|
What
is a potential pitfall of this design?
You answered:
 Some
patients in the positive control group may develop adverse
reactions to opioids, because their total dose will be higher
than their baseline dose of 120 mg/day, which had been optimized
before study entry.
CORRECT
Although
patients who have been chronically taking opioids are usually
somewhat tolerant to opioid side effects, their total dose
will increase for at least the duration of action of the
first sustained-release dose and they may encounter prolonged
side effects. If Drug L potentiates opioid side effects
as well as analgesia, the same concern may hold true for
the group treated with that experimental drug.
This
concern may be lessened by converting patients’ analgesic
regimen to immediate release morphine before randomization
and to increase the strength of the immediate-release morphine
capsules by 50% in the positive control group (See table
below.) Using only immediate release opioid lessens the
duration of any relative overdosing that may occur.
|
Group
|
MS-SR
|
MS-IR
|
Test
drug
|
|---|
|
Placebo
|
0
|
120
mg/day
|
placebo
|
|
Drug
L
|
0
|
120
mg/day
|
Drug
L
|
|
Positive
control
|
0
|
180
mg/day
|
placebo
|
|
A drawback
of this latter design is that it is cumbersome and differs
from optimal current practice, which is to use mostly sustained-release
opioid.
|