Renee L. Gennarelli

OBJECTIVE: To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. STUDY SELECTION: Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. DATA EXTRACTION: Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. RESULTS: 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. CONCLUSIONS: Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse events may be common.

BACKGROUND: Financial payments from the drug industry to U.S. physicians are common. Payments may influence physicians' clinical decision making and drug prescribing. PURPOSE: To evaluate whether receipt of payments from the drug industry is associated with physician prescribing practices. DATA SOURCES: MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science, and EconLit were searched without language restrictions. The search had no limiting start date and concluded on 16 September 2020. STUDY SELECTION: Studies that estimated the association between receipt of industry payments (exposure) and prescribing (outcome). DATA EXTRACTION: Pairs of reviewers extracted the primary analysis or analyses from each study and evaluated risk of bias (ROB). DATA SYNTHESIS: = 6) had a mix of positive and null findings. No study had only null findings. Of 101 individual analyses, 89 identified a positive association. Payments were associated with increased prescribing of the paying company's drug, increased prescribing costs, and increased prescribing of branded drugs. Nine studies assessed and found evidence of a temporal association; 25 assessed and found evidence of a dose-response relationship. LIMITATION: The design was observational, 21 of 36 studies had serious ROB, and publication bias was possible. CONCLUSION: The association between industry payments and physician prescribing was consistent across all studies that have evaluated this association. Findings regarding a temporal association and dose-response suggest a causal relationship. PRIMARY FUNDING SOURCE: National Cancer Institute.

Although the importance of community engagement in research has been previously established, there are few evidence-based approaches for measuring the level of community engagement in research projects. A quantitative community engagement measure was developed, aligned with 11 engagement principles (EPs) previously established in the literature. The measure has 96 Likert response items; 3-5 quality items and 3-5 quantity items measure each EP. Cronbach's alpha is used to examine the internal consistency of items that measure a single EP. Every EP item group had a Cronbach's alpha > .85, which indicates strong internal consistency for all question groups across both scales (quality and quantity). This information determines the level of community engagement, which can be correlated with other research outcomes.

Background: Stage T1a renal cell carcinoma (RCC) (tumors <4 cm) is usually curable. Nephron-sparing partial nephrectomy (PN) has replaced radical nephrectomy (RN) as the standard of care for these tumors. Radical nephrectomy remains the first alternative treatment option, whereas percutaneous ablation (PA), a newer, nonsurgical treatment, is recommended less strongly because of the relative paucity of comparative PA data. Objective: To compare PA, PN, and RN outcomes. Design: Observational cohort analysis using inverse probability of treatment-weighted propensity scores. Setting: Population-based SEER (Surveillance, Epidemiology, and End Results) cancer registry data linked to Medicare claims. Patients: Persons aged 66 years or older who received treatment for T1a RCC between 2006 and 2011. Interventions: PA versus PN and RN. Measurements: RCC-specific and overall survival, 30- and 365-day postintervention complications. Results: 4310 patients were followed for a median of 52 months for overall survival and 42 months for RCC-specific survival. After PA versus PN, the 5-year RCC-specific survival rate was 95% (95% CI, 93% to 98%) versus 98% (CI, 96% to 99%); after PA versus RN, 96% (CI, 94% to 98%) versus 95% (CI, 93% to 96%). After PA versus PN, the 5-year overall survival rate was 77% (CI, 74% to 81%) versus 86% (CI, 84% to 88%); after PA versus RN, 74% (CI, 71% to 78%) versus 75% (CI, 73% to 77%). Cumulative rates of renal insufficiency 31 to 365 days after PA, PN, and RN were 11% (CI, 8% to 14%), 9% (CI, 8% to 10%), and 18% (CI, 17% to 20%), respectively. Rates of nonurologic complications within 30 days after PA, PN, and RN were 6% (CI, 4% to 9%), 29% (CI, 27% to 30%), and 30% (CI, 28% to 32%), respectively. Ten percent of patients in the PN group had intraoperative conversion to RN. Seven percent of patients in the PA group received additional PA within 1 year of treatment. Limitations: Analysis of observational data may have been affected by residual confounding by provider or from selection bias toward younger, healthier patients in the PN group. Findings from this older study population are probably less applicable to younger patients. Use of SEER-Medicare linked files prevented analysis of patients who received treatment after 2011, possibly reducing generalizability to the newest PA, PN, and RN techniques. Conclusion: For well-selected older adults with T1a RCC, PA may result in oncologic outcomes similar to those of RN, but with less long-term renal insufficiency and markedly fewer periprocedural complications. Compared with PN, PA may be associated with slightly shorter RCC-specific survival but fewer periprocedural complications. Primary Funding Source: Association of University Radiologists GE Radiology Research Academic Fellowship and Society of Interventional Radiology Foundation.

OBJECTIVE: The objective of this study was to determine the costs of clinically significant postoperative pancreatic fistula (POPF) and to evaluate the cost-effectiveness of routine pasireotide use. SUMMARY OF BACKGROUND DATA: We recently completed a prospective randomized trial that demonstrated an 11.7% absolute risk reduction of clinically significant POPF with use of perioperative pasireotide in patients undergoing pancreaticoduodenectomy or distal pancreatectomy [POPF: pasireotide (n = 152), 9% vs placebo (n = 148), 21%; P = 0.006]. METHODS: An institutional modeling system was utilized to obtain total direct cost estimates from the 300 patients included in the trial. This system identified direct costs of hospitalization, physician fees, laboratory tests, invasive procedures, outpatient encounters, and readmissions. Total direct costs were calculated from the index admission to 90 days after resection. Costs were converted to Medicare proportional dollars (MP$). RESULTS: Clinically significant POPF occurred in 45 of the 300 randomized patients (15%). The mean total cost for all patients was MP$23,400 (MP$8,000 - MP$202,500). The mean cost for those who developed clinically significant POPF was MP$39,700 (MP$13,800 - MP$202,500) versus MP$20,500 (MP$8,000 - MP$62,900) for those who did not (P = 0.001). The mean cost of pasireotide within the treatment group (n = 152) was MP$3,300 (MP$300 - MP$3,800). The mean cost was lower in the pasireotide (n = 152) group than the placebo (n = 148) group; however, this did not reach statistical significance (pasireotide, MP$22,800 vs placebo, MP$23,900: P = 0.571). CONCLUSIONS: The development of POPF nearly doubled the total cost of pancreatic resection. In this randomized trial, the routine use of pasireotide significantly reduced the occurrence of POPF without increasing the overall cost of care.