External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer.

BACKGROUND: Data for selpercatinib [a selective REarranged during Transfection (RET) inhibitor] from a single-arm trial (LIBRETTO-001, NCT03157128) in RET-fusion-positive advanced/metastatic non-small-cell lung cancer (NSCLC) were used in combination with external data sources to estimate comparative efficacy [objective response rate (ORR), progression-free survival, and overall survival (OS)] in first- and second-line treatment settings. METHODS: Patient-level data were obtained from a de-identified real-world database. Patients diagnosed with advanced/metastatic NSCLC with no prior exposure to a RET inhibitor and one or more prior line of therapy were eligible. Additionally, individual patient-level data (IPD) were obtained from the pemetrexed + platinum arm of KEYNOTE-189 (NCT03950674, first line) and the docetaxel arm of REVEL (NCT01168973, post-progression). Patients were matched using entropy balancing, doubly robust method, and propensity score approaches. For patients with unknown/negative RET status, adjustment was made using a model fitted to IPD from a real-world database. RESULTS: In first-line unadjusted analyses of the real-world control, ORR was 87.2% for LIBRETTO-001 versus 66.7% for those with RET-positive NSCLC (P = 0.06). After adjustment for unknown RET status and other patient characteristics, selpercatinib remained significantly superior versus the real-world control for all outcomes (all P < 0.001 except unadjusted RET-fusion-positive cohort). Similarly, outcomes were significantly improved versus clinical trial controls (all P < 0.05). CONCLUSIONS: Findings suggest improvement in outcomes associated with selpercatinib treatment versus the multiple external control cohorts, but should be interpreted with caution. Data were limited by the rarity of RET, lack of mature OS data, and uncertainty from assumptions to create control arms from external data.

Patient preferences for palliative treatment of locally advanced or metastatic gastric cancer and adenocarcinoma of the gastroesophageal junction: a choice-based conjoint analysis study from Germany.

BACKGROUND: Decisions on palliative chemotherapy (CT) for locally advanced or metastatic gastric cancer (mGC) require trade-offs between potential benefits and risks for patients. Healthcare providers and payers agree that patient-preferences should be considered. We conducted a choice-based conjoint (CBC) analysis study in pre-treated patients from Germany with mGC or locally advanced or metastatic adenocarcinoma of the gastroesophageal junction (mGEJ-Ca), to evaluate their preferences when hypothetically selecting a CT regimen. METHODS: German oncologists and gastroenterologists were contacted to identify patients with mGC or mGEJ-Ca who had completed ≥2 cycles of palliative CT in first or later lines of therapy (CT ongoing or complete). The primary objective was to quantify patient preferences for palliative CT by CBC analysis. Six in-depth qualitative interviews identified 3 attributes: treatment tolerability, quality of life in terms of ability of self-care, and additional survival benefit. The CBC matrix was constructed with 4 factor levels per attribute and each participant was presented with 15 different iterations of these levels. A minimum of 50 participants was needed. Consenting patients completed the CBC survey, choosing systematically among profiles. CBC models were estimated by multinomial logistic regression (MLR) and hierarchical Bayesian (HB) analysis. Estimates of importance for each attribute and factor-level were calculated. RESULTS: Fifty-five patients participated in the CBC survey (78.2% male, median age 63 years, 81.8% currently receiving CT). Across this sample, low treatment toxicity was ranked highest (44.6% relative importance, MLR analysis), followed by ability to self-care (32.3%), and an additional survival benefit of up to 3 months (3 months 23.1%, 2 months 18.3%, 1 month 11.2%). The MLR analysis showed high validity (certainty 37.9%, chi square p < 0.01, root-likelihood 0.505). The HB analysis yielded similar results. CONCLUSIONS: Patients' preferences related to a new hypothetical palliative CT of mGC or mGEJ-Ca can be assessed by CBCanalysis. Although in real-life, patients initially need to decide on CT before they have any experience, and patients' varied experiences with CT will have impacted specific responses, low toxicity and self-care ability were considered as most important by this group of patients with mGC or mGEJ-Ca.

Day of week of procedure and 30 day mortality for elective surgery: retrospective analysis of hospital episode statistics.

OBJECTIVES: To assess the association between mortality and the day of elective surgical procedure. DESIGN: Retrospective analysis of national hospital administrative data. SETTING: All acute and specialist English hospitals carrying out elective surgery over three financial years, from 2008-09 to 2010-11. PARTICIPANTS: Patients undergoing elective surgery in English public hospitals. MAIN OUTCOME MEASURE: Death in or out of hospital within 30 days of the procedure. RESULTS: There were 27,582 deaths within 30 days after 4,133,346 inpatient admissions for elective operating room procedures (overall crude mortality rate 6.7 per 1000). The number of weekday and weekend procedures decreased over the three years (by 4.5% and 26.8%, respectively). The adjusted odds of death were 44% and 82% higher, respectively, if the procedures were carried out on Friday (odds ratio 1.44, 95% confidence interval 1.39 to 1.50) or a weekend (1.82, 1.71 to 1.94) compared with Monday. CONCLUSIONS: The study suggests a higher risk of death for patients who have elective surgical procedures carried out later in the working week and at the weekend.

Increased health burden associated with Clostridium difficile diarrhoea in patients with inflammatory bowel disease.

BACKGROUND: Clostridium difficile (C. difficile) infection in hospitals in developed countries continues to be a major public health hazard despite increased control measures including review of antibiotic policies and hygiene measures. Patients with colitis are thought to be particularly vulnerable to C. difficile associated diarrhoea (CDAD). Identifying the clinical burden among hospitalised patients admitted with inflammatory bowel disease is an essential first step towards identifying and treating severe C. difficile infection in such individuals. AIM: To determine excess morbidity and in-hospital mortality associated with hospital acquired CDAD in patients with inflammatory bowel disease (IBD-CDAD-HAI) admitted to NHS hospitals in England compared with those admitted for inflammatory bowel disease alone. METHODS: Time trends study of all admissions to NHS hospitals between 2002/03 and 2007/08. We developed case definitions for IBD-CDAD-HAI patients. The primary outcomes were in-hospital mortality and length of stay. The secondary outcome was gastrointestinal surgery. RESULTS: Patients in the IBD-CDAD-HAI group were more likely to die in hospital (adjusted OR 6.32), had 27.9 days longer in-patient stays and higher gastrointestinal surgery rates (adjusted OR 1.87) than patients admitted for inflammatory bowel disease alone. CONCLUSION: Patients with inflammatory bowel disease admitted to NHS hospitals in England with co-existent C. difficile infection are at risk of greater in-hospital mortality and morbidity than patients admitted for inflammatory bowel disease alone.

Descriptive study of selected healthcare-associated infections using national Hospital Episode Statistics data 1996-2006 and comparison with mandatory reporting systems.

SUMMARY: Using Hospital Episode Statistics (HES) data from England for the period 1996-2006, we performed a descriptive study to compare records of Clostridium difficile for inpatients aged >or=65 years and for all patients following any of four types of orthopaedic procedures. Results showed that infection rates for C. difficile increased whereas rates for orthopaedic surgical site infections (SSIs) decreased. Both types of infection were more common in older female patients and in patients with greater comorbidity, but showed little difference in rates between areas with varying deprivation scores. For 2004 and 2005, we compared the HES data with mandatory reporting data from the Health Protection Agency (HPA). This showed recording of C. difficile infection to be higher from HPA data than from HES data. In contrast, compared with HPA data for orthopaedic SSIs, there were many more SSIs and numbers of procedures recorded from HES data for all four orthopaedic procedures, although the infection rates themselves were broadly similar. These findings reflect the limitations of both methods used and we suggest that there is a case for using both sources of information, either independently or linked at an individual level in order to obtain a more complete picture of these important healthcare-associated infections. If better coding could be encouraged or made mandatory within HES data, then the current dual system of recording might be unnecessary for effective surveillance of orthopaedic SSIs.