Chapter 1: Clinical Trials of Pain Treatment: Repeated Dose Trials

Outcome Measures

In placebo-controlled studies where background or rescue analgesia is available, both pain report and rescue analgesic consumption should be examined as primary outcome measures.

Some investigators use rescue analgesic consumption as the sole outcome measure. Reasons why this is not ideal include:

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Figure 4.1: Repeated Dose Trial of Ibuprofen vs. Placebo with Rescue Analgsic for Metastatic Bone Pain

Graphic depiction of repeated dose trial of ibuprofen vs. placebo with rescue analgesic for metastatic bone pain, described in text.

Many patients may not change their analgesic demands enough to completely offset any difference in pain between treatment groups (as in Figure 4.1).

The reduction of analgesic consumption alone is not a compelling clinical advantage, unless pain or analgesic side effects can also be shown to be reduced.

The statistical power of a study to detect an effect of the experimental drug may be diluted if the therapeutic benefit shows up partly in reduced pain scores and partly in reduced use of rescue medication. For this reason, when one is doing a study to establish analgesic efficacy—for example, in the first controlled study of a new compound—many experts prefer a single-dose comparison in which patients agree to postpone taking rescue analgesic until pain becomes severe, after which time pain scores are imputed to be at the level at the time of rescue (Max, 1994). In this type of study, there is generally a larger separation between pain scores among the treatment groups than when rescue medication is allowed. In an attempt to recover the "lost power" of rescue dose paradigms, an analytic method has been proposed that combines each patient’s rank score for pain level and analgesic into a single summary variable (Silverman et al., 1993), but methodological study of this proposed method has not gone beyond the small number of patients in the original report.