Comparison of Methods to Generalize Randomized Clinical Trial Results Without Individual-Level Data for the Target Population.

Our study explored the application of methods to generalize randomized controlled trial results to a target population without individual-level data. We compared 4 methods using aggregate data for the target population to generalize results from the international trial, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), to a target population of trial-eligible patients in the UK Clinical Practice Research Datalink (CPRD). The gold-standard method used individual data from both the trial and CPRD to predict probabilities of being sampled in the trial and to reweight trial participants to reflect CPRD patient characteristics. Methods 1 and 2 used weighting methods based on simulated individual data or the method of moments, respectively. Method 3 weighted the trial's subgroup-specific treatment effects to match the distribution of an effect modifier in CPRD. Method 4 calculated the expected absolute benefits in CPRD assuming homogeneous relative treatment effect. Methods based on aggregate data for the target population generally yielded results between the trial and gold-standard estimates. Methods 1 and 2 yielded estimates closest to the gold-standard estimates when continuous effect modifiers were represented as categorical variables. Although individual data or data on joint distributions remains the best approach to generalize trial results, these methods using aggregate data might be useful tools for timely assessment of randomized trial generalizability.

Epidemiology and health outcomes associated with hyperkalemia in a primary care setting in England.

BACKGROUND: Real-world incidence, clinical consequences, and healthcare resource utilization (HRU) of hyperkalemia (HK) remain poorly characterized, particularly in patients with specific comorbidities. METHODS: Data from the Clinical Practice Research Datalink and Hospital Episode Statistics databases were analyzed to determine incidence of an index HK event, subsequent clinical outcomes, and HRU in the English population. Factors associated with index HK in a primary care setting were also identified for those with an index HK event during the study period (2009-2013) and matched controls. RESULTS: The overall incidence rate of an index HK event was 2.9 per 100 person-years. Use of renin-angiotensin-aldosterone system inhibitors was strongly associated with HK (odds ratio, 13.6-15.9). Few patients (5.8%) had serum potassium (K+) retested ≤ 14 days following the index event; among those retested, 32% had HK. Following an index HK event, all-cause hospitalization, HK recurrence, and kidney function decline were the most common outcomes (incidence rates per 100 person-years: 14.1, 8.1, and 6.7, respectively), with higher rates in those with comorbidities or K+ > 6.0 mmol/L. Mortality and arrhythmia rates were higher among those with K+ > 6.0 mmol/L. Older age, comorbid diabetes mellitus, and mineralocorticoid receptor antagonist use were associated with HK recurrence. Relatively few patients received testing or prescriptions to treat HK following an event. CONCLUSIONS: Severe index HK events were associated with adverse outcomes, including arrhythmia and mortality. Despite this, retesting following an index event was uncommon, and incidence of recurrence was much higher than that of the index event.

Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population.

Statins are indicated in patients with elevated levels of high-sensitivity C-reactive protein and normal low-density lipoprotein cholesterol based on results of the multicountry trial, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) (2003-2008), but the benefit in real-world populations remains unknown. We sought to generalize JUPITER results to trial-eligible population using data from the UK Clinical Practice Research Datalink (CPRD), 2001-2014. We multiply imputed missing baseline characteristics for the CPRD population and selected the trial-eligible participants as the target population based on observed and imputed values. Trial participants were weighted to be representative of the CPRD population (n = 383,418) based on individual predicted probability of selection into the trial. Trial participants were also standardized to the CPRD population without missing values (n = 2,677). In JUPITER, rosuvastatin reduced cardiovascular risk with a 3-year risk difference of -2.0% (95% confidence interval (CI): -2.9, -1.1). The rosuvastatin effect was muted in the first 2 years but remained strong at 3 years after standardizing to the imputed CPRD population (3-year risk difference = -2.7%; 95% CI: -5.8, 0.4) and the CPRD population without missing data (3-year risk difference = -1.7%; 95% CI: -3.5, 0.1). The study serves as an illustration of possible approaches to understanding generalizability of trials using real-world databases given limitations due to missing data on inclusion/exclusion criteria.

Burden of cardio-renal-metabolic conditions in adults with type 2 diabetes within the Diabetes Collaborative Registry.

We examined the prevalence of cardio-renal-metabolic (CaReMe) conditions and their combinations among 530 747 adults with type 2 diabetes in a USA-based outpatient registry of 271 primary care, cardiology and endocrinology offices. We evaluated the following CaReMe conditions: hypertension, hyperlipidaemia, coronary artery disease (CAD), chronic kidney disease (CKD), cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and gout or hyperuricaemia; prevalence estimates were adjusted based on the distribution of diabetes by age in the US population in 2015. We found that it was uncommon for patients to have isolated type 2 diabetes without other CaReMe conditions, with only 6.4% having no other CaReMe conditions and 51% having ≥3 other CaReMe conditions. The most prevalent individual conditions were hypertension (83%), hyperlipidemia (81%), CAD (32%) and CKD (20%), and the most common combinations included various groupings of hypertension, hyperlipidaemia, atherosclerotic cardiovascular disease and CKD. Older age, male sex and tobacco use were each associated with increased numbers of CaReMe conditions. These findings highlight the clinical need for novel treatment strategies for diabetes that address both glycaemia and coexisting disease states.

Opioid-Induced Constipation Among Patients with Chronic Noncancer Pain in the United States, Canada, Germany, and the United Kingdom: Laxative Use, Response, and Symptom Burden Over Time.

PURPOSE: Estimate rate of laxative inadequate response (LIR) over time among patients with chronic noncancer pain with opioid-induced constipation (OIC). METHODS: A prospective longitudinal study was conducted in United States, Canada, Germany, and United Kingdom. Patients on opioid therapy for ≥4 weeks for chronic noncancer pain and OIC completed an Internet-based survey at Baseline and Weeks 2, 4, 6, 8, 12, 16, 20, and 24. 1xLIR was defined as sufficient laxative use (≥1 laxative ≥ 4 times in past 2 weeks) and inadequate response (<3 bowel movements or ≥ 1 constipation symptom rated Moderate or greater). 2xLIR was sufficient laxative use of ≥2 laxatives from different drug classes and inadequate response. Descriptive statistics and logistic regressions were performed. RESULTS: 489 patients (62% female; 85% white) completed Baseline; 27% reported no laxative use; 25% had insufficient laxative use; 48% had sufficient laxative use. During follow-up, 21-28% of patients had no or insufficient laxative use. Prevalence of 1xLIR was 93% at Baseline and ranged from 59-81% across follow-up; 26% met criteria for 2xLIR (follow-up range: 11-20%). CONCLUSIONS: OIC among noncancer pain patients is a persistent and significant condition with varying utilization and response to laxatives thus increasing the ongoing burden of chronic pain. © 2014 Wiley Periodicals, Inc.

The role of prediction modeling in propensity score estimation: an evaluation of logistic regression, bCART, and the covariate-balancing propensity score.

The covariate-balancing propensity score (CBPS) extends logistic regression to simultaneously optimize covariate balance and treatment prediction. Although the CBPS has been shown to perform well in certain settings, its performance has not been evaluated in settings specific to pharmacoepidemiology and large database research. In this study, we use both simulations and empirical data to compare the performance of the CBPS with logistic regression and boosted classification and regression trees. We simulated various degrees of model misspecification to evaluate the robustness of each propensity score (PS) estimation method. We then applied these methods to compare the effect of initiating glucagonlike peptide-1 agonists versus sulfonylureas on cardiovascular events and all-cause mortality in the US Medicare population in 2007-2009. In simulations, the CBPS was generally more robust in terms of balancing covariates and reducing bias compared with misspecified logistic PS models and boosted classification and regression trees. All PS estimation methods performed similarly in the empirical example. For settings common to pharmacoepidemiology, logistic regression with balance checks to assess model specification is a valid method for PS estimation, but it can require refitting multiple models until covariate balance is achieved. The CBPS is a promising method to improve the robustness of PS models.

Variable selection for propensity score models when estimating treatment effects on multiple outcomes: a simulation study.

PURPOSE: It is often preferable to simplify the estimation of treatment effects on multiple outcomes by using a single propensity score (PS) model. Variable selection in PS models impacts the efficiency and validity of treatment effects. However, the impact of different variable selection strategies on the estimated treatment effects in settings involving multiple outcomes is not well understood. The authors use simulations to evaluate the impact of different variable selection strategies on the bias and precision of effect estimates to provide insight into the performance of various PS models in settings with multiple outcomes. METHODS: Simulated studies consisted of dichotomous treatment, two Poisson outcomes, and eight standard-normal covariates. Covariates were selected for the PS models based on their effects on treatment, a specific outcome, or both outcomes. The PSs were implemented using stratification, matching, and weighting (inverse probability treatment weighting). RESULTS: PS models including only covariates affecting a specific outcome (outcome-specific models) resulted in the most efficient effect estimates. The PS model that only included covariates affecting either outcome (generic-outcome model) performed best among the models that simultaneously controlled measured confounding for both outcomes. Similar patterns were observed over the range of parameter values assessed and all PS implementation methods. CONCLUSIONS: A single, generic-outcome model performed well compared with separate outcome-specific models in most scenarios considered. The results emphasize the benefit of using prior knowledge to identify covariates that affect the outcome when constructing PS models and support the potential to use a single, generic-outcome PS model when multiple outcomes are being examined.

Guidelines for good database selection and use in pharmacoepidemiology research.

The use of healthcare databases in research provides advantages such as increased speed, lower costs and limitation of some biases. However, database research has its own challenges as studies must be performed within the limitations of resources, which often are the product of complex healthcare systems. The primary purpose of this document is to assist in the selection and use of data resources in pharmacoepidemiology, highlighting potential limitations and recommending tested procedures. This guidance is presented as a detailed text with a checklist for quick reference and covers six areas: selection of a database, use of multiple data resources, extraction and analysis of the study population, privacy and security, quality and validation procedures and documentation.

Characterizing real world safety profile of oral Janus kinase inhibitors among adult atopic dermatitis patients: evidence transporting from the rheumatoid arthritis population.

OBJECTIVE: To address potential safety concerns of Janus Kinase Inhibitors (JAK-Is), we characterized their safety profile in the atopic dermatitis (AD) patient population. METHODS: In this retrospective observational study, we used propensity score-based methods and a Poisson modeling framework to estimate the incidence of health outcomes of interest (HOI) for the AD patient. To that end, two mutually exclusive cohorts were created using a real world data resource: a rheumatoid arthritis (RA) cohort, where we directly quantify the safety risk of JAK-Is on HOIs, and an AD cohort, that comprises the target population of interest and to whom we transport the results obtained from the RA cohort. The RA cohort included all adults who filled at least one prescription for a JAK-I (tofacitinib, baricitinib, or upadacitinib) between 1 January 2017 and 31 January 2020. The AD cohort consisted of all adults diagnosed with AD during the same period. We first estimated the incidence rate of each HOI in the RA cohort, and then transported the results to the AD population. RESULTS: The RA and AD cohorts included 5,296 and 261,855 patients, respectively. On average, patients in the AD cohort were younger, more often male, more likely to be Asian, and had higher household income. They also had a lower prevalence of several comorbid conditions including hypertension, chronic kidney disease, obesity, and depression. Overall, the transported incidence rates of the HOIs to the AD cohort were lower than those obtained in the RA cohort by 13-50%. CONCLUSION: We applied transportability methods to characterize the risk of the HOIs in the AD population and found absolute risks higher than that of the general population. Future work is needed to validate these conclusions in comparable populations.

Immunolab: Combining targeted real-world data with advanced analytics to generate evidence at scale in immunology.

Real-world evidence (RWE) has traditionally been used by regulatory or payer authorities to inform disease burden, background risk, or conduct post-launch pharmacovigilance, but in recent years RWE has been increasingly used to inform regulatory decision-making. However, RWE data sources remain fragmented, and datasets are disparate and often collected inconsistently. To this end, we have constructed an RWE-generation platform, Immunolab, to facilitate data-driven insights, hypothesis generation and research in immunological diseases driven by type 2 inflammation. Immunolab leverages a large, anonymized patient cohort from the Optum electronic health record and claims dataset containing over 17 million patient lives. Immunolab is an interactive platform that hosts three analytical modules: the Patient Journey Mapper, to describe the drug treatment patterns over time in patient cohorts; the Switch Modeler, to model treatment switching patterns and identify its drivers; and the Head-to-Head Simulator, to model the comparative effectiveness of treatments based on relevant clinical outcomes. The Immunolab modules utilize various analytic methodologies including machine learning algorithms for result generation which can then be presented in various formats for further analysis and interpretation.

Bridging the Gap Between RCTs and RWE Through Endpoint Selection.

This commentary is authored by several industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of Industry Leaders who have come together as non-competitive partners to understand and respond to RWD/E challenges and opportunities with a single expert voice. Here, the forum discusses the value in bridging the industry disconnect between RTCs and RWE, with a view to promoting the use of RWE in the RCT environment. RCT endpoints are explored along several axes including their clinical relevance and their measure of direct patient benefit, and then compared with their real-world counterparts to identify suitable paths, or gaps, for assimilating RWE endpoints into the RCT environment.

Strengthening pharma's contract with society: the value of trusted partnerships between pharma and healthcare facilitated by real-world data.

This White Paper is authored by 11 industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of industry leaders who come together as noncompetitive partners to understand and respond to internal or external RWD/E challenges and opportunities with a single expert voice. Herein we aim to clarify the rules of engagement between pharma and healthcare in order to establish trust-based partnerships, which will unlock unique value for society, including the medical community and the ultimate beneficiary, the patient.

Designing, Conducting, Monitoring, and Analyzing Data from Pragmatic Randomized Clinical Trials: Proceedings from a Multi-stakeholder Think Tank Meeting.

In late 2018, the Food and Drug Administration (FDA) outlined a framework for evaluating the possible use of real-world evidence (RWE) to support regulatory decision-making. This framework was created to facilitate studies that would generate high-quality RWE, including pragmatic clinical trials (PCTs), which are randomized trials designed to inform clinical or policy decisions by assessing the real-world effectiveness of an intervention. There is general agreement among experts that the use of existing healthcare and patient-generated data holds promise for making randomized trials more efficient, less costly, and more generalizable. Yet the benefits of relying on real-world data sources must be weighed against difficulties with ensuring data integrity and completeness. Additionally, appropriately monitoring patient safety in randomized trials of new drugs using healthcare system data that might not be available in real time can be quite difficult. Recognizing that these and other concerns are critical to the development and acceptability of PCTs, a group of stakeholders from academia, industry, professional organizations, regulatory bodies, government agencies, and patient advocates discussed a path forward for PCT growth and sustainability at a think tank meeting entitled "Monitoring and Analyzing Data from Pragmatic Streamlined Randomized Clinical Trials," which took place in January 2019 (Washington, DC). The goals of this meeting were to: (1) evaluate study design and methodological options specific to PCTs that have the potential to yield high-quality evidence; (2) discuss best practices to ensure data quality in PCTs; and (3) identify appropriate methods for study monitoring. Proceedings from the think tank meeting are summarized in this manuscript.

Transition to managed care impacts health care service utilization by children insured by Medicaid.

Purpose. To evaluate the impact of transition to managed care from fee for service on asthma service utilization among Maryland Medicaid insured children. Methods. Healthcare claims from 1997-2000 for children with asthma insured by Maryland Medicaid were extracted and analyzed. Results. Between 1997-2000, inhaled corticosteroid use increased as a proportion of all asthma medications. Outpatient asthma visits increased from 4.2% to 5.9% of all outpatient claims as both asthma-related hospitalizations and emergency department visits decreased. Conclusions. Restructuring of Maryland Medicaid for children from fee for service to managed care was associated with improvement in asthma-related healthcare utilization claims.

Risk areas for pediatric acute care: asthma differs from upper and lower respiratory illness.

OBJECTIVE: To determine if emergency department utilization for pediatric respiratory illness varies across small geographic jurisdictions within a large urban city. DESIGN: A retrospective analysis of Maryland Health Services Cost Review Commission Emergency Department discharge data. SETTING/PATIENTS: All non-neonatal, Baltimore City residents <18 years old with valid diagnoses admitted and discharged from emergency departments (ED) in the state of Maryland from April 1, 1997 to December 31, 2000 (n=245,339). MAIN OUTCOME MEASURES: Crude and adjusted ED visit rates for asthma, upper and lower respiratory illnesses (per 1000 population). To evaluate the effect of geography on pediatric ED visit rates, odds of an asthma ED visit, URI, or LRI vs. non-respiratory ED visit were compared across regions of the city. RESULTS: We determined that residential areas with high ED utilization rates for upper and lower respiratory illnesses, as well as non-respiratory illnesses correlate with regions of high ED utilization for asthma, even after adjusting for race, gender and age of the population. The regions with high odds ratios that an ED visit was for asthma were different from those with high ORs for URI and LRI after also controlling for poverty. CONCLUSIONS: This suggests that poverty accounts for high utilization of the ED in urban settings, but suggests that environmental exposures that increase the risk of ED care for asthma differ from those that lead to URI and LRI.

The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports.

BACKGROUND: Opioid-induced constipation (OIC), a common side effect of opioid treatment for chronic pain, affects patient health-related quality of life (HRQL) and may prompt some patients to lower the dose or alter adherence to their opioid medication, compromising pain relief. Although health care providers (HCPs) are aware of the potential for OIC, patients may not inform their HCPs of their OIC symptoms, and HCPs may not initiate conversation regarding OIC if their patients' pain is controlled. Patients often try to address OIC symptoms on their own by using natural approaches or over-the-counter options. When OIC is discussed in an office visit, HCPs typically recommend conventional laxatives to relieve symptoms, but the efficacy of this approach is unproven and often suboptimal. In many areas of medicine, HCP perceptions of the impact of adverse effects of treatment on a patient's HRQL do not align with the patient's experience. OBJECTIVES: To (a) describe HCP-reported understanding of his or her patients' experiences with OIC and (b) evaluate the level of agreement or discordance in perception between patients and their HCPs of OIC's impact on clinical outcomes. METHODS: This was a prospective, longitudinal, observational cohort study conducted in the United States, Canada, Germany, and the United Kingdom (NCT01928953) in patients aged 18 to 85 years who had been receiving daily opioid therapy for ≥ 4 weeks for chronic noncancer pain with presence of OIC in the past 2 weeks. Data were collected from retrospective chart reviews, HCP questionnaires, and web-based patient surveys. Eligible patients enrolled online and completed the Patient Assessment of Constipation-Symptoms, the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem, the EuroQOL 5 Dimensions, and the Global Assessment of Treatment Benefit, Satisfaction, and Willingness to Continue standardized questionnaires. The patient-reported component included 1 baseline survey and 8 follow-up surveys over 24 weeks. HCPs completed a web-based survey at baseline and at week 24 to assess their perceptions of OIC burden, treatment patterns, laxative use, and overall treatment satisfaction. The correspondence of patient- and HCP-reported data was evaluated for all similar outcomes from these 2 databases. RESULTS: Patients (N = 489) reported a mean (SD) number of bowel movements (BMs) per week and spontaneous BMs per week of 3.7 (2.9) and 1.4 (2.3), respectively, at baseline. Most (87%) reported chronic pain of ≥ 2 years duration; 65% had used opioids for ≥ 2 years; and the mean pain score at baseline was 6.3, consistent with a moderate-to-severe pain population. Most (97%) patients at baseline reported any gastrointestinal-related symptom of at least moderate intensity, with 82% reporting the same intensity of any symptom at week 24. Of the 405 patients who had seen their HCPs in the past month, 63% reported that they had spoken to their HCPs about constipation, and 62% reported that their HCPs had asked them if they had constipation in the past month. The proportion of agreement between HCPs and their patients on the presence of constipation at baseline was 61%. Similar average pain ratings between HCPs and patients (5.9 vs. 6.0) at week 24 suggested clear communication regarding the level of pain experienced by the patient; however, OIC symptoms, laxative use and effectiveness, and impact of OIC on pain management and HRQL were not fully appreciated by HCPs. CONCLUSIONS: The importance and severity of OIC are perceived differently by patients and their HCPs, a discordance that complicates pain management and demonstrates a need for greater communication. These disparate perceptions indicate a need for clinical education and coordination of care by HCPs to improve understanding and proactively manage OIC in patients with chronic noncancer pain.

Satisfaction with Therapy Among Patients with Chronic Noncancer Pain with Opioid-Induced Constipation.

BACKGROUND: Greater satisfaction with medication is associated with better adherence; however, specific to opioid-induced constipation (OIC), data on the relationship between medication satisfaction and efficacy are lacking. OBJECTIVE: To understand satisfaction with therapy among patients with chronic noncancer pain and OIC. METHODS: A prospective longitudinal study was conducted in the United States, Canada, Germany, and the United Kingdom using web-based patient surveys. Patients on daily opioid therapy for ≥ 74 weeks for the treatment of chronic noncancer pain with OIC were recruited from physician offices and completed a web-based survey at baseline and weeks 2, 4, 6, 8, 12, 16, 20, and 24. When completing each survey, patients selected the remedies used in the previous 2 weeks to relieve constipation; options included natural/behavioral therapies, over-the-counter (OTC) therapies, and prescription laxatives. Patients selected the amount of relief and satisfaction with each selected therapy. Descriptive statistics were calculated; Spearman's correlations were calculated for symptom relief and satisfaction. RESULTS: Mean age of the 489 patients who met the criteria for OIC and completed the baseline survey was 52.6 ± 11.6 years; 62% were female; 85% were white. Increasing levels of relief from constipation were associated with increasing levels of satisfaction for all agents; correlations were > 0.55 and statistically significant (P < 0.001). Among the patients who had used OTC therapies in the 2 weeks prior to baseline, 54% to 73% reported that they were somewhat or very satisfied with the therapy. Yet, of these satisfied patients, 28% to 63% experienced no or only slight relief from the therapy. Twenty percent to 79% of the patients who had used prescription laxatives in the 2 weeks prior to baseline reported being at least somewhat satisfied with the therapy. CONCLUSIONS: These results indicate that there is a high rate of inadequate response to laxatives for patients with OIC that persisted for the 6 months of this study. While increased relief from constipation was associated with increased satisfaction for all therapies, there remains a substantial number of patients who report satisfaction despite having only inadequate relief from OIC that merits further investigation.

Opioid-Induced Constipation among a Convenience Sample of Patients with Cancer Pain.

BACKGROUND: Little is known regarding the burden of opioid-induced constipation (OIC) among patients who suffer from cancer-related pain. METHODS: A prospective longitudinal study was conducted among cancer patients in the United Kingdom (UK), Canada, and Germany, which included medical record data abstraction, Internet-based patient surveys, and physician surveys. Patients on daily opioid therapy (≥30 mg for ≥4 weeks) for treatment of cancer pain with self-reported OIC were recruited. Response to laxatives was defined by classifying participants into categories of laxative use and evaluating the prevalence of inadequate response. Descriptive statistics were used to evaluate outcomes, including the patient assessment of constipation-symptom (PAC-SYM), patient assessment of constipation-quality of life, EuroQOL-5 dimensions, and global assessment of treatment benefit, satisfaction, and willingness to continue. RESULTS: Recruitment was difficult for this study with only 31 participants completing the baseline survey and meeting criteria for opioid use and OIC (26 UK, 1 Canada, and 4 Germany). Fifty-two percent (n = 16) of participants were male, and all were White. Breast (23%, n = 7), pancreatic (13%, n = 4), and multiple myeloma (13%, n = 4) were the most common cancers. Mean duration of chronic pain and opioid use were 2.3 and 1.3 years, respectively. Participants reported having a mean of 4.4 bowel movements/week in the 2 weeks prior to baseline, of which a mean of 0.9 were spontaneous. Most participants (90%, n = 28) were using at least 1 lifestyle approach to manage their constipation; 65% (n = 20) were taking ≥1 over-the-counter laxative; 19% (n = 6) were taking ≥1 prescription laxative; 23% (n = 7) reported no laxative use in the prior 2 weeks. Moderate-to-severe constipation symptoms on the PAC-SYM were common, and mean scores on health-related quality of life outcomes were comparable to chronic pain populations. CONCLUSION: In this primarily UK sample, there appears to be considerable unmet OIC treatment needs among cancer patients.

Laxative utilization over time in chronic pain patients with opioid-induced constipation.

AIM: To determine laxative utilization over time among chronic noncancer pain patients with opioid-induced constipation (OIC). SETTING: A prospective longitudinal study conducted in the USA, Canada, Germany and UK. METHODS: Patients on daily opioid therapy for treatment of chronic noncancer pain with OIC were recruited from clinics to complete a survey at Baseline and weeks 2, 4, 6, 8, 12, 16, 20 and 24. RESULTS: 489 patients completed baseline with 452 completing one or more follow-up visits. 128 (28%) were nonlaxative users, 112 (25%) were insufficient laxative users and 212 (47%) were sufficient laxative users. The consistent sufficient laxative users reported the most bowel movements per week. CONCLUSION: The majority of OIC patients do not take or only intermittently take laxatives.