Biases in Clinical

Research
 Objective
• Identify and differentiate between various selection
and information biases in clinical research.
 Biases in Clinical Research
Identifiable, and sometimes
quantifiable, circumstances
• Participation • Response bias

Selection

Information
that are systematically (nonresponse) bias • Recall bias
introduced by actions or • Admission rate
(Berkson) bias
• Attention bias
• Exposure suspicion
decisions made by persons • Prevalence- bias
incidence • Unmasking
connected to the research and (Neyman) bias bias/mimicry bias
• Medical
that lead to errors in the surveillance bias
•
•
Sample size bias
Missing data
interpretation of study results. • Detection bias
• Procedure selection
bias/withdrawal
bias
bias • Migration
• Membership bias (contamination)
bias
• Compliance
(adherence) bias
• Scale degradation
bias
• Reference bias
• Rhetorical bias
• Publication bias
Selection
Bias Participation (Nonresponse) Bias
• Occurs when the subjects who are willing to
participate have different characteristics than those
who are unwilling to participate

Minimize the Bias

• Identify individual characteristics that could
result in differences in response to the
exposure and incorporate sampling
techniques that encourage equal participation
if individuals with and without those
characteristics
Selection
Bias Admission Rate (Berkson) Bias
• Occurs when the rates of exposed and unexposed
individuals enrolled differ from the rates of
individuals not enrolled as a result of the setting in
which the subjects are selected

Minimize the Bias

• Ensure that samples are representative of
their entire respective populations such as
including only subjects who are identified
at the time of diagnosis, regardless of the
setting in which this occurs
Selection
Bias Prevalence-Incidence (Neyman) Bias

• Occurs when cases that are mild and self-resolving

and those that are rapidly fatal are not captured,
resulting in a failure to include these cases

Minimize the Bias

• Identifying subjects as they are
first exposed to the element of
interest, rather than picking them
up at some point thereafter
Selection
Bias Medical Surveillance Bias
• Occurs in retrospective studies when the inclusion of
subjects is limited to those who have received a
certain nonroutine screening or diagnostic test

Minimize the Bias

• Conducting interventional studies
when screening for the condition
is not routine for all individuals
Selection
Bias Detection Bias
• Occurs when the methods of screening for the
condition differ between the control group and the
experimental group

Minimize the Bias

• Ensuring that the techniques used for all
potential subjects in all groups are
identical and that the timing of subjects’
assignments to groups is relatively similar
• Block randomization
Selection
Bias Procedure Selection Bias
• Occurs when individual subjects are decidedly assigned
to groups based on clinical judgment instead of being
randomly assigned, and that assignment leads to
differences between groups

Minimize the Bias

• Randomizing subjects
to groups
Selection
Bias Membership Bias
• Occurs when subjects in one group have a higher prevalence
of a characteristic that may alter their outcomes than subjects
in another group have, and that characteristic is systematically
tied to another characteristic upon which group assignments
are based

Minimize the Bias

• Identifying the known and probable
biasing characteristics that could
alter the results and balancing them
• Stratified randomization
Information
Bias Response Bias
• Occurs when subjects respond to questions in a way
that they believe the researcher wishes them to
answer, rather than in a truthful way

Minimize the Bias

• Use objective measurements or take
precautions not to lead subjects in a
particular direction with regard to
self-reported responses
Information
Bias Recall Bias
• Occurs when subjects in one group remember events
from the past more inaccurately than subjects in
another group

Minimize the Bias

• Conducting studies that do not rely as
heavily on subject memory or enrolling
subjects as quickly as possible
following the event of interest
Information
Bias Attention Bias
• Occurs when subjects change their behavior because
they know that their actions are being observed
• Related to the Hawthorne and placebo effects

Minimize the Bias

• Minimizing the intrusion of
study observation and
frequent data collection
Information
Bias Exposure Suspicion Bias
• Occurs when subjects in one group are systematically
exposed to diagnostic procedures or investigations
that subjects in another group are not as a result of the
researchers’ knowledge or beliefs about the group to
which subjects have been assigned

Minimize the Bias

• Using appropriate blinding
and dummying techniques
Information
Bias Unmasking Bias
• Occurs when an inciting condition that is unrelated to a
condition of interest creates a situation in which the
condition of interest is more likely to be discovered

Minimize the Bias

• Identifying potential
unmaskers and accounting
for them in study design
Information
Bias Sample Size Bias
• Occurs when too few or too many subjects than are
appropriate are included in the study
• Too few subjects leads to insufficient power
• Too many subjects leads to oversensitivity

Minimize the Bias

• Determining and enrolling
appropriate sample sizes
Information
Bias Missing Data Bias
• Occurs when disproportionate numbers of subjects between
groups, or high numbers of subjects in all groups, have absent
outcome data
• Called “withdrawal bias” when this is a result of subjects
dropping out

Minimize the Bias

• Anticipate missing data and
determine appropriate
method to account for them
 Handling Missing Data
• Use data from all subjects who were
Intention-to-treat enrolled in the study, even if some data
(ITT) analyses must be assumed

• Slightly altered ITT analyses (usually

Modified ITT include only subjects who received the
(mITT) analyses first study maneuver)

Per-protocol • Use data from only those subjects who

analyses completed the study properly
Information
Bias Migration (Contamination) Bias
• Occurs when subjects unintentionally move from one
group to another during the course of the study, but
whose outcome data are treated as still belonging to
their assigned group

Minimize the Bias

• Implement measures that
minimize migration and properly
account for data from migratory
subjects
Information
Bias Compliance (Adherence) Bias
• Occurs when more subjects in one group fail to properly
follow study protocols than subjects in another group
because of inconvenience of, or intolerance to, their
assigned intervention

Minimize the Bias

• Frequent follow-up and
protocol reinforcement
Information
Bias Scale Degradation Bias
• Occurs when data are not analyzed in the most
specific and precise manner possible

Minimize the Bias

• Using high precision
measurement
Information
Bias Reference Bias
• Occurs when a published article’s citations do
not accurately represent the entire body of
knowledge on the topic

Minimize the Bias

• Authors presenting their
research in the context of all
previous evidence
Information
Bias Rhetorical Bias
• Occurs when authors of scientific literature use
language and innuendo to lead the reader to a
conclusion that is not supported by evidence

Minimize the Bias

• Authors limiting their statements to
what can be supported by the evidence
and avoiding making assumptions or
connections that are not fully
substantiated
Information
Bias Publication Bias
• Occurs when researchers fail to submit
negative studies, and publishers fail to publish
negative studies

Minimize the Bias

• Researchers submitting and
publishers publishing articles
describing well-conducted
negative studies