Week 2 - Randomised Control Trials

Question 1

What is Quantitative research?

Answer 1

A structured, systematic method of collecting and analysing numerical data (numbers and measurements).,
In order to explain phenomena, patterns, test theories or make predictions.

May involve performing statistical tests and analysis.

Question 2

Quantitative research is either Observational or Experimental.

What is meant by Observational?

Answer 2

The researcher observes the patients.
But they don’t interfere with their care.

Question 3

Quantitative research is either Observational or Experimental.

What is meant by Experimental?

Answer 3

The researcher does intervene in some way.
To ensure that a group of patients receives a particular treatment or diagnostic test.

Question 4

What does Qualitative research use?

Answer 4

Thoughts.
Feelings.
Opinions.

Question 5

What is a Randomised Control Trial?

Answer 5

A form of a clinical trial or scientific procedure.

Question 6

What does a RCT help determine?

Answer 6

The effectiveness of a treatment, medicine or intervention.

Question 7

It is useful to find out if a treatment or intervention is effective, or better than an alternative intervention.

Question 8

A RCT is considered to be the ‘gold standard’ for evidence.

Question 9

What is the design of a RCT? - what are the 3 parts to it?

Answer 9

It should be Controlled -
Patients split into 2 groups - an intervention group and a control group.
Only difference between the 2 groups is the intervention.
The 2 groups are compared (this is part of the study’s design).

It should be Randomised -
Patients are randomly assigned to either the intervention or the control group (not chosen to a specific group).
E.g. done by the role of a dice.

And then there is the actual Trial -
It is the experimentation of the patient’s care.
Some subjects receive it whilst other’s don’t.

Question 10

What is assumed after Randomisation?

Answer 10

The 2 groups are considered to be equal.

Question 11

Randomisation is a powerful way to ensure what?

Answer 11

That the characteristics, and the spread of these across the 2 groups, is equal.

Question 12

What are the 2 arms/groups to the trial?

Answer 12

1. Intervention.
2. Control / Placebo.

Question 13

What type of variable is the intervention that is given to the 1st group?

Answer 13

An independent variable.

Question 14

2nd group is the control.
What do they receive?

Answer 14

Standard treatment - a placebo - does nothing.
Will be a dummy drug or sham treatment.

Question 15

After the trial, there are some outcome measures that measure the level of the impact of the intervention.
E.g. finds the % of patients who dies as a result of a specific surgery.

Question 16

Look at onenote for detailed labelled diagram of an RCT layout.

Answer 16

Start - have a target population.
Gain a sample of these people - these get screened for eligibility (if not eligible = excluded).
Now we have the study sample (the sample of target pop. that does meet eligibility criteria).
Now need to take baseline measurements of this sample (characteristics like age, gender, demographics).
Then randomise them into either of the 2 groups - ensure an equal split of characteristics.
One group receives the intervention, the other is the control group.
A follow-up of both groups happens after the initial trial, and their outcomes are measured.
Compare the outcomes of the 2 groups against each other - maybe establish if there’s a statistical significance between the 2.
Then make inferences about the whole target population (from this information from the sample).

Question 17

Breaking down an RCT -
What are the main parts needed for it?

Answer 17

Need a hypothesis, and a null hypothesis.
Need the inclusion criteria of the participants and certain features.
Need the intervention procedure.
And the placebo procedure.
And decided what the post-test measure will be.

Question 18

An RCT is an appropriate design, why?

Answer 18

It’s the best available design to test with.

E.g. it can test if a medical intervention works - like a drug, diagnostic screening test, or radiotherapy treatment.

E.g. it can test if a new intervention is use prior to an existing treatment or not - compare a current drug to a new one for the same thing. Done by comparing outcomes of 2 groups that have received either drug.
Make it measurable.

E.g. it can test if a new, cheaper, or less invasive intervention is equivalent in its effects to the current extensive or invasive procedure.

Question 19

An RCT is to do with comparing 2 different groups.
It find if there’s a statistically significant difference.

Question 20

Examples of some clinical questions that can be answered by performing an RCT?

Answer 20

Is this drug better than a placebo or a different drug for a particular disease.

Is a new surgical procedure better than the currently favoured practice?

Will changing from a diet high in saturated fats to one high in polyunsaturated fats affect serum cholesterol levels?

Question 21

Example of RCT?

Answer 21

Clinical research question -
Can dietary supplements before surgery reduce post-operative complications?
So will use oral supplementary drinks before a major operation to treat cancer.

Intervention -
High energy protein drink consumed daily.

Control -
No drink.

Patients are randomly allocated to either one of these groups.

Results showed that post-operative conditions weren’t significantly affected by dietary supplements.

Question 22

What are the 3 main features of an RCT?

Answer 22

Randomisation - this ensures the 2 groups only differ according to if they received the intervention or not, not due to different characteristics. Need the same number and range fo characteristics in both groups.
Ensure all other factors have been controlled for - weight, smokers, cancer etc.).
Controlled.
Trial.,

Question 23

RCT has become the only acceptable way of judging the true benefit of a treatment.
Treatment could be a drug, procedure or operation.

Question 24

Why would we not just have a treated group in an RCT?
Why do we also need the control group?

Answer 24

If the treated patients were to get better, it may have been for reasons unconnected to the treatment used in the experiment.
E.g. the issue may have resolved itself overtime, not because of the treatment.

So we need a control group - to know exactly or not if was the treatment that made people better.

Question 25

What is the only way to tell if a difference in the outcomes is actually a result of differences between treatment and control?

Answer 25

If the 2 groups are equal. Through random allocation. Expect the intervention vs control.

Question 26

What is a Confounding Factor?

Answer 26

An ‘extra’ variable in a study. That correlates/associates with both eh supposed cause (independent v) and supposed effect (dependant v). Just associates with them - isn’t causative of them, even though it suggests it is. So it can distort results of the study - make it look like there’s a causal link when there actually isn’t. So can falsely suggest a relationship between varauivkes, and lead to biased conclusions. So produces a false result, distorted by a factor other than the variables stated. E.g. temperature affecting both ice-cream sales and crime. It is the reason for why randomisation is very important. It ensures characteristics of both groups are very very similar.

Question 27

The researcher can’t allocate the participants. Participants can’t allocate themselves. Why?

Answer 27

Because groups need to be fully random.

Question 28

Participants shouldn’t have any control over the group they’re allocated to. Why?

Answer 28

They may perceive the intervention (e.g. the drug) a certain way, and so act differently if they knew which outcome they were receiving. And this would cause bias in the results.

Question 29

Researchers shouldn’t have any control over the group allocation of their participants. Why?

Answer 29

Because they may purposely allocate healthy individuals to the drug group to influence the result - make it look better than it actually is. They may consciously or unconsciously do this.

Question 30

Participants shouldn’t be placed in a certain group based on characteristics they have, or the severity of this. Should be fully random. To ensure equal chance of being assigned to either of the study’s arms.

Question 31

Equal characteristic groups are crucial. Why?

Answer 31

To ensure any differences in outcomes are ONLY due to the intervention. And not due to the participants or researchers self-selecting into one group or the other.

Question 32

what sections should be included in an RCT?

Answer 32

An Objective. Design. Setting. Subjects. Intervention. Outcome Measure. Result. Conclusion.

Question 33

Look at onenote for RCT’s in radiography.

Question 34

RCTs and Blinding - What is Blinding?

Answer 34

When the control/placebo group don’t know if they have received the intervention or not.

Question 35

RCTs and Blinding - What is meant by Single Blind?

Answer 35

When only either the researchers or participants know which group they are in. Usually it is the researchers that know and not the participants. This may occur when, e.g. there’s a surgical procedure needing to be done on the patient, so the surgeon must know the full extent of what they are actually doing, in order to be as safe as possible.

Question 36

RCTs and Blinding - What is meant by Double Blind?

Answer 36

Neither the researcher or the participants know which group the participants are in.

Question 37

RCTs and Blinding - Why would a lack of blinding be a problem?

Answer 37

Blinding is needed for investigating the diagnostic accuracy of alternative tests. Outcome measure relates to the observer interpretation of imaging signs, rather than to the degree of improvement in the health status of the patient.

Question 38

What is a Placebo?

Answer 38

Something fake but poses something real. Like a fake drug or a fake substance that would be injected intravenously. Fake - has no active ingredient - just mimics the look of the treatment it’s being compared to. Must be the same size, shape, colour as the real thing - shouldn’t be able to differentiate it to the real treatment (this is preventing un-blinding). It is used to help test the effectiveness of the real version.

Question 39

Who are placebo’s given to?

Answer 39

The control group.

Question 40

What does giving the control group a placebo help to minimise?

Answer 40

Bias.

Question 41

What is a Null Hypothesis?

Answer 41

A negatively phrased statement. Which asserts that there is no difference between 2 groups.

Question 42

What is the aim of an RCT?

Answer 42

To determine if the null hypothesis can be confirmed or rejected.

Question 43

If the null hypothesis is rejected, what have the results shown?

Answer 43

Results would show no difference between the groups.

Question 44

What criteria do the sample of participants have to pass?

Answer 44

Eligibility criteria - Inclusion and exclusion criteria.

Question 45

What are Inclusion Criteria?

Answer 45

Identify the study subjects (participants) in a consistent, reliable, uniform and objective manner. All participants must pass these if they are able to be included in the study.

Question 46

What are Exclusion Criteria?

Answer 46

The characteristics that make the recruited population ineligible for the study. If participants have any of these criteria, then they would be disqualified from the study. They may become the confounders of the outcome parameter.

Question 47

When are baseline characteristics of the intervention and control groups measured, and why?

Answer 47

At the start of the study. It’s to ensure they are all similar.

Question 48

What size should the sample size be?

Answer 48

Large enough to generate a statistically significant result. To help see if there is a true difference in outcomes between arms of the trial

Question 50

What can help calculate the correct sample size?

Answer 50

The Power Calculation.

Question 51

The study could be underpowered. What does this mean?

Answer 51

That there is too small of a sample size to make many valid findings.

Question 52

The study could be overpowered. What does this mean?

Answer 52

There is an unnecessarily large sample size.

Question 53

Clinical trials should be reported according to the CONSORT guidelines. CONSORT - consolidated standards of reporting trials. This is so patients are kept track of.

Answer 53

Look at labelled diagram in onenote for more detail.

Question 54

What is a P-Value?

Answer 54

A value. Helps to compare 2 groups against one another. To give a probability of any observed difference having happened by chance. It gives the probability which states that the null hypothesis is true. So we need to create a null hypothesis for between the 2 groups. Null hypothesis should state there is no difference between the 2 groups. Usually we try to disprove the null hypothesis. Because we are more interested in if there is a difference between the 2 groups. E.g. for a blood pressure drug - We would be interested in whether the drug has had a positive effect in lowering the blood pressure or not,. Lower p-value = less likely that the difference happened by chance, and so the higher significance of the findings.

Question 55

Interpretations P-Values -

Answer 55

Look at onenote for table. 0.5 = not statistically significant. 0.5 in 1 / 50:50. 0.05 = statistically significant. 1 in 20. 0.01 = highly significant. 1 in 100. 0.001 = very highly significant. 1 in 1000.

Question 56

Look at onenote for P-Value example.

Question 57

What are some Advantages of RCTs -

Answer 57

They are considered the ‘gold-standard’ of evidence, and so are more publishable. They provide good evidence for a causal link between the intervention and the disease / diagnosis. The randomisation it uses minimises allocation bias. The randomisation minimised confounding factors too - by making characteristics of 2 groups a s similar as possible. Blinding researchers and participants minimises bias. Its outcomes are supported by statistics that show the significance.

Question 58

What are some Disadvantages of RCTs -

Answer 58

They can be difficult / complex to conduct, due to their logistics (e.g. a very large sample size that is needed, or the requirement for multiple sites), due to it being time-consuming, and because it can be costly. They can be difficult to detect small effects - as that would require a very large sample size, which may e an issue when investigating rare outcomes (e.g. sudden infant death syndrome). The trials aren’t conducted under a highly controlled setting - so may not apply to an actual clinical situation. Some research can’t be performed for ethical reasons - e.g. an RCT on the effects of parachutes on the mortality of skydivers.