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Efforts to quantify the uncertainty in weather forecasts began more than 75 years ago, and many studies and experiments involving objective and subjective probability forecasting have been conducted in meteorology in the intervening period. Moreover, the U.S. National Weather Service (NWS) initiated a nationwide program in 1965 in which precipitation probability forecasts were formulated on an operational basis and routinely disseminated to the general public. In addition, the NWS now prepares objective probability forecasts for many variables, using statistical procedures. Hence probability forecasting in meteorology is unique in that very large sets of probability forecasts that have been subjected to detailed evaluation are available. This article has four objectives: (a) to review the history of probability forecasting in meteorology to acquaint statisticians with this body of literature; (b) to describe recent methodological, experimental, and operational activities in this field; (c) to examine current issues in probability forecasting; and (d) to discuss briefly the relationship between probability forecasting in meteorology and probability forecasting in other fields. Results of operational and experimental weather forecasting programs are presented, methods of verifying and evaluating probability forecasts in common use in meteorology are discussed, and an extensive list of references is provided. [ABSTRACT FROM AUTHOR]

SUMMARY This paper briefly describes some results of operational and experimental programmes in the United States involving subjective probability forecasts of precipitation occurrence and of maximum and minimum temperatures. These results indicate that weather forecasters can formulate such forecasts in a reliable manner. [ABSTRACT FROM AUTHOR]

Proper scoring rules are overall evaluation measures that reward accurate probabilities. Specific rules encountered in the literature and used in practice are invariably symmetric in the sense that the expected score for a perfectly-calibrated probability assessor (or model generating probabilities) is minimized at a probability of one-half. A family of asymmetric scoring rules that provide better measures of the degree of skill inherent in the probabilities and render scores that are more comparable in different situations is developed here. One member of this family, a quadratic asymmetric rule, is applied to evaluate an extensive set of precipitation probability forecasts from the U.S. National Weather Service. Connections to previous characterizations of proper scoring rules are investigated, and some relevant issues pertaining to the design of specific asymmetric rules for particular inferential and decision-making problems are discussed briefly. [ABSTRACT FROM AUTHOR]

A risk assessment model is developed to relate adverse health effects to alternative carbon monoxide standards. The analysis requires information in the form of available data and expert judgments concerning factors such as ambient CO level, human exposure to CO, physiological responses, and dose-response relationships. Quantitative estimates, including probabilities, are obtained for selected summary measures of adverse health effects. [ABSTRACT FROM AUTHOR]

The article presents information on various developments related to statistics. Although some work concerning the assessment of subjective probabilities has been reported in the statistical literature in recent years, much of this work has been conducted by statisticians rather than by psychologists. Most statisticians are probably not aware of the voluminous literature on the psychology of judgment. Clearly, psychological factors are relevant and important in the assessment of subjective probabilities, and psychologists tend to approach the topic from a somewhat different viewpoint than statisticians, as might be expected. The area of cognitive processes may have important implications for probability assessment, and further work needs to be done to investigate such implications. Of course, the assessment of probabilities forces people to recognize uncertainty explicitly and to quantify it. The lack of encouragement, together with the related lack of familiarity, sometimes causes negative reactions to statements involving probability. For example, the decision of the U.S. National Weather Service a decade ago to issue precipitation probabilities to the public on a regular basis drew some negative response.

Background: Trifluridine/tipiracil showed activity and was well tolerated in a phase 2 study of pretreated patients with advanced gastric cancer done in Japan. We investigated whether the treatment was efficacious compared with placebo in a global population.Methods: TAGS was a randomised, double-blind, placebo-controlled, phase 3 trial done in 110 academic hospitals in 17 countries. Patients aged 18 years or older with histologically confirmed, non-resectable, metastatic gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) as defined by the American Joint Committee on Cancer staging classification (7th edition) who had received at least two previous chemotherapy regimens and had experienced radiological disease progression were eligible for inclusion. Patients were randomly assigned (2:1) via dynamic randomisation from a centralised interactive voice-response system to receive either oral trifluridine/tipiracil (35 mg/m2 twice daily on days 1-5 and days 8-12 every 28 days) plus best supportive care or placebo plus best supportive care. Participants were allocated to groups by study-site personnel. Randomisation was stratified by region (Japan vs rest of world), ECOG performance status (0 vs 1), and previous treatment with ramucirumab (yes vs no). Both patients and investigators were masked to treatment allocation. The primary endpoint was overall survival. Efficacy was assessed in the intention-to-treat population and safety in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, number NCT02500043. The trial, including follow-up of all participants, has been completed.Findings: Between Feb 24, 2016, and Jan 5, 2018, 507 patients were enrolled and randomly assigned, 337 to the trifluridine/tipiracil group and 170 to the placebo group. Median overall survival was 5·7 months (95% CI 4·8-6·2) in the trifluridine/tipiracil group and 3·6 months (3·1-4·1) in the placebo group (hazard ratio 0·69 [95% CI 0·56-0·85]; one-sided p=0·00029, two-sided p=0·00058). Grade 3 or worse adverse events of any cause occurred in 267 (80%) patients in the trifluridine/tipiracil group and 97 (58%) in the placebo group. The most frequent grade 3 or worse adverse events of any cause were neutropenia (n=114 [34%]) and anaemia (n=64 [19%]) in the trifluridine/tipiracil group and abdominal pain (n=15 [9%]) and general deterioration of physical health (n=15 [9%]) in the placebo group. Serious adverse events of any cause were reported in 143 (43%) patients in the trifluridine/tipiracil group and 70 (42%) in the placebo group. One treatment-related death was reported in each group (because of cardiopulmonary arrest in the trifluridine/tipiracil group and because of toxic hepatitis in the placebo group).Interpretation: Trifluridine/tipiracil significantly improved overall survival compared with placebo and was well tolerated in this heavily pretreated population of patients with advanced gastric cancer. Trifluridine/tipiracil could be a new treatment option in this population who represent a high unmet medical need.Funding: Taiho Oncology and Taiho Pharmaceutical. [ABSTRACT FROM AUTHOR]

Background In the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups. Methods Primary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue ( KRAS ) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics. Results Eight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged ≥65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59–0.81; P = 0.0001). Median OS in the three regions was 6.5–7.8 months in the trifluridine/tipiracil arm and 4.3–6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34–0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48–0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57–1.00; P = 0.0470). Median PFS was 2.0–2.8 months for trifluridine/tipiracil and 1.7–1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability. Conclusions Trifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status. This trial is registered with ClinicalTrials.gov: NCT01607957 . [ABSTRACT FROM AUTHOR]

Aims: Trifluridine/tipiracil (FTD/TPI) prolongs survival in refractory metastatic colorectal cancer, but limited data exist on its use in patients with hepatic impairment. This Phase I, open-label, nonrandomized study investigated the safety, tolerability and pharmacokinetics of FTD/TPI in patients with advanced solid tumours (except breast cancer) and varying degrees of hepatic impairment, to provide dosing recommendations., Methods: Patients aged ≥18 years with advanced solid tumours and normal hepatic function, or mild, moderate or severe hepatic impairment according to National Cancer Institute criteria, were planned to be enrolled. Patients received FTD/TPI 35 mg/m 2 orally twice daily on days 1-5 and 8-12 of each 28-day cycle., Results: Twenty-four patients were enrolled to the normal hepatic function (n = 8) and mild (n = 10) and moderate (n = 6) hepatic impairment cohorts. Overall, 12 patients (50.0%) had at least 1 adverse event leading to study discontinuation. In the moderate hepatic impairment cohort, 5 of 6 patients experienced grade ≥ 3 elevation in bilirubin. No patients with severe hepatic impairment were enrolled. FTD area under the curve at steady state decreased by 18% and 22% in the mild and moderate cohorts, respectively; however, no clear change was observed in TPI area under the curve., Conclusions: FTD/TPI can be safely administered in patients with normal hepatic function and mild hepatic impairment, with no initial dose adjustment. FTD/TPI is not recommended for use in patients with moderate hepatic impairment because of findings of grade 3 or 4 increased blood bilirubin. Therefore, FTD/TPI is not recommended for patients with moderate or severe hepatic impairment., (© 2019 The British Pharmacological Society.)