Research Designs and RCT

Dr. Shahistha Parveen

Assistant Professor
RAKCODS
Learning Outcome

Collect and analyze relevant knowledge from various resources in order

to make appropriate clinical decisions for patient’s oral health care
Research design
 Randomized Controlled Trial

A study design that randomly assigns participants into an experimental group or a

control group. As the study is conducted, the only expected difference between the
control and experimental groups in a randomized controlled trial (RCT) is the
outcome variable being studied

Three elements

1. Randomization

2. Intervention

3. Blinding
 The Randomized Control Trial

It is a trial in which subjects are randomly assigned to one of two groups:

1. One (the experimental group) receiving the intervention that is being tested, and

2. The other (the comparison group or control) receiving an alternative (conventional)

treatment

The two groups are then followed up to see if there are any differences between them
in outcome

RCTs are the most stringent way of determining whether a cause-effect relation exists
between the intervention and the outcome
 Features of a well designed RCT

1. Appropriate sample size: The sample to be studied will be appropriate to the hypothesis
being tested so that any results are appropriately generalizable

2. The study will recruit sufficient patients to allow it to have a high probability of
detecting a clinically important difference between treatments if a difference truly exists

3. There will be effective (concealed) randomization of the subjects to the

intervention/control groups (to eliminate selection bias and minimize confounding
variables)

4. Both groups will be treated identically in all respects except for the intervention being
tested and to this end patients and investigators will ideally be blinded to which group an
individual is assigned.
 Features of a well designed RCT

1. The investigator assessing outcome will be blinded to treatment allocation.

2. Patients are analysed within the group to which they were allocated, irrespective

of whether they experienced the intended intervention (intention to treat

analysis).

3. Analysis focuses on testing the research question that initialy led to the trial (that

is, according to the a priori hypothesis being tested), rather than “checking” to

find a significant difference.

 Disadvantages

1. Expensive in terms of time and money

2. Volunteer biases: The population that participates may not be

representative of the whole

3. Loss to follow-up attributed to treatment

4. High dropout when the intervention has undesirable side-effects

5. The expected variation of improvement in the sample in order to calculate

the RCT sample size
 Why Randomization required??

Randomization ensures that each patient has an equal chance of receiving any of the
treatments under study, comparable intervention groups,

1. It eliminates the selection bias, balances the groups with respect to many known and
unknown confounding variables

2. A randomized experiment is an essential tool for testing the efficacy of the treatment

3. Proper randomization ensures no a priori knowledge of group assignment

The common methods of simple randomization
1. The sides of the coin

2. Shuffled deck of cards

3. Throwing a dice

4. A random number table

 Blinding

Blinding at the stage of applying the intervention and measuring the outcome is essential if
bias is to be avoided. Blinding is achieved by making the intervention and the control
appear similar

Blinding/Masking
• When the groups that have been randomly selected from a population do not know if they are
in the control group or the experimental group
1. Single blinded trial
• A single blinded trial involves blinding of any one group of individuals
• Usually, the subjects receiving the intervention or the outcome assessors are blinded to the
intervention assignments
 Blinding

Double blinded trial:

• When the researchers conducting a blinded study do not know which participants are in the
control group of the experimental group.

• The subject and the investigator should ideally be blinded to the assignment (double blind),
but even where this is not possible, a blinded third party can measure outcome

Triple blinded trial:

• Three groups of people are blinded to the intervention assignments in a triple blinded study.
Usually, the subjects, the investigators, and the outcome assessors are blinded
 Enrollment Assessed for eligibility (n= )
Excluded (n= )
¨ Not meeting inclusion criteria (n= )
¨ Declined to participate (n= )
¨ Other reasons (n= )
Randomized (n= )

Allocated to intervention (n= ) Allocation • Allocated to intervention (n= )

¨ Received allocated intervention (n= ) • Received allocated intervention (n= )
¨ Did not receive allocated intervention (give reasons) (n= ) • Did not receive allocated intervention (give reasons) (n=)

Lost to follow-up (give reasons) (n= ) Lost to follow-up (give reasons) (n= )
Discontinued intervention (give reasons) (n=) Follow-Up Discontinued intervention (give reasons) (n= )

Analysed (n= ) Analysed (n= )

¨ Excluded from analysis (give reasons) (n= )
Analysis ¨ Excluded from analysis (give reasons) (n= )
CONSORT 2010 Flow Diagram
 Types of RCT

1. Parallel group study

2. Cross-over study

3. Split-mouth study
 1. Parallel group study

1. Randomized Controlled Trials are often parallel design

2. A parallel design includes independent study groups and each group receives a
different treatment regimen or intervention

3. Parallel design is more useful for studying conditions which are prone to change over
time (pain, acute exacerbations of a disease, remissions)

Example: In a study to evaluate the efficacy of beta blockers for hypertension, 24 patients
are randomized into two groups of 12 patients. One group is then treated with a beta
blocker and the other treated with placebo.
1. Parallel group study
 1. Parallel group study

1. Randomization into treatment A & B

2. At end, compare average effects A & B

3. Compare A with B from 2 independent samples: inter-individual

Comparison

1. Example: comparison of fillings in patients with 1 filling

2. Group 1 receives filling A & group 2 receives filling B

3. Compare 5-year success rates of filling material

 2. Crossover trial

Crossover trials are trials in which participants do not only receive one intervention,
but multiple, and the effect of the interventions are measured on the same individuals.
It is also described as participants receiving a sequence of interventions
 2. Crossover trial
Advantages
• By using a crossover trial in order to compare several interventions, a
researcher can minimize the risk of confounding because all interventions
are measured on the same participants

• One can say that study participants serve as their own control. This leads
to another advantage which is less study participants are required
 Limitations

1. Crossover trials can only be conducted when the disease persists for a longer
period of time, hence, crossover trials are mostly used in studying chronic diseases.

2. There is a risk that there might be a carry-over from the effect of the previous
intervention on to the effect of the next intervention

3. In contrast to parallel designs, crossover trials consist of two study periods. This
means that they usually take up more time, and statistical analysis can be more
complicated if participants do not complete all stages of the trial.
 A carryover effect

The effect of the treatment from the previous time period on the response at the
current time period

• When the effects of the drug given during the first period persists into the second
period

• Carryover effects only affect the treatment response in the 2nd time period

• Can be eliminated by using a washout period between treatments this allows the
patient to return to baseline levels before the 2nd treatment is started
How to deal with this carryover effect?

• The incorporation of lengthy washout periods in the experimental design can diminish
the impact of carryover effects.

A washout period: the time between treatment periods

How long of a washout period should there be?

• Based on an investigator’s expertise

• For example, in a trial involving pharmaceutical products a washout period equivalent

to 5 (or more) times the length of the half-life of the drug concentration in the blood
 3. The split-mouth design

• The split-mouth design is a popular design in oral health research. In the most common

split-mouth study, each of two treatments are randomly assigned to either the right or

left halves of the dentition.

• The attractiveness of the design is that it removes a lot of inter-individual variability from

the estimates of the treatment effect.in split-mouth designs, each intervention is

randomly allocated to a different site or sites within the mouth of each individual
 3. The split-mouth design

• Split-mouth designs were introduced in periodontics by Ramjford in the late sixties,

but their use has been relatively limited

• Split-mouth designs are appropriate for certain orthodontic interventions due to their

efficiency and the decreased sample required compared with conventional parallel

designs.
 Limitations

1. Carry-across effects, period effects and difficulty in recruiting patients with

similarity between randomization units (jaws, quadrants)

2. A further problem of split-mouth designs is encountered when it is difficult

to find appropriate and similar pairs of sites within patients.

3. For example, if we were to conduct a split-mouth design evaluating two root

canal methods, we may require similarity between quadrant
However, in orthodontics, split-mouth designs for certain interventions are likely to be
more appropriate

For example, we could very well perform a split-mouth design to assess bond failures of
two adhesives by bonding in two randomly selected quadrants with one adhesive and
bonding with the second adhesive in the other two quadrants as no carry-across effects
are expected
Example 1. En-masse retraction after maxillary premolar extraction using sliding mechanics on passive
self-ligating or conventional orthodontic appliance
References

1. Hackshaw A, Paul E, Davenport E. Evidence-Based Dentistry: An

Introduction. 2007 [2. ed.] Blackwell Munksgaard, Oxford OX4 2DQ, UK

2. Forrest J L. Evidence-Based decision making : a translational guide for

dental professionals. 2009 [1. ed.] Wolters Kluwer Health/Lippincott
Williams & Wilkins, Philadelphia (Pa.)
Thank you