Transcript Evaluating the Literature: Clinical Trials

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Module 6: Part Two
Experimental Studies
+USA Today 3/11/2013:
Kraft Macaroni & Cheese too yellow?

Two moms “blogging” in NC started petition

Obtained 200,000 signatures in 5 days

Issue: Petitioners want yellow dye 5 and yellow dye 6
removed from list of additives in Kraft mac & cheese (already
being done in Europe without a difference noted in taste)
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Claim: These two food dyes have been associated with
hyperactivity in children, allergies, migraines
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Other concerns: Because they are petroleum-based, these
dyes may be associated with various cancers as well
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How do we scientifically investigate these claims?
“True” Experimental Strategy
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If you want to draw a cause-effect conclusion,
you must run an experimental design or
strategy.
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Key features include:
 A. Manipulation of an independent variable
 B. Control condition
 C. Random assignment of participants to
groups
Or, more specifically:
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1.
Must be manipulation of the independent variable to
see the effect on the dependent variable.
2.
Must have comparison of the dependent variable
results in at least two conditions (experimental and
control group)
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Experimental Group: Receives the manipulation of the
independent variable.
Control Group: Does not receive the manipulation of the
independent variable (everything else is held constant).
3.
Must randomly assign participants to the
experimental and control conditions before the
manipulation of independent variable.
4.
Must control the unwanted effects of extraneous
variables on the dependent variable.
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 The
experimental design is the
considered the “gold standard” of designs
because, if done properly, it allows:
 Causal
Inference = a conclusion where one
variable or event causes another.
 Also called a cause-effect conclusion.
 Cause-effect
conclusion can be made if all
of the following criteria are met:
1.
2.
3.
Co-variation of variables
Causal time sequence
Elimination of all other plausible causes.
+ Unwanted sources of variance
 Sometimes
extraneous variables that the
researcher was unaware of can influence the
dependent variable.
 Drinking
coffee
Cardiovascular disease
Smoking
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Attrition
 Refers
to a loss of participants during the
course of the study.
 Differential
attrition refers to the situation
when participants are leaving one
independent condition at a higher rate than
another.
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Bias
 There
are 2 main sources of bias:
Participant Bias (Hawthorne Effect)
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Behavior on the part of the subject due to their awareness of
being observed
Note: Participants often behave the way they perceive the
experimenter wants them to behave; called the good-participant
effect
Experimenter Bias (Rosenthal Effect)
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The experimenter knows how participants are expected to
respond and may unwittingly coach them to respond in a
particular way.
 The
optimal approach to the elimination of these biases
is to utilize a “Double-Blind” procedure.
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Neither the participants nor the experimenter knows who is in
each experimental condition.
The Clinical Trial
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National Institutes of Health
 www.clinicaltrials.gov
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Biomedical or health-related research studies
in human beings that follow a pre-defined
protocol
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Interventional or observational
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Interventional studies:
 Research subjects are assigned by the
investigator to a treatment (or other
intervention)
 Outcomes are measured
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Observational studies:
 Individuals are simply observed
 Outcomes are measured
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Types of Clinical Trials

Treatment trials

Prevention trials
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Diagnostic trials
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Screening trials
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Quality of life trials
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KEY DEFINITIONS - PROTOCOL
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A study plan on which all clinical trials are
based
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The plan is carefully designed to safeguard
the health of the participants as well as
answer specific research questions
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Protocol
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Describes:
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What types of people may participate in
the trial
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The schedule of tests, procedures,
medications, and dosages
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The length of the study
+ KEY DEFINITIONS - PLACEBO
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An inactive pill, liquid, or powder that has
no treatment value.
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Experimental treatments are often
compared with placebos to assess the
experimental treatment's effectiveness.
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In some studies, participants in the control
group will receive placebo instead of an
active drug or experimental treatment.
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Phases of Clinical Trials
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Phase I - researchers test an
experimental drug or treatment
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small group of people (10-80)
first time to be evaluated
determine safety, safe dosage range, and
identify side-effects
Phase II - experimental study drug or
treatment given to a larger group of
people (100-300)
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see if it is effective, further evaluate its safety
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Phases of Clinical Trials
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Phase III - experimental study drug or
treatment given to large groups of people
(1,000-3,000)
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confirm its effectiveness, monitor side effects,
compare it to commonly used treatments, and
collect information that will allow the
experimental drug or treatment to be used safely
Phase IV - post-marketing studies delineate
additional information including the drug's
risks, benefits, and optimal use
Participating in a Clinical Trial
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INCLUSION/EXCLUSION CRITERIA:
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Medical or social standards determining whether a
person may or may not be allowed to enter a clinical
trial:
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Criteria based on such factors as age, gender,
type and stage of a disease, previous treatment
history, and other medical conditions
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Criteria not used to reject people personally, but
rather to identify appropriate participants and
keep them safe
Informed Consent
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Risks and potential benefits are
explained in the informed consent
document
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The participant then decides whether
or not to sign the document
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Informed consent is not a contract, and
the participant may withdraw from the
trial at any time
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Study Type: Interventional
Study Design: Crossover Assignment, Double blind
 In
a double-blind, crossover study, participants receive
either real treatment or placebo for a time, and then
are switched ("crossed over") to the opposite
treatment. Thus, researchers can get “double mileage”
out of their participants—each person gets both
placebo and treatment.
 The
advantage of a crossover trial is that it effectively
doubles the number of people in a trial. This makes it
easier for researchers to obtain statistically significant
results.
+ The Tuskegee Experiment:
Ethical concerns in research
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Public Health Service, working with the Tuskegee Institute
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1932: Nearly 400 lower-income African-American men
with syphilis from Macon County, Alabama were enrolled
in the study.
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Were never told they had syphilis, nor were they ever
treated for it
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According to the Centers for Disease Control, the men
were told they were being treated for "bad blood," a local
term used to describe several illnesses, including syphilis,
anemia and fatigue
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For participating in the study, the men were given free
medical exams, free meals and free burial insurance
+ At the start of the study, no proven treatment for syphilis
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Penicillin became a standard cure for the disease in 1947,
medicine was still withheld from the men
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The Tuskegee scientists wanted to continue to study how the
disease spreads and kills
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Experiment lasted four decades, until public health workers
leaked the story to the media.
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By then, dozens of the men had died, and many wives and children
had been infected.
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In 1973, NAACP filed a class-action lawsuit; $9 million settlement
was divided among the study's participants. Free health care was
given to the men who were still living, and to infected wives,
widows and children.
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It wasn't until 1997 that the government formally apologized for
the unethical study. President Clinton delivered the apology.