Based on calculations of minimal clinically important differences (MCIDs), reductions in quality of life scores of >1.0 in patients with chronic non-cancer pain and opioid-induced constipation (OIC) are clinically important. These findings are based on a study published in Clinical Gastroenterology and Hepatology.
The Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires are used to measure treatment-related changes in patient-reported outcomes (PROs) in OIC. However, it remains unclear whether these changes are of value to the patient. To bridge this gap, researchers analyzed data from patients with chronic non-cancer pain and OIC to determine PAC-SYM and PAC-QOL MCID values.
Integrated data from the double-blind, controlled, Phase 3 COMPOSE-1 (ClinicalTrials.gov Identifier: NCT01965158) and COMPOSE-2 (ClinicalTrials.gov Identifier: NCT01993940) trials of naldemedine in chronic non-cancer pain and OIC were used for this analysis. PAC-SYM and PAC-QOL questionnaires were used to determine MCID. The PAC-SYM and PAC-QOL were evaluated on day 1 (pre-dose), week 2, week 4, and week 12 or upon early termination. In both studies, participants completed a Bowel Movement and Constipation Assessment log daily via eDiary. At the end of the study, patients rated their degree of satisfaction.
Investigators utilized an anchor-based approach to calculate estimated MCIDs for PAC-SYM and PAC-QOL scores. The anchor-based approach provides a comparison of changes in a specific PRO of interest, such as the PAC-SYM or PAC-QOL total score, with changes in a different assessment for which a clinically important improvement can be better understood.
For this analysis, there were 6 anchors: 5 were from the Bowel Movement and Constipation Assessment and 1 was patient global satisfaction. Receiver operating characteristic (ROC) curves were used to determine MCID cutoff values for the change in total PAC-SYM and PAC-QOL scores.
The researchers analyzed data from 1095 patients (549 naldemedine and 546 placebo). The mean age of the study participants was approximately 53.4 years, and more than half were women (60.5%). At baseline, the mean duration of opioid use was approximately 5 years, and the mean number of spontaneous bowel movements per week was 1.24.
The area under the curve for the ROC curves (ranges: 0.719 to 0.798 for PAC-SYM and 0.734 to 0.833 for PAC-QOL) demonstrated that both instruments can discriminate responders and nonresponders for each anchor.
Based on the 6 anchors, the cut off values for PAC-SYM ranged from -1.04 to -0.83 and the cut off values for PAC-QOL ranged from -0.93 to -0.82.
Based on these data, reductions in PAC-SYM and PAC-QOL scores of >1.0 should be regarded as clinically meaningful in patients with non-cancer pain and OIC.
This study had several limitations, such as the possibility of recall bias. Additionally, the COMPOSE-1 and COMPOSE-2 trials did not have PRO measures. These measures would allow for the assessment of more generalizable health utilities. Lastly, the PAC-SYM and PAC-QOL tools may not be applicable in a routine clinical practice setting due to their length.
The study authors concluded, “The current analysis is the first to estimate an MCID for these measures based on naldemedine clinical trial data in patients with chronic non-cancer pain and OIC. Using an anchor-based approach, an MCID value of >1.0 was determined for these questionnaires in this patient population.”
They added, “Establishing such MCIDs for instruments measuring [health-related quality of life] HRQOL is important to understanding patient-perceived treatment success, as well as to help identify when adjustments in treatment may be needed.”
Disclosure: Some study authors declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.
Disclosure: This research was supported by multiple sources. Please see the original reference for a full list of disclosures.
Tack J, Camilleri M, Hale M, et al. Establishing minimal clinically important differences in quality of life measures in opioid-induced constipation. Clin Gastroenterol Hepatol. Published online May 6, 2021. doi: 10.1016/j.cgh.2021.05.004