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Compared
to trials of treatments for structural disease, symptom treatment
trials are susceptible to both false positive and false negative
results. A major source of both false positives and negatives
is the placebo effect, which in analgesic trials is often substantial
and may have a duration of
weeks or months
(Turner
et al., 1994), but appears to have minimal effects on measures
of established
structural disease. The frequency of placebo effects and their
implications for pain studies effects varies among analgesic studies
from zero to more than 60% (Turner
et al., 1994; Moore
et al.,1998). Efforts to identify and exclude "placebo responders"
from analgesic trials have not succeeded; given repeated opportunities,
most people will manifest a placebo response. (Investigators in
other fields, such as affective disorders, often try to identify
placebo responders to a placebo run-in period and exclude them
from further study.)
Several factors are recognized to increase the magnitude of the
placebo analgesic response, including patients’ expectations that
they would get relief, clinicians’ warmth, prestige, and positive
attitude, and the invasiveness of the intervention. Price
(1988) has shown that type of placebo nerve block, saline
injections of the stellate ganglion, produced an average of 19
hours of near-complete pain relief in patients with complex regional
pain syndromes. Full scale surgical procedures produce even more
dramatic placebo responses. A variety of operations that later
proved to be useless, including gastric freezing for duodenal
ulcers and actual or sham internal mammary artery ligation for
angina pectoris, were initially reported to improve or eliminate
the pain of 60-100% of patients for a year after surgery (Turner
et al., 1994).
If
one is to avoid false positives, one must strive to maximize the
effectiveness of blinding procedures, and check to see if patients
can guess their study assignment by the appearance, taste, or
side effects of the treatments (Moscucci
et al., 1987). In studies of drugs that have unmistakeable
side effects, some investigators use "active placebos" that mimic
the side effects of the analgesic (Max,
1991; Greenberg and Fisher,
1994) (Figure 2.1 ; from
Max
et al., 1988).
Click on image to enlarge
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