Study designs

Question 1

Name the (8) basic steps in research.

Answer 1

1. Identify the research problem
2. Review literature
3. Form the research question, objectives and hypotheses.
4. Choose the study design
5. Decide the sample design
6. Collect the data from the research sample
7. Process and analyse the collected data
8. Write the research report, develop a research proposal, disseminate and utilize the results.

Question 2

What are the 5 components of the methodology cycle for empirical research? Also describe what the 5 components mean.

Answer 2

• Observation → proposing the hypothesis and gathering empirical data through observation.
• Induction → inductive reasoning to form a general conclusion based on the data that is gathered by observation.
• Deduction → deducting a conclusion that is based on logic and rationality (so that the conclusion is specific and unbiased).
• Testing → returning to empirical methods to test hypothesis (e.g. with the use of statistical methods).
• Evaluation → putting forth the data, including a conclusion and arguments, stating limitations and tips for follow-up study.

Question 3

What is the difference between quantitative and qualitative empirical research?

Answer 3

• Quantitative empirical research → used to gather information using numerical data (can be different types of study designs)
• Qualitative empirical research → used to gather information via non-numerical data such often semi- or unstructured methods (e.g. via surveys, interviews, etc.)

Question 4

In regard to Randomized Controlled Trials (RCTs), what is:

• Simple randomisation
• Restricted randomisation

Answer 4

• Simple randomisation → randomisation based on a single sequence of random assignments (e.g. flipping a coin)
• Restricted randomisation → randomisation where balance between study groups is achieved in size or baseline characteristics.

Question 5

For restricted randomisation, participants can be randomised via block randomisation or via stratified randomisation. For what are the two types of restricted randomisation used?

Answer 5

• Block randomisation → used to ensure that the groups will be of approximately the same size
• Stratified randomisation → used to ensure that equal numbers of participants with one or more baseline characteristics are balanced within each stratum (e.g. age).

Question 6

What is a placebo controlled trial?

Answer 6

A trial in which there are two (or more) groups. One groups gets the active treatment, the other gets the placebo. Everything else is held the same between the two groups, so that any difference in their outcome can be attributed to the active treatment.

Question 7

Describe what blinding means during a clinical trial.

Answer 7

It is a procedure where one or more parties in a trial are kept unaware of which treatment participants have received. The parties that are kept ‘blind’ can be: patients, investigators, observer, analyst or a combination of one or more of the above.

Question 8

Regarding experimental designs, what is a parallel design?

Answer 8

Here, two or more treatments are compared and the participants are randomised to the treatments that are being compared. A parallel design is seen as the golden standard for Phase 3 medicine trials.

Parallel designs can be:

• with the use of a control group
• Standard-of-care vs new treatment
• Treatment vs sham
• Two active treatment groups
• Treatment vs no-intervention

Question 9

Regarding experimental designs, what is a crossover trial?

Answer 9

A crossover trial has a repeated measures design in which each patient is assigned to a sequence of two or more treatments (each patient receives these treatments in a different order), of which one may be a standard treatment or a placebo.

Question 10

Name advantages and disadvantages of a experimental crossover trial.

Answer 10

• Advantages → higher statistical power
• Disadvantages → it is needed to take into account the washout period (the length of time that someone is enrolled in a trial and must not receive any treatment before receiving the trial’s experimental therapy) and the carry-over effect (the treatment in the first period has an effect on the treatment in the following second period)

Question 11

The analysis of a crossover trial is complex. What can be tested?

Answer 11

• Period effect → implies that the effect of the same treatment that is received at two different periods is different for each period.
• Treatment effect → the causal effect of a given treatment or intervention on an outcome variable of interest.

Note: you can test for the period effect → if there is no difference in period effect → test for treatment effect → if there is a difference in treatment effect, only period 1 is usable.

Question 12

Regarding experimental design, what is a cluster trial?

Answer 12

It is a type of a randomised controlled trial, where groups of subjects are randomised (groups can be wards, hospitals, provinces, educational levels). With this type of trial, a novel therapy is evaluated in a particular group.

Question 13

What is an advantage of a cluster trial?

Answer 13

It helps to prevent contamination (=aspects of the intervention are applied to the non-intervention group).

Question 14

Regarding experimental designs, what is a factorial trial?

Answer 14

In a factorial trial, two (or more) intervention comparisons are carried out simultaneously. E.g. participants may be randomised to receive aspirin or a placebo, and are also randomised to receive a behavioural intervention or standard care.

Question 15

There are 3 main types of factorial trial designs:

• Within subject factorial design
• Between subject factorial design
• Mixed factorial design

Describe their characteristics.

Answer 15

• Within subject factorial design → all of the independent variables (factors) are manipulated within subjects (e.g. a participant is tested both while using a cell phone and while not using a cell phone and both during day and during night)
• Between subject factorial design → the subjects are assigned to different conditions and each subject only experiences one of the experimental conditions.
• Mixed factorial design → at least one within subject variable and one between subject variable.

Question 16

What are advantages of RCTs?

Answer 16

Question 17

What are disadvantages of RCTs?

Answer 17

Question 18

RCTs can be analysed via intention-to-treat (ITT) or via per-protocol analysis. What is the meaning of these two analyses and what is the difference between the two?

Answer 18

• Intention-to-treat → all participants who are randomized are included in the statistical analysis and analysed according to the group they were originally assigned to, regardless of what treatment (if any) they received. Thus, here the effect of assigning a drug is assessed.
• Per-protocol → only the participants who have received a certain treatment within the RCT are assessed for the effectivity of the treatment. Thus, here the effect of receiving the assigned treatment is assessed.

Question 19

What are the advantages of intention-to-treat analysis?

Answer 19

Accurate, unbiased conclusions regarding the effectiveness of the intervention. Preserves the benefit of randomisation.

Question 20

What are the disadvatages of per-protocol analysis?

Answer 20

Overestimation, misinterpretation and inaccurate (biased) assessment of the effectiveness of the intervention.

Question 21

Describe the characteristics of observational studies. Also name examples of types of observational studies.

Answer 21

The researcher observes the effect of a risk factor, diagnostic test, treatment or other invention without trying to change who is or isn’t exposed to it.

• Examples are: case control, cohort and cross-sectional studies

Question 22

Describe the characteristics of an observational case control study.

Answer 22

• Researchers identify people with an existing health problem (i.e. ‘cases’) and a similar group without the problem (‘controls’) and then compare them with respect to the exposure(s).
• The exposure is in the past, then comes the disease.

Question 23

Describe the characteristics of an observational cross-sectional study.

Answer 23

• These studies look at a population at a single point in time, like taking a slice or cross-section of a group, and variables are recorded for each participant.

Question 24

Describe the characteristics of an observational cohort study.

Answer 24

• The definition of cohort = a group of people with defined/shared characteristics who are followed up to determine incidence of, or mortality from, some specific disease, all causes of death, or some other outcome.

Question 25

What are two types of observational study design that aid in evaluating associations between diseases and exposures?

Answer 25

Cohort studies and case-control studies.

Question 26

What is the definition of a prospective (observational) study?

Answer 26

A prospective study follows people from present to future and looks ahead to examine a causal relationship between the determinants that can be established in the present and certain outcomes (e.g. disease) that develops in the future.

Question 27

What is the definition of a retrospective (observational) study?

Answer 27

A retrospective study is a study where the outcome is established in the present (e.g. disease) and where the determinants of e.g. the disease lie in the past.

Question 28

What are the advantages and disadvantages of a retrospective observational study?

Answer 28

Disadvantages:

• The investigator has limited control over data collection.
• The existing data may be incomplete, inaccurate, or inconsistently measured (recall bias)

Advantages:

• Because of the immediate availability of data, this study design is comparatively less costly and shorter than prospective cohort studies.

Question 29

Describe the phases of drug research.

Answer 29

• Preclinical → testing of drug in non-human subjects to gather efficacy, toxicity and pharmacokinetic information.
• Phase 0 → pharmacokinetics, particularly oral bioavailability and half-life of the drug in a max. number of 10 people.
• Phase I → dose-ranging on 20-100 healthy volunteers for safety (or cancer patients for cancer drugs)
• Phase II → testing of drug on 100-300 participants (with a specific disease) to assess efficacy and side effects
• Phase III → testing of drug on 300-3.000 participants (with a specific disease) to assess efficacy, effectiveness and safety.
• Phase IV → post-marketing surveillance in public (anyone seeking treatment from a physician)

Question 30

What is the Medicines Evaluation Board (MEB)?

Answer 30

MEB assesses and guards the efficacy, safety and quality of both human and veterinary medicinal products. MEB is the primary source of information on new medicinal products, new applications, and current risk information in the Netherlands.

Question 31

There are three classes in Medical Device Research (MDR) ranging from low- to high-risk devices. Name examples of these classes.

Answer 31

• Class I devices/low-risk devices → e.g. bandages, handheld surgical instruments, and nonelectric wheelchairs.
• Class II devices/intermediate-risk devices → e.g. CT scanners or infusion pumps for intravenous medications.
• Class III devices/high-risk devices → are very important to health or sustaining life → e.g. pacemakers and deep brain stimulators.

Question 32

Medical Device Research (MDR) also needs to be regulated. For this, the FDA, CE Mark and some notifying bodies (e.g. DEKRA, UK international, etc.) are important. Describe their role in MDR.

Answer 32

• FDA → regulate the sale of medical device products in the U.S. and monitors the safety of all regulated medical products.
• CE mark → a CE mark guarantees that the essential requirements are met and thus that the performance, safety and benefits of the medical device have been considered proven for the circumstances of use intended by the manufacturer. CE marking must first be approved by a notified body.
• Notifying body → an organisation designated by an EU country to assess the conformity of certain products before being placed on the market.

Question 33

For Medical Device Regulations, devices must comply with manufacturing and quality control standards.

• What are some important regulations for class II and III devices?

Answer 33

• Class II devices must submit a 510(k) review. With a 510(k) review it is demonstrated to the FDA that the device to be marketed is as safe and effective, i.e. substantially equivalent, to a legally marketed device. With a 510(k) review, it is not needed to perform clinical trials.
• Class III devices must submit a premarket approval (PMA). This contains manufacturing and safety data, as well as results from clinical studies.

Question 34

What is postmarketing monitoring?

Answer 34

The FDA monitors side effects and device performance. Manufacturers also have postmarket surveillance requirements specific to different device types.

Question 35

What is the hierarchical evidence pyramid?

Answer 35

Studies are assigned levels of evidence based on their methodology. Here, the evidence pyramid is an easy way to visualize this hierarchy of evidence.

Question 36

What does the hierarchical evidence pyramid contain?

Answer 36

• At the top of the pyramid is filtered evidence including systematic reviews, meta-analyses, and critical appraisals. These studies evaluate and synthesize the literature. The top of the pyramid represent the strongest evidence (→ systematic review).
• At the base of the pyramid is unfiltered evidence including RCTs, cohort studies and case-controls (i.e. primary literature).

Question 37

Name every type of study that is included in the hierarchical evidence pyramid from weakest to strongest evidence.

Answer 37

• Background information or expert opinion.
• Case-control studies
• Cohort studies
• RCTs
• Critical-appraised individual articles (articles that are selected and rated for clinical relevance by physicians)
• Critical-appraised topics (short summary of the best available evidence on a focused question)
• Systematic reviews

Question 38

For the following clinical questions, think of what type of study designs fits best with the clinical question:

• therapy
• etiology
• dianosis
• prevention
• prognosis
• meaning
• quality improvement
• cost

Answer 38

• therapy → RCT, meta-analysis (or cohort study, case-control study)
• etiology → RCT, meta-analysis, cohort study (or case-control study)
• diagnosis → RCT (or cohort study)
• prevention → RCT, meta-analysis (or prospective study, cohort study, case-control study)
• prognosis → cohort study (or case-control study)
• meaning → qualitative study
• quality improvement → RCT (or qualitative study)
• cost → economic evaluation

Question 39

What is the EQUATOR network?

Answer 39

• EQUATOR → Enhancing the QUAlity and Transparency Of health Research
• The EQUATOR Network is aimed at promoting transparent and accurate reporting of health research studies to enhance the value and reliability of medical research literature.

Question 40

What is a reporting guideline?

Answer 40

It is a simple, structured tool for health researchers to use while writing manuscripts. A reporting guideline provides a minimum list of information.

Question 41

Why do you use a reporting guideline?

Answer 41

It is used to ensure a manuscript can be:

• understood by a reader
• replicated by a researcher
• used by a doctor to make a clinical decision
• included in a systematic review

Question 42

For observational studies, the reporting guideline that is used is the STROBE reporting guideline. Think of how an article looks like according to a reporting guideline.

Answer 42

Question 43

For RCT studies, the reporting guideline that is used is the CONSORT reporting guideline. What (among others) is included in the article according to the CONSORT reporting guideline?

Answer 43

A flowchart.