Study types

Question 1

Definition of systematic review

Answer 1

review which identifes, appraises & synthesizes all evidence that meets pre-specified eligibility criteria for a specific research question

Question 2

Definition of meta-analysis

Answer 2

statistical analysis that combines results of multiple scientific studies

Question 3

Definition of RCT

Answer 3

comparison outcomes of group receiving intervention with control group

Question 4

Definition of Prospective vs retrospective Cohort study

Answer 4

groups classified based on exposure followed up prospectively to analyse outcomes

groups classified based on outcome look at retrospectively to analyse exposures

Question 5

Definition of Case-control study

Answer 5

groups classified based on outcome and analysed retrospectively regarding exposure

Question 6

Definition of Cross-sectional study

Answer 6

survey of a defined population at a single point in time

Question 7

Phase I Clinical Trial

Answer 7

These are “first in human” studies usually conducted on a small number of healthy volunteers to determine the tolerability and safety of a new drug, as well as its pharmacokinetics and pharmacodynamics

Question 8

Phase II Clinical Trial

Answer 8

These are “dose-finding” trials usually on patients - a lower number than Phase III but larger than Phase I - assessing optimal dosing (giving different doses and following up to determine the efficacy and tolerability/toxicity) and efficacy (biological effect of the drug)

Question 9

Phase III Clinical Trial

Answer 9

These trials assess the effectiveness of a new drug/ intervention, as compared to the gold standard therapy (whilst always ensuring its safety), to inform the value of the new intervention in clinical practice. They are usually multi-centre randomised control trials on large numbers of patients.

Question 10

Post-marketing surveillance (Phase IV)

Answer 10

Monitors safety of the drug after it is being marketed (pharmacovigilance), to detect any rare or long-term adverse events or side effects that were not detected during previous trials

Question 11

Randomisation

Answer 11

The process of assigning trial subjects to treatment or control groups using an element of chance, so that each participant has an equal chance of being allocated to either group.

This is to reduce allocation bias and balance known and unknown possible confounding factors, such that any difference between the two groups is purely by chance.

Question 12

Stratified randomisation

Answer 12

Prevents imbalance between treatment groups for known factors that influence prognosis or treatment responsiveness. As a result, stratification may prevent type I error and improve power for small trials (<400 patients), but only when the stratification factors have a large effect on the prognosis.

Question 13

Allocation concealment

Answer 13

Refers to masking the randomisation code or sequence before patients are recruited so that investigators don’t know what group the next patient will be randomised to, thus avoiding selection bias

Question 14

Blinding

Answer 14

Involves masking the allocation of the treatment group after randomisation, so one or more parties involved in the trial are not aware whether the participants are in the intervention or control group. This aims to remove bias, including performance and observer bias.

Question 15

Efficacy

Answer 15

The capacity for the therapeutic effect of a given intervention, e.g. whether a drug demonstrates a health benefit over a placebo or other intervention when tested in an ideal situation. These are called explanatory trials.

Question 16

Effectiveness

Answer 16

How well an intervention works in practice, i.e. in the real world outside a clinical trial. This tends to be lower than the efficacy. There are called pragmatic trials

Question 17

Placebo

Answer 17

Traditionally refers to a substance or treatment with no active therapeutic effect. In medical research, it is unethical to give a substance without therapeutic effect when one is available. Hence, a placebo refers to the control used, for example, the gold-standard intervention in which the intervention of interest is being measured against.

Question 18

Surrogate endpoint

Answer 18

A variable that is relatively easily measured and which predicts a rare or distant outcome of the intervention tested. It is not a direct measure of either harm or clinical benefit.

Question 19

Surrogate outcome

Answer 19

Markers that are substituted in for a clinical outcome e.g. ejection fraction as an indicator of disease severity in heart failure

Question 20

Composite outcome
pros vs cons

Answer 20

A combination of variables e.g. a scoring tool. Useful when each variable in the scoring tool is rare as it gives power to the study. Difficult to interpret.

Question 21

Internal validity

Answer 21

the degree to which the causal relationships found in a study can be trusted (with bias reducing this).

Question 22

Secondary research

Answer 22

E.g. systematic review/literature review. This means research that amalgamates the results of many studies, largely negating the influence of bias on the results.

Question 23

Advantages of SR and MA

Answer 23

More accurate assessment of the ‘true’ population effect.
Larger patient numbers lead to increased power and reduce type II error (which is the erroneous conclusion that an intervention has no effect).
Less bias (funnel plot → publication bias assessment, heterogeneity analysis → method and data collection)

Question 24

Disadvantages of SR and MA

Answer 24

Direct comparisons between studies are difficult, due to differing methodology.
It can introduce types of bias (selection, publication (consider grey literature), and language bias (non-English articles), selective reporting bias)

Question 25

Steps followed in a SR

Answer 25

Check for existing reviews/protocols Identify your research question Define inclusion/exclusion criteria Search for studies Select studies for inclusion based on pre-defined criteria Extract data from included studies Evaluated risk of bias of included studies Present results and assess quality of evidence

Question 26

Steps followed in a MA

Answer 26

Frame a question (based on a theory): PICOK method. Run a search Screen Extract data Determine the quality of information in the articles (assess internal validity but also use GRADE criteria). Critically appraise the information contained within each study. You must decide if the study meets the internal validity criteria. A method to ascertain the quality of each outcome within an article is to use the GRADE criteria (grading recommendations assessment, development, and evaluation). Determine the extent to which these articles are heterogeneous. Estimate the summary effect size in the form of ORs and using both fixed and random effects models. Construct a forest plot Determine the extent to which these articles have publication bias and run a funnel plot. Conduct subgroup analyses and meta regression to test if there are subsets of research that capture the summary effects.

Question 27

What is the problem with surrogate outcomes?

Answer 27

May not reflect outcomes that are important to patients

Question 28

RCT pros

Answer 28

Gold standard for studying treatment effects Random allocation reduces selection bias and equally distributes confounding factors between arms Prospective: allows one to conclude causation between intervention and outcome (and outcomes determined a priori) Reliably measures efficacy Allows for meta-analyses

Question 29

RCT cons

Answer 29

Difficult Time-consuming Expensive May be prone to underpowering Ethical problems in giving different treatments to the groups

Question 30

Prospective cohort study pros

Answer 30

Can answer questions about aetiology and prognosis Direct estimation of disease incidence rates Can assess temporal relationships and causal links Can assess multiple outcomes (that may be associated with multiple exposures…) Good for rare exposures Can estimate risk ratios and odds ratios

Question 31

Prospective cohort study cons

Answer 31

Can take a long time from exposure to measured outcomes Cannot be used if diseases have long latency period Expensive to set up and maintain Bias is an issue if subjects drop out over time (often a large cohort is needed)

Question 32

Advantage of prospective vs. retrospective cohort studies

Answer 32

Prospective: able to control design, sampling, data collection and follow-up methods, and can measure all variables of interest. Retrospective: time efficient and inexpensive, and easy to obtain large samples.

Question 33

Case-control pros

Answer 33

Good for studying rare disease Useful when there is a long latency period between a risk factor and an outcome Quick and cheap as few subjects required Requires fewer patients - no loss to follow up

Question 34

Case-control cons

Answer 34

Can be difficult to match to the control group (a potential source of bias is the precise definition of who counts as a case. Subject to selection bias.) Rely on recall and records to identify risk factors (recall bias) Temporal relationship difficult as subjects forget about sequence of events (symptom appearance) - relies on reverse causation

Question 35

Retrospective design is susceptible to reverse causation. What is this?

Answer 35

A form of protopathic bias - this is when the applied treatment for disease appears to cause the outcome

Question 36

What do cross-sectional studies aim to do?

Answer 36

Cross-sectional studies aim to take an overview of the whole population (entire hospital population) and not a subgroup which is seen in case-control studies (pregnant women).

Question 37

What is a downside to cross-sectional studies?

Answer 37

It is purely descriptive and can only show correlation, not causation (e.g. pregnancy shown to correlate with deep vein thrombosis but not cause it).

Question 38

What is a case report?

Answer 38

An account of the presentation, diagnosis, treatment, and follow-up of an individual patient. Case reports often combine the accounts of multiple patients with similar presentations or diagnoses.

Question 39

What is the purpose of a case report?

Answer 39

They are often used to describe unusual associations between symptoms and disease, novel treatments, and new insights into the pathogenesis of a disease. The evidence produced is anecdotal and for that reason is often used as a springboard for more robust research e.g., a case-control study.

Question 40

The registration of clinical trials has been a formal condition of

Answer 40

Research Ethics Committee approval

Question 41

Registration of a trial should ideally occur

Answer 41

Before the first participant is recruited

Question 42

Randomisation techniques

Answer 42

Fixed randomisation: simple, block, stratified. Other: cluster, adaptive

Question 43

Ethical points to consider

Answer 43

Who funded the study? Conflicts of interest? Study population? Able to consent? How recruited? Intervention? Participants potentially being given an inferior treatment? Risks or side effects? Primary outcome? Implications of trial?

Question 44

Autonomy

Answer 44

Respect for the patient’s right to self-determination

Question 45

Beneficence

Answer 45

Acting in the best interest of others

Question 46

Non-maleficence

Answer 46

Avoiding and minimising potential harm

Question 47

Justice

Answer 47

Ensuring fair allocation of resources

Question 48

The subject’s welfare and autonomy must always take preference over the benefit to science - true or false?

Answer 48

True

Question 49

What is a cross over trial?

Answer 49

All participants will be exposed to the intervention and control, in a random order, usually with a washout period inbetween

Question 50

Advantages of cross over

Answer 50

each subject acts as his or her own control, and that a smaller number of patients are required in comparison to parallel-group studies

Question 51

Disadvantages of cross over

Answer 51

LOTS Longer in duration Drop outs that only complete one treatmetnt contribute little the analysis Carryover effect from one treatment to the next

Question 52

What is a nested case control study?

Answer 52

cases of a disease that occur in a defined cohort are identified and, for each, a specified number of matched controls is selected from among those in the cohort who have not developed the disease by the time of disease occurrence in the case Differs from case-control study as controls are sampled from pre-defined source population with known sample size vs an unknown size for standard case-control

Question 53

Define parallel group

Answer 53

In parallel group randomisation, participants are randomised to one or two or more arms (groups), there should be an equal number in each arm

Question 54

Single vs double blind

Answer 54

In a single-blind study, patients do not know which study group they are in (for example whether they are taking the experimental drug or a placebo). In a double-blind study, neither the patients nor the researchers/doctors know which study group the patients are in.

Question 55

Pros and cons of multicentre trials

Answer 55

Pros: Increased generalisability Shorter recruitment period Diverse population Larger sample size Cons: Methodological problems/inconsistencies Centre-specific bias

Question 56

Superiority study design

Answer 56

a trial with the primary objective of showing that the response to the investigational product is superior to a comparative agent (active or placebo control).

Question 57

Non-inferiority study design

Answer 57

are intended to show that the effect of a new treatment is not worse than that of an active control by more than a specified margin.

Question 58

Random sampling

Answer 58

Each element in the population has an equal chance of occuring. While this is the preferred way of sampling, it is often difficult to do. It requires that a complete list of every element in the population be obtained. Computer generated lists are often used with random sampling.

Question 59

Systematic sampling

Answer 59

easier to do than random sampling In systematic sampling, the list of elements is "counted off". That is, every kth element is taken. This is similar to lining everyone up and numbering off "1,2,3,4; 1,2,3,4; etc". When done numbering, all people numbered 4 would be used.

Question 60

Convenience sampling

Answer 60

very easy to do, but it's probably the worst technique to use. In convenience sampling, readily available data is used. That is, the first people the surveyor runs into.

Question 61

Cluster sampling

Answer 61

dividing the population into groups -- usually geographically. These groups are called clusters or blocks. The clusters are randomly selected, and each element in the selected clusters are used.

Question 62

Stratified sampling

Answer 62

divides the population into groups called strata. However, this time it is by some characteristic, not geographically. For instance, the population might be separated into males and females. A sample is taken from each of these strata using either random, systematic, or convenience sampling.

Question 63

Types of randomisation

Answer 63

Simple Block Stratified Covariate Adaptive

Question 64

Nuremberg Code

Answer 64

a set of ethical research principles for human experimentation created by the court in U.S. v Brandt Basic principles include: voluntary consent of the human subject is absolutely essential experiment should be such as to yield fruitful results for the good of society experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease

Question 65

Declaration of Helsinki

Answer 65

The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data Basic priniciples: Duty of researchers to protect the: Life Health Dignity Integrity Right to self-determination Privacy Confidentiality

Question 66

Audit

Answer 66

the process of examining and reviewing documents and records to ensure accuracy, and that care complies with the current standards, rules and regulations within the medical field

Question 67

Quality improvement project

Answer 67

identifying a deficit in quality of care and aiming to improve, by making small cumulative changes and measuring their effects

Question 68

Audit vs QIP

Answer 68

Audits can improve the quality of care but by definition must compare current practice to a 'standard'. In contrast, QIPs allow creativity by enabling improvements in areas that might not have easily identifiable 'standards'.

Question 69

Hierarchy of evidence

Answer 69

1. Systematic reviews and meta-analyses 2. RCTs 3. Cohort studies 4. Case-control studies 5. Case series, Case reports 6. Editorials, Expert opinion