Comprehensive assessment of patients with irritable bowel syndrome with constipation and chronic idiopathic constipation using deterministically linked administrative claims and patient-reported data: the Chronic Constipation and IBS-C Treatment and Outcomes Real-World Research Platform (CONTOR)

Abstract

Aims

To characterize a US population of patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) using CONTOR, a real-world longitudinal research platform that deterministically linked administrative claims data with patient-reported outcomes data among patients with these conditions.     

Validation of the Bowel Function Index to detect clinically meaningful changes in opioid-induced constipation

Abstract

Objective: The Bowel Function Index (BFI) is a clinician-administered, patient-reported, 3-item questionnaire to evaluate opioid-induced constipation in cancer and non-cancer chronic pain patients. The objective of the present analysis was to evaluate the psychometric characteristics of the BFI using data from clinical studies of oral prolonged release (PR) oxycodone/naloxone.

Methods: OXN2401 was a multicenter, controlled, randomized, double-blind, parallel-group study including oral PR oxycodone combined with oral PR naloxone as well as oral PR oxycodone combined with corresponding naloxone placebo. OXN3401 and OXN3001 were 12-week multicenter, controlled, randomized, double-blind, parallel-group studies of a fixed combination of oral PR oxycodone/naloxone versus PR oxycodone. In addition, a placebo group was included in study OXN3401. BFI psychometric characteristics (reliability, reproducibility, convergent/known groups validity, and responsiveness) were evaluated.

Results: Demographic data (n=985) were comparable and analyses indicated a high degree of internal consistency (Cronbach's alpha >0.7). Change of less than 5 points in BFI was indicative of high reproducibility. Correlations between BFI item and total scores to stool frequency were statistically significant and in the low-to-moderate range (OXN2401 –0.23 to –0.29, p < 0.001; OXN3401 range –0.26 to –0.40, p < 0.001; OXN3001 –0.14 to –0.15, p < 0.05). Data indicate that a BFI score change of ≥12 points represents a clinically meaningful change in constipation.

Limitations: This publication for validation of BFI only includes data from three clinical trials. However, another publication of an additional specifically designed cross-sectional validation study is in preparation.

Conclusion: The BFI is a valid and reliable instrument for the assessment of opioid-induced constipation in chronic pain patients. Psychometric analyses from clinical trials support the BFI's psychometric properties.     

论胶原蛋白对人类健康的特殊作用

胶原蛋白在人体中含量很多,过去一直被人们视为非常普通的物质而未加留意和重视。二十世纪七十年代以来,国际上对于胶原蛋白的研究相当活跃,取得了惊人的进展。现已发现,胶原蛋白具有提高免疫力、预防癌症、防治慢性病、促进细胞新陈代谢、提高钙的吸收力、消除便秘等功能,与人类健康不但息息相关,且具有非常重要的作用。     

Economic evaluation of linaclotide for the treatment of adult patients with irritable bowel syndrome with constipation in the United States

Abstract

Objectives:

To use techniques of decision-analytic modeling to evaluate the effectiveness and costs of linaclotide vs lubiprostone in the treatment of adult patients with irritable bowel syndrome with constipation (IBS-C).

Methods:

Using model inputs derived from published literature, linaclotide Phase III trial data and a physician survey, a decision-tree model was constructed. Response to therapy was defined as (1) a ≥14-point increase from baseline in IBS-Quality-of-Life (IBS-QoL) questionnaire overall score at week 12 or (2) one of the top two responses (moderately/significantly relieved) on a 7-point IBS symptom relief question in ≥2 of 3 months. Patients who do not respond to therapy are assumed to fail therapy and accrue costs associated with a treatment failure. Model time horizon is aligned with clinical trial duration of 12 weeks. Model outputs include number of responders, quality-adjusted life-years (QALYs), and total costs (including direct and indirect). Both one-way and probabilistic sensitivity analyses were conducted.

Results:

Treatment for IBS-C with linaclotide produced more responders than lubiprostone for both response definitions (19.3% vs 13.0% and 61.8% vs 57.2% for IBS-QoL and symptom relief, respectively), lower per-patient costs ($803 vs $911 and $977 vs $1056), and higher QALYs (0.1921 vs 0.1917 and 0.1909 vs 0.1894) over the 12-week time horizon. Results were similar for most one-way sensitivity analyses. In probabilistic sensitivity analyses, the majority of simulations resulted in linaclotide having higher treatment response rates and lower per-patient costs.

Limitations:

There are no available head-to-head trials that compare linaclotide with lubiprostone; therefore, placebo-adjusted estimates of relative efficacy were derived for model inputs. The time horizon for this model is relatively short, as it was limited to the duration of available clinical trial data.

Conclusions:

Linaclotide was found to be a less costly option vs lubiprostone for the treatment of adult patients with IBS-C.     

逍遥散加减的临床运用

逍遥散源于宋钱塘医陈师文《太平惠民和剂局方》是治疗肝郁脾虚的常用主方，临床上每见各种原因导致的肝郁脾症每用本方加减应用均收到满意效果。     

Cost-effectiveness analysis of oxycodone with naloxone versus oxycodone alone for the management of moderate-to-severe pain in patients with opioid-induced constipation in Canada

Background:

Approximately 20–30% of Canadians suffer from chronic pain. Guidelines for the management of chronic pain support the use of controlled-release (CR) opioids to treat chronic pain. Although effective in managing chronic pain, oxycodone is associated with high rates of opioid-induced constipation (OIC). The cost-effectiveness of a combination of oxycodone for the management of pain and naloxone for the relief of OIC has not previously been evaluated for Canada.

Methods:

A decision analytic model was developed to estimate the cost-utility of combination oxycodone/naloxone compared to oxycodone alone in four populations. Drug costs for managing pain and healthcare costs related to managing OIC were included in the analysis and the primary measure of effectiveness was quality adjusted life years (QALYs) derived from OIC rates observed in clinical trials. The analysis was conducted from a healthcare system perspective, used a 1-year time horizon, and results were expressed in 2015 Canadian dollars.

Results:

In all four patient populations, there was a trade-off between slightly higher total expected costs for Targin treated patients compared to oxycodone treated patients, but also improved clinical benefits in terms of reduced OIC, which resulted in higher QALYs for patients. Although analgesic costs were found to be slightly higher for Targin treated patients, Targin also resulted in cost offsets to the healthcare system in terms of less rescue laxative drug use and other resources required for the management of OIC. The resulting 1-year cost-utility of Targin compared to oxycodone ranged from $2178–$7732 per QALY gained in the base case analysis, and it was found that these cost-utility results remained robust and at low values throughout a series of one-way deterministic analyses of uncertainty.

Conclusion:

The clinical effectiveness of oxycodone/naloxone in managing pain and OIC compared to CR oxycodone alone resulted in low cost-utility estimates.     

Quality of life in relation to constipation among opioid users

Abstract

Objective: Opioid users often experience constipation. In this study the impact of constipation on QoL was assessed in patients using opioids either for non-advanced illness or advanced illness.

Methods: Patients using opioids, recruited via public pharmacies, were asked to complete questionnaires on opioid use, constipation and the EuroQol five-dimension questionnaire (EQ-5D). Patients with a severe non-curable disease and relatively short life-expectancy were classified as having an advanced illness; a disabling yet not directly life-threatening condition was defined as non-advanced illness. Constipation was assessed based on questions on opioid side-effects and laxative use. EQ-5D index scores were compared between patients with and without constipation using Wilcoxon two-samples test.

Results: Questionnaires were returned by 588 patients with non-advanced illness, of whom 326 (55%) were classified as having constipation and by 113 patients with advanced illness, of whom 76 (67%) were classified as having constipation. The median EQ-5D index, a weighted health state index score with 1 = full health, was lower in patients with constipation than in patients without constipation (0.31 vs. 0.65, p<?0.01 for non-advanced illness and 0.41 vs. 0.61, p=0.12 for advanced illness).

Conclusion: The results of this study suggest that, in patients using opioids either for non-advanced illness or advanced illness, constipation negatively influences QoL. By separately analysing patients with advanced illness and patients with non-advanced illness, possible selective non-response and confounding was accounted for, but not completely solved.     

Prevalence and impact of constipation and bowel dysfunction induced by strong opioids: a cross-sectional survey of 520 patients with cancer pain: DYONISOS study

Abstract

Objective:

To describe the prevalence of opioid-induced constipation (OIC) in patients with cancer pain according to the Knowles-Eccersley-Scott symptom score (KESS), the different symptoms of opioid-induced bowel dysfunction (OIBD), and to assess the impact of OIBD on patient’s quality-of-life.

Methods:

A cross-sectional observational study, using the KESS questionnaire and the physician’s subjective assessment of constipation, and other questionnaires and questions on constipation, OIBD, and quality-of-life, carried out on 1 day at oncology day centres and hospitals.

Results:

Five hundred and twenty patients were enrolled at 77 centres in France; 61.7% of patients (n?=?321) showed a degree of constipation that is problematic for the patient according to KESS (between 9–39). Even more patients, 85.7% (n?=?438), were considered constipated according to the physician’s subjective assessment—despite laxative use (84.7% of patients). Quality-of-life was significantly reduced in constipated vs non-constipated patients for both PAC-QoL (p?<?0.0001 for total score and each dimension) and the SF-12 questionnaires (statistically significant for all dimensions except physical state and role physical). OIC and OIBD led to hospitalization (16% of patients), pain (75% of patients), and frequent changes in opioid and laxative treatment.

Key limitations:

This cross-sectional study, in a selected population of cancer patients, has measured prevalence and impact of OIBD. Further confirmation could be sought through the use of longitudinal studies, and larger populations, such as non-cancer pain patients treated with opioids

Conclusions:

Cancer patients taking opioids for pain are very frequently constipated, even if they are prescribed laxatives. This leads to relevant impairments of quality-of-life.