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Trial Design: Pain Sections
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Currently selected section: Introduction
Placebo Effects
Single Dose Trials
Repeated Dose Trials
Explanatory Versus Pragmatic
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Chapter 1: Clinical Trials of Pain Treatment: Introduction
 
        

OPTIONAL MATERIAL: BRIEF REVIEW OF PAIN MEASURES USED AS OUTCOMES OF ANALGESIC CLINICAL TRIALS

The most common pain measures that have been used in short-term analgesic trials have been category scales for pain intensity and pain relief and visual analog scales.

Table 1.2: Four point pain intensity scale from zero to three: none, mild, moderate, severe. Five point pain intensity scale from zero to four: none, slight, moderate, lots, complete. Visual Analogue scale of pain intensity. A line ranging from least possible pain to worst possible pain. Visual Analogue scale of pain relief. A line ranging from no relief of pain to complete relief of pain

Analgesics are withheld until patients report moderate to severe pain, and study medication is given at a time defined as zero. Figure1.2 shows the hypothetical time course of pain relief that a patient might describe if relief were continuously assessed. The actual interview points and relief readings on a visual analog scale are represented by the open circles. In most analgesic studies, measurements are taken hourly, except for the first hour, during which more frequent measurements may be taken. The patient is usually questioned by a nurse observer, although some outpatient studies rely on the patient to complete the assessments alone.

Click on image to enlarge

Figure 1.2: Approximating the Analgesic Time-Effect Curve with Intermittent Pain and Relief Measures: Reduction in pain is plotted against time elapsed since administration of study medication. Open circles correspond to the patient's pain assessment at scheduled interviews. Onset and duration of meaningful analgesia are indicated by arrows (top panel); in this example, onset occurs well before the first scheduled interview. The area under this hypothetical curve (bottom panel, shaded) is often approximated by the sum of the products of each pain relief reading at a scheduled interview and the time since the previous interview.

To account for differences in baseline pain intensity among patients in the study, pain intensity category and VAS scores are converted into "pain intensity difference (PID) scores by subtracting them from the pain score taken at baseline. Positive scores indicate reduction in pain, making the PID scores analogous to pain relief scores. (An alternative method is to use analysis of covariance). PID or relief scores are commonly summed over the observation period, weighted for the time between observations, and the summed scores respectively termed SPID (summed pain intensity difference) or TOTPAR (total pain relief). These summary variables are estimates of the area under the time-effect curve (AUC) as illustrated by the shaded area in Figure 1.2 (bottom). Some investigators compute "% SPID" defined as SPID/maximum possible SPID. The maximum possible SPID is the value of SPID that would be obtained if the patient were pain-free for the total period of observation. This adjustment may partly correct for the bias that patients who start off with higher pain scores tend to have larger pain reductions -- higher PID scores -- if pain is reduced to zero or any other fixed endpoint.

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