The validity of administrative data and patterns of chemotherapy use among elderly colorectal cancer patients

Chemotherapy represents an integral part of the treatment plan for many cancer patients, proven to decrease recurrence and overall mortality. Recent trials demonstrated that adding oxaliplatin to 5-fluorouracil/leucovorin significantly improved survival for stage III colon cancer patients. However, few studies have examined the translation of these findings into routine practice, particularly among the elderly, who are underrepresented in trials. Two population-based data sources were linked to assess the utility of Medicare claims in identifying chemotherapy and specific agents administered to elderly stage II/III colorectal cancer (CRC), in-situ/early stage breast, non-small cell lung, and ovarian cancer patients. The National Cancer Institute's Patterns of Care (POC) studies collected data on chemotherapy by reviewing hospital and medical records and contacting physicians. POC data were linked and compared to Medicare claims and measures of agreement and validity were estimated. Using validated definitions, we constructed a cohort of stage II/III CRC patients from the Surveillance, Epidemiology, and End Results program (SEER)-Medicare linked database to 1) estimate trends in the utilization of agents over time and 2) identify patient, physician, and hospital characteristics associated with the receipt of oxaliplatin using Poisson regression models and a generalized estimating equation (GEE) strategy for non-nested clustering. Overall, the sensitivity and specificity of Medicare claims to identify any chemotherapy were high; however, we found variation across agents, sites and administration modalities. Shifts in utilization of specific agents were seen from 2000-2007, with increasing oxaliplatin and capecitabine use. Younger age, being married, fewer comorbidities, low-poverty areas, colon cancer diagnosis, and stage III disease were associated with oxaliplatin use. Validated Medicare definitions identified a substantial increase in oxaliplatin utilization from 2004-2007 for both on- and off-label indications. Patient characteristics were most influential in explaining the variation in oxaliplatin receipt. Off-label use of chemotherapeutic agents was relatively common. Physicians should carefully weigh the minimal (if any) or unknown benefits of treatment against potentially serious side effects when deciding whether to treat a patient off-label

Comparative effectiveness of postoperative chemotherapy among older patients with non-metastatic rectal cancer treated with preoperative chemoradiotherapy

Postoperative chemotherapy is standard following preoperative chemoradiation therapy (CRT) and curative resection for clinically staged II/III rectal cancer. Recent trials have questioned whether postoperative chemotherapy improves overall survival. We evaluated the comparative effectiveness of postoperative chemotherapy following CRT or radiation therapy (RT) with specific attention on the impact of age on postoperative chemotherapy effectiveness

Methodological Challenges for Epidemiologic Studies of Deprescribing at the End of Life

Purpose of Review: To describe approaches to measuring deprescribing and associated outcomes in studies of patients approaching end of life (EOL). Recent Findings: We reviewed studies published through 2020 that evaluated deprescribing in patients with limited life expectancy and approaching EOL. Deprescribing includes reducing the number of medications, decreasing medication dose(s), and eliminating potentially inappropriate medications. Tools such as STOPPFrail, OncPal, and the Unnecessary Drug Use Measure can facilitate deprescribing. Outcome measures vary and selection of measures should align with the operationalized deprescribing definition used by study investigators. Summary: EOL deprescribing considerations include medication appropriateness in the context of patient goals for care, expected benefit from medication given life expectancy, and heightened potential for medication-related harm as death nears. Additional data are needed on how EOL deprescribing impacts patient quality of life, caregiver burden, and out-of-pocket medication-related costs to patients and caregivers. Investigators should design deprescribing studies with this information in mind

Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma

Phase III trials show sorafenib improves survival in advanced hepatocellular carcinoma (HCC). Because of narrow trial eligibility, results may not be generalizable to a broader HCC population. We sought to evaluate the effectiveness of initial sorafenib versus no treatment among Medicare beneficiaries with advanced HCC

Comparison of SEER Treatment Data With Medicare Claims

The population-based Surveillance, Epidemiology, and End Results (SEER) registries collect information on first-course treatment, including surgery, chemotherapy, radiation therapy, and hormone therapy. However, the SEER program does not release data on chemotherapy or hormone therapy due to uncertainties regarding data completeness. Activities are ongoing to investigate the opportunity to supplement SEER treatment data with other data sources

Long-term risk of gastrointestinal cancers in persons with gastric or duodenal ulcers

Peptic ulcer predicts gastric cancer. It is controversial if peptic ulcers predict other gastrointestinal cancers, potentially related to Helicobacter pylori or shared lifestyle factors. We hypothesized that gastric and duodenal ulcers may have different impact on the risk of gastrointestinal cancers. In a nationwide cohort study using Danish medical databases 1994-2013, we quantified the risk of gastric and other gastrointestinal cancers among patients with duodenal ulcers (dominantly H. pylori-related) and gastric ulcers (dominantly lifestyle-related) compared with the general population. We started follow-up 1-year after ulcer diagnosis to avoid detection bias and calculated absolute risks of cancer and standardized incidence ratios (SIRs). We identified 54,565 patients with gastric ulcers and 38,576 patients with duodenal ulcers. Patient characteristics were similar in the two cohorts. The 1-5-year risk of any gastrointestinal cancer was slightly higher for gastric ulcers patients (2.1%) than for duodenal ulcers patients (2.0%), and SIRs were 1.38 (95% CI: 1.31-1.44) and 1.30 (95% CI: 1.23-1.37), respectively. The SIR of gastric cancer was higher among patients with gastric ulcer than duodenal ulcer (1.92 vs. 1.38), while the SIRs for other gastrointestinal cancers were similar (1.33 vs. 1.29). Compared with gastric ulcer patients, duodenal ulcer patients were at lower risk of smoking- and alcohol-related gastrointestinal cancers. The risk of nongastric gastrointestinal cancers is increased both for patients with gastric ulcers and with duodenal ulcers, but absolute risks are low. H. pylori may be less important for the development of nongastric gastrointestinal cancer than hypothesized

Conditioning on future exposure to define study cohorts can induce bias: the case of low-dose acetylsalicylic acid and risk of major bleeding

A principle of cohort studies is that cohort membership is defined by current rather than future exposure information. Pharmacoepidemiologic studies using existing databases are vulnerable to violation of this principle. We evaluated the impact of using data on future redemption of prescriptions to determine cohort membership, motivated by a published example seeking to emulate a “per-protocol” association between continuous versus never use of low-dose acetylsalicylic acid (ASA) and major bleeding (e.g., cerebral hemorrhage or gastrointestinal bleeding)

Should Cause of Death From the Death Certificate Be Used to Examine Cancer-Specific Survival? A Study of Patients With Distant Stage Disease

Death certificates are used to classify cause of death for studies of cancer survival and mortality. Using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, we evaluated cause of death (site-specific, cancer cause-specific, or other cause of death) for 229,181 patients with distant stage disease during 1994–2003 who died by 2005. Agreement between coded cause of death and initial diagnosis was 85% in patients with only one primary and 64% in patients with more than one primary. Our findings support the usefulness of site and cancer cause-specific causes of death reported on the death certificate for distant stage patients with a single cancer

Trends in Antibiotic Use by Birth Season and Birth Year

OBJECTIVES: We examined 2 birth cohort effects on antibiotic prescribing during the first year of life (henceforth, infancy) in Denmark: (1) the birth season effect on timing and overall occurrence of antibiotic prescribing, and (2) the birth year effect amid emerging nationwide pneumococcal vaccination programs and changing prescribing guidelines. METHODS: We linked data for all live births in Denmark from 2004 to 2012 (N = 561 729) across the National Health Service Prescription Database, Medical Birth Registry, and Civil Registration System. Across birth season and birth year cohorts, we estimated 1-year risk, rate, and burden of redeemed antibiotic prescriptions during infancy. We used interrupted time series methods to assess prescribing trends across birth year cohorts. Graphical displays of all birth cohort effect data are included. RESULTS: The 1-year risk of having at least 1 redeemed antibiotic prescription during infancy was 39.5% (99% confidence interval [CI]: 39.3% to 39.6%). The hazard of a first prescription increased with age throughout infancy and varied by season; subsequently, Kaplan-Meier-derived risk functions varied by birth season cohort. After rollout of a first vaccination program and new antibiotic prescribing guidelines, 1-year risk decreased by 4.4% over 14 months (99% CI: 3.4% to 5.5%); it decreased again after rollout of a second vaccination program by 6.9% over 3 years (99% CI: 4.4% to 9.3%). CONCLUSIONS: In Denmark, birth season and birth year cohort effects influenced timing and risk of antibiotic prescribing during infancy. Future studies of antibiotic stewardship, effectiveness, and safety in children should consider these cohort effects, which may render some children inherently more susceptible than others to downstream antibiotic effects