CHAPTER 4

2. Double dummy: use of multiple controls to

maintain blinding
a) Example: To compare two medicines, one
presented as blue tablets and one as red
capsules, researchers could also supply blue
placebo tablets and red placebo capsules so
that both groups of patients would take one
blue tablet and one red capsule
3. Active control: use of an established therapy as
the comparative group
4. Crossover: patients serve as their own control
by receiving multiple interventions
F. Methods
G. Institutional review board (IRB), ethics committees
H. Intervention, duration of treatment
I. Monitoring
J. Follow-up
K. Compliance
1. Measure of adherence
L. Outcome Measures
1. Primary/secondary endpoints
2. Surrogate endpoints: easily measured
substitute markers in place of more clinically
meaningful endpoints (e.g., CD4 count used as a
surrogate endpoint for a trial regarding HIV
infection)
M. Statistics
1. Goal: to be confident that the probability
statement (p value) is valid and to maximize the
possibility of detecting a difference when one
actually exists1
N. Results
O. Reporting adverse effects (MedWatch)
III. Assessing Trial Results
A. Findings related to primary outcomes
1. What type of data are presented?
a) Categorical (qualitative data)
(1) Nominal: named categories (e.g., blood
type, gender, race)
(a) Mutually exclusive
(2) Ordinal: ordered categories of data; often
sequenced (e.g., poor, good, excellent)
(a) Mutually exclusive
b) Numerical (quantitative data)
(1) Continuous: ordered, sequenced, and has
a set of distance or values between rank
(e.g., blood pressure, glucose levels)
B. Were the findings statistically significant?
1. Hypothesis testing
a) Tests against the null hypothesis
(1) Null hypothesis (Ho): states that the
variable of interest is equal to a given
value or that no relationship exists
between various variables
2. Statistical and clinical significance
a) Statistical: probability that the results are due
to chance or due to a true effect of treatment
b) Clinical: importance of the practical relevance
or variation of a difference in outcomes
(1) A statistically significant outcome may
not be clinically significant
3. P value
a) The probability of the observed result or a
more extreme result occurring by chance alone

Drug Information Resources

29

b) The probability of the observed difference

occurring if the null hypothesis is true
4. Types of error
a) Type I error (false-positive error)
(1) Rejecting the null hypothesis when it
should be accepted
(2) Relates to validity
(3) Alpha level
(a) It is the risk of finding a difference
when there is not one (risk of
experiencing a type I error)
(b) Usually 5% by designation,
indicating there is a less than 5%
possibility that a finding is due to
chance (does not really exist)
b) Type II error (false-negative error)
(1) Accepting the null hypothesis when it
should have been rejected (there was a
difference that was not detected)
(2) Relates to power
(3) Beta level
(a) The chance researchers are willing
to risk that a difference will not be
detected
(b) The probability of committing a
Type II error
(c) Type II error (or beta)
(d) Usually 20% by designation
5. Confidence interval (CI)
a) The range of values in which researchers can
be certain that the true point estimate will
fall
b) 95% CI most commonly reported
(1) 95% probability that the true result lies
within the range of results found, and
there is a 5% probability that the true
range lies outside the interval
c) CI is calculated by subtracting from and
adding to the sample mean the appropriate
number of standard errors of the mean
d) The narrower the CI, the greater the
reliability and more precise the data
C. How large is the treatment effect (when the
primary outcome shows a statistically significant
difference)?
1. Relative risk (RR)
a) The reduction in the risk from one therapy
relative to another (RR events in treatment
group  events in placebo group)
(1) A RR of 1 means that there is no
difference.
(2) A RR that is <1 (e.g., 0.75) means that
risk is decreased
(3) A RR that is >1 (e.g., 1.15) means that
risk is increased
b) Commonly used to express the therapeutic
benefit of a drug
2. Absolute reduction risk (ARR)
a) The absolute difference between the
probabilities of the treatment event rate and
control event rate (ARR Probability of
events in placebo group [PB]  Probability
of events in the active treatment group [PA])
b) Expressed as a percentage