Alternative Test Methods Research Articles

Efficacy of SCMs to mitigate ASR in systems with higher alkali contents assessed by pore solution method

This study demonstrates the efficacy of supplementary cementitious materials (SCMs) to mitigate alkali-silica reaction (ASR) even when used in conjunction with cement of higher alkali contents (up to 1% Na2Oeq). The expansion of concrete prisms was studied immersed in simulated pore solution in order to address the limitations of conventional ASR testing methods, accelerated mortar bar test (AMBT) and concrete prism test (CPT). Expansion results demonstrate that 25% fly ash and 50% slag are both sufficient to mitigate ASR even with cements with alkali content up to 1% Na2Oeq and that the pore solution method is a viable alternative ASR testing method. Massive amounts of ASR products (~20 μm thickness) were observed in concretes without SCMs consistent with high degree of expansion and extensive cracking. Small amounts of ASR products (≤5 μm thickness) were also observed in concrete with SCMs despite absence of significant expansion.

Laboratory measurements of vehicle exhaust emissions in conditions reproducing real traffic

The measurement of exhaust emissions is an important element of the vehicle type-approval. The tests in this area are carried out mainly under laboratory conditions, and the obligatory road tests in force since 2017 supplement them. One of the most important requirements in relation to the laboratory tests is the best possible representation of real traffic conditions, as well as ensuring the reliability of the results obtained. Laboratory measurement cycles carried out nowadays assume an unchangeable way of recreating the trip under specific measurement conditions. This is conducive to misuse and, in many cases, obtaining the results that do not reflect the actual exhaust emission. Therefore, it is necessary to develop an alternative test method that would ensure a better representation of the road traffic conditions and allow the test to be individualized according to the type of vehicle or the professional group that uses it. This is possible owing to the proposed, differentiated speed profile during the exhaust emission tests under the laboratory conditions, with simultaneous reliable reconstruction of the road traffic conditions during bench measurements. The article describes a new measurement method that meets these requirements, based on a random selection of measurement sections. It was also validated by comparing the obtained results with the actual exhaust emission recorded during road tests. It has been proven that the method developed corresponds to the random nature of road traffic conditions, while maintaining the similarity of the emissions of toxic exhaust components, and therefore constitutes an effective and expected alternative to the currently used type-approval procedures.

Test method for minimum and maximum densities of small quantities of soil

The minimum and maximum void ratios are required to establish the relative density of sandy soil. Undisturbed simple shear test specimens are often too small to provide enough material to employ the Japanese Standard JIS A 1224:2009 Test Method. An alternative test method for evaluating the dry minimum and maximum densities of soil is proposed for those cases when a test specimen does not provide enough material to use the standard-size mold. The alternative test method was applied to soil from 42 small test specimens. Soil from test specimens of the same material were subsequently mixed to produce eight soil composites for which their minimum and maximum densities could be determined using both the standard and alternative methods. The minimum and maximum void ratios determined by both methods for the composite soil are in good agreement. Moreover, trends in the dataset are consistent with those from previous studies on sand and non-plastic fine-grained soil.

Systematic review in evidence-based risk assessment.

Systematic reviews provide a structured framework for summarizing the available evidence in a comprehensive, objective, and transparent manner. They inform evidence-based guidelines in medicine, public policy, and more recently, in environmental health and toxicology. Many regulatory agencies have extended and adapted the well-established systematic review methods, initially developed for clinical studies, for their assessment needs. The use of systematic reviews to summarize evidence from existing human, animal, and mechanistic studies can reduce reliance on animal test data in risk assessment and can help avoid unnecessary duplication of animal experiments that have already been conducted. As alternative test methods can be expected to play an increasing role in human health risk assessment in the future, systematic reviews can be particularly helpful in validating these alternatives. The field of evidence-based toxicology has undergone extensive development since its first meeting in 2007 as a result of collaborative efforts among international experts and public health agencies, particularly with respect to the use of mechanistic data and evidence integration. The continued development and wider adoption of systematic review methodology can lead to better 3R implementation. As undertaking a systematic review can be a complex and lengthy process, it is important to understand the main steps involved. Key steps, along with current best practices, are described with references to guidance from organizations with expertise in evidence synthesis. Applications of systematic reviews in clinical, observational, and experimental studies are presented. Finally, software tools available to facilitate and increase the efficiency of completing a systematic review are described.

ALTERNATIVE METHOD OF NON-DESTRUCTIVE TESTING FOR NUCLEAR POWER PLANT

This study presents the results of electrophysical non-destructive testing of collectors welded joints to the body of steam generators PGV 1000Mof the reactor WWER-1000. The studied steam generators located in the Resource Сenter of National Research Nuclear University MEPhI at the site of reactors construction factory “Atommash” in Volgodonskcity-Russia. The primary loop collector was welded to the body of steam generators PGV 1000Mand the technical condition of welded joints was investigated by electrophysical non-destructive testing (EPhT). In steam generatorsmay appear corrosion and cracks due to corrosive environment and effect of stresses however,EPhTcan detect early stages of cracks. The study highlights the theoretical part of electrophysical diagnostics and control method, using modern mathematical signals analysis, and issues related to the practical implementation of EPhT in the factory. The novel alternative method of non-destructive testing can be used in diagnostic oil and gas pipelines, elements of complex technical structures and industrial equipment. It can be used in many industries where it is necessary to process control of the entire structure or its individual parts under operating conditions. Based on control results, potentiograms were constructed for various structural levels of the diagnostic signal. The results of controlled welded joints in steam generators showed their satisfactory condition.

HDRS - Hybrid Diffuse Reflectance Spectroscopy: Non-Erythemal In Vivo Driven SPF and UVA-PF Testing.

In order to define a label SPF of topically applied sunscreens, in vivo test methods like ISO 24444, FDA Guideline, and the Australian Standard are used worldwide. The basis of all these methods is to induce an erythemal skin reaction by UV irradiation to find the level of MEDu and MEDp (Minimal Erythmal Dose unprotected and protected). In vitro methods replacing the human skin by any kind of nonhuman material are still not available. Thus, offering the new hybrid diffuse reflectance spectroscopy (HDRS) technique that can maintain an in vivo level for SPF testing while neglecting the UV-dose-related erythemal skin reaction is a perfect combination to take care of sun protection and any ethical concerns in SPF testing nowadays. HDRS is a combination of in vivo diffuse reflectance spectroscopy measurements on the skin and in vitro transmission measurements of a sunscreen on a roughened polymethylmethacrylate plate. By this technique, the in vivo behavior of the investigated sunscreen on the skin is measured as well as the UVB absorption, which is still nonvisible in the reflectance technique. In order to establish an alternative method for in vivo SPF and UVA-PF testing, a huge number of sunscreens (250 samples) were measured by HDRS and compared with the worldwide accepted standards ISO 24444, ISO 24442, and ISO 24443. The variety of sunscreens measured reflect a wide range of different types of formulations as well as a wide range of SPFs (5-120) to validate this new alternative SPF testing procedure. Far-reaching statistical data analyses show an excellent link between the new nonerythemal-driven HDRS-SPF technique and ISO 24444 results. In the same way, HDRS-UVA-PF results can be correlated with UVA-PF values calculated from ISO 24442 as well as from ISO 24443. The importance of the inclusion of a spectral ratio of photodegradation is shown in the comparison of photostable and photounstable products. Owing to the elimination of any erythemal-relevant UVB and UVA doses, absolutely no skin reaction occurs during the HDRS experiment. Consequently, there is no need to define an MED anymore. For the first time, an alternative way to arriving at SPF and UVA-PF values is shown, without any ethical concerns of SPF testing in vivo and/or any restriction of SPF testing in vitro. Regardless of the type of formulation or the level of protection, an excellent correlation between SPFHDRSand SPF24444as for sunscreen labeling could be found. By this new alternative nonerythemal technique, not only SPF values can be measured but also UVA-PF values can be calculated with a linear correlation to ISO 24442 as well as to ISO 24443 from the same set of data. By this a robust alternative test method of SPF and UVA-PF values is described, taking into account the interaction of sunscreen formulation and skin.

Study on Alternative Test Method of Real Driving Emissions for Heavy-duty Vehicle by Using Engine Bench System

Study on Alternative Test Method of Real Driving Emissions for Heavy-duty Vehicle by Using Engine Bench System

Impact of primary nozzle area ratio on the performance of ejector refrigeration system

This paper proposes an experimental investigation to demonstrate the impact of the primary nozzle area ratios on the ejector performance in an R141b ejector refrigeration system. The experimental refrigerator was tested based on the alternative testing method in which the generator temperature and condenser pressure were held constant for particular test cases. Three primary nozzles were studied which had identical throat diameter but different nozzle area ratios which produced different exit Mach numbers. Three primary nozzles were equipped with one mixing chamber with throat diameter of 9 mm. With the alternative testing method, two critical evaporator temperatures were found, the lower and upper critical evaporator temperatures. It was also found that the change in the nozzle exit Mach number and the primary fluid mass flow rate (using different generator temperatures) had significant impact on these two critical points which affected the entire ejector performance. The primary fluid expansion coefficient (Cprimary), which is key to indicate the limited range of the working condition, was introduced. It indicates the expansion wave formation which has significant impact on two critical points. Hence, the proper value of Cprimary under various primary nozzle area ratios was determined for this present work.

Evaluation of the Skin Sensitization Potential of Carbon Nanotubes Using Alternative In Vitro and In Vivo Assays.

Carbon nanotubes (CNTs) are one of the major types of nanomaterials that have various industrial and biomedical applications. However, there is a risk of accidental exposure to CNTs in individuals involved in their large-scale production and in individuals who use products containing CNTs. This study aimed to evaluate the skin sensitization induced by CNTs using two alternative tests. We selected single-wall carbon nanotubes and multi-walled carbon nanotubes for this study. First, the physiochemical properties of the CNTs were measured, including the morphology, size, and zeta potential, under various conditions. Thereafter, we assessed the sensitization potential of the CNTs using the ARE-Nrf2 Luciferase KeratinoSens™ assay, an in vitro alternative test method. In addition, the CNTs were evaluated for their skin sensitization potential using the LLNA: BrdU-FCM in vivo alternative test method. In this study, we report for the first time the sensitization results of CNTs using the KeratinoSens™ and LLNA: BrdU-FCM test methods in this study. This study found that both CNTs do not induce skin sensitization. These results suggest that the KeratinoSens™ and LLNA: BrdU-FCM assay may be useful as alternative assays for evaluating the potential of some nanomaterials that can induce skin sensitization.

Theoretical and Experimental Substantiation of Alternative Methods for Quality Control of Live Anthrax Vaccine

Preventive immunisation against anthrax is carried out in accordance with the national Immunisation Schedule for Epidemic Settings. The vaccination is performed using a live vaccine—a freeze-dried suspension of Bacillus anthracis STI-1 vaccine strain spores in a stabilizing media. Improvement of the quality control of immunobiological medicines is a pressing issue and an integral part of the quality management system.The aim of study was to streamline quality control of live anthrax vaccine in terms of the following test parameters: identification and specific activity (total spore concentration).Materials and methods: identification and specific activity (total spore concentration) tests were performed for samples of live anthrax vaccine, batch 266, produced by the 48 Central Scientific Research Institute. The identification test was performed using the B. anthracis immunochromatography test kit for express detection and identification of anthrax pathogen spores produced by the State Research Center for Applied Microbiology and Biotechnology (Obolensk). The specific activity (total spore concentration) was assessed by the visual method and calculated in the Goryaev chamber using the industry reference standard of bacterial suspension turbidity equivalent to 10 IU—OSO 42-28-85 (by the Scientific Centre for Expert Evaluation of Medicinal Products). The number of live spores in live anthrax vaccine was determined by the microbiological method (by inoculating media). The statistical processing of the results was performed using Excel and Statistica 10.0.Results: the authors provided theoretical and experimental substantiation to support the feasibility of using immunochromatography as an alternative identification test method for live anthrax vaccine. Test samples dilutions of 108 microbial cells per millilitre and 109 microbial cells per millilitre are used in the test. The authors developed a test procedure for determination of the total spore concentration (specific activity) in live anthrax vaccine using an industry reference standard of turbidity equivalent to 10 IU, and proposed a formula for calculation of the total spore concentration.Conclusions: the developed test procedures could be recommended for inclusion in the live anthrax vaccine specification files as alternative methods of quality control.

Prediction of the skin sensitization potential of polyhexamethylene guanidine and triclosan and mixtures of these compounds with the excipient propylene glycol through the human Cell Line Activation Test.

Household products often contain an antimicrobial agent such as biocides, polyhexamethylene guanidine (PHMG), triclosan (TCS), and propylene glycol (PG) as an excipient to dissolve the active ingredients. The skin sensitization (SS) potentials of each of these substances or mixtures of PHMG or TCS with PG have not been investigated through in vitro alternative test methods. The in vitro alternative assay called human Cell Line Activation Test (h-CLAT) served to address these issues. The h-CLAT assay was conducted in accordance with OECD TG 442E. On three independent runs, all the three substances were predicted to be sensitizers according to the SS positivity with relative fluorescence intensity of CD86 ≥ 150% and/or CD54 ≥ 200% at any tested concentrations. Mixtures of PHMG or TCS with PG at ratios of 9:1, 4:1, or 1:4 weight/volume were all positive in terms of SS potential. Since humans can be occupationally or environmentally exposed to mixtures of excipients with active ingredients of biocides, the present study may give insights into further investigations of the SS potentials of various chemical mixtures.

HIV testing and self-testing coverage among men and women in South Africa: an exploration of related factors.

Uptake of HIV testing is critical to halting the spread of HIV. Our study aimed to examine the coverage of HIV testing and self-testing and the individual-level, household-level and community-level factors associated with HIV testing and self-testing awareness. We analysed data of 12 312 men and women from 2016 SADHS and used multilevel mixed-effects models to examine the factors associated with uptake of HIV testing and self-testing awareness. About 80% of participants had ever tested for HIV, and 64% had tested in the past year. Only 49% of adolescents aged 15-19years had ever tested for HIV compared with over 80% of adults. Self-testing awareness was low (22%), and only 2.9% of respondents had ever self-tested for HIV. The odds of having ever tested for HIV were significantly higher among respondents who were aged 25-29 (AOR: 4.02; 95% CI: 3.27-4.95), had a higher level of education (AOR: 3.18; 95% CI: 2.19-4.61), were married (AOR: 1.63; 95% CI: 1.36-1.94), had high media exposure (AOR: 1.23; 95% CI: 1.06-1.44) and had ever had sex (AOR: 5.57; 95% CI: 4.67-6.64), but lower among men (AOR: 0.39; 95% CI: 0.35-0.44). In conclusion, HIV testing coverage is high in South Africa relative to most countries in sub-Saharan Africa, but falls short of the UNAIDS first 95. We found no evidence of socioeconomic and geographic inequalities in access to HIV testing. However, adolescents had a lower level of HIV testing uptake, suggesting a need for interventions to expand testing in this age group.

Application of Six Detection Methods for Analysis of Paralytic Shellfish Toxins in Shellfish from Four Regions within Latin America.

With the move away from use of mouse bioassay (MBA) to test bivalve mollusc shellfish for paralytic shellfish poisoning (PSP) toxins, countries around the world are having to adopt non-animal-based alternatives that fulfil ethical and legal requirements. Various assays have been developed which have been subjected to single-laboratory and multi-laboratory validation studies, gaining acceptance as official methods of analysis and approval for use in some countries as official control testing methods. The majority of validation studies conducted to date do not, however, incorporate shellfish species sourced from Latin America. Consequently, this study sought to investigate the performance of five alternative PSP testing methods together with the MBA, comparing the PSP toxin data generated both qualitatively and quantitatively. The methods included a receptor binding assay (RBA), two liquid chromatography with fluorescence detection (LC-FLD) methods including both pre-column and post-column oxidation, liquid chromatography with tandem mass spectrometry (LC-MS/MS) and a commercial lateral flow assay (LFA) from Scotia. A total of three hundred and forty-nine shellfish samples from Argentina, Mexico, Chile and Uruguay were assessed. For the majority of samples, qualitative results compared well between methods. Good statistical correlations were demonstrated between the majority of quantitative results, with a notably excellent correlation between the current EU reference method using pre-column oxidation LC-FLD and LC-MS/MS. The LFA showed great potential for qualitative determination of PSP toxins, although the findings of high numbers of false-positive results and two false negatives highlighted that some caution is still needed when interpreting results. This study demonstrated that effective replacement methods are available for countries that no longer wish to use the MBA, but highlighted the importance of comparing toxin data from the replacement method using local shellfish species of concern before implementing new methods in official control testing programs.

CDKN2A and MTAP Are Useful Biomarkers Detectable by Droplet Digital PCR in Malignant Pleural Mesothelioma: A Potential Alternative Method in Diagnosis Compared to Fluorescence In Situ Hybridisation.

BackgroundThe diagnosis of malignant pleural mesothelioma (MPM) can be difficult, in part due to the difficulty in distinguishing between MPM and reactive mesothelial hyperplasia (RMH). The tumor suppressor gene, CDKN2A, is frequently silenced by epigenetic mechanisms in many cancers; in the case of MPM it is mostly silenced via genomic deletion. Co-deletion of the CDKN2A and methylthioadenosine phosphorylase (MTAP) genes has been researched extensively and discovered to be a highly specific characteristic of MPM. Most studies have used FISH to detect the deletion of CDKN2A and IHC for MTAP as a surrogate for this. In this study, we aim to investigate and validate droplet digital PCR (ddPCR) as an emerging alternative and efficient testing method in diagnosing MPM, by particularly emphasizing on the loss of MTAP and CDKN2A.MethodsThis study included 75 formalin fixed paraffin embedded (FFPE) MPM tissue, and 12 normal pleural tissue and 10 RMH as control. Additionally, primary MPM cell lines and normal pleural samples were used as biomarker detection controls, as established in our previous publication. All FFPE specimens were processed to isolate the DNA, that was subsequently used for ddPCR detection of CDKN2A and MTAP. FFPE samples were also analyzed by fluorescence in situ hybridization (FISH) for CDKN2A and MTAP deletion, and for MTAP IHC expression. Concordance of IHC and ddPCR with FISH were studied in these samples.Results95% and 82% of cases showed co-deletion of both MTAP and CDKN2A when determined by FISH and ddPCR respectively. ddPCR has a sensitivity of 72% and specificity of 100% in detecting CDKN2A homozygous loss in MPM. ddPCR also has a concordance rate of 92% with FISH in detecting homozygous loss of CDKN2A. MTAP IHC was 68% sensitive and 100% specific for detecting CDKN2A homozygous loss in MPM when these losses were determined by ddPCR.ConclusionOur study confirms that MTAP is often co-deleted with CDKN2A in MPM. Our in-house designed ddPCR assays for MTAP and CDKN2A are useful in differentiating MPM from RMH, and is highly concordant with FISH that is currently used in diagnosing MPM. ddPCR detection of these genetic losses can potentially be utilized as an alternative method in the diagnosis of MPM and for the future development of a less-invasive MPM-specific detection technique on MPM tumor tissue DNA.

Antibiotic Stewardship Through Standardized Diagnosis and Treatment of Small Bowel Bacterial Overgrowth in Pediatric Patients With Short Bowel Syndrome Reduces Antibiotic Exposure and Improves Cost of Health Care.

Small bowel bacterial overgrowth (SBBO) is difficult to diagnose in pediatric patients with short bowel syndrome due to the invasive nature of the gold standard testing. Alternative testing methods also have barriers leaving providers to diagnose clinically. This has led to antibiotic overprescribing in this population. An algorithm for SBBO identification and standardized treatment is proposed. Standardize SBBO identification and treatment in pediatric short bowel syndrome. 1-year retrospective chart review and literature review. Final analysis of 146 admissions revealed diagnostic and antibiotic prescribing inconsistencies. In total, 28% (n = 41) received antibiotics for SBBO including those who continued home antibiotic (n = 27), those prescribed an antibiotic based on clinical suspicion (n = 12), and those prescribed an antibiotic based on duodenal aspirate (n = 2). In 10.2% (n = 15) patients, antibiotics were prescribed without clear clinical indication resulting in 342 antibiotic exposed days and $24,000 in prescription costs. Clinical research is greatly needed as it relates to SBBO. In the meantime, the proposed algorithm guides providers through diagnosis and treatment decision-making. Thoughtful antibiotic prescribing is key to optimizing outcomes while minimizing adverse effects of antibiotics. The algorithm empowers nursing to minimize antibiotic overuse through collaborative teamwork.

A New Direct Tension Test Method for Soils and Soft Rocks

Abstract Tensile strength plays a crucial role in many engineering activities involving soils and soft rocks. Currently, several methods for tensile strength determination exist, the most common of which include the direct tension method, Brazilian test, ring test, axial fracturing test, bending test, and hydraulic fracturing test. However, outstanding problems associated with these methods, e.g., undesirable eccentric forces and damage of specimen ends, significantly affect obtained tensile strength values. To overcome these problems, we propose an alternative direct tension test method together with the newly developed apparatus. The proposed method uses an annular specimen that is tension-loaded on the inner hole. The method was evaluated through a series of tests on undisturbed soil and remolded gypsum-sand mixture specimens. For validation, comparison of results between the proposed method and the International Society for Rock Mechanics (ISRM)-suggested method was performed. Based on the results of the experimental program, the proposed method is considered more capable of and more suitable for determining the tensile strength of soils and soft rocks than the ISRM-suggested method.

Exploration of alternatives of elastic recovery and conventional fatigue tests of modified binders

For characterizing polymer modified binders, different state Departments of Transportation (DOTs) use a variety of laborious and empirical Performance Grade (PG) “Plus” test methods such as elastic recovery (ER) and tenacity. However, the effects of elasto meric and/or plastomeric polymers are not been accurately identified through these conventional tests. The main research goal of this study is to recommend alternative test method(s), which can be pursued by using a, commonly available, dynamic shear rheometer (DSR). To this end, efficacies of test methods such as multiple stress creep recovery (MSCR), elastic recovery using a DSR (ER-DSR), linear amplitude sweep (LAS), and binder yield energy test (BYET) were explored in this study. Also, a viscoelastic continuum damage (VECD) model was developed to characterize the fatigue cracking of asphalt binders. Two types of polymer modi fied binders from ten sources approved by the Arkansas Department of Transportation (ARDOT) and Texas Department of Transportation (TXDOT) were evaluated in the laboratory. Test results and analyses suggest that without risking the suppliers or users, either the ER-DSR or MSCR test can be a good replacement of the ER test method. A new ER-DSR binder grading system has been proposed. Among the selected fatigue tests, the BYET results were found to be highly related to fatigue damage.

Migration of surrogate contaminants from paperboard to foods: Effect of food and surrogate properties

ABSTRACT The current research describes an alternative test method to evaluate the impact of food properties and compound characteristics on migration from paperboard to food. Tightly sealed bottles containing paperboard spiked with surrogate components as a donor, together with modified polyphenylene oxide (MPPO or Tenax®) or one of the nine considered foods as a receptor, were stored at 22°C. Instead of analysing the receptor, migration from donor to receptor was followed up by evaluating the recovery of surrogates from the donor over time, thus avoiding challenges in the analysis of the foods as such. Free fat content affected the migration more than the specific surface area of the food, reaching a plateau at fat contents >8.1%. The highest migration was observed to fatty foods such as biscuits (8% to 25% fat) and chocolate (40% fat). Intermediate migration occurred to starchy and particulate foods such as egg-based wheat pasta (2.6% fat), wheat flour (1% fat) and rice flour (0.5% fat). Low migration occurred in the case of paperboard in contact with wheat pasta (0.4% fat). Native starch was found to be more sensitive to migration than gelatinised starch. Volatility was identified as the most important characteristic of the migrating compounds. MPPO was considered as a suitable surrogate for dry foods as it did not underestimate migration in any case. However, for low-fat foods such as wheat pasta, clear overestimations could occur, but only for volatile surrogates with vapour pressure over 1.45 mTorr.

Empirical power comparison of statistical tests in contemporary phase III randomized controlled trials with time-to-event outcomes in oncology

More than 95% of recent cancer randomized controlled trials used the log-rank test to detect a treatment difference making it the predominant tool for comparing two survival functions. As with other tests, the log-rank test has both advantages and disadvantages. One advantage is that it offers the highest power against proportional hazards differences, which may be a major reason why alternative methods have rarely been employed in practice. The performance of statistical tests has traditionally been investigated both theoretically and numerically for several patterns of difference between two survival functions. However, to the best of our knowledge, there has been no attempt to compare the performance of various statistical tests using empirical data from past oncology randomized controlled trials. So, it is unknown whether the log-rank test offers a meaningful power advantage over alternative testing methods in contemporary cancer randomized controlled trials. Focusing on recently reported phase III cancer randomized controlled trials, we assessed whether the log-rank test gave meaningfully greater power when compared with five alternative testing methods: generalized Wilcoxon, test based on maximum of test statistics from multiple weighted log-rank tests, difference in t-year event rate, and difference in restricted mean survival time with fixed and adaptive . Using manuscripts from cancer randomized controlled trials recently published in high-tier clinical journals, we reconstructed patient-level data for overall survival (69 trials) and progression-free survival (54 trials). For each trial endpoint, we estimated the empirical power of each test. Empirical power was measured as the proportion of trials for which a test would have identified a significant result (p value < .05). For overall survival, t-year event rate offered the lowest (30.4%) empirical power and restricted mean survival time with fixed offered the highest (43.5%). The empirical power of the other types of tests was almost identical (36.2%-37.7%). For progression-free survival, the tests we investigated offered numerically equivalent empirical power (55.6%-61.1%). No single test consistently outperformed any other test. The empirical power assessment with the past cancer randomized controlled trials provided new insights on the performance of statistical tests. Although the log-rank test has been used in almost all trials, our study suggests that the log-rank test is not the only option from an empirical power perspective. Near universal use of the log-rank test is not supported by a meaningful difference in empirical power. Clinical trial investigators could consider alternative methods, beyond the log-rank test, for their primary analysis when designing a cancer randomized controlled trial. Factors other than power (e.g. interpretability of the estimated treatment effect) should garner greater consideration when selecting statistical tests for cancer randomized controlled trials.

Towards a tiered test strategy for plant protection products to address mixture toxicity by alternative approaches in human health assessment.

Plant protection products (PPPs) consist of pesticide active substances and co-formulants. Generally, active substance effects are assumed to dominate in PPP toxicity. Nevertheless, co-formulants may well affect the toxicity of PPPs via toxicodynamic and toxicokinetic interaction. To account for potential mixture effects and improve PPP data requirements for application in risk assessment, a tiered test strategy is proposed. The strategy is based on a comparison of PPP and active substance toxicity, which enables the prioritisation of PPPs for further testing, adaptation of the toxicological threshold value or removal of toxic co-formulants from the PPP. Moreover, it focuses on the integrative assessment of existing information and newly generated data using alternative test methods. The proposed strategy will improve PPP toxicological assessment by accounting for mixture toxicity, providing a set of regulatory options for risk assessment and the necessary data for hazard assessment. The predictivity of alternative methods for PPPs will improve by evaluation of their reliability and uncertainty. © 2020 The Authors. Pest Management Science published by JohnWiley & Sons Ltd on behalf of Society of Chemical Industry.