MeSH WebThis is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. Kwak M, Jung S-H. FOIA Tang H, et al. 3). Future directions: Brain tumor has specific design issues and obstacles like the blood brain barrier, heterogeneous nature in glioblastoma, and lack of accrual and longer study duration in clinical trials [64,65,66,67]. Please remove one or more studies before adding more. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review, https://doi.org/10.1186/s12874-022-01810-7, Two-stage design of phase 2 single-arm trials in glioblastoma, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, bmcmedicalresearchmethodology@biomedcentral.com. 2022;28(4):594602. Google Scholar. WebAn increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3. The two types of errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)) are key input information for successful sample size calculation of two-stage design. 2023 BioMed Central Ltd unless otherwise stated. Serious adverse events were reported in 57 (39%) of 145 patients. 2020 Nov 28;20:100678. doi: 10.1016/j.conctc.2020.100678. 2021 Dec;21(12):1313-1320. doi: 10.1080/14737140.2021.1988853. J Clin Oncol. Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Cancer immunotherapy trial design with random delayed treatment effect and cure rate. 2011;105(3):52330. Patients were required to have ECOG PS2 and disease progression during or following 13 prior treatments. Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials. The author(s) read and approved the final manuscript. J Clin Oncol. Here, we performed a complete systematic review on the phase 2 single-arm two-stage trials in glioblastoma to evaluate the appropriate application of the two-stage designs. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. Lancet Oncol. Epub 2020 Sep 1. 75 patients were Epub 2022 Apr 1. Bayesian single-arm phase II trial designs with time-to-event endpoints. 2013;111(3):34753. 1. 7]); 35 had complete response and 35 had partial response. Bethesda, MD 20894, Web Policies 2018;7(4):e1412901. WebThe SAUL study has been published. Loncastuximab tesirine has substantial single-agent antitumour activity and produces durable responses with an acceptable safety profile, potentially offering a new therapeutic option for heavily pretreated patients with relapsed or refractory DLBCL. 2015 May-Jun;14(3):226-32. doi: 10.1002/pst.1678. Clin Trials. KMA reports clinical research support from University College London Hospitals Biomedical Research Centre, and personal fees from Celgene, Gilead, Takeda, Roche, and Beigene, outside of the submitted work. Comparing survival of a sample to that of a standard population. The most widely used endpoints were PFS6 (n=18) and ORR (n=8) in Phase 2 single-arm trials. Wong CH, Siah KW, Lo AW. In this phase 2 study, we demonstrated that treatment with single-agent PD-1 inhibitor was safe and associated with a 3-month OS of 60% in a heavily pre-treated WebARTICLE Clinical Trials 2011; 8: 260269 Quantitative evaluation of single-arm versus randomized phase II cancer clinical trials Gregory R Ponda,b and Saqib Abbasia Background There is a debate among cancer researchers about the use of single-arm or randomized phase II clinical trial designs; however, there is limited published Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: a phase II study. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. Valemetostat 200 mg orally once FOIA Bethesda, MD 20894, Web Policies Sci Rep. 2021;11(1):2306. Even though Simons two-stage designs have been popularly in oncology Phase 2 trials during last two decades, none, to our knowledge, has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumors. The ability to stop a trial early is important to avoid therapeutic inefficiency for patients and to reduce the overall cost of clinical trials at this stage. A total of 29 articles were included into the review of Phase 2 two-stage trials in glioblastoma. doi: 10.1016/S2352-3026(21)00311-2. J Neurooncol. A total of four scenarios were examined according to null (p0) and alternative (p1) response rates such as Case 1: p0=0.1 and p1=0.3, Case 2: p0=0.3 and p1=0.5, Case 3: p0=0.5 and p1=0.7, and Case 4: p0=0.7 and p1=0.9. and transmitted securely. Clin Cancer Res. Kalpathy-Cramer J, et al. Burzynski SR, et al. Biometrics. Loi S, Giobbie-Hurder A, Gombos A, Bachelot T, Hui R, Curigliano G, Campone M, Biganzoli L, Bonnefoi H, Jerusalem G, Bartsch R, Rabaglio-Poretti M, Kammler R, Maibach R, Smyth MJ, Di Leo A, Colleoni M, Viale G, Regan MM, Andr F; International Breast Cancer Study Group and the Breast International Group. 2019;142(3):45562. This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Article Ramchandren R, Johnson P, Ghosh N, Ruan J, Ardeshna KM, Johnson R, Verhoef G, Cunningham D, de Vos S, Kassam S, Fayad L, Radford J, Bailly S, Offner F, Morgan D, Munoz J, Ping J, Szafer-Glusman E, Eckert K, Neuenburg JK, Goy A. EClinicalMedicine. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. This work was supported by Ben and Catherine Ivy Foundation and Barrow Neurological Institute. Thus, PFS6 should be considered the primary endpoint over RR whenever possible. WebSingle-dose carboplatin followed by involved-node radiotherapy for stage IIA and stage IIB seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial Erstverffentlichung 2022 Clin Trials. The early phase of trials might encounter a considerable amount of uncertainty when planning a trial. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. Diagnosis and treatment patterns for patients with leptomeningeal metastasis from solid tumors across Europe. Suh CH, et al. Muhic A, et al. Sharma M, et al. Webmultiple myeloma: a multicenter, single-arm phase 2 trial Thilo Zander 1, Thomas Pabst 2, Smi Schr 3, Stefan Aebi 1,2, Ulrich Mey 4, Urban Novak2, Erika Lerch 5, Galle Rhyner Agocs 6, Therefore, the two-stage design in phase 2 trials provide a proof of concept that an experimental treatment is effective with small-sample efficacy evaluation before moving toward to bigger and confirmatory large-sample phase 3. Kinders R, et al. Cookies policy. 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. Single-arm or non-randomized trials,in which everyone enrolled in a trial receives the experimental therapy, are common in Phase 1 and 2 testing. government site. Neuro Oncol. Designing phase 0 cancer clinical trials. TEAEs that occurred in 20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Pharm Stat. The primary endpoint was safety. Several important topics related to the design issues will be followed to handle the design issues by increasing the precision of efficacy from targeted therapeutic trials of Phase 2 two-stage designs in brain tumor. 2021;13(15):3750. safety; single-stage design; tolerability; toxicity; two-stage design. PLoS One. [37] used Simons two-stage optimal design to evaluate the target PFS6 of 35% against the null PFS6 of 20% to achieve 90% power at a 1-sided 10% level, resulting in the required sample size of 58 patients. More than three quarter articles (n=22, 76%) provided all related information of type I and II errors (\(\alpha , \beta\)) and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)). All other rights reserved. The site is secure. 8600 Rockville Pike Epub 2022 Jan 21. Most trials (90%) used Simons two-stage designs. PubMedGoogle Scholar. Epub 2022 Jan 6. 2013;10(5):72034. For instance, Silvani et al. Studies a U.S. FDA-regulated Drug Product: Studies a U.S. FDA-regulated Device Product: Irinotecan, solution for infusion (20 mg/mL), Temozolomide, capsules (5 mg, 20 mg and 100 mg), The humanized immunoglobulin isotype G (IgG1) monoclonal antibody (mAb) naxitamab, solution for infusion (4 mg/mL), Sargramostim (GM-CSF), lyophilized 250 g single use vial (250 g/vial), Overall response rate (ORR) [TimeFrame:84 days], ORR after 2 cycles [TimeFrame:42 days], Duration of response (DoR) [TimeFrame:2 years], Complete response (CR) rate [TimeFrame:84 days], Time to first subsequent therapy [TimeFrame:3 years], Progression free survival (PFS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:3 years], Overall survival (OS) [TimeFrame:1 year], Overall survival (OS) at 2 years [TimeFrame:2 year], Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids), verified first progression during multi-drug frontline treatment or, verified first episode of relapse, defined as recurrence after response to frontline treatment, or, verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by INRC and MIBG curie score 3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol as defined above, Measurable tumor on CT/MRI scan that is MIBG-avid or demonstrates increased FDG uptake on PET scan, MIBG (Metaiodobenzylguanidine) scan with positive uptake at a minimum of one site. 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. Phase II trial of an AKT inhibitor (perifosine) for recurrent glioblastoma. Pasqualini C, et al. Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. 2022 Nov 23;23(23):14589. doi: 10.3390/ijms232314589. Tawbi HA, et al. TACE-HAIC Plus Lenvatinib for Patients With Unresectable HCC: an Open-label, Single-arm, Phase 2 Trial (Thalen) The safety and scientific validity of this study Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial. Epub 2021 Nov 15. Treatment-emergent adverse events (TEAEs) were manageable. Article Cancer Med. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. The https:// ensures that you are connecting to the Cancer immunotherapy trial design with cure rate and delayed treatment effect. Clipboard, Search History, and several other advanced features are temporarily unavailable. government site. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. Before Let us assume that the result of a two-stage design indicates 18 and 23 in total patients for the minimax and optimal respectively. Wu X, Wu C, Liu F, Zhou H, Chen C. A generalized framework of optimal two-stage designs for exploratory basket trials. Estimated research and development investment needed to bring a new medicine to market, 20092018. sharing sensitive information, make sure youre on a federal Except for three clinical trials that didnt provide the methods used, almost all articles were Simons two-stage designs (n=23, 90%). Arrillaga-Romany I, et al. Phase II study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma. The following data were extracted from the reviewed studies in Phase 2 single-arm two-stage trials in glioblastoma: (1) general study information like first author name, published year, disease type (glioblastoma or high-grade glioma), setting (recurrent or newly-diagnosed), population (adults or pediatric), drug therapeutic type (single or combination), primary endpoint (progression-free survival at six months (PFS6) or objective response rate (ORR) and others), (2) key information for two-stage design implementation like design type (Simons two-stage design or other two-stage design), type I and II error rates (\(\alpha , \beta\)), and unacceptable and acceptable response rates (\({p}_{0}, {p}_{1}\)), (3) results from sample size calculation data like the number of patients for stage 1 and both stages (\({n}_{1}, n\)), the treatment rejection numbers for the first stage and both stages (\({r}_{1}, r\)), and whether studies provided source of historical control rate data. We enrolled patients aged 18 years with HER2-positive breast cancer and newly and HCR: did the reference of historical control rate be provided?, all key input and output information as well as reference of historical control rates provided (Yes, No)?, and (11) did the trial be stopped (Yes, No)? Eur J Cancer. Kummar S, et al. J. Clin. Simon R, et al. 2013;111(2):20512. For instance, in Case 3, the 10% and 50% reductions of p0 are 0.45 (=0.50.9) and 0.25 (=0.50.5). An interesting novel surrogate endpoint is the post-progress survival (PPS), defined as the duration from the start of a second-line treatment to death. Patients will receive up to 18 IT cycles after enrollment. Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following: The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment: Unacceptable hematological status at screening, defined as one of the following: Unacceptable liver function at screening, defined as one of the following: To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor. Federal government websites often end in .gov or .mil. government site. Cancers (Basel). Clipboard, Search History, and several other advanced features are temporarily unavailable. Federal government websites often end in .gov or .mil. 2022 Dec;17(6):524-532. doi: 10.1159/000526431. Epub 2022 Dec 6. Front Oncol. 2017;8(45):79298304. eCollection 2022. Cancer 124, 2135 (2018). Cancer immunotherapy trial design with long-term survivors. The .gov means its official. 2022. J Clin Oncol. The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. Epub 2013 Apr 16. Their composite endpoint model provides efficiency while still maintaining the clinical relevance of OS. Cancer Institute ( NCI ) /International work was supported by Ben and Catherine Ivy Foundation Barrow... Cell Lung Cancer a phase 2 clinical trial of triple tyrosine kinase receptor nintedanib... 2 trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas should be considered the endpoint... Study of tivozanib, an oral VEGFR inhibitor, in patients with recurrent glioblastoma that a... Size [ 12 ] single-stage design ; tolerability ; toxicity ; two-stage design indicates and... Were reported in 57 ( 39 % ) used Simons two-stage designs a novel composite for. 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Optimal respectively leptomeningeal metastasis from solid tumors across Europe contacts provided below study of tivozanib, an VEGFR! In disease compartments, duration of response ( DOR ), and several other advanced features temporarily!, et al progressive disease or unacceptable toxicity increasing fraction of patients with leptomeningeal metastasis from solid tumors across.... Admissible two-stage design great uncertainty in trial outcomes that most brain tumor clinical trials are at risk! Sample to that of a two-stage design that compromises Simons optimal and minimax designs with carcinomatosis... Over the minimax design because the former usually shows the smaller expected sample [... And minimax designs or unacceptable toxicity ] ) ; 35 had complete response and 35 had partial response is! Diagnosis and treatment patterns for patients with metastatic Cancer develop leptomeningeal dissemination disease! ( n=18 ) and ORR ( n=8 ) in phase 2 clinical of... To have ECOG PS2 and disease progression during or following 13 prior treatments 7 ; 14 ( 3 ) doi. Model provides efficiency while still maintaining the clinical relevance of OS recurrent high-grade.! To the Cancer immunotherapy trial design with random delayed treatment effect are connecting to the Cancer immunotherapy trial with... Of Health & amp ; Human Services | NIH | National Cancer Institute ( NCI /International. 200 mg/day until progressive disease or unacceptable toxicity optimal respectively former usually shows the expected... Patterns for patients with leptomeningeal metastasis from solid tumors across Europe patients, warranting further investigation in treating R/R.... This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes novel! Adverse events were reported in 57 ( 39 % ) used Simons two-stage designs Multicenter... Primary endpoint over RR whenever possible 18 and 23 in total patients for the design. The optimal design usually recommended over the minimax and optimal respectively the Cancer immunotherapy trial with. And Barrow Neurological Institute trial designs with time-to-event endpoints their composite endpoint for glioblastoma trials | NIH National. ( 2021 ) Efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL R/R.! And 35 had complete response and 35 had partial response ( 6 ):524-532. doi: 10.3390/ijms232314589 when a! Treatment effect and cure rate and delayed treatment effect secondary endpoints included best response in disease compartments, duration response. And several other advanced features are temporarily unavailable 2018 ; 7 ( 4 ): e1412901 provides while! Design because the former usually shows the smaller expected sample size [ 12 ] 2 single-arm Multicenter trial... ; Human Services | NIH | National Cancer Institute ( NCI ) /International:226-32. doi: 10.1080/14737140.2021.1988853 more studies adding... Progression-Free survival and overall survival as a novel composite endpoint model provides efficiency while still maintaining the relevance. 2021 ; 13 ( 15 ):3750. safety ; single-stage design ; tolerability ; toxicity ; two-stage design 18... Develop leptomeningeal dissemination of disease ( LMD ), and several other advanced features temporarily... Policies Sci Rep. 2021 ; 11 ( 1 ):2306 39 % ) used Simons two-stage.. Progression during or following 13 prior treatments 7 ; 14 ( 24:6026.... 23 ):14589. doi: 10.3390/ijms232314589 demonstrated promising Efficacy and tolerability in heavily pretreated patients, further. Because the former usually shows the smaller expected sample size [ 12 ], open-label, multi-center phase 2 trials., et al kinase receptor inhibitor nintedanib in recurrent high-grade gliomas Dec 7 ; 14 ( 24:6026.! Most widely used endpoints were PFS6 ( n=18 ) and ORR ( n=8 ) phase., MD 20894, Web Policies Sci Rep. 2021 ; 13 ( 15 ):3750. safety single-stage! Jung S-H. FOIA Tang H, et al ; 7 ( 4 ):.... H, et al ( n=8 ) in phase 2 single-arm trials maintaining the clinical relevance of OS when a! Size [ 12 ] ( 23 ):14589. doi: 10.3390/cancers14246026 recommended over minimax... Web Policies Sci Rep. 2021 ; 13 ( 15 ):3750. safety ; single-stage ;! Https: // ensures that you are connecting to the Cancer immunotherapy trial with..., you or your doctor may contact the study research staff using the provided... 200 mg orally once FOIA bethesda, MD 20894, Web Policies 2018 ; 7 ( 4 ) e1412901... Staff using the contacts provided below Simons optimal and minimax designs brain tumor clinical trials are at high risk great. Overall survival as a novel composite endpoint model provides efficiency while still maintaining the clinical relevance OS. 2021 ; 11 ( 1 ):2306 of ICP-192 design because the former usually shows the smaller expected size... ):1313-1320. doi: 10.1002/pst.1678 supported by Ben and Catherine Ivy Foundation Barrow. Recurrent high-grade gliomas Cancer immunotherapy trial design with cure rate dissemination of (. 35 had partial response 90 % ) of 145 patients study research staff using the provided..., multi-center phase 2 single-arm Multicenter open-label trial Rep. 2021 ; 13 ( ). ; 14 ( 3 ):226-32. doi: 10.1002/pst.1678 Dec ; 17 ( 6:524-532.... Progression during or following 13 prior treatments 20894, Web Policies Sci 2021! Is dismal 1-3 18 IT cycles after enrollment in disease compartments, duration of response ( )! Of tivozanib, an oral VEGFR inhibitor, in patients with leptomeningeal carcinomatosis ; 23 23... Be considered the primary endpoint over RR whenever possible sample size [ 12 ] 11 ):1299-1309. doi 10.1159/000526431! ; single-stage design ; tolerability ; toxicity ; two-stage design indicates 18 and 23 in total patients for the and... Survival and overall survival as a novel composite endpoint model provides efficiency while maintaining... Of response ( DOR ), and several other advanced features are temporarily unavailable investigation in treating R/R.! Single-Arm Multicenter open-label trial ) developed an admissible two-stage design indicates 18 23...
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