Experimental study - week 5

Question 1

What are experimental studies?

Answer 1

Experimental or therapeutic studies involve an active attempt to change a variable in a group (e.g. disease, behaviour) via an intervention.

The effects of an intervention are measured by comparing the outcome incidence in the group who have experienced the intervention (experimental group) with that of the group you haven’t intervened with (control group).

Question 2

Randomised control trial

Answer 2

In a randomised control trial (RCT) patients are randomly allocated to a treatment group (exposed group) or a control group (unexposed group).
‘Gold standard’ for studying cause and effect
• Critical aspects are random allocation and allocation concealment (to ensure there is
no confounding)

Question 3

STRENGTHS of randomized control trials

Answer 3

The ‘gold standard’ epidemiological studies
Lower risk of bias and confounding than any other epidemiological study
Provide strong evidence of causal relationships
Can be used to study multiple outcomes
Measure the incidence rate of an outcome

Question 4

LIMITATIONS of randomized control trials

Answer 4

often expensive 
Ethical issues
Generalisability needs to be carefully assessed
Require large study group
Long follow-up period

Question 5

Is RCT a prospective study

Answer 5

Since the patients in each group are followed prospectively, the study is often called a prospective study.

Question 6

Randomisation

Procedure

Answer 6

1- Before admission to a study, every participant must be suitable for either treatment
2- Randomisation must occur AFTER commitment to participate as bias can arise if patients/doctors know the treatment to be allocated and then decide to withdraw
3- Participants allocated to treatment groups by chance (easily achieved through the use of random number generators) – all participants have an equal chance of being allocated to treatment or control
4- All participants must be followed-up and included in the study regardless of later compliance

Question 7

Benefit of Randomisation

Answer 7

BENEFITS
Produces groups that are not systematically different with regard to known and unknown prognostic factors
Any difference between groups that arise after randomisation could be due to consequences of the randomised treatment assignment
Permits a valid analysis
Permutation test is justified by randomisation
Standard analyses are valid approximations of the correct permutation test
Eliminates selection bias e.g. doctors selecting sicker patients to be in the new treatment group

Question 8

Allocation concealment

Answer 8

Those responsible for recruiting participants must not know what groups they will be allocated to. This often requires a third party to maintain a private list of consenting participants and their random allocation.
Doctors may manipulate the allocation process for their patients which undermines the validity of the study. Allocation concealment prevents this from occurring.
• Simple random allocation
• Stratified allocation

Question 9

Blinding

Answer 9

Blinding is the most effective way of eliminating systematic error.

However, in some case it is not possible to have blinding as it will be obvious a patient is in the treatment group i.e. if there are pronounced side effects of the drug or the intervention is considerably different to the control (e.g no exercise vs exercise).

If an emergency occurs it may be necessary to divulge the treatment the patients were receiving. This would often require a third party to hold the code and “break” it if needed.

Question 10

What is the main purpose of randomisation?

a. To control for confounding by distributing known and unknown confounders equally
b. To ensure that participants adhere to the study protocol
c. To prevent the placebo effect by ensuring participants do not know if they are taking the placebo of the intervention
d. To prevent researchers from manipulating their test subjects in order to have fabourable results

Answer 10

To control for confounding by distributing known and unknown confounders equally

Question 11

An advantage of a double-blinded randomised control trial is:

Creates a group of people representative of the target population
Equally distributes known and unknown confounders
Encourages participants to adhere to the study protocol
Prevents the bias that arises from researchers being able to influence collected data with the knowledge of allocated groups

Answer 11

Prevents the bias that arises from researchers being able to influence collected data with the knowledge of allocated groups

Question 12

What is random selection?

Randomly selecting people from the target population to form the sample population
Randomly assigning subjects into control and intervention groups
A term synonymous with random allocation

Answer 12

Randomly selecting people from the target population to form the sample population

Question 13

blinding why ?

Answer 13

Process where either, or both, the participant and the investigator remain
unaware of which trial group the participants are in
• Why?
• Performance bias
• refers to systematic differences between groups in the care that is provided, or in
exposure to factors other than the interventions of interest.
Easier to do with drug trials in which can use a placebo
• Must be same colour, shape, size…

Question 14

Placebo or control group

Answer 14

• an inert substance or procedure or standard care
• used in clinical trials as a baseline
• Placebo effect or response is believing that the treatment will work
i.e. that a fake treatment is the real thing

Question 15

Different types of RCTs

Answer 15

Open RCT
• Everybody involved knows which intervention is given to each patient
Single-blind
• One group of individuals does not know the identity of the intervention
given to participants
Double-blind
• Two groups of individuals do not know the identity of the intervention
given to participants
• Performance bias and detection bias are minimised

Question 16

performance bias and detection bias

Answer 16

Performance bias: refers to differences that occur due to knowledge of interventions allocation, in
either the researcher or the participant
Detection bias: refers to systematic differences between groups in how outcomes are determined

Question 17

Cross-over trial

Answer 17

A crossover design is a repeated measurements design such that each experimental unit (patient) receives different treatments during the different time periods, i.e., the patients cross over from one treatment to another during the course of the trial

Question 18

What are field trials?

Answer 18

As the name suggests field trials are trials that are conducted in the ‘field’. They are aimed at disease-free people in the population – participants do not have the disease of interest but are at risk.

Their aim is to evaluate interventions (preventive studies or strategies) to reduce specific exposures. Examples could include:

Education methods (e.g. skin cancer education)
Training procedures (e.g. workplace safety)
Other

Question 19

Cross over trial advantage and limitation

Answer 19

Advantages
• Patients serve as own controls
• Sample size
Limitations
• Order of events?
• Not feasible
• Not ethical

Question 20

N of 1 trial

Answer 20

• A single case is the participant of the trial

* Also can be an open ‘before and after’ trial

Question 21

Advantage and disadvantage of N of 1 trial

Answer 21

Advantages
• Can confirm causality and effectiveness
• Useful for piloting treatment
Limitations
• Generalisability

Question 22

Cluster randomised trials

Answer 22

• Cluster means that the unit of randomisation is not the individual.
• Often used when a study is done in the community and there is risk of
“contamination”

Question 23

RCT CANNOT BE USED FOR

Answer 23

It may not be possible to do an RCT so information from other study
designs must be used
• We cannot use an RCT to establish what patterns of blood lipids predispose people
to developing coronary heart disease - this will require a cohort study
• We can use RCTs to answer simple questions

Question 24

Principles of systematic reviews

Answer 24

Overview of medical literature with reproducible objectives and
methodology
• Validity of individual trials assessed by specific criteria
• Summary of results via qualitative and quantitative methodology
• e.g. meta-analysis

Question 25

Differences between systematic

and narrative reviews

Answer 25

Narrative
Lack rigour
• Broad in scope
• Author can use literature to support
viewpoint
• Limited critical appraisal
• Broad summary of ‘state of affairs’ 
Systematic
Rigorous – minimise bias
• Answers a specific question (PICO)
• Protocol (Cochrane)
• Comprehensive search strategy
documented
• Quality of studies appraised according
to set criteria
• Summary of data
• Regularly updated (Cochrane)

Question 26

Steps involved in a systematic

review

Answer 26

1. Formulate a structured clinical question (PICO)
2. Conduct an extensive search documenting search strategy
3. Select studies for inclusion, justifying any exclusions (ie, pre-defined
   inclusion criteria)
4. Assessment of methodological quality of included studies (according to
   pre-determined criteria)
5. Abstraction of relevant data
6. Data synthesis (meta-analysis)

Question 27

DATA SYNTHESIS

Answer 27

A meta-analysis does not just
simply add up numbers across
studies!
• It identifies results from
individual studies and
calculates a weighted averag

Question 28

Blinding is the process where either, or both, the participant and the investigator remain unaware of which trial group the participants are in. This measure minimises ………… bias.

Answer 28

Performance

Question 29

What are the correct steps involved in a systematic review?

Answer 29

1. → Formulate a structured clinical question (PICO), 2. → Conduct an extensive search documenting search strategy, 3. → Select studies for inclusion, justifying any exclusions, 4. → Assessment of methodological quality of included studies, 5. → Abstraction of relevant data, 6. → Data synthesis (meta-analysis)

Question 30

Which of the following are true regarding cross over trials?

Select one or more:

a. Great number of patients are required
b. Need a separate control group
c. Patients serve as own controls
d. Not a strong study design
e. Smaller number of patients are required

Answer 30

The correct answers are: Patients serve as own controls, Smaller number of patients are required

Question 31

In a randomised double-blind trial to compare a new analgesic with ibuprofen (a nonsteroidal anti-inflammatory drug), a standard treatment, for the control of pain in arthritis, the difference in pain scores between the two regimes was not significant. We can conclude that:

Select one:

a. The new drug is useless
b. The difference between the drugs is very small
c. There are no important differences in the analgesic properties of the drugs
d. The trial has failed to demonstrate a difference in analgesia
e. There is no difference in analgesia between the two drugs

Answer 31

The correct answer is: The trial has failed to demonstrate a difference in analgesia

Question 32

Penicillin has been the drug of choice for treating streptococcal pharyngitis if the patient is not allergic to it. Suppose that a new antibiotic is developed which appears in preliminary tests to be more effective than penicillin for this condition. In setting up a clinical trial of the new drug for the treatment of streptococcal pharyngitis, which of the following randomly selected control groups would you prefer?
Select one:
a. Two control groups, one receiving the standard dose of penicillin and one receiving a placebo
b. A control group that receives the standard dose of penicillin
c. A control group that received a placebo
d. A control group that receives a small dose of penicillin

Answer 32

The correct answer is: A control group that receives the standard dose of penicillin

Question 33

The major purpose of random assignment in a clinical trial is to:
Select one:
a. Reduce selection bias in allocation of treatment
b. Facilitate double-blinding
c. Help ensure that study subjects are representative of the general population
d. Facilitate measurement of outcome variables
e. Ensure that the study groups are comparable on baseline characteristics

Answer 33

The correct answer is: Reduce selection bias in allocation of treatment

Question 34

All of the following are potential benefits of a randomised clinical trials, EXCEPT:

Select one:

a. Self-selection for a particular treatment is eliminated
b. External validity of the study is increased
c. The therapy a subject receives is not influenced by either conscious or subconscious bias of the investigator
d. The likelihood that the study groups will be comparable is increased
e. Assignment of the next subject cannot be predicted

Answer 34

the correct answer is: External validity of the study is increased

Question 35

An advertisement in a medical journal states that “2000 subjects with sore throats were treated with our new medicine. Within four days, 94% were asymptomatic.” The advertisement claims that the medicine was effective. Based on the evidence given above, the claim:

Select one:

a. May be incorrect because no test of statistical significance was used
b. May be incorrect because the conclusion is not based on a rate
c. May be incorrect because no control or comparison group was involved
d. Is correct
e. May be incorrect because of failure to recognise a long-term cohort effect

Answer 35

c. May be incorrect because no control or comparison group was involved

Question 36

To see if hypnosis could reduce chronic pain, investigators randomly assigned 120 volunteers with osteoarthritis to either hypnosis therapy or a control group. Pain levels were checked among the subjects every three months during the 12-month study using validated pain measures. Those assigned to the hypnosis group reported reduced pain compared to those in the control group after three and six months, but not after nine and twelve months of follow-up.

What type of study is this?

Select one:

a. Clinical trial
b. Cohort study
c. Case series
d. Case control study
e. Cross sectional study

Answer 36

a. Clinical trial

Question 37

True or false, a systematic review refers to the entire process of selecting, evaluating, and synthesizing all available evidence, while meta-analysis refers to the statistical approach to combining the data derived from a systematic-review?

Select one:
True
False

Answer 37

True

Question 38

Vietnam Experience Study: Subjects were several thousand soldiers stationed in Vietnam from 1969-1971 and several thousand soldiers stationed in Europe from 1969-1971.

In the mid-1980’s, investigators determined and compared the death rate and prevalence of illness in both groups.

Case-control study
Retrospective cohort study
Ecological study
Prospective cohort study

Answer 38

Retrospective cohort study

Question 39

Subjects were persons with laboratory-confirmed trichinosis, and one healthy friend of each. All subjects were asked about their consumption of pork and other meat products.

Case-control study
Cross-sectional study
Cohort study
Retrospective cohort study
Check

Answer 39

Case-control study

Question 40

study examines the death rates from cervical cancer in each of the 50 US states in relation to the average percentage of women in each state undergoing annual PAP smear screening.

Prospective cohort study
Ecological study
Cross-sectional study
Case-control study

Answer 40

Ecological study

Question 41

A study compares the prevalence of back pain among current members of the plumbers and pipe-fitters union with that of current members of the bakers and confectionary union.

Case-series study
Prospective cohort study
Randomised control trial
Cross-sectional study
Check

Answer 41

Cross-sectional study

Question 42

The “BUPA Foundation Health and Wellbeing after Breast Cancer study” recruited women with a primary breast cancer between 2004 – 2006 within a year of their diagnosis.

They filled in an enrolment questionnaire, and were followed up once a year for 5 years in subsequent questionnaires. Data about stage at diagnosis and treatment was linked to the death register for deaths data.

Prospective cohort study
Cross-sectional study
Retrospective cohort study
Randomised control trial

Answer 42

Prospective cohort study