Experimental study design Randomised Controlled Trials MSc Physician Associate Practice Master’s Phy

Question 1

Descriptive epidemiology tends to focus on?

Answer 1

generating hypotheses

Question 2

Analytical epidemiology tends to focus on?

Answer 2

Testing hypotheses

Question 3

What is descriptive epidemiology?

Answer 3

Descriptive Epidemiology is the study of the amount and distribution of
disease or other health-related characteristics in human populations by
person, place and time.

Descriptive epidemiology identifies who is affected,
when, and where the situation is occurring in the community or population
of interest. This is an important tool for health services planning and
programming.

Question 4

What is an experimental study?

Answer 4

A study in which conditions are under the direct control of the investigator.
In epidemiology a study in which a population is selected for a planned trial
of a regimen whose effects are measured by comparing the outcome of the
regimen (e.g. new medication) in the experimental group with the outcome
of an alternative regimen (standard) in a control group.

Question 5

To avoid bias in experimental studies what should take place?

Answer 5

To avoid bias, members of the experimental and control group should be
comparable in all variables except in the regimen that is offered them.
Allocation of individuals to experimental and control groups is ideally by
randomisation.

Question 6

Most common experimental studies

Answer 6

1. Randomised controlled trial (individuals)
2. Community trials (communities, clusters)

Question 7

Since the interventions are strictly determined by the study protocol, ethical
considerations are of paramount importance in the design of these studies. True or false?

Answer 7

True

Question 8

What experimental study is the most reliable study design? Why?

Answer 8

Randomised controlled trial.

Most reliable study design due to randomisation and control of all other
variables except for the intervention (eliminates confounding)
• Regarded as the golden standard among primary study designs

Question 9

Golden standard primary study design?

Answer 9

RCT

Question 10

In RCT, groups are followed up to see how effective the experimental intervention was. Outcomes are measured at specific times and any difference in response between the groups is assessed statistically.
This method is also used to reduce ?

Answer 10

Bias

Question 11

What does H0 tell?

Answer 11

Null hypothesis – almost always no difference between the two treatments

Question 12

What does H1 tell?

Answer 12

Alternative hypothesis

Question 13

What do all hypotheses tests use to weigh the strength of the
evidence (what the data is telling you about the population)?

Answer 13

P- value

Question 14

What is the p value.

Answer 14

The p-value is a number between 0 and 1 and interpreted in the following
way:
– A small p-value (typically < 0.05) indicates strong evidence against the null
hypothesis, so you reject the null hypothesis. Thus you accept the alternative
hypothesis

– A large p-value (typically > 0.05) indicates weak evidence against the null
hypothesis, so you fail to reject the null hypothesis. Thus you accept the null
hypothesis

Question 15

P values indicate the believability that the null hypothesis is true given the sample
data. True or false?

Answer 15

True

Question 16

Why are P-values are an integral part of inferential statistics ?

Answer 16

P-values are an integral part of inferential statistics because they help you use your
sample to draw conclusions about a population.

Question 17

Statistically significant means the difference is large or
scientifically / clinically important, true or false?

Answer 17

False

Question 18

What type of question is statistical significance?

Answer 18

Mathematical

Question 19

What type of question is a Clinical importance?

Answer 19

• Requires clinical judgment
  – Must be considered & addressed before it is possible to ask about
  statistical significance

Question 20

Randomisation should equally distribute any
confounding variables between the two groups, although it is important to be
aware that differences in confounding variables may arise through?

Answer 20

chance

Question 21

Randomisation ensures each individual (or each group in the case of cluster
randomisation) ?

Answer 21

Has the same chance of being allocated to either group

Question 22

What prevents (conceal) advanced knowledge of what intervention
group people have been assigned to prior to the start of the RCT?

Answer 22

Concealment

Question 23

Concealment should be done by?

Answer 23

Someone who is not responsible for recruiting people into the trial

Question 24

This process prevents researchers from (unconsciously or otherwise)
influencing which people are assigned to a given group, intervention or
control

Answer 24

Concealment

Question 25

Randomisation performance: Coin toss: heads = control, and tails = intervention/treatment. Throwing a dice: three or under three = control, and over three = intervention/treatment. A shuffled deck of cards: odds, and evens. Drawing allocations out of a hat.

Answer 25

Simple randomisation

Question 26

Randomisation performance: Maybe appropriate for smaller trials to ensure equal numbers in each group. With two treatment groups, block size of either 4, 6 or 8

Answer 26

Blocked randomisation

Question 27

Randomisation performance: Ensures that a potential baseline confounding variable is equally distributed between the two groups is achieved by generating a separate block for each combination of covariates, and subjects are assigned to the appropriate block of covariates. Consider genetic variations as an example

Answer 27

Stratified randomisation

Question 28

Randomisation performance: (e.g.pharmacy) The clinician contacts this facility by telephone when he is ready to randomise the next patient; the initials and study number of the patient are read to the person performing the randomisation, who records it and then reads back the randomisation for that subject. Appropriate for large, multicentred trials

Answer 28

Use of remote randomisation facility

Question 29

Analysis of the results should occur based on the initial randomisation, irrespective of what may subsequently have happened to the subject (this is – intention to treat analysis). E.g. rescue mechanisms True or false?

Answer 29

True

Question 30

Advantages of RCT: minimised risk of bias

Answer 30

Participants are similar at the study entry Protocols, Clinical Trial Registry, PICOS concept, strictly defined eligibility criteria Matching control group: All baseline characteristics are the same (no statistical differences of outcomes between the groups at the beginning of the study – baseline) All variables are kept the same (except the treatment) Groups differ only in terms of the treatment they receive (intervention & comparison) which minimizes the confounding factors Randomisation & concealment of allocation ensures equal distribution of any confounding variables between the two groups. Once the patient has given consent to be included in the trial, he/she is then irreversibly randomised by opening the next sealed envelope containing his/her assignment. Blinding or masking is a way to prevent researchers, patients (receiving the treatment) and healthcare professionals (assessing outcomes) from knowing which study group each patient is in so they cannot influence the results.

Question 31

Type of blinding: One of the parties is blinded to treatment e.g. patients do not know which study group they are in (for example whether they are taking the experimental drug or a placebo), or researchers

Answer 31

Single-blind study

Question 32

Type of blinding: neither the patients nor the researchers/clinicians know which study group the patients are in.

Answer 32

Double-blind

Question 33

Type of blinding: the patients, clinicians and the people carrying out the statistical analysis do not know which treatment patients had.

Answer 33

Triple blind study

Question 34

Procedure where masking is not done – masking can not always be performed, but use of objective outcomes (rather then subjective ones) can ensure that lack of masking does not undermine validity – surgical interventions, for example

Answer 34

Open-label

Question 35

Sources of bias in RCT domains: Sequence generation

Answer 35

Selection bias

Question 36

Sources of bias in RCT domains: Allocation concealment

Answer 36

Selection bias

Question 37

Sources of bias in RCT domains: Blinding of participants and personnel

Answer 37

Performance bias

Question 38

Sources of bias in RCT domains: Blinding of outcome assessment

Answer 38

Detection bias

Question 39

Sources of bias in RCT domains: Incomplete outcome data

Answer 39

Attrition bias

Question 40

Sources of bias in RCT domains: Selective outcome reporting

Answer 40

Reporting bias

Question 41

What are ethical issues?

Answer 41

Ethical issues are those involving actions and policies that are right or wrong, fair or unfair, just or unjust

Question 42

All epidemiological studies must be reviewed and approved by ethical review committees. True or false?

Answer 42

True

Question 43

The ethical principles that apply to epidemiological practice and research include:

Answer 43

- Informed consent - Confidentiality - Respect for human rights - Scientific integrity

Question 44

This is the most widely known and influential guideline in medical research worldwide. It is an official policy of the World Medical Association (WMA), which was adopted for the first time in 1964 and has since undergone a number of revisions. The Declaration can be regarded as the expression of the WMA’s effort in balancing the need to generate sound medical knowledge with the need to protect the health and interests of research participants.

Answer 44

Declaration of Helsinki

Question 45

This is a short document on moral principles that was published in 1978 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, in the aftermath of scandals of research misconduct that were uncovered in the 1970s.

Answer 45

The Belmont Report

Question 46

The Belmont Report is especially know for?

Answer 46

establishing a framework of basic moral principles—respect for persons, beneficence, and justice—which should guide the conduct of research

Question 47

Ethical values in RCTs to be respected

Answer 47

Experiments should be socially valuable and scientifically valid, and people have to be selected fairly, and respected. The risks and benefits to participants and the benefits to society need to be weighted against each other, and there needs to be an independent outside review of the ethics of the experiment

Question 48

What was one of the most high profile examples of corporate meddling ?

Answer 48

One of the most high profile examples of corporate meddling was the revelation, 2015, that Coca-Cola had paid scientists to push the message that exercise was a more effective weight loss tool than cutting down on food and drink. The beverage giant went so far as to create a non-profit called the Global Energy Balance Network to push the message that Americans spend too much time focusing on cutting calories, and not enough time exercising. Following an investigation by the New York Times, the non-profit announced it was disbanding. In a bid to be more transparent, Coca-Cola revealed it had spent $132.8m on scientific research and partnerships between 2010 and 2015

Question 49

RCTS advantage summary

Answer 49

- Comparative - minimise bias - minimises confounding factors - statistical reliability - sample size - publishable

Question 50

Disadvantages of RCTs

Answer 50

- logistics : Power calculation might demand vast samples size, which require more resources from the investigators - external validity (generalisability) & applicability - statistics - ethical limitations - some research cannot be ethically performed as an RCT