Evaluation of the Use of Cancer Registry Data for Comparative Effectiveness Research.

Importance: Researchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective, nonrandomized design of these analyses raises questions about study validity. Objective: To examine the extent to which comparative effectiveness analyses using observational cancer registry data produce results concordant with those of randomized clinical trials. Design, Setting, and Participants: In this comparative effectiveness study, a total of 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types were identified. Data on participants within the National Cancer Database (NCDB) diagnosed between 2004 and 2014, matching the eligibility criteria of the randomized clinical trial, were obtained. The present study was conducted from August 1, 2017, to September 10, 2019. The trials included 85 118 patients, and the corresponding NCDB analyses included 1 344 536 patients. Three Cox proportional hazards regression models were used to determine hazard ratios (HRs) for overall survival, including univariable, multivariable, and propensity score-adjusted models. Multivariable and propensity score analyses controlled for potential confounders, including demographic, comorbidity, clinical, treatment, and tumor-related variables. Main Outcomes and Measures: The main outcome was concordance between the results of randomized clinical trials and observational cancer registry data. Hazard ratios with an NCDB analysis were considered concordant if the NDCB HR fell within the 95% CI of the randomized clinical trial HR. An NCDB analysis was considered concordant if both the NCDB and clinical trial P values for survival were nonsignificant (P ≥ .05) or if they were both significant (P < .05) with survival favoring the same treatment arm in the NCDB and in the randomized clinical trial. Results: Analyses using the NCDB-produced HRs for survival were concordant with those of 141 randomized clinical trials in 79 univariable analyses (56%), 98 multivariable analyses (70%), and 90 propensity score models (64%). The NCDB analyses produced P values concordant with randomized clinical trials in 58 univariable analyses (41%), 65 multivariable analyses (46%), and 63 propensity score models (45%). No clinical trial characteristics were associated with concordance between NCDB analyses and randomized clinical trials, including disease site, type of clinical intervention, or severity of cancer. Conclusions and Relevance: The findings of this study suggest that comparative effectiveness research using cancer registry data often produces survival outcomes discordant with those of randomized clinical trial data. These findings may help provide context for clinicians and policy makers interpreting observational comparative effectiveness research in oncology.

No Benefit of Concomitant 5-Aminosalicylates in Patients With Ulcerative Colitis Escalated to Biologic Therapy: Pooled Analysis of Individual Participant Data From Clinical Trials.

OBJECTIVES: 5-aminosalicylates (5-ASA) are frequently continued in patients with moderate-severe ulcerative colitis (UC), even after escalation to biologic agents, without evaluation of the benefit of this approach. We conducted an individual participant data (IPD) pooled analysis of trials of infliximab and golimumab in UC, to evaluate whether concomitant use of 5-ASA modifies clinical outcomes among anti-tumor necrosis factor (TNF)-α-treated patients. METHODS: We included IPD from five trials of infliximab and golimumab in patients with moderate-severe UC (ACT-1 and -2, PURSUIT-SC, PURSUIT-M, NCT00336492). Patients treated with infliximab or golimumab were categorized as receiving concomitant 5-ASA or not at time of trial entry. Primary outcome was clinical remission (Mayo Clinic Score < 3) at last follow-up for each trial; secondary outcomes were clinical response and mucosal healing. Using multivariable logistic regression analysis, we evaluated association between concomitant 5-ASA and clinical remission, after adjusting for sex, smoking, baseline disease activity, disease extent, biochemical variables (C-reactive protein, albumin, hemoglobin), and concomitant prednisone and immunomodulators. RESULTS: We included 2183 infliximab-treated or golimumab-treated patients (1715 [78.6%] on 5-ASA). Concomitant use of 5-ASA was not associated with odds of achieving clinical remission (adjusted OR, 0.67 [95% CI, 0.45-1.01], p = 0.06), clinical response (aOR, 0.89 [0.60-1.33], p = 0.58) or mucosal healing (aOR, 1.12 [0.82-1.51], p = 0.48). These results were consistent in trials of induction and maintenance therapy, and in trials of infliximab and golimumab. CONCLUSIONS: Based on IPD pooled analysis, in patients with moderate-severe UC who are escalated to anti-TNF therapy, continuing 5-ASA does not improve clinical outcomes.

[A microarray study on the molecular mechanism for the therapeutic effect of Antidotal and Myogenic Ointment on the foot ulcer in diabetic rats].

OBJECTIVE: To investigate the underlying mechanism for the therapeutic effect of a traditional Chinese medicinal recipe, Antidotal and Myogenic Ointment (AMO), on the foot ulcer in diabetic rat using cDNA microarray technology. METHODS: 45 rats were made diabetic by i. p. injection of streptozocin. The treated animals were then fed for 6 months,and subjected to the dissection of distal popliteal artery after ligation of the vessels. Another month later, grade II burn injury was produced on the bottom of their foot as a model of diabetic foot ulcer. The rats were then randomly divided into three groups (15 each) to receive AMO, epidermal growth factor (EGF) and saline for 30 days, with dressing change in every 2 days. The area of ulcer wound and their healing rate were recorded before and after the treatment. Total RNA was extracted from the tissue samples collected near the wound, and the expression profile of cytokine genes demonstrated using the microarry for rats. RESULTS: In comparison with the saline group, difference in the level of expression was found in 25 genes (23 of them were up-regulated and 2 down-regulated) in EGF group, and 30 genes in AMO groups (29 of them up-regulated and 1 down-regulated ). In comparison with EGF group, difference in level of expression was found in 16 genes in AMO group, with 11 up-regulated and 5 down-regulated. Neurotrophic factors and chemotactic factors, etc were among the genes involved. CONCLUSION: In comparison with EGF, AMO is more effective in the treatment of foot ulcer in diabetic rats. It is possible that AMO produces such effects through the regulation of balance in cytokine expression.