Once-daily OROS hydromorphone ER compared with placebo in opioid-tolerant patients with chronic low back pain.

OBJECTIVE: This multicenter, double-blind, placebo-controlled study using a randomized withdrawal design evaluated the efficacy and safety of once-daily OROS hydromorphone ER in the treatment of opioid-tolerant patients with chronic moderate-to-severe low back pain (LBP). MAIN OUTCOME MEASURES: The primary efficacy assessment was mean change in pain intensity based on patient diary Numeric Rating Scale (NRS) scores from baseline to final visit of the 12-week double-blind phase. Secondary endpoints included mean change from baseline to each visit in patient diary NRS scores; and office NRS scores; time to treatment failure; Patient Global Assessment; rescue medication use; and Roland Morris Disability Questionnaire total scores. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00549042. RESULTS: For the primary outcome measure, hydromorphone ER significantly reduced pain intensity compared to placebo (p < 0.001). Median diary NRS score change from baseline to endpoint was significantly lower for OROS [corrected] hydromorphone ER (0.2 units) compared to placebo (1.6 units). [corrected] A significantly higher proportion of hydromorphone ER (60.6%) vs. placebo (42.9%) patients had at least a 30% reduction in diary NRS pain score from screening to endpoint (p < 0.01). Hydromorphone ER was well-tolerated, although 60 (13%) discontinued during the enrichment phase for adverse events and more active (9, 6.7%) than placebo (4, 3.0%) patients discontinued treatment for adverse events during the randomized phase. CONCLUSIONS: These results provide evidence for the efficacy and safety of hydromorphone ER in opioid-tolerant patients with chronic moderate-to-severe LBP. Potential limitations include the shortened dose-conversion/titration phase, limiting the daily allowable dose of hydromorphone ER to 64 mg, and the allowance of limited rescue medication throughout the entire double-blind phase. Other trial design elements such as the use of an enrichment phase and the inclusion of only opioid tolerant patients may limit the generalizability of these results.

Measuring complete diagnostic evaluation in colorectal cancer screening.

Complete diagnostic evaluation, or CDE (i.e., a colonoscopy or combined barium enema X-ray and flexible sigmoidoscopy) is recommended for individuals who have an abnormal screening fecal occult blood test result. Accurate measures of CDE use are needed in colorectal cancer (CRC) screening programs. This study compares the sensitivity and specificity of different methods for measuring CDE recommendation and performance. We identified 17 primary-care practices with 120 patients who had a positive fecal occult blood test result in a CRC screening program operated by a managed-care organization. Approaches used to measure CDE recommendation and performance included external chart audit (ECA) only; internal chart audit (ICA) only; administrative data review (ADR) of electronic claims data; ICA plus ADR; and ECA plus ADR (the "gold standard"). Sensitivity and specificity of each method were assessed relative to CDE recommendation and performance as measured by ECA plus ADR. For CDE recommendation, sensitivity measures were ECA only, 0.926; ICA only, 0.790; ADR only, 0.617; and ICA plus ADR, 0.901. The specificity of each method for CDE recommendation was no less than 0.95. In terms of CDE performance, sensitivity measures were ECA only, 0.877; ICA only, 0.790; ADR only, 0.877; and ICA plus ADR, 0.965. The specificity of each method for CDE performance was 1.0. The ICA-plus-ADR method was a highly sensitive and specific measure of CDE use. This method should be considered in situations that involve primary-care physician follow-up of patients with abnormal CRC screening test results.