A Principled Approach to Characterize and Analyze Partially Observed Confounder Data from Electronic Health Records.

Objective: Partially observed confounder data pose challenges to the statistical analysis of electronic health records (EHR) and systematic assessments of potentially underlying missingness mechanisms are lacking. We aimed to provide a principled approach to empirically characterize missing data processes and investigate performance of analytic methods.

Methods: Three empirical sub-cohorts of diabetic SGLT2 or DPP4-inhibitor initiators with complete information on HbA1c, BMI and smoking as confounders of interest (COI) formed the basis of data simulation under a plasmode framework.

smdi: an R package to perform structural missing data investigations on partially observed confounders in real-world evidence studies.

Objectives: Partially observed confounder data pose a major challenge in statistical analyses aimed to inform causal inference using electronic health records (EHRs). While analytic approaches such as imputation are available, assumptions on underlying missingness patterns and mechanisms must be verified. We aimed to develop a toolkit to streamline missing data diagnostics to guide choice of analytic approaches based on meeting necessary assumptions.

Postapproval Comparative Safety Study of Tofacitinib and Biological Disease-Modifying Antirheumatic Drugs: 5-Year Results from a United States-Based Rheumatoid Arthritis Registry.

Objective: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5-year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease-modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry.

Methods: IRs (number of first events/100 patient-years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow-up through January 31, 2019).

Real-World Evidence to Contextualize Clinical Trial Results and Inform Regulatory Decisions: Tofacitinib Modified-Release Once-Daily vs Immediate-Release Twice-Daily for Rheumatoid Arthritis.

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation.

Methods: Two noninterventional cohort studies were conducted.

Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis.

Introduction: No published studies exist comparing the effectiveness of tofacitinib with other advanced therapies for the treatment of rheumatoid arthritis (RA) in real-world clinical practice. Here, we report differences in effectiveness of tofacitinib compared with standard of care, tumor necrosis factor inhibitors (TNFi), with or without concomitant methotrexate (MTX), using US Corrona registry data.

Methods: This observational cohort study included RA patients receiving tofacitinib (from 6 November 2012; N = 558) or TNFi (from 1 November 2001; N = 8014) with or without MTX until 31 July 2016.

Outcomes of infliximab dose escalation in patients with rheumatoid arthritis.

Introduction: Dose escalation of infliximab in both primary and secondary nonresponders is widely reported; however, the usefulness of dose escalation has been disputed. The objective of this analysis is to evaluate trends in clinical efficacy following multiple infliximab dose escalations in patients with rheumatoid arthritis (RA).

Methods: Patients enrolled in a US RA registry were included if they initiated infliximab at 3 mg/kg every 8 weeks, received ≥ 1 infliximab dose escalation within 12 months of initiation, and had ≥ 1 visit following dose escalation.

One-year risk of serious infection in patients treated with certolizumab pegol as compared with other TNF inhibitors in a real-world setting: data from a national U.S. rheumatoid arthritis registry.

Background: Registry studies provide a valuable source of comparative safety data for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA), but they are subject to channeling bias. Comparing safety outcomes without accounting for channeling bias can lead to inaccurate comparisons between TNFi prescribed at different stages of the disease. In the present study, we examined the incidence of serious infection and other adverse events during certolizumab pegol (CZP) use vs other TNFi in a U.

The pelvic floor complication scale: a new instrument for reconstructive pelvic surgery.

Objective: The purpose of this study was to develop and test a unique, new pelvic floor surgery complication scale and compare it with an existing validated measure.

Study Design: Surgeons from 2 clinical trials networks rated complications based on perceived patient bother, severity, and duration of disability to develop a pelvic floor complication scale (PFCS). PFCS scores were calculated for subjects in 2 multicenter pelvic floor surgical trials.

A randomized trial of urodynamic testing before stress-incontinence surgery.

Background: Urodynamic studies are commonly performed in women before surgery for stress urinary incontinence, but there is no good evidence that they improve outcomes.

Methods: We performed a multicenter, randomized, noninferiority trial involving women with uncomplicated, demonstrable stress urinary incontinence to compare outcomes after preoperative office evaluation and urodynamic tests or evaluation only. The primary outcome was treatment success at 12 months, defined as a reduction in the score on the Urogenital Distress Inventory of 70% or more and a response of "much better" or "very much better" on the Patient Global Impression of Improvement.

Adverse events over two years after retropubic or transobturator midurethral sling surgery: findings from the Trial of Midurethral Slings (TOMUS) study.

Objective: To describe surgical complications in 597 women over a 24-month period after randomization to retropubic or transobturator midurethral slings.

Study Design: During the Trial of Midurethral Slings study, the Data Safety Monitoring Board regularly reviewed summary reports of all adverse events using the Dindo Surgical Complication Scale. Logistic regression models were created to explore associations between clinicodemographic factors and surgical complications.

Lessons from a patient experience survey in a randomized surgical trial of treatment of stress urinary incontinence in women.

Introduction And Hypothesis: To understand the patient burden of study procedures/measures at completion of a randomized controlled trial (RCT) requiring extensive testing and follow-up visits.

Methods: A survey sent after completing the 2-year visit of an RCT comparing Burch colposuspension and fascial retropubic sling to treat stress urinary incontinence assessed degree of bother for seven study procedures, eight study-related factors, and possible motivations to participate in the study.

Results: A total of 450 study participants (88%) returned the survey.

Perineal surface electromyography does not typically demonstrate expected relaxation during normal voiding.

Aims: To describe perineal surface patch electromyography (EMG) activity during urodynamics (UDS) and compare activity between filling and voiding phases and to assess for a relationship between preoperative EMG activity and postoperative voiding symptoms.

Methods: 655 women underwent standardized preoperative UDS that included perineal surface EMG prior to undergoing surgery for stress urinary incontinence. Pressure-flow studies were evaluated for abdominal straining and interrupted flow.

Demographic and clinical predictors of treatment failure one year after midurethral sling surgery.

Objective: To identify clinical and demographic factors predictive of midurethral sling failure.

Methods: Overall treatment failure was defined by one or more of the following objective outcomes: a positive stress test, positive 24-hour pad test or retreatment for stress urinary incontinence (SUI); subjective outcomes: self reported SUI by the Medical, Epidemiologic and Social Aspect of Aging questionnaire, incontinent episodes by 3-day diary, or retreatment for SUI, or a combination of these. Logistic regression models adjusting for sling type and clinical site were used to predict odds of overall treatment failure after univariable analysis.

Preoperative voiding detrusor pressures do not predict stress incontinence surgery outcomes.

Introduction And Hypothesis: The aim of this study was to determine whether preoperative voiding detrusor pressures were associated with postoperative outcomes after stress incontinence surgery.

Methods: Opening detrusor pressure, detrusor pressure at maximum flow (p (det) Q(max)), and closing detrusor pressure were assessed from 280 valid preoperative urodynamic studies in subjects without advanced prolapse from a multicenter randomized trial comparing Burch and autologous fascia sling procedures. These pressures were compared between subjects with and without overall success, stress-specific success, postoperative detrusor overactivity, and postoperative urge incontinence using independent sample t tests.

Retropubic versus transobturator midurethral slings for stress incontinence.

Background: Midurethral slings are increasingly used for the treatment of stress incontinence, but there are limited data comparing types of slings and associated complications.

Methods: We performed a multicenter, randomized equivalence trial comparing outcomes with retropubic and transobturator midurethral slings in women with stress incontinence. The primary outcome was treatment success at 12 months according to both objective criteria (a negative stress test, a negative pad test, and no retreatment) and subjective criteria (self-reported absence of symptoms, no leakage episodes recorded, and no retreatment).

The impact of obesity on urinary incontinence symptoms, severity, urodynamic characteristics and quality of life.

Purpose: We compared urinary incontinence severity measures and the impact of stress urinary incontinence in normal, overweight and obese women.

Materials And Methods: Baseline characteristics of subjects in the SISTEr (655) and the TOMUS (597) were analyzed. Body mass index was defined as normal (less than 25 kg/m(2)), overweight (25 to less than 30 kg/m(2)) and obese (30 kg/m(2) or greater).

Design of the Value of Urodynamic Evaluation (ValUE) trial: A non-inferiority randomized trial of preoperative urodynamic investigations.

Background And Purpose: Urodynamic studies (UDS) are routinely obtained prior to surgery for stress urinary incontinence (SUI) despite a lack of evidence that UDS information has an actual impact on outcome. The primary aim of this non-inferiority randomized clinical trial is to determine whether women with symptomatic, uncomplicated SUI who undergo only a basic office evaluation (BOE) prior to SUI surgery (No UDS arm) have non-inferior treatment outcomes compared to women who have BOE and UDS (UDS arm). Secondary aims are: 1) to determine how often physicians use preoperative UDS results to alter clinical and surgical decision-making, 2) to compare the amount of improvement in incontinence outcomes, and 3) to determine the incremental cost and utility of performing UDS compared with not performing UDS.

Complications in women undergoing Burch colposuspension versus autologous rectus fascial sling for stress urinary incontinence.

Purpose: We determined the clinicodemographic factors associated with complications of continence procedures, the impact of concomitant surgery on the complication rate and the relationship between the incidence of cystitis and the method of postoperative bladder drainage.

Materials And Methods: We reviewed serious adverse events and adverse events in the Stress Incontinence Surgical Efficacy Trial, a randomized trial comparing Burch colposuspension to the autologous rectus fascial sling. Clinicodemographic variables were analyzed to determine those associated with adverse events using logistic regression analysis.

Two-year outcomes after surgery for stress urinary incontinence in older compared with younger women.

Objective: To estimate whether perioperative and postoperative outcomes after Burch colposuspension or pubovaginal sling for stress urinary incontinence (SUI) differed with age.

Methods: This study was a prospective secondary analysis of the Stress Incontinence Surgical Treatment Efficacy Trial. Baseline characteristics, adverse events, and 2-year outcomes of women at least 65 years old were compared with those younger than 65 years using chi(2) and t tests.

Behavioral therapy to enable women with urge incontinence to discontinue drug treatment: a randomized trial.

Background: Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy.

Objective: To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared with drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy.

Design: 2-stage, multicenter, randomized clinical trial conducted from July 2004 to January 2006.

Burch colposuspension versus fascial sling to reduce urinary stress incontinence.

Background: Many surgical procedures are available for women with urinary stress incontinence, yet few randomized clinical trials have been conducted to provide a basis for treatment recommendations.

Methods: We performed a multicenter, randomized clinical trial comparing two procedures--the pubovaginal sling, using autologous rectus fascia, and the Burch colposuspension--among women with stress incontinence. Women were eligible for the study if they had predominant symptoms associated with the condition, a positive stress test, and urethral hypermobility.

The relationships among measures of incontinence severity in women undergoing surgery for stress urinary incontinence.

Purpose: We assessed the relationships among severity measures of urinary incontinence in women with stress predominant symptoms enrolled in a randomized clinical trial comparing 2 surgical techniques (Burch colposuspension vs pubovaginal sling) for stress urinary incontinence.

Materials And Methods: A total of 655 women underwent a standardized preoperative assessment that included the Medical, Epidemiological and Social Aspects of Aging questionnaire, Urogenital Distress Inventory, Incontinence Impact Questionnaire, 3-day voiding diary, 24-hour pad test, a supine empty bladder stress test and Valsalva leak point pressure measurements. Correlations were estimated using Spearman correlation coefficients and 95% confidence intervals.

Factors associated with incontinence frequency in a surgical cohort of stress incontinent women.

Objective: The aim of this study was to identify factors associated with urinary incontinence severity at baseline in women undergoing surgery for stress incontinence.

Study Design: Baseline data were obtained from 650 women (age 28 to 81 years) with stress incontinence participating in a randomized surgical trial. Severity of incontinence was defined by the mean number of incontinence episodes per day recorded in a 3-day bladder diary.