scholarly journals Bayesian model selection techniques as decision support for shaping a statistical analysis plan of a clinical trial: An example from a vertigo phase III study with longitudinal count data as primary endpoint

2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Christine Adrion ◽  
Ulrich Mansmann
Keyword(s):  
Clinical Trial ◽  
Decision Support ◽  
Statistical Analysis ◽  
Model Selection ◽  
Count Data ◽  
Bayesian Model ◽  
Statistical Analysis Plan ◽  
Phase Iii ◽  
Longitudinal Count Data ◽  
Phase Iii Study

Bayesian Model Selection for Longitudinal Count Data

Sankhya B ◽  
2021 ◽  
Author(s):  
Oludare Ariyo ◽  
Emmanuel Lesaffre ◽  
Geert Verbeke ◽  
Adrian Quintero
Keyword(s):  
Model Selection ◽  
Count Data ◽  
Bayesian Model ◽  
Bayesian Model Selection ◽  
Longitudinal Count Data ◽  
Selection For

scholarly journals PRECIOUS: PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke—statistical analysis plan of a randomised, open, phase III, clinical trial with blinded outcome assessment

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jeroen C. de Jonge ◽  
◽  
Lisa J. Woodhouse ◽  
Hendrik Reinink ◽  
H. Bart van der Worp ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Statistical Analysis ◽  
Elderly Patients ◽  
Acute Stroke ◽  
Outcome Assessment ◽  
Statistical Analysis Plan ◽  
Phase Iii ◽  
Improve Outcome ◽  
Risk Of Death ◽  
Increased Risk

Abstract Rationale Aspiration, infections, and fever are common in the first days after stroke, especially in older patients. The occurrence of these complications has been associated with an increased risk of death or dependency. Aims and design PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke (PRECIOUS) is an international, multi-centre, 3 × 2 factorial, randomised, controlled, open-label clinical trial with blinded outcome assessment, which will assess whether prevention of aspiration, infections, or fever with metoclopramide, ceftriaxone, paracetamol, respectively, or any combination of these in the first 4 days after stroke onset improves functional outcome at 90 days in elderly patients with acute stroke. Discussion This statistical analysis plan provides a technical description of the statistical methodology and unpopulated tables and figures. The paper is written prior to data lock and unblinding of treatment allocation. Trial registration ISRCTN registry ISRCTN82217627. Registered on 22 September 2015. The trial was prospectively registered.

Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5599-TPS5599
Author(s):  
Rebecca Christian Arend ◽  
Bradley J. Monk ◽  
Thomas J. Herzog ◽  
Jonathan A. Ledermann ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
Ca 125 ◽  
Recist 1.1 ◽  
Platinum Resistant ◽  
Phase Iii Study

TPS5599 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism of action that includes a broad antiangiogenic effect and induction of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer showed that VB-111 in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58% with a trend for improved survival. The favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent platinum-resistant epithelial ovarian cancer with measurable disease (RECIST 1.1), and may have been previously treated with up to 5 prior lines of therapy. Patient are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The efficacy endpoints are OS, PFS and ORR by RECIST 1.1 and by CA-125 (GCIG criteria). A pre-planned interim analysis was performed by the DSMC in the first 60 patients evaluable for CA-125 response. The analysis met the pre-defined criteria of a CA-125 ORR (GCIG) in the treatment arm at least 10% higher than in the control arm. Study enrolment is ongoing and over 220 patients were enrolled in the US, EU, and Israel. Enrolment of the full sample size of 400 patients is expected to complete by the end of 2021. Clinical trial information: NCT03398655.

Statistical analysis plan for evaluating different intensities of blood pressure control in the ENhanced Control of Hypertension And Thrombolysis strokE stuDy

2018 ◽  
Vol 14 (5) ◽  
pp. 555-558 ◽  
Author(s):  
Craig S Anderson ◽  
Mark Woodward ◽  
Hisatomi Arima ◽  
Xiaoying Chen ◽  
Richard I Lindley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Body Weight ◽  
Statistical Analysis ◽  
Lower Risk ◽  
Standard Dose ◽  
Statistical Analysis Plan ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Stroke Study

Background The ENhanced Control of Hypertension And Thrombolysis strokE study (ENCHANTED) trial was initiated as a 2 × 2 partial-factorial active-comparison, prospective, randomized, open, blinded endpoint clinical trial to evaluate in thrombolysis-eligible acute ischemic stroke (AIS) patients whether: (1) Arm A – low-dose (0.6 mg/kg body weight) intravenous (iv) alteplase has noninferior efficacy and lower risk of symptomatic intracerebral hemorrhage (sICH) compared with standard-dose (0.9 mg/kg body weight) iv alteplase; and (2) Arm B – early intensive blood pressure (BP) lowering (systolic target 130–140 mmHg) has superior efficacy and lower risk of ICH compared with guideline-recommended BP control (systolic target <180 mmHg). Arm A was completed in 2016; Arm B is now concluding. Objective To outline in detail and make public the predetermined statistical analysis plan (SAP) for the ‘BP control’ arm of this study. Methods All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons to be made between groups are planned and described. Results A SAP was developed for the results of the BP control arm of this study that is transparent, available to the public, verifiable, and predetermined before completion of data collection. Conclusions We have developed a predetermined SAP for the ENCHANTED BP control arm to be followed to avoid analysis bias arising from prior knowledge of the study findings. Clinical trial registration ClinicalTrials.gov (NCT01422616); ISRCTN Register (ISRCTN82387104); Australian New Zealand Clinical Trial Registry (ACTRN12611000236998); EU Clinical Trials Register (2011-005545-12); and Clinical Trials Registry – India (REF/2017/05/014334).

The efficacy and safety of sunitinib in patients with advanced well-differentiated pancreatic neuroendocrine tumors.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 380-380 ◽  
Author(s):  
Eric Raymond ◽  
Matthew H. Kulke ◽  
Shukui Qin ◽  
Michael Schenker ◽  
Antonio Cubillo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neuroendocrine Tumors ◽  
Phase Iii ◽  
Pancreatic Neuroendocrine Tumors ◽  
Pivotal Phase ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Well Differentiated

380 Background: Sunitinib was approved by the FDA in 2011 for treatment of progressive, well-differentiated, advanced pancreatic neuroendocrine tumors (pNETs) based on a pivotal phase III study (NCT00428597) that showed a significant increase in progression-free survival (PFS) over placebo following early study termination. Subsequently, the FDA requested a post-approval study to support these findings. Methods: In this open-label, phase IV clinical trial (NCT01525550), patients with progressive, well-differentiated, unresectable advanced/metastatic pNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study. Primary endpoint was investigator-assessed PFS per RECIST 1.0. This study is ongoing. Results: Sixty one treatment-naïve and 45 previously treated patients with progressive pNETs were treated with sunitinib: mean age, 54.6 years; males, 59.4%; white, 63.2%; ECOG PS 0, 65.1% or PS 1, 34.0%; and prior somatostatin analog, 48.1% (treatment-naïve, 39.3%; previously treated, 60.0%). At the data cutoff date, 82 (77%) patients discontinued treatment, mainly due to disease progression (46%). Median duration of treatment was ~11.9 months. Investigator-assessed median PFS (mPFS) was 13.2 months (95% CI, 10.9–16.7) in the overall population, with comparable mPFS in treatment-naïve and previously treated patients (13.2 vs 13.0 months). mPFS per independent radiologic review was 11.1 months (95% CI, 7.4–16.6). Objective response rate (ORR) per RECIST was 24.5%: 21.3% in treatment-naïve and 28.9% in previously treated patients. Median overall survival, although not yet mature, was 37.8 months. Treatment-emergent, all-causality adverse events (AEs) reported by ≥ 20% of all patients included neutropenia, diarrhea, leukopenia, fatigue, hand–foot syndrome, hypertension, abdominal pain, dysgeusia, and nausea. Most common grade 3/4 AEs were neutropenia (22%) and diarrhea (9%). Conclusions: The mPFS of 13.2 months and ORR of 24.5% observed in this study support the outcomes of the pivotal phase III study of sunitinib in pNETs and confirm its activity in this setting. AEs were consistent with known safety profile of sunitinib. Clinical trial information: NCT01525550.

Study protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial

2020 ◽  
Vol 22 (2) ◽  
pp. 133-141
Author(s):  
Alexis P Poole ◽  
◽  
Mark E Finnis ◽  
James Anstey ◽  
Rinaldo Bellomo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Intensive Care ◽  
Blood Glucose ◽  
Statistical Analysis ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Analysis Plan

BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial — the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial — which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0–14.0 mmol/L) or usual care (target 6.0–10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.

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