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Trial Design: Pain Sections
Author Bio
Introduction
Currently selected section: Placebo Effects
Single Dose Trials
Repeated Dose Trials
Explanatory Versus Pragmatic
Dose-Response
Parallel Group Versus Crossover
Conclusion
 

 

Chapter 1: Clinical Trials of Pain Treatment: Placebo Effects and Their Implications for Pain Studies     
 
 

It is not clear whether one needs to exactly match the magnitude of the side effects of the two treatments to eliminate this bias. A single-dose comparison of several different drugs in postherpetic neuralgia (Max et al., 1988) suggested that most of the side-effect induced placebo response occurs with the detection of the first mild symptom (Figure 2.2), but further research is needed.

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Figure 2.2: Do Stronger Side Effects Produce Stronger Pain Relief? Patients with post-herpetic neuralgia were given oral doses of clonidine, codeine, ibuprofen, or lactose placebo (from Max et al., 1988b). The three drugs tested produced little or no analgesia relative to placebo (not shown), so data from all treatments are represented here to illustrate the association of pain relief with side effects. Summed pain relief over 6 hours is plotted against a total side effect score obtained by summing all hourly reports of adverse effects, each rated on a three-point scale. Patients who reported any side effect, even if slight effect, which we thought was "side effect-triggered placebo analgesia", did not increase at higher total side effect scores. If confirmed, this result would suggest that if a drug showed a positive dose-response curve for analgesia above the dose level where most patients have at least mild side effects, one could infer that analgesia was due to a specific effect on pain mechanisms, not just an "active placebo" effect.

Potential drawbacks of active placebos include the possibility that the active drug may worsen the underlying symptom, thereby contributing to a false positive result; improve the symptom, making it more difficult for the experimental drug to show an effect; or cause adverse reactions.

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