ensure that causal relationships are not biased

b) To ensure that the interpretation of results of the tests being studied are not influenced
by a knowledge of the outcome

Correcto
a), c) and e) are not relevant to diagnostic research, but instead describe issues in
therapeutic (intervention research). Blinding will not improve the accuracy of the reference
standard, but it may sometimes be necessary to blind the clinicians who measure the
reference standard to the results of the tests under investigation.

c) To ensure that the two treatment arms are comparable

d) To improve the accuracy of the reference standard

e) To prevent confounding

Pregunta 6
Incorrecto
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6. Pregunta 6
Is the following statement true or false?

“Prognostic models that do not specify a time period for predictions (eg. 1-year risk of
mortality) are not useful in clinical practice”.

True

False

Esto no debería estar seleccionado

For predictions to have a meaning, the time period (otherwise known as the “prediction
horizon”) must be specified. The predictions a model might make for a patient’s 1-year risk
of mortality and 1-day risk of mortality could be completely different, and the determinants
of 1-year risk and a 1-day risk could be very different.

Pregunta 7
Correcto
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7. Pregunta 7
Is the following statement true or false?
“Validation is an essential part of prognostic research, as newly developed models may not
perform as well in new populations as they did in the original study population”.

True

Correcto
This is absolutely true. In fact, it is a good idea to start planning a validation study as soon
as you consider developing a new prediction model.

False

Pregunta 8
Correcto
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8. Pregunta 8
It is becoming increasingly recognized that for a prognostic model to be used widely in
practice, there should be some evidence that it has a positive impact on patient health. In
general, which kind of study design is most suitable when investigating the impact of a
prognostic model, and why?

a) A prospective cohort study (observational)

b) Cross-sectional study

c) Randomized controlled trial

Correcto
Prognostic impact studies are interested in the causal relationship between using the
prognostic model and some kind of patient or hospital outcome. As with diagnostic impact
studies, they can be seens as a kind of intervention study, and a randomized controlled trial
is an excellent tool for measuring the effects of an intervention.

d) A retrospective study

e) A case-control study

Pregunta 9
 Correcto
1 / 1 puntos

9. Pregunta 9
In recent years, there has been a drive away from efficacy research towards effectiveness
research. Is the following statement true or false?:

“The major advantage of effectiveness research compared to efficacy research is that it

measures the effect of a drug on individual patient outcomes in a highly controlled setting”.

True

False

Correcto
This sentence describes efficacy research. Effectiveness research is especially useful as it
provides insight into how beneficial the treatment is likely to be taking into account factors
such as patient preferences and uptake of the drug, closely reflecting use of the drug in
practice.

Pregunta 10
Correcto
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10. Pregunta 10
When might a randomized control trial NOT be suitable for studying the efficacy of a
therapy?

a) When it takes a very long time to observe the effects of a therapy

b) When the outcome being assessed is very rare

c) When controlling the allocation of a treatment is unethical

d) All of the above

Correcto
When the outcome is very rare or takes a long time to observe, a trial would need to recruit
a very large number of people or be continued for a very long time, often making it too
expensive to be conducted. There are also many situations where an experimental design
simply is not ethical.

e) None of the above

Pregunta 11
Correcto
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11. Pregunta 11
Is the following statement true or false?:

“Placebo control is more useful in pragmatic trials (effectiveness research) than explanatory
trials (efficacy research)”.

True

False

Correcto
The opposite is true. Pragmatic trials aim to collect evidence of the effectiveness of a
treatment in practice, and placebo is not relevant to real-life practice.

Pregunta 12
Correcto
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12. Pregunta 12
In diagnostic and prognostic research, what is meant by “added value”?

a) The additional improvement in patient health when a prediction model is used in practice

b) The improvement seen in the performance of an existing prediction model, upon the
addition of a new predictor to the model.

Correcto
a) and c) describes the impact of a prediction model in practice. d) refers to the benefits of
validation.

c) The improvement in cost-effectiveness when a prediction model is used in practice

d) The improvement in the value of a model after testing in a new population

e) None of the above

Pregunta 13
Correcto
1 / 1 puntos

13. Pregunta 13
Is the following statement true or false?

“One result of restricting the domain of a research problem to a very narrow subset of
patients is that the results of the study may not be generalizable to many future patients”.

True

Correcto
If the domain is very narrow, the results of the study will not be widely applicable. However,
in many cases this is not a bad thing as the clinical problem may only be relevant to a very
specific subset of patients (people with a certain disease, or a specific set of
characteristics).

False

Pregunta 14
Correcto
1 / 1 puntos

14. Pregunta 14
Is the following statement true or false?

“Assessing the effectiveness of a new vaccine is not a kind of intervention research, as the
term ‘intervention research’ only applies to research into active treatments and not
preventative treatments (prophylaxis)”.

True

False

Correcto
Think back to the pneumococcal vaccine trial we talked about a few weeks ago. An
intervention is not necessarily something that treats sick patients- it can also be something
given to people by clinicians to prevent the occurrence of disease.

Pregunta 15
Correcto
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15. Pregunta 15
Below you will see three different examples of research problems in clinical epidemiology.
For each example, you need to decide which branch of clinical epidemiology is most
relevant, then select a research question that you think is most appropriate/complete and
finally answer a question about the design of the study.

“Timely identification of non-alcoholic fatty liver disease (NAFLD) is vital in the prevention of
cirrhosis. Several tests are available to determine whether or not a patient has NAFLD, but
none of these are perfect. Furthermore, the most accurate tests are invasive tests, which
carry a small risk of complications. It is not clear which combination of tests would best
guide clinicians in reaching a decision.”

In which area of the DEPTh model does this clinical problem primarily lie?

a) Diagnostic

Correcto
The main problem here is identifying whether or not people actually have NAFLD.

b) Etiologic

c) Prognostic

d) Therapeutic

e) None (This is not relevant to clinical epidemiology)

Pregunta 16
Correcto
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16. Pregunta 16
A group of researchers decide to conduct a study to address this issue. Which of the
following would be the most appropriate domain for the study?

a) Patients diagnosed with NAFLD

b) Patients who have been treated for NAFLD

c) Healthy patients (from the general population)

d) Patients suspected of having NAFLD

Correcto
Remember that the research topic is diagnostic. The clinical problem relates to any patients
who enter the clinic who may or may not have NAFLD. The general population is too broad,
so the findings of this study (and any diagnostic model developed as a part of this study)
would not be applicable to patients who are not suspected of having NAFLD.

e) Patients who have been confirmed not to have NAFLD

Pregunta 17
Correcto
1 / 1 puntos

17. Pregunta 17
The researchers decide to develop a new multivariable prediction model for use in clinical
practice. Which of the following do you think could be a major goal of this research?

a) Faster decision making in practice

b) Greater accuracy in the identification of NAFLD

c) Fewer invasive procedures being used, so less burden on patients

d) Fewer invasive procedures being used, so a reduction in costs

e) All of the above

Correcto
Any of the goals could justify the decision to develop a new prediction model. The model
could be developed with the aim of improving diagnostic accuracy. Alternatively a non-
invasive model could be useful to reduce the burden on patients, and reduce costs.

Pregunta 18
Correcto
1 / 1 puntos

18. Pregunta 18
Is the following statement true or false?

“It will be important for the researchers to think about validating their model”.

True

Correcto
Although we have mainly discussed validation in the context of prognostic research, it is
equally important to demonstrate whether a diagnostic model performs well in new
populations before it can be used in clinical practice.

False

Pregunta 19
Correcto
1 / 1 puntos

19. Pregunta 19
The prognosis of patients who have an acute ischemic stroke can vary greatly, making it
challenging for doctors to prescribe the best course of treatment. It has been suggested
that imaging tests could be used alongside other patient information, to help predict the
short-term course (within a month) of an AIS patient’s health, but more evidence is needed
to confirm this. A group of researchers decide to conduct a prognostic study to address this
issue.

Which of the following research questions would you recommend the researchers base
their study on?

a) Which imaging test best predicts the the risk of mortality of AIS patients within 30 days of
having a stroke?
b) Which combination of imaging tests and patient information best identifies patients with
AIS?

c) Which combination of imaging tests and patient information best predicts the the risk of
mortality of AIS patients within 30 days of having a stroke?

Correcto
a) only refers to a single test, but this is a multivariable problem (“imaging tests… alongside
other patient information”). b) This is a diagnostic research question. d)The time frame of
the prognostic problem should be specified. e) This is a (prognostic) intervention research
question (“does using a specific set of tests compared to another cause patients to have
have better health outcomes?”)

d) Which combination of imaging tests and patient information best predicts the risk of
mortality in AIS patients

e) Which combination of imaging tests is most effective in improving survival beyond 30

days in patients with AIS

Pregunta 20
Correcto
1 / 1 puntos

20. Pregunta 20
Is the following statement true or false?

“As the study is prognostic by nature, researchers should not enroll AIS patients in their
study”.

True

False

Correcto
The aim of this study is to develop a model for the prediction of short-term health outcomes
in AIS patients, and therefore the study population should consist of AIS patients. If the
study aimed to develop a model to predict the occurrence of AIS, then patients at risk of
AIS should be recruited and followed to see whether they have an AIS.

Pregunta 21
 Correcto
1 / 1 puntos

21. Pregunta 21
The researchers decide to collect data for their study retrospectively, using an existing
medical database. Do you think missing information could be a problem in their study?

Yes

Correcto
Missing information can be problem in prognostic research, where patient information is
collected over time. Things become more difficult in retrospective studies, where there may
not be full information available for all patients, and even the outcomes of patients may not
be available. Furthermore, it may even be the case that not all of the determinants of
interest have been recorded in the database.

No

Pregunta 22
Correcto
1 / 1 puntos

22. Pregunta 22
Which of the following suggestions for prediction model building would you not suggest to
the researchers?

a) They could create an app to help clinicians use the model in practice

b) They could consider using a regression technique such as Cox proportional hazards
modelling to develop their model

c) They could use automated statistical selection techniques as the primary means of
deciding which determinants should be included in their model

Correcto
a), b) and d) are good suggestions, and while automated selection methods can be useful
when building a prognostic model, it is important that the choice of which variables to
include in the prediction model should be primarily based on evidence from literature or
expert opinions.
d) They should consider using methods to deal with missing data (if appropriate)

e) None of the above (they are all excellent suggestions)

Pregunta 23
Correcto
1 / 1 puntos

23. Pregunta 23
A computerized tool was developed to help clinicians assign a probability of having acute
cardiac ischemia (ACI) to symptomatic (but not confirmed) patients. This would then help
the clinician to decide whether the patient should be hospitalized. A group of researchers
conducted a study to determine whether using the tool actually helped to reduce the
number of unnecessary hospital referrals (reduce the number of people without ACI being
sent to hospital).

What kind of research is described here?

a) Therapeutic intervention research

b) Prognostic intervention research

c) Diagnostic intervention research

Correcto
The research problem lies in the area of diagnosis (does the patient have ACI or not), but
the research is really interested in the causal effect of using the diagnostic tool on patient
outcomes (in this case hospital referral).

d) Prognostic research

e) Diagnostic research

Pregunta 24
Correcto
1 / 1 puntos

24. Pregunta 24
Why do you think the researchers decided to present their prediction model in the form of a
computerized tool?
a) It could reduce the chance of calculation errors when used in practice

b) It is easier and more convenient for clinicians to use in practice

c) It is the only way to present models for use in clinical practice

d) Answer a) and b) are right

Correcto
There are several ways that a prediction model can be presented for use in practice.
Commonly, mathematical models are converted into score charts or nomograms. Apps
have even been developed for clinicians to use on their smartphones in practice, providing
a very convenient and accessible means of using the models (for those with access to
smartphones!).

e) Answer a), b) and c) are right

Pregunta 25
Correcto
1 / 1 puntos

25. Pregunta 25
The ACI-TIPI score is the main intervention in the study. Will it be necessary to have a
comparator group, or should the ACI-TIPI be used for all patients in the study?

a) A comparator is necessary (a group in whom the model is not used)

Correcto
This research is a kind of (diagnostic) intervention research, and to establish whether the
model improves patient outcomes in the long-run, it will be important to assess patient
outcomes after using the model compared to patient outcomes when the model has not
been used.

b) A comparator is not necessary

Pregunta 26
Correcto
1 / 1 puntos
26. Pregunta 26
Is the following statement true or false?

“Randomization could be useful to ensure the results are valid and free for bias”.

True

Correcto
Randomized allocation of the intervention (use of the diagnostic model) would help to
ensure that the individuals in each of the groups, intervention and comparator, are
comparable with respect to their baseline characteristics. The researchers could choose to
randomize at the patient level or potentially at the clinic level (if several different clinics are
recruited in the study- known as a “cluster randomized trial”).

False

Pregunta 27
Correcto
1 / 1 puntos

27. Pregunta 27
“Fluoroquinolones are an important class of drugs used in the treatment of serious bacterial
infections. Case reports suggested a possible association between fluoroquinolone use and
acute liver injury, though the occurrence of acute liver injury seems very uncommon and
unpredictable. A group of researchers decide to investigate this association by conducting
a case-control study.”

In this example, what kind of side effect is acute liver injury?

Type A

Type B

Correcto
Type B side effects are rare, hard to predict and do not usually show a dose-dependent
relationship with the drug (unlike type A side-effects).

Pregunta 28
Incorrecto
0 / 1 puntos

28. Pregunta 28
Why do you think the researchers chose to use a case control study design?

a) It has has a lower risk of bias than a randomized trial

b) Acute liver failure is a rare outcome

c) Less time and money will need to be invested in a study with this design

d) Anwer b) and c) are right.

e) Answer a), b) and c) are right.

Esto no debería estar seleccionado

Case control studies are generally more susceptible to bias than randomized controlled
trials. However, in this kind of setting, where confounding by indication is not an issue, and
the prognoses of patients in the case and control groups will be comparable, a case control
design have a low risk of bias.

Pregunta 29
Correcto
1 / 1 puntos

29. Pregunta 29
What will be the determinant in their study?

a) Fluoroquinolone use

Correcto
Fluoroquinolone is the factor that we are interested in, whereas acute liver injury is the
outcome.

b) Bacterial infection

c) Acute liver injury

d) Mortality
e) None of the above

Pregunta 30
Correcto
1 / 1 puntos

30. Pregunta 30
Is this kind of research descriptive or causal by nature?

Descriptive

Causal

Correcto
The researchers want to know whether use of fluoroquinolone causes acute liver injury.