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Problem
4.4
Positive controls in studies
of chronic neuropathic pain
You
wish to study Drug N, a compound with a novel mechanism,
in patients with painful diabetic polyneuropathy. Among
the available patient population:
- 20%
each are already on the two most solidly established
treatments for this condition, amitriptyline and gabapentin;
- 20%
are taking opioids; and
- The
remaining 40% are taking nothing.
All
told, 80% of the study population have tried amitriptyline
or another tricyclic antidepressant and 80% have tried
gabapentin, most stopping the medication because of poor
relief.
In
your study design, you wish to include a positive control
group and opt for amitriptyline, 100 mg/day. The three
arms of your study therefore include:
- Drug
N;
- Placebo;
and
- Positive
control (amitriptyline).
You
write a protocol that specifies that patients must stop
all pain medications for two weeks before randomization
and then take either Drug N, placebo, or amitriptyline.
What problems might you encounter?
 Patients
already getting relief from amitriptyline may be unwilling
to stop the medication, thereby reducing enrollment and
perhaps biasing the results in the amitriptyline group
towards a negative response.
 Patients
who have already tried amitriptyline and found it ineffective
may be unwilling to try it again, reducing enrollment and
potentially biasing the results in the amitriptyline group
towards a positive response.
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