Estimates of Overall Survival in Patients With Cancer Receiving Different Treatment Regimens: Emulating Hypothetical Target Trials in the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked Database.

Importance: The Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database may provide insights into the comparative effectiveness of oncological treatments for elderly individuals who are underrepresented in clinical trials. Objective: To evaluate the suitability of SEER-Medicare data for assessing the effectiveness of adding a drug to an existing treatment regimen on the overall survival of elderly patients with cancer. Design, Setting, and Participants: This comparative effectiveness study analyzed SEER-Medicare data from 9549 individuals who received a new diagnosis of stage II colorectal cancer (2008-2012) and 940 patients who received a new diagnosis of advanced pancreatic adenocarcinoma (2007-2012), with follow-up to December 31, 2013 (SEER-Medicare data released in 2015). Two (hypothetical) target trials were designed and emulated based on 2 existing randomized clinical trials: (1) adjuvant fluorouracil after curative surgery for individuals with stage II colorectal cancer and (2) erlotinib added to gemcitabine for individuals with advanced pancreatic adenocarcinoma. Data were analyzed January 2018 to March 2019. Exposures: The following treatment strategies were compared: (1) fluorouracil initiation vs no initiation within 3 months of tumor resection and (2) erlotinib initiation vs no initiation within 12 weeks of gemcitabine initiation. Main Outcomes and Measures: All-cause mortality within 60 months of baseline for the fluorouracil trial and within 72 weeks for the erlotinib trial. Results: Compared with 3293 individuals in the existing fluorouracil trial, 9549 eligible individuals included in the present analyses were more likely to have colon cancer (8565 [90%] vs 2291 [71%]) and were older (median [interquartile range], 79 [73-84] vs 63 [56-68] years). The 5-year risk difference for initiation vs noninitiation of fluorouracil after surgery was -3.8% (95% CI, -14.8% to 12.6%), and the mortality hazard ratio (HR) was 0.95 (95% CI, 0.85-1.04). Compared with 569 individuals in the existing erlotinib trial, 940 eligible patients included in the present analysis were older (median [range], 74 [66-93] vs 64 [36-92] years) and more likely to be male (547 [58%] vs 298 [52%]). The 1-year risk difference for initiation vs noninitiation of erlotinib was 4.7% (95% CI, -9.4% to 18.0%), and the corresponding mortality HR was 1.04 (95% CI, 0.86-1.42). In naive analyses, the mortality HR estimate was 1.14 (95% CI, 0.95-1.36) for the fluorouracil emulation and 0.68 (95% CI, 0.54-0.87) for the erlotinib emulation. Conclusions and Relevance: The present estimates were similar to those from randomized clinical trials that studied adding the same cancer drugs to existing regimens. The published HR was 1.02 (95% CI, 0.70-1.48) in the fluorouracil trial for individuals aged 70 or older and 0.96 (95% CI, 0.74-1.24) in the erlotinib trial for individuals aged 65 years or older. The SEER-Medicare database may be adequate for studying the real-world effectiveness of adding a drug to treatment regimens used for elderly individuals with cancer.

Oral Mechanical Bowel Preparation for Colorectal Surgery: Systematic Review and Meta-Analysis.

BACKGROUND: Oral mechanical bowel preparation is often used before elective colorectal surgery to reduce postoperative complications. OBJECTIVE: The purpose of this study was to synthesize the evidence on the comparative effectiveness and safety of oral mechanical bowel preparation versus no preparation or enema. DATA SOURCES: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and CINAHL without any language restrictions (last search on September 6, 2013). We also searched the US Food and Drug Administration Web site and ClinicalTrials.gov and supplemented our searches by asking technical experts and perusing reference lists. STUDY SELECTION: We included English-language, full-text reports of randomized clinical trials and nonrandomized comparative studies of patients undergoing elective colon or rectal surgery. For adverse events we also included single-group cohort studies of at least 200 participants. INTERVENTIONS: Interventions included oral mechanical bowel preparation, oral mechanical bowel preparation plus enema, enema only, and no oral mechanical bowel preparation or enema. MAIN OUTCOME MEASURES: Anastomotic leakage, all-cause mortality, wound infection, peritonitis/intra-abdominal abscess, reoperation, surgical site infection, quality of life, length of stay, and adverse events were measured. We synthesized results across studies qualitatively and with Bayesian random-effects meta-analyses. RESULTS: A total of 18 randomized clinical trials, 7 nonrandomized comparative studies, and 6 single-group cohorts were included. In meta-analyses of randomized clinical trials, the credibility intervals of the summary OR included the null value of 1.0 for comparisons of oral mechanical bowel preparation and either no oral preparation or enema for overall mortality, anastomotic leakage, wound infection, peritonitis, surgical site infection, and reoperation. These results were robust to extensive sensitivity analyses. Evidence on adverse events was sparse. LIMITATIONS: The study was limited by weaknesses in the underlying evidence, such as incomplete reporting of relevant information, exclusion of non-English and relevant unpublished studies, and possible missed indexing of nonrandomized studies. CONCLUSIONS: Our results could not exclude modest beneficial or harmful effects of oral mechanical bowel preparation compared with no preparation or enema.