Lecture 4 - Analytical Study Design Part 2 - RCT and NRCT Flashcards
Randomized control studies
“Randomized” Allocation/Assignment
The main purpose of randomization is to prevent any potential biases on the part of the investigators from the influencing the assignment of participants into different treatment groups.
May be done by assigning random numbers or by a program that generates random assignments
Each subject has an equal chance of being assigned to each group (control or intervention)
Randomization strives for comparability of the different treatment groups; however, its not guaranteed.
Randomized control studies
The main purpose of randomization is to….
prevent any potential biases on the part of the investigators
(from the influencing the assignment of participants into different treatment groups.)
Randomized control studies
May be done by….
assigning random numbers or by a program that generates random assignments
Randomized control studies
Each subject has an equal chance of….
being assigned to each group (control or intervention)
Randomization _______ of the different treatment groups; however, its _____.
strives for comparability
not guaranteed
Randomized control studies
“Controlled” implies predefined:
Specified hypotheses
Primary and secondary endpoints to address hypotheses
Methods for enrollment and follow up
Eligibility/Exclusionary criteria
Rigorous monitoring
Analysis plans and stopping rules
Randomized control studies
Why Controlled?
Seek to eliminate confounding variables
Attempt to minimize bias
LOOK AT FIGURE 7-1 ON SLIDE 9
UNDERSTAND THIS FLOW
Enrollment in Randomized control studies
Criteria for determining selection must be…
Want to ensure that participants….
Carefully select sample based on a reference population.
… specified before the study is begun
…actually have the disease of interest
Allocation in Randomized control studies
Randomization is the best approach in the design of a trial, and the critical element of randomization is….
….the unpredictability of the next assignment.
the best approach in the design of a trial?
randomization
Allocation in Randomized control studies
If conducted properly we don’t have to worry that…
…any subjective biases of the investigator, either overt or covert, may be in introduced into the process of selecting patients.
How is randomization accomplished:
Computer programs
Envelope System – The treatment assignment that is designated by a random number is written on a card, and this card is placed inside an envelope. Each envelope is labeled on the outside: Patient 1, Patient 2, Patient 3…..etc. When the first patient is enrolled and consented the investigator opens the envelope and the treatment assignment is determined.
Only open the enveloped after a subject is consented and meets eligibility criteria!
We hope that randomization achieves comparability of characteristics between the treatment groups; however….
this not guaranteed!
Envelope System:
Only open the enveloped after a subject is….
consented and meets eligibility criteria!
– utilized when we are concerned about the comparability of the groups in terms of one or a few important characteristics.
Stratified Randomization
Stratified Randomization:
This is conducted by stratifying our study population by each variable that we consider important, and then…
randomize participants to treatment groups within each stratum.
Treatment (Assigned vs Received)
Important to know if the patient was assigned to receive treatment A, but did not comply.
Why?
Conversely, it is also clearly important to know whether a patient who was not assigned to receive treatment A may have…
A subject may agree to be randomized, but may later change his or her mind and refuse to comply.
…taken treatment A on his or her own, often without realizing.
OUTCOME OF RANDOMIZED CONTROL STUDY:
Comparable measurements in all study groups in particularly true for measures of the outcome. So you can measure?
Improvement
Side Effects or Adverse Reaction
OUTCOME OF RANDOMIZED CONTROL STUDY:
Explicitly stated criteria for all outcomes to be measured in a study
Potential pitfall of outcomes being measured more carefully in those….
how do we avoid this problem?
…receiving a new drug than in those receiving currently available therapy must be avoided.
Blinding can prevent much of this problem; however, blinding is not always possible.
(Behavioral Interventions if not possible)
Randomized control studies
Blinding:
The ______ from one or more individuals involved in a clinical research study.
concealment of group allocation
Randomized control studies
Blinding:
Usually is used in research studies that compare….
Used to make sure that knowing the type of treatment does not affect: (three things)
…two or more types of interventions.
1) A participant’s response to the treatment
2) A health care provider’s behavior
3) The assessment of the treatment effects
After being observed for a certain period of time on one therapy; any changes are measured; patients are switched to the other therapy.
Planned Crossover
Occurs when subjects who are randomized cross-over to the other group.
If we analyze according to treatment that the patient actually receive, we will have broken and therefore lost the benefits of randomization.
Unplanned crossover
Each patient can serve as his or her own control, holding constant the variation between individuals in many characteristics that could potentially affect a comparison of effectiveness of two agents.
Must have a washout period!
Planned Crossover
what must have a washout period?
planned crossover in the randomized control study
Unplanned Crossover:
Current practice to perform the analysis by ________-according to the original randomized assignment.
If bias occurs typically biases towards the null; typically provides a more conservative estimate
intention to treat
intention to treat in an unplanned crossover, typically biases that occur provide…
a more conservative estimate
Randomized control studies
What are the blinding types?
Single Blinding
Double Binding
Triple Binding
Blinding types
_______: Allocation is concealed from only one group (researchers or subjects)
_______: Allocation is concealed from both groups (researchers and subjects)
_______: Allocation is unknown to the subjects, the individuals who administer the treatment or intervention, and the individuals who assess the outcomes.
Single blinding
Double blinding
Triple blinding
researcher OR subjects are blinded
single blinding
researcher AND subjects are blinded
double blinding
researcher AND subjects are blinded PLUS….
Individuals who assess outcomes are blinded
triple blinding
What is noncompliance?
Subjects may agree to be randomized, but following randomization they may not comply with the assignment treatment.
May be Overt or Covert!
The Net Effect of non-compliance on the study results will be to reduce any ________, because the treatment group will include some who did not receive the therapy, and the no-treatment group may include some who received the treatment.
observed differences
what is the gold-standard of a trial?
Double-blinded Randomized Control Trial
Double-blinded Randomized Control Trial is known as the….
gold-standard
Double-blinded Randomized Control Trial AKA the gold-standard, minimizes….
the chance for bias if randomization and blinding are done CORRECTLY
What are the limitations of Randomized control studies
Large trials (may affect statistical power)
Long term follow-up (possible losses)
Compliance
Expensive
Possible ethical questions (Primum Non Nocere / ‘First Do No Harm’)
– Attempted to learn if the drug, surgical procedure, or administrative program works under ideal circumstance.
Efficacy Trial
– Within the confines of the study, results appear to be accurate and the interpretation of the investigators I supported.
Internal Validity
– Ability to apply results obtained from a study population to a broader population. Also called generalizability.
External Validity
Efficacy Trial
– Attempted to learn if the drug, surgical procedure, or administrative program works under ideal circumstance.
Internal Validity
– Within the confines of the study, results – appear to be accurate and the interpretation of the investigators I supported.
External Validity
– Ability to apply results obtained from a study population to a broader population. Also called generalizability.
Look at slide 22…. this will let you know external validity vs internal validity
YUP
Non-randomized control studies
How are these different from RCTs?
1) Also called…
2) what’s predetermined?
1) Also called quasi-experiments
2) In non-randomized controlled trials, the control group is predetermined (without random assignment) and compared to a control group
- –Volunteer to join the study OR
—Are geographically close to the study site OR
—Conveniently turn up (at a clinic, school) while the study is being conducted
—Like the studies recruiting with fliers posted in the restroom
There are several reason why a non-randomized control study may be conducted.
RCT are often logistically complex and very expensive
Sometime it’s not feasible to randomize all evaluation
Ethical problems may be perceived to occur in health services evaluation studies
By the time RTCs are completed and data analyzed results may not be relevant anymore
Before-After Design (Historical Design) ---Pre/Post program evaluation ------Data may not be comparable. ------Making casual inferences is very difficult Simultaneous Nonrandomized Design ---Cohort-like design ---Difficulty to determine exposure/unexposed groups ---Difficult to make inferences
Comparison of Utilizers and Non-Utilizers
Comparison of Eligible and Non-Eligible Populations
Non-randomized control studies
Non-randomized control studies
Before-After Design (Historical Design)
Simultaneous Nonrandomized Design
Comparison of Utilizers and Non-Utilizers
Comparison of Eligible and Non-Eligible Populations
Non-randomized control studies:
Limitations
Study group characteristics may not be balanced at baseline… if this occurs it could?
Baseline differences between groups may confound the study’s results
Non-randomized control studies:
Attempting to correct for baseline differences
-Among the strategies commonly used to ensure equivalence is a technique called ____
—–Matching requires selecting pairs of participants or clusters of individuals who are _______
—–Example: A researcher interested in comparing visual acuity among smokers and non smokers tries to balance the two groups by selecting pairs of smokers and non smokers who are same….
matching
comparable to one another on important variables
age, sex, and medical history
Typical confounding variables include…
age, educational level, motivation, severity of illness, socio-economic status, income, comorbidities
Randomized and Non-randomized control studies
Four major areas of methodological concern:
Enrollment – How was the study population chosen?
Allocation – How were the subjects assigned to their study group?
Follow Up – How long are patients followed for?
Analysis – How was the data collected analyzed?
Randomized and Non-randomized control studies:
Enrollment - Understanding the study what would you want to know?
What were the inclusion and exclusion criteria?
Is the actual study population representative of the population to which the results will be applied?
Are controls similar to case subjects?
Randomized and Non-randomized control studies:
Allocation - Understanding the study what would you want to know?
Was randomization and blinding conducted?
How was it done?
Was it done correctly?
Nonrandom sampling (consecutive or convenience) may not be generalizable and has strong potential for bias
Randomized and Non-randomized control studies:
Follow Up - Understanding the study what would you want to know?
Adherence
How well did the study subjects adhere to the treatment protocol?
Was the intervention too difficult to continue to participate?
Attrition
How many subjects were lost to follow-up?
Why were they lost? Did they quit or die?
Adherence are measured from the ____ of the Randomized and Non-randomized control studies
Follow up
Randomized and Non-randomized control studies:
Analysis - What would you want to know about the anaylsis to evaluate the study?
- Are the effects of the intervention clearly defined?
- Is there a clearly defined end point?
- Did they provide an “intent to treat” analysis?
—–Compares subject outcomes based on their original group assignment even if they dropped out or were non-compliant
—–Primary reason is to preserve randomization
-To what did they compare their data?
