Ultrasound guidance enables visualization of the needle insertion site for thoracentesis and paracentesis. The improved accuracy of needle placement using ultrasound may reduce risk of complications ...and their costs associated with these procedures. Using claims data from the Premier Perspective hospital database from January 1, 2007, through December 31, 2008, we conducted an observational cohort study examining the effect of ultrasound guidance on risk of pneumothorax among patients undergoing thoracentesis and on risk of bleeding complications after paracentesis. Patients at elevated risk of these outcomes for reasons beyond the procedure of interest were excluded. Adjusted risk of events was assessed using multivariate logistic regression controlling for patient and hospitalization characteristics. Hospitalization cost and length of stay (LOS) were estimated using multivariate ordinary least squares regression of log-transformed values. We analyzed 61,261 thoracentesis and 69,859 paracentesis patient records. Approximately 45% of these procedures were ultrasound guided. Pneumothorax occurred in 2.7% (n = 1,670) of patients undergoing thoracentesis. Of patients undergoing paracentesis, 0.8% (n = 565) experienced bleeding complications. After adjustment, ultrasound guidance reduced the risk of pneumothorax after thoracentesis by 19% (OR, 0.81; 95% CI, 0.74-0.90) and by 68% for bleeding complications after paracentesis (OR, 0.32; 95% CI, 0.25-0.41). Pneumothorax increased the total cost of hospitalization by $2,801 ( P < .001) and LOS by 1.5 days ( P < .001). Bleeding complications increased cost by $19,066 ( P < .0001) and LOS by 4.3 days ( P < .0001). The data indicate that ultrasound guidance is associated with decreased risk of pneumothorax with thoracentesis and of bleeding complications with paracentesis. These complications resulted in measurable increases in hospitalization costs and LOS.
Marketing approval of pharmaceutical products is often based on data from several thousand subjects or fewer. Evaluation of safety is greatly enhanced by augmenting the safety database with ...postapproval studies.
We conducted a pooled analysis of adverse event data from 19 randomized, double-blind, placebo-controlled trials with tiotropium in patients with obstructive lung disease. We computed incidence rates and rate ratios (RRs) for various reported adverse event end points of interest. Patients contributed person-time to the analysis as long as they were in the study until 30 days after treatment (tiotropium, placebo), or until they had the event of interest, whichever came first. Studies were pooled using the Mantel-Haenszel estimator, and we used 95% confidence intervals (CIs) to assess the precision of effect estimates.
The pooled trial population includes 4,435 tiotropium patients and 3,384 placebo patients contributing 2,159 person-years of exposure to tiotropium and 1,662 person-years of exposure to placebo. Dyspnea, dry mouth, COPD exacerbation, and upper respiratory tract infection were the most commonly reported events. There was a higher relative risk of dry mouth in the tiotropium group (RR, 3.60; 95% CI, 2.56 to 5.05). There was a lower risk of dyspnea (RR, 0.64; 95% CI, 0.50 to 0.81) and COPD exacerbation (RR, 0.72; 95% CI, 0.64 to 0.82) in patients receiving tiotropium compared to patients receiving placebo. Other results of interest are as follows: (1) all-cause mortality (RR, 0.76; 95% CI, 0.50 to 1.16); (2) cardiovascular mortality (RR, 0.57; 95% CI, 0.26 to 1.26); and (3) respiratory mortality (RR, 0.71; 95% CI, 0.29 to 1.74). The relative risk of urinary retention was 10.93 (95% CI, 1.26 to 94.88).
Pooling of adverse event data from preapproval and postapproval tiotropium clinical trials increase the precision of effect estimates and supports the present safety profile of tiotropium.
To determine the relationship between diagnosed and treated COPD and the incidence of cardiovascular disease (CVD) hospitalization and mortality.
Retrospective matched cohort study.
Northern ...California Kaiser Permanente Medical Care Program (KPNC), a comprehensive prepaid integrated health-care system.
Case patients (n = 45,966) were all KPNC members with COPD who were identified during a 4-year period from January 1996 through December 1999. An equal number of control subjects without COPD were selected from KPNC membership and were matched for gender, year of birth, and length of KPNC membership.
Follow-up conducted for hospitalization and mortality from CVD end points through December 31, 2000. CVD study end points included cardiac arrhythmias, angina pectoris, acute myocardial infarction, congestive heart failure (CHF), stroke, pulmonary embolism, all of the aforementioned study end points combined, other CVD, and all CVD end points. The mean follow-up time was 2.75 years for case patients and 2.99 years for control subjects. The risk of hospitalization was higher in COPD case patients than in control subjects for all CVD hospitalization and mortality end points. The relative risk (RR) for hospitalization for the composite measure of all study end points was 2.09 (95% confidence interval CI, 1.99 to 2.20) after adjustment for gender, preexisting CVD study end points, hypertension, hyperlipidemia, and diabetes, and ranged from 1.33 (stroke) to 3.75 (CHF). The adjusted RR for mortality for the composite measure of all study end points was 1.68 (95% CI, 1.50 to 1.88), ranging from 1.25 (stroke) to 3.53 (CHF). Younger patients (ie, age < 65 years) and female patients had higher risks than older and male participants.
COPD was a predictor of CVD hospitalization and mortality over an average follow-up time of nearly 3 years. The finding of a stronger relationship of COPD to CVD outcomes in patients < 65 years of age suggests that CVD risk should be monitored and treated with particular care in younger adults with COPD.
There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer.
We conducted a cohort study of breast cancer patients initiating palbociclib and ...fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted.
There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1-8.4).
This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).
Purpose
The proportional reporting ratio (PRR) is the proportion of spontaneous reports for a given drug that are linked to a specific adverse outcome, divided by the corresponding proportion for all ...or several other drugs. The PRR is similar to the proportional mortality ratio (PMR), an old epidemiologic measure calculated from death registries and constructed in similar fashion to the PRR. The PMR has important deficiencies, however, which the PRR shares. Miettinen and Wang demonstrated that the PMR could be improved by reformulating it as an odds ratio and applying the principles of a case‐control study to the measure. In this paper, we review the problem with the PRR and show how the corresponding odds ratio represents an improvement over the PRR.
Methods
The method used is discussion and illustration by way of a hypothetical example.
Results
The PRR does not estimate relative risk. If, however, a spontaneous report database is viewed as source data for a case‐control study, the reporting odds ratio (ROR) can be used to estimate relative risk. Treating the data as source data for a case‐control study allows for further reduction of bias by the judicious choice of controls.
Conclusions
Calculating the ROR in spontaneous report databases offers advantages over the PRR. It allows for estimation of the relative risk, and focuses attention on which people or reports should be included or excluded from the control series, permitting more deliberate elimination of biases. It also highlights the inherent weaknesses in spontaneous report data, which become more evident in light of the usual principles of control selection in case‐control studies.
Purpose
Claims databases offer large populations for research, but lack clinical details. We aimed to develop predictive models to identify estrogen receptor positive (ER+) and human epidermal growth ...factor negative (HER2−) early breast cancer (ESBC) and advanced stage breast cancer (ASBC) in a claims database.
Methods
Female breast cancer cases in Anthem's Cancer Care Quality Program served as the gold standard validation sample. Predictive models were developed from clinical knowledge and empirically from claims data using logistic and lasso regression. Model performance was assessed by classification rates and c‐statistics. Models were applied to the HealthCore Integrated Research Database (claims) to identify cohorts of women with ER+/HER2− ESBC and ASBC.
Results
The validation sample included 3184 women with ER+/HER2− ESBC and 1436 with ER+/HER2− ASBC. Predictive models for ER+/HER2− ESBC and ASBC included 25 and 20 factors, respectively. Models had robust discrimination in identifying cases (c‐stat = 0.92 for ESBC and 0.95 for ASBC). Compared with a traditional a priori algorithm developed with clinical insight alone, the ER+/HER2− ASBC‐predictive model had better positive predictive value (PPV) (0.91, 95% CI, 0.90‐0.93, vs 0.69, 95% CI, 0.66‐0.73) and sensitivity (0.54 vs 0.35). Models were applied to the claims database to identify cohorts of 33 001 and 3198 women with ER+/HER2− ESBC and ASBC.
Conclusion
We conducted a validation study and developed predictive models to identify in a claims database cohorts of women with ER+/HER2− ESBC and ASBC. The models identified large cohorts in the claims data that can be used to characterize indications in the evaluation of targeted therapies.
Background Detailed epidemiologic descriptions of large populations of advanced stage ovarian cancer patients have been lacking to date. This study aimed to describe the patient characteristics, ...treatment patterns, survival, and incidence rates of health outcomes of interest (HOI) in a large cohort of advanced stage ovarian cancer patients in the United States (US). Methods This cohort study identified incident advanced stage (III/IV) ovarian cancer patients in the US diagnosed from 2010 to 2018 in the HealthCore Integrated Research Database (HIRD) using a validated predictive model algorithm. Descriptive characteristics were presented overall and by treatment line. The incidence rates and 95% confidence intervals for pre-specified HOIs were evaluated after advanced stage diagnosis. Overall survival, time to treatment discontinuation or death (TTD), and time to next treatment or death (TTNT) were defined using treatment information in claims and linkage with the National Death Index. Results We identified 12,659 patients with incident advanced stage ovarian cancer during the study period. Most patients undergoing treatment received platinum agents (75%) and/or taxanes (70%). The most common HOIs (> 24 per 100 person-years) included abdominal pain, nausea and vomiting, anemia, and serious infections. The median overall survival from diagnosis was 4.5 years, while approximately half of the treated cohort had a first-line time to treatment discontinuation or death (TTD) within the first 4 months, and a time to next treatment or death (TTNT) from first to second-line of about 6 months. Conclusions This study describes commercially insured US patients with advanced stage ovarian cancer from 2010 to 2018, and observed diverse treatment patterns, incidence of numerous HOIs, and limited survival in this population. Keywords: Epidemiology, Ovarian Cancer, Advanced stage, Treatment patterns, Health outcome of interest, Survival
Treatment for pulmonary arterial hypertension (PAH) has evolved over the past decade, including approval of new medications and growing evidence to support earlier use of combination therapy. Despite ...these changes, few studies have assessed real‐world treatment patterns, healthcare resource utilization (HCRU), and costs among people with PAH using recent data. We conducted a retrospective cohort study using administrative claims from the HealthCore Integrated Research Database®. Adult members with claims for a PAH diagnosis, right heart catheterization, and who initiated PAH treatment (index date) between October 1, 2015 and November 30, 2020 were identified. Members had to be continuously enrolled in the health plan for 6 months before the index date (baseline) and ≥30 days after. Treatment patterns, HCRU, and costs were described. A total of 843 members with PAH (mean age 62.3 years, 64.2% female) were included. Only 21.0% of members received combination therapy as their first‐line treatment, while most members (54.6%) received combination therapy as second‐line treatment. All‐cause HCRU remained high after treatment initiation with 58.0% of members having ≥1 hospitalization and 41.3% with ≥1 emergency room visit. Total all‐cause costs declined from $15,117 per patient per month at baseline to $14,201 after treatment initiation, with decreased medical costs ($14,208 vs. $6,349) more than offsetting increased pharmacy costs ($909 vs. $7,852). In summary, despite growing evidence supporting combination therapy, most members with PAH initiated treatment with monotherapy. Total costs decreased following treatment, driven by a reduction in medical costs even with increases in pharmacy costs.
PDF
