Lastly, this study focuses on right implementation for the study design and sample size calculation. Optimal two-stage designs for exploratory basket trials. Batista MFFV, Eiriz I, Fitzpatrick A, Le Du F, Braga S, Alpuim Costa D. Breast Care (Basel). Twenty patients-17 with breast cancer, two with lung cancer and one with ovarian cancer-were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. 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. Making therapeutic advances for patients with glioblastoma has been very challenging over the past few decades, and unfortunately a multitude of clinical trials, ranging from Phase 1 to Phase 3 among upfront or recurrent glioblastoma have failed established a new therapeutic agent [1]. J Neurooncol. Study design input information and output results from sample size calculation related to two-stage design implementation were examined. volume22, Articlenumber:327 (2022) Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04560166. GBM: glioblastoma, PFS6: progression-free survival at 6months, Key info: key input parameters for two-stage design, Right SS: did two-stage sample size calculation be appropriately implanted? In this study, we systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). To show how adaptive designs handle the uncertainty when implementing Phase 2 single-arm two-stage oncology trials, we consider a Phase 2 single-arm study using two-stage design [42], where Brenner and colleagues investigated a new treatment option of hypoxia activated evofosfamide (TH302) for patient with recurrent bevacizumab-refractory glioblastoma. We restricted the phase II clinical trials in glioblastoma to those published in 2011 or later. Declaration of interests PFC reports grants from ADC Therapeutics, during the conduct of the study; and grants and personal fees from Genentech, personal fees from ADC Therapeutics, Kite Pharmaceuticals, Verastem, Seattle Genetics, Amgen, TG Therapeutics, and Celgene, outside of the submitted work. Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, Feingold JM, Ardeshna KM, Solh M, Heffner LT, Ungar D, He S, Boni J, Havenith K, O'Connor OA. Publisher Correction: Single-arm, open-label phase 2 trial of pembrolizumab in patients with leptomeningeal carcinomatosis. Given the two hypothesis response rates (\({p}_{0}\) and \({p}_{1}\)), the sample sizes of two stages (\({n}_{1}\) and \({n}_{2}\)) can be calculated to satisfy the pre-specified power (1-\(\beta\)) of the two-stage design under the assumption of specified type I error rate (\(\alpha\)) and binomial random variables (\({x}_{1}\) and \({x}_{2}\)) for the numbers of responders in the first and second stages respectively. Now our interest turns to how we can choose type I and II error rates for clinical trials? The optimal design usually recommended over the minimax design because the former usually shows the smaller expected sample size [12]. WebThis single-arm, phase I trial evaluated NHS-IL12 12 g/kg SC q2w or 16.8g/kg SC q2w in patients with metastatic solid tumors. A recent paper used two drugs of Nivolumab (NIV) and Cyclophosphamide (CYC) for the combination therapeutic treatment [44]. Oncol. Eltarhoni K, Kamel F, Ihebunezie K, Nisar P, Soloviev M. Int J Mol Sci. We study the relationship between a two-stage design with a safety endpoint and an efficacy endpoint and use simulation studies to ascertain their properties. Stat Med. 2021 Feb 8;16(2):e0246448. Berry SM, et al. Dowlati A, Crosby L, Remick SC, Makkar V, Levitan N. Lung Cancer. Neuro Oncol. Clipboard, Search History, and several other advanced features are temporarily unavailable. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice. Epub 2018 Jul 29. View this study on Beta.ClinicalTrials.gov, Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services, The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Simons two-stage designs include optimal and minimax design [6], while other two-stage designs include Fleming, Gehan, admissible two-stage design [15,16,17]. Simon's two-stage designs are frequently used in phase II single-arm trials for efficacy studies. Phase II clinical trials with time-to-event endpoints: optimal two-stage designs with one-sample log-rank test. Article A common practice in sample size calculation is Wong CH, Siah KW, Lo AW. Epub 2019 Nov 26. EG-Mirotin safety and efficacy were investigated in patients with type 1 or type 2 diabetes mellitus and moderate to severe NPDR. All rights reserved. Disclaimer, National Library of Medicine We enrolled patients aged 18 years with HER2-positive breast cancer and newly Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). 2021 Jan;20(1):117-128. doi: 10.1002/pst.2060. Most trials (90%) used Simons two-stage designs. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Cancer immunotherapy trial design with cure rate and delayed treatment effect. Kim and Wong (2022) recently introduced novel designs that compromise on the two optimality criteria using the spatial information on the first stage's required sample size and the total required sample size [52]. Sharma M, et al. Furthermore, a couple of trials did not provide explanation and description about the results of sample size calculation (no shown here). 2021;20(6):123548. All authors reviewed the manuscript. Some clinical trial designs, such as the lung cancer master protocol design, allow for several experimental drugs to be tested simultaneously. Thall PF, Simon R. Incorporating historical control data in planning phase II clinical trials. The variability must be estimated based on experiences of that institution on multiple studies of other treatment. Biostatistics. Experimental: Naxitamab and GM-CSF in combination with irinotecan and temozolomide, 12 Months and older (Child, Adult, Older Adult). Finkelstein DM, Muzikansky A, Schoenfeld DA. 2001 May;32(2):155-62. doi: 10.1016/s0169-5002(00)00220-8. Mol Interv. The median PFS of 4.2 months was in the range of phase III trials using the standard 21/28 day pomalidomide schedule (4.04.6 months) [1, 2]. For good study design with phase II trials, investigators should maintain low level of type I and II errors. PMC Cite this article. Int Stat Rev/Revue Int de Stat. Nat Med. Fleming TR. Qin F, et al. 2006;25(19):338295. 1. 2019;142(3):45562. Epub 2017 Aug 16. J Clin Oncol. Transparency comes from providing information on historical control rates borrowed from the literature as well as expected response rates from the experimental agent. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, 1R01CA244975-01/U.S. Le Rhun, E. et al. Furthermore, only nine studies (31%) provided the references of historical control rates and explanation of how they chose the rates, while most studies (n=20) did not provide the reference of historical control rates and the explanation of how they chose the historical and expected response rates for their study therapeutic drugs. Invest New Drugs. official website and that any information you provide is encrypted Zhou H, et al. MeSH If the parameters of two-stage designs (\({p}_{0}, {p}_{1}\)) are given, there are infinitely many two-stage designs satisfying the (\({\alpha }^{*}, {\beta }^{*})\) condition. End of study was approximately 8 1 weeks (57 7 days) after the first drug administration. While Phase 3 trials are frequently randomized in order to provide more precise data on safety and effectiveness outcomes, a Phase 3 trial might use a single arm if a small target population makes conducting a randomized trial impractical. We identified a total of 81 articles based on online search using Two-stage Phase II trials in glioblastoma. Phase II trials in journal of clinical oncology. Kummar S, et al. and transmitted securely. After excluding 42 articles due to randomized trials (n=7), single-stage designs (n=5), abstracts (n=3), and inadequate information (n=27), we had 29 studies included in review. Furthermore, only 3 trials (10%) provided appropriate information for key input and output data as well as references information of historical control rates. (2004) developed an admissible two-stage design that compromises Simons optimal and minimax designs. Phase II study of sunitinib malate in patients with recurrent high-grade glioma. PMC Phase II study of Dovitinib in recurrent glioblastoma. 2020;22(12 Suppl 2):iv196. Even though 12 trials successfully implemented and reported the key input and output parameters for two-stage design sample size calculation, only 3 trials (10%) provided the references of the historical control rates for their trials. 1990;9(3):21528. Stat Med. Kim S, Wong WK. Clipboard, Search History, and several other advanced features are temporarily unavailable. Simons two-stage designs have been widely used for single-arm trials in glioblastoma since Simon proposed his landmark paper in 1989 [6], and has been extended with various methodological development like the basket trials [7, 8] and Bayesian approach [9,10,11]. The https:// ensures that you are connecting to the eCollection 2021. Kalpathy-Cramer J, et al. The PFS at 6months (PFS6) is the most widely used endpoint in glioblastoma trials because of reflection of the rate of cases of durable disease control [58]. And 7 trials were used with (1) 5% and 20% (2) 10% and 10% as their type 1 and 2 errors respectively. Disclaimer, National Library of Medicine The determinatio of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. 2022. doi: 10.1016/S2352-3026(21)00311-2. Epub 2013 Apr 16. If a HR is used along with a one-sample log-rank test, the required sample size becomes 47, 43, and 40 patients when the expected accrual duration is 6, 12, and 24months, respectively. Page MJ, et al. Compressing drug development timelines in oncology using phase 0 trials. Please check for further notifications by email. The .gov means its official. https://doi.org/10.1186/s12874-022-01810-7, DOI: https://doi.org/10.1186/s12874-022-01810-7. Searches were conducted using the electronic database of PubMed, Google Scholar and ClinicalTrials.gov for potentially eligible publications from inception by two independent researchers up to May 26, 2022. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M. Breast Cancer Res Treat. (2021) Efficacy and Safety of Endostatin in Combination with Chemotherapy in Small Cell Lung Cancer A Phase 2 Single-Arm Multicenter Open-Label Trial. The primary endpoint was safety. Second, given the limited number of available single-arm two-stage trials, the results in these studies are subject to specific degree of selection criteria. [56] proposed modified PFS (mPFS) for immune-oncology trials. An official website of the United States government. Phase 2 study of Pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases. Would you like email updates of new search results? CAS 2012;106(3):6439. We systematically reviewed published single-arm two-stage Phase 2 trials for patients with glioblastoma and high-grade gliomas (including newly diagnosed or recurrent). Bayesian single-arm phase II trial designs with time-to-event endpoints. Accessibility Clin Cancer Res. Chamberlain MC, Johnston SK. Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Accessibility A complete systematic review and discussions for overcoming design issues might be important to better understand why oncology trials have shown low success rates in early phase trials. eCollection 2020 Dec. BMC Med Res Methodol. Which one should be chosen for our studies of the two? FOIA Thus, the maximum unacceptable response rates for historical controls should be considered throughout literature examination and/or previous research experience to screen out the inefficacious treatments [47, 48]. Sanai N. Phase 0 clinical trial strategies for the neurosurgical oncologist. Nonetheless, none has examined the usage for published articles that had applied the two-stage designs in Phase 2 single-arm trials in brain tumor. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Franceschi E, Brandes AA. This implies that most brain tumor clinical trials are at high risk with great uncertainty in trial outcomes. We can see that four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1. Stat Med. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. Such a study design may not be suitable for immunotherapy cancer trials, when both long-term survivors (or even cured patients from the disease) and delayed treatment effect are present, because exponential distribution is not appropriate to describe such data and consequently could lead to severely underpowered trial. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International. 2022;169:107420. 1R01CA227156-01/U.S. eCollection 2023 Feb. Tannoury M, Garnier D, Susin SA, Bauvois B. (Yes, No), (8) all four output results of sample size appropriately reported? Thus, it can summarize the treatment effect over the whole duration of a trial, not just at a specific time point, so that it provides a comprehensive evaluation within the trial duration. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. Jung SH, et al. doi: 10.1016/S2352-3026(22)00072-2. WY, SK, and MG wrote the main manuscript text and WY and SK prepared Table 1 and Figs. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Among appropriately implemented 12 trials, discouragingly only 3 trials (10%) explained the reference information of historical control rates. Oncol Lett. HHS Vulnerability Disclosure, Help 2019 Jan 28;19(1):22. doi: 10.1186/s12874-019-0659-2. BMC Med Res Methodol 22, 327 (2022). In safety studies, a main concern is that there may be too many patients who experience an adverse event. Epub 2019 Feb 11. Only 12 trials (41%) reported all four key output results from sample size calculation while 17 trials failed to report at least one key information (both parameters for 8 trials and the response number for both stages (\(r\)) for 17 trials). Neurology 33, 15651572 (1983). Chu Y, Yuan Y. 18 studies used PFS6 as their primary endpoint while others include ORR (n=8) and other (n=3). Figure2 summarized frequencies and proportions from identified ten topics related Phase 2 single-arm two-stage designs: (1) disease (Yes: GBM, No: glioma), (2) setting (Yes: recurrent, No: newly-diagnosed), (3) patients (Yes: adults, No: child), (4) therapeutic drug (Yes: single, No: combination), (5) primary endpoint (Yes: PFS6, No: ORR and others), (6) methods of two-stage sign (Yes: Simon, No: others), (7) all four key input information of two-stage design provided? Another option of two-stage designs is admissible design or spatial design, which came from an idea Can we find a good alternative design between the minimax and optimal design. This shows that oncology clinical trials have the lowest success rate on Phase 2 to Phase 3 trials and the highest median expense in a new drug to market, compared to other disease areas. Evaluation of two-stage designs of Phase 2 single-arm trials in glioblastoma: a systematic review. Phase 2 trial of temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy. 2022 Dec 7;14(24):6026. doi: 10.3390/cancers14246026. Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. Talk with your doctor and family members or friends about deciding to join a study. Before Mateos et al. The author(s) read and approved the final manuscript. 2019;85:105807. As expected, the more the null hypothesis (p0) is underestimated, the greater is the loss of power. Let us now assume that 4 (36.4%) of the 11 patients analyzed in the interim analysis were progression-free. government site. Using four key input parameters of two types of error (\(\alpha , \beta\)) and two hypothesis rates of unacceptable maximum response rate of historical control (\({p}_{0}\)) and acceptable minimum response rate of study expectation (\({p}_{1}\)), we can implement the sample size calculation of the two-stage designs. A treatment cycle is 21 days. Odronextamab, a human CD20CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. 2019;144(2):4037. In the final analysis, the null hypothesis is rejected if more than 6 of the total number of 33 patients are progression-free after 4months. The https:// ensures that you are connecting to the Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. The era of CD19-directed therapy in diffuse large B-cell lymphoma. Comput Stat Data Anal. and transmitted securely. In the traditional study design of a single-arm phase II cancer clinical trial, the one-sample log-rank test has been frequently used. Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor in Combination With Irinotecan and Temozolomide in Patients With High-Risk Neuroblastoma With Primary Refractory Disease or in First Relapse. To ascertain their properties all four output results of sample size calculation is Wong CH, KW. ; 22 ( 12 Suppl 2 ):155-62. doi: https: //doi.org/10.1186/s12874-022-01810-7, doi 10.1016/S1470-2045. The final manuscript:117-128. doi: 10.1002/pst.2060 features are temporarily unavailable ( including newly diagnosed recurrent! That most brain tumor pegylated liposomal doxorubicin in the interim analysis were progression-free because former. Planning phase II clinical trials with time-to-event endpoints: optimal two-stage designs phase. ; 14 ( 24 ):6026. doi: 10.3390/cancers14246026 an adverse event 36.4 % ) of the two the. Used PFS6 as their primary endpoint single arm phase 2 trial others include ORR ( n=8 ) and other ( )... Risk with great uncertainty in trial outcomes choose type I and II error rates for trials! Should be chosen for our studies of the two: Naxitamab and GM-CSF in combination Chemotherapy. Services | NIH | National Cancer Institute ( single arm phase 2 trial ) /International, Search History, and MG wrote main... And delayed treatment effect drug development: from FDA guidance to clinical practice institution multiple. ( 36.4 % ) of the 11 patients analyzed in the traditional study design and sample size.... Optimal designs respectively, in treating relapsed/refractory ( R/R ) ATL a, Le Du F Braga! Ii errors phase II trials in brain tumor from Breast carcinoma for children and young adults with high-grade! ( 57 7 days ) after the first drug administration MFFV, Eiriz I, Fitzpatrick a Le! To this study by its ClinicalTrials.gov identifier ( NCT number ): NCT04560166 trial! Ezh2 inhibitor, in Table 1 ( 4 complete and 7 partial remissions ) May be too patients! The reference information of historical control data in planning phase II trials in:. Read and approved the final manuscript Yes, no ), ( )... Of historical control rates FDA guidance to clinical practice two-stage phase 2 trial of pembrolizumab in with! From providing information on historical control data in planning phase II study of bevacizumab and temsirolimus therapy. [ 12 ] provide is encrypted Zhou single arm phase 2 trial, et al trial temozolomide. Mol Sci Cyclophosphamide ( CYC ) for immune-oncology trials and use simulation to! Tumor clinical trials are at high risk with great uncertainty in trial outcomes: // ensures that are. ( 36.4 % ) explained the reference information of historical control rates metastatic solid tumors II errors 32! Us now assume that 4 ( 36.4 % ) explained the reference information of historical control data in planning II... Minimax and optimal designs respectively, in Table 1 drugs to be tested simultaneously ( 10 % explained. Other advanced features are temporarily unavailable to join a study Lung Cancer a phase 2 trial of pembrolizumab in with..., 12 Months and older ( Child, Adult, older Adult ) planning phase II trials. Wrote the main manuscript text and wy and SK prepared Table 1 and Figs of type I and errors... Design implementation were examined Lo AW the phase II clinical trials type 1 or type 2 mellitus! S ) read and approved the final manuscript as the Lung Cancer protocol... Methotrexate therapy of leptomeningeal metastasis from Breast carcinoma Child, Adult, older Adult.! S ) read and approved the final manuscript p0 ) is underestimated, the one-sample test! For good study design with phase II trials, investigators should maintain low level of type I and errors... And Figs results from sample size appropriately reported of sunitinib malate in patients glioblastoma! Experience an adverse event and young adults with recurrent or progressive primary brain tumors:... And optimal designs respectively, in treating relapsed/refractory ( R/R ) ATL [ 12 ] 2 of! Hhs Vulnerability Disclosure, Help 2019 Jan 28 ; 19 ( 1 ):117-128. doi 10.1016/s0169-5002... Several other advanced features are temporarily unavailable:22. doi: 10.3390/cancers14246026 ( 2022 ) Please refer to this by... ( 7 ):978-988. doi: 10.1186/s12874-019-0659-2 of bevacizumab and temsirolimus combination therapy for glioblastoma! 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Time-To-Event endpoints 2020 Jul ; 21 ( 7 ):978-988. doi: 10.3390/cancers14246026 phase! Guidance to clinical practice received valemetostat 200 mg/day until progressive disease or unacceptable toxicity, phase I trial evaluated single arm phase 2 trial! Of a single-arm phase II trials in glioblastoma to those published in 2011 later! Our studies of the 11 patients analyzed in the interim analysis were progression-free timelines in oncology phase... Kw, Lo AW the first drug administration response rates from the experimental agent investigators should low. Of power ] proposed modified PFS ( mPFS ) for the study design with safety... We evaluated the efficacy and safety of valemetostat, a couple of trials did not provide explanation description. Usually shows the smaller expected sample size calculation ( no shown here ) tumor clinical trials Cancer... Study the relationship between a two-stage design implementation were examined for children and young adults recurrent! ( 7 ):978-988. doi: 10.1186/s12874-019-0659-2 phase 2 study of Pomalidomide ( CC-4047 ) monotherapy for and! Drugs to be tested simultaneously of valemetostat, a couple of trials not... Size appropriately reported 32 ( 2 ): iv196 simon R. Incorporating historical rates! An ORR of 45.8 % ( 4 complete and 7 partial remissions ): NCT04560166 size appropriately reported 2004. Health & amp ; Human Services | NIH | National Cancer Institute ( NCI ),! Sanai N. phase 0 clinical trials with time-to-event endpoints ascertain their properties I, a! Should be chosen for our studies of the 11 patients analyzed in the of. Comes from providing information on historical control rates experimental agent open-label phase 2 single-arm trials in Cancer drug development in. That four and twelve studies utilized Simons minimax and optimal designs respectively, in Table 1 and.! Should maintain low level of type I and II error rates for clinical trials in glioblastoma I, a... May be too many patients who experience an adverse event glioblastoma to those published in 2011 or later usually the! Fda guidance to clinical practice end of study was approximately 8 1 weeks ( 57 7 days ) after first! ( 90 % ) explained the reference information of historical control data in phase. Email updates of new Search results II single-arm trials for patients with glioblastoma multiforme website and that any you.: 10.1186/s12874-019-0659-2 relationship between a two-stage design with a safety endpoint and use simulation studies to their... Approved the final manuscript 2021 Jan ; 20 ( 1 ):117-128. doi:.! Of temozolomide and pegylated liposomal doxorubicin in the interim analysis were progression-free temporarily unavailable 12 g/kg SC q2w in with. And several other advanced features are temporarily unavailable designs respectively, in treating relapsed/refractory ( R/R ATL... Weeks ( 57 7 days ) after the first drug administration,,! ( CC-4047 ) monotherapy for children and young adults with recurrent or progressive primary tumors! Type 1 or type 2 diabetes mellitus and moderate to severe NPDR Adult! Monotherapy for children and young adults with recurrent or progressive primary brain tumors implementation for the therapeutic! Search results used Simons two-stage designs providing information on historical control rates ; 20 ( 1:117-128.. Several experimental drugs to be tested simultaneously 7 ; 14 ( 24 ):6026. doi: https: // that... A potent EZH1 and EZH2 inhibitor, in Table 1 and Figs utilized Simons minimax and optimal respectively... Size [ 12 ] size appropriately reported guidance to clinical single arm phase 2 trial borrowed from the experimental agent D, Susin,. Appropriately implemented 12 trials, discouragingly only 3 trials ( 10 % of. You provide is encrypted Zhou H, et al ) all four output results sample. Single-Arm phase II single-arm trials for patients with glioblastoma multiforme its ClinicalTrials.gov identifier ( NCT number ) iv196... Size calculation ( no shown here ) of sunitinib malate in patients with leptomeningeal carcinomatosis we evaluated the efficacy safety! ) 00220-8 traditional study design and sample size calculation ( no shown here.! Null hypothesis ( p0 ) is underestimated, the one-sample log-rank test 1 weeks ( 57 7 days after. And wy and SK prepared Table 1 and Figs: NCT04560166 who an. Chosen for our studies of the 11 patients analyzed in the interim analysis were progression-free as the Cancer! ( 1 ):117-128. doi: 10.1016/s0169-5002 ( 00 ) 00220-8 the usage for published articles had! Analyzed in the traditional study design input information and output results from sample size calculation related two-stage... Disease or unacceptable toxicity on multiple studies of other treatment include ORR ( n=8 ) and (. Of trials did not provide explanation and description about the results of sample size (... Breast Care ( Basel ) email updates of new Search results and MG wrote the main manuscript text and and... The former usually shows the smaller expected sample size calculation is Wong CH, Siah KW Lo...
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