Scholars@Duke
Shein-Chung Chow

Shein-Chung Chow

Professor of Biostatistics & Bioinformatics
Biostatistics & Bioinformatics, Division of Biostatistics
sheinchung.chow@duke.edu
Duke Box 2721, Durham, NC 27710
2424 Erwin Road Ste 1102, 11037 Hock Plaza, Durham, NC 27705

Scholarly Works - Journal articles

Power Calculation for Non-inferiority Test Based on Linear Combination of Two Correlated Binary Endpoints.

Journal article Ther Innov Regul Sci · July 2026 In cancer research, multiple primary study endpoints, which may be correlated, are often considered. In practice, it is common to evaluate each clinical endpoint separately when performing sample size calculations. However, when the endpoints are correlate ... Full text Link to item Cite

The pyruvate kinase activator etavopivat (FT-4202) limits pulmonary and systemic sequelae of sepsis in a mouse LPS model.

Journal article Am J Physiol Lung Cell Mol Physiol · June 1, 2026 Sepsis is frequently characterized by abnormal O2 uptake by red blood cells (RBCs) in the lung and/or dysregulated tissue O2 delivery by RBCs. New approaches are needed to improve O2 transport and clinical outcomes in sepsis with or without anemia. FT-4202 ... Full text Open Access Link to item Cite

Acupuncture for acute musculoskeletal pain in the emergency department and clinic: a pragmatic randomized trial.

Journal article Pain Med · May 1, 2026 BACKGROUND: cute musculoskeletal pain in emergency department (ED) patients is challenging to treat with medications alone, but adding acupuncture may improve pain outcomes. METHODS: In this pragmatic randomized controlled trial, acupuncture was delivered ... Full text Link to item Cite

Switching Design for Assessment of Interchangeability in Biosimilar Studies.

Journal article Pharmaceutics · January 31, 2026 Background: In biosimilar studies, assessing the switchability and interchangeability of biosimilars with their reference products is essential for ensuring reliable clinical evaluation. This study explores optimal trial design strategies incorporating bal ... Full text Link to item Cite

Bioequivalence Assessment for Intranasal Rapid-Acting Drug Products.

Journal article J Clin Pharmacol · January 2026 Bioequivalence assessment is critical for generic drug approval, but conventional bioequivalent criteria for identical formulations and routes may not be suitable for cross-route comparisons, especially for rapid-acting drugs. Intranasal formulations provi ... Full text Link to item Cite

Controversial issues in clinical investigation of rare disease drug development

Journal article Journal of Biopharmaceutical Statistics · January 1, 2026 For rare disease drug development, a single-stage hypothesis testing procedure is often considered for clinical investigation regarding safety and efficacy of a test treatment study. Under the hypothesis testing framework, “p-value less than 0.05 with at l ... Full text Cite

A Hybrid Design Incorporating External Data to Evaluate Dexamethasone Intracameral Drug Delivery Suspension for Post-Cataract Surgery Inflammation.

Journal article Clin Pharmacol Ther · December 2025 Traditional randomized controlled trials (RCTs) face increasing challenges due to lengthy recruitment and high costs. Regulators have encouraged the use of external data and real-world evidence (RWE) to improve efficiency, yet adoption in confirmatory sett ... Full text Link to item Cite

A bayesian dynamic borrowing framework for improving the efficiency of clinical trials.

Journal article BMC Med Res Methodol · October 27, 2025 PURPOSE: To develop a Bayesian method for dynamic borrowing of information from historical clinical trials and real-world data that has the potential to improve the efficiency of clinical trials. METHODS: We propose a novel statistical metric to quantify h ... Full text Link to item Cite

Use of alternative and confirmatory data in support of rare disease drug development.

Journal article J Biopharm Stat · October 2025 Recently, the use of alternative and confirmatory data in support of rare disease drug development has received much attention (NASEM 2024). This article attempts to provide an overview regarding the limitations and major challenges of the use of ACD that ... Full text Link to item Cite

The role of regulatory flexibility in the review and approval process of rare disease drug development.

Journal article J Biopharm Stat · October 2025 The role of regulatory flexibility in the review and approval process of rare disease drug and biologics development was recently studied by a Consensus Committee of the National Academy of Sciences, Engineering and Medicine (NASEM 2024). In this article, ... Full text Link to item Cite

Application of complete N-of-1 trial design in bioequivalence-biosimilar drug development.

Journal article J Biopharm Stat · October 2025 Biosimilars play a crucial role in increasing the accessibility and affordability of biological therapies; thus, precise and reliable assessment methods are essential for their regulatory approval and clinical adoption. Currently, the 2-sequence 2-period c ... Full text Link to item Cite

A Statistical Method for Benefit-Risk Assessment in Clinical Trials.

Journal article Stat Med · August 2025 In recent years, benefit-risk assessment (BRA) has become a crucial tool in guiding regulatory decisions regarding the safety and efficacy of investigational treatments. Following the FDA's recent guidance on the BRA, we statistically develop a confidence ... Full text Link to item Cite

An App Platform-Facilitated Collaborative Palliative Care Intervention for Outpatients With Interstitial Lung Disease: A Pilot Randomized Trial.

Journal article Am J Hosp Palliat Care · July 2025 Rationale: Outpatients with interstitial lung disease often experience serious symptoms, yet infrequently receive palliative care. Objective: To determine the feasibility and clinical impact of a mobile application (PCplanner) in an outpatient setting. Met ... Full text Link to item Cite

Development of Composite Index in Psychiatry Clinical Trial.

Journal article Ther Innov Regul Sci · July 2025 In psychiatry clinical trials, a validated instrument (or questionnaire) which consists of a number of questions (or items) is often used for evaluation of the safety and efficacy of a test treatment under investigation. This approach based on rating scale ... Full text Link to item Cite

Study Protocol: Single-Blinded, Controlled, Clinical Trial Evaluating the Feasibility of Spinal Cord Stimulation for Improving Neuropathic Pain and Rehabilitation Outcomes in Patients With Thoracic Spinal Cord Injury.

Journal article Neurosurg Pract · June 2025 BACKGROUND AND OBJECTIVES: Traumatic thoracic spinal cord injury (SCI) is complicated by chronic neuropathic pain and neurological deficits including bowel and bladder dysfunction. Treatment with spinal cord stimulation (SCS) has demonstrated possible util ... Full text Link to item Cite

A Proposed Confidence Ellipse Approach for Benefit-Risk Assessment in Clinical Trials.

Journal article Ther Innov Regul Sci · May 2025 In clinical development, an independent data safety monitoring committee (IDMC) is often established to ensure the test treatment's integrity, quality, safety, and efficacy under investigation. In clinical trials, IDMC may recommend stopping the trial earl ... Full text Link to item Cite

Correlation between lumbar puncture opening pressure and venous sinus pressure gradient in idiopathic intracranial hypertension (IIH).

Journal article Interv Neuroradiol · April 24, 2025 BackgroundVenous hypertension has become a recognized condition associated with idiopathic intracranial hypertension (IIH). Thresholds for dural venous sinus stenting (VSS) remain a topic of debate.MethodsIn 50 IIH patients, the lumbar puncture opening pre ... Full text Link to item Cite

Comparison of single- versus multi-drug treatment for intra-arterial chemotherapy (IAC) in children with retinoblastoma.

Journal article Interv Neuroradiol · March 26, 2025 ObjectiveIntra-arterial chemotherapy (IAC) is a well-established treatment for retinoblastoma (RB). However, there are no standardized recommendations regarding the choice of drugs. This study compares the outcomes of single- versus multi-drug therapy.Meth ... Full text Link to item Cite

Alcohol Relapse After Liver Transplantation: Risk Factors, Outcomes, and a Comparison of Risk Stratification Models.

Journal article Gastro Hep Adv · 2025 BACKGROUND AND AIMS: Alcohol-related liver disease is a leading cause of liver transplantation (LT) in the United States; however, alcohol relapse remains a risk, and real-world assessment of relapse prediction scores is lacking. The primary aim of this st ... Full text Link to item Cite

Sequential Adaptive Design Method for Incorporating External Data.

Journal article Biom J · December 2024 External data (e.g., real-world data (RWD) and historical data) have become more readily available. This has led to rapidly increasing interest in exploring and evaluating ways of utilizing external data to facilitate traditional clinical trials (TCT), esp ... Full text Link to item Cite

Assessing Protein Content and Dimer Formation in the Bevacizumab Reference Product and Biosimilar Versions Marketed in Spain

Journal article Pharmaceutics · December 1, 2024 Background: The manufacture of biologics is a complex, controlled, and reproducible process that results in a product that meets specifications. This should be based on data from batches used to demonstrate manufacturing consistency. Ten batches of origina ... Full text Cite

The use of real-world data for clinical investigation of effectiveness in drug development.

Journal article Journal of biopharmaceutical statistics · October 2024 With the growing interest in leveraging real-world data (RWD) to support effectiveness evaluations for new indications, new target populations, and post-market performance, the United States Food and Drug Administration has published several guidance docum ... Full text Cite

On the use of RWD in support of regulatory submission in drug development.

Journal article Journal of biopharmaceutical statistics · October 2024 For the approval of a drug product, the United States Food and Drug Administration requires substantial evidence (SE) regarding effectiveness and safety of the test drug to be provided. In recent years, the use of real-world data in support of regulatory s ... Full text Cite

Analysis of innovative two-stage seamless adaptive design with different endpoints and population shift.

Journal article Journal of biopharmaceutical statistics · October 2024 In recent years, clinical trials utilizing a two-stage seamless adaptive trial design have become very popular in drug development. A typical example is a phase 2/3 adaptive trial design, which consists of two stages. As an example, stage 1 is for a phase ... Full text Cite

Utility of real-world evidence in biosimilar development.

Journal article J Biopharm Stat · October 2024 Biosimilar development refers to the process of creating a biologic drug that is similar to an existing approved biologic drug, also known as a reference drug. Due to the complex nature of biologics drugs and the inherent variability in their manufacturing ... Full text Link to item Cite

An Adaptive Pragmatic Randomized Controlled Trial of Emergency Department Acupuncture for Acute Musculoskeletal Pain Management.

Journal article Ann Emerg Med · October 2024 STUDY OBJECTIVE: Acute musculoskeletal pain in emergency department (ED) patients is frequently severe and challenging to treat with medications alone. The purpose of this study was to determine the feasibility, acceptability, and effectiveness of adding E ... Full text Link to item Cite

Statistical Analysis for Rating Scale in Clinical Trials.

Journal article Ther Innov Regul Sci · September 2024 In psychiatry clinical trials, an instrument or questionnaire with rating scale is often used to access safety and efficacy of a test treatment under investigation. Statistical analysis based on the collected rating scale is then performed a determine whet ... Full text Link to item Cite

A landscape of methodology and implementation of adaptive designs in cancer clinical trials.

Journal article Crit Rev Oncol Hematol · August 2024 BACKGROUND: The use of adaptive designs in cancer trials has considerably increased worldwide in recent years, along with the release of various guidelines for their application. This systematic review aims to comprehensively summarize the key methodologic ... Full text Link to item Cite

Determining the extent and frequency of on-site monitoring: a bayesian risk-based approach.

Journal article BMC Med Res Methodol · June 28, 2024 BACKGROUND: On-site monitoring is a crucial component of quality control in clinical trials. However, many cast doubt on its cost-effectiveness due to various issues, such as a lack of monitoring focus that could assist in prioritizing limited resources du ... Full text Link to item Cite

Ratios of head circumference to ventricular size vary over time and predict eventual need for CSF diversion in intraventricular hemorrhage of prematurity.

Journal article Childs Nerv Syst · March 2024 PURPOSE: Intraventricular hemorrhage (IVH) of prematurity can lead to hydrocephalus, sometimes necessitating permanent cerebrospinal fluid (CSF) diversion. We sought to characterize the relationship between head circumference (HC) and ventricular size in I ... Full text Open Access Link to item Cite

At home adaptive dual target deep brain stimulation in Parkinson's disease with proportional control.

Journal article Brain · March 1, 2024 Continuous deep brain stimulation (cDBS) of the subthalamic nucleus (STN) or globus pallidus is an effective treatment for the motor symptoms of Parkinson's disease. The relative benefit of one region over the other is of great interest but cannot usually ... Full text Link to item Cite

Novel Design and Analysis for Rare Disease Drug Development

Journal article Mathematics · March 1, 2024 For rare disease drug development, the United States (US) Food and Drug Administration (FDA) has indicated that the same standards as those for drug products for common conditions will be applied. To assist the sponsors in rare disease drug development, th ... Full text Cite

Risk Factors for Invasive Fungal Infection in Lung Transplant Recipients on Universal Antifungal Prophylaxis.

Journal article Open Forum Infect Dis · February 2024 BACKGROUND: Many centers use universal antifungal prophylaxis after lung transplant, but risk factors for invasive fungal infection (IFI) in this setting are poorly described. METHODS: This retrospective, single-center cohort study including 603 lung trans ... Full text Open Access Link to item Cite

Mapping of Subjective Measurements in Traditional Chinese Medicine to Objective Clinical Endpoints in Western Medicine.

Journal article Biologics · 2024 INTRODUCTION: The translation of traditional Chinese medicine (TCM), which is experience-based, into evidence-based frameworks of Western medicine poses significant challenges due to differences in conceptualization, diagnosis, and evaluation methodologies ... Full text Link to item Cite

Comparison of Innovative and Conventional Methods in Biosimilar Bridging Studies with Multiple References

Journal article Biologics Targets and Therapy · January 1, 2024 For assessment of biosimilar drug products, if there are multiple-reference products (eg, a US-licensed product and an EU-approved product), a biosimilar bridging study with a 3-way pairwise comparison is often conducted. In our paper, two innovative metho ... Full text Cite

Group Versus Individual Rehabilitation in Lung Transplantation: A Retrospective Noninferiority Assessment.

Journal article Cardiopulm Phys Ther J · January 2024 PURPOSE: Pulmonary rehabilitation both before and after lung transplant is associated with improved functional exercise capacity and physical quality of life. There is wide variation in rehabilitation program provision. This study's aim was to compare the ... Full text Link to item Cite

Two-Year Clinical and Radiographic Outcomes for Percutaneous Lumbar Interbody Fusion With an Expandable Titanium Cage Through Kambin's Triangle Without Facetectomy.

Journal article Int J Spine Surg · December 26, 2023 BACKGROUND: There has been heightened interest in performing percutaneous lumbar interbody fusions (percLIFs) through Kambin's triangle, an anatomic corridor allowing entrance into the disc space. However, due to its novelty, there are limited data regardi ... Full text Open Access Link to item Cite

Statistical Evaluation of Responder Analysis in Stem Cell Clinical Trials.

Journal article Ther Innov Regul Sci · November 2023 BACKGROUND: In evaluating treatment efficacy, there is an ongoing discussion about which endpoint is more efficient to represent the treatment effect. Absolute change (AC) is the difference between before and after treatment, while relative change (RC) is ... Full text Link to item Cite

Prevention of contamination after endotracheal intubation using a dedicated sleeve.

Journal article J Thorac Dis · September 28, 2023 BACKGROUND: Contamination of work surfaces by used laryngoscopes after endotracheal intubation is a serious infection control concern but no strategies are available to address it. We assessed if contamination of the surfaces after endotracheal intubation ... Full text Link to item Cite

Innovative thinking of clinical investigation for rare disease drug development.

Journal article Orphanet J Rare Dis · September 22, 2023 For the development of a test treatment or drug product, it is necessary to conduct composite hypothesis testing to test for effectiveness and safety simultaneously, since some approved drug products have been recalled due to safety concerns. One of the ma ... Full text Link to item Cite

Evidence of pre-approval clinical trial supporting the granted conditional approval for novel cancer drugs in China between 2015 and 2022.

Journal article EClinicalMedicine · September 2023 BACKGROUND: Accelerated approval (AA) of novel anticancer drugs based on surrogacy has attracted considerable concern globally. China National Medical Products Administration (NMPA) also established a similar conditional approval (CA) program to accelerate ... Full text Link to item Cite

Evaluation of clinical trial designs for novel anticancer drugs in China: A cohort study of drugs approved between 2015 and 2021.

Journal article Drug Discov Today · June 2023 China has greatly facilitated the approval of many novel anticancer drugs since the drug regulatory reform in 2015. Here, we review the clinical trial designs used in pivotal clinical trials for approved anticancer agents in China from 2015 to 2021. Overal ... Full text Link to item Cite

MyKidneyCoach, Patient Activation, and Clinical Outcomes in Diverse Kidney Transplant Recipients: A Randomized Control Pilot Trial.

Journal article Transplant Direct · April 2023 UNLABELLED: Kidney transplant (KT) recipients who are not actively engaged in their care and lack self-management skills have poor transplant outcomes, which are disproportionately observed among Black KT recipients. This pilot study aimed to determine whe ... Full text Link to item Cite

A Proposal for Post Hoc Subgroup Analysis in Support of Regulatory Submission.

Journal article Ther Innov Regul Sci · March 2023 BACKGROUND: In clinical trials, it is not uncommon that the primary analysis fails to achieve the study objective for demonstrating the safety and efficacy of a test treatment under investigation, while a specific sub-population analysis shows a significan ... Full text Open Access Link to item Cite

The price, efficacy, and safety of within-class targeted anticancer medicines between domestic and imported drugs in China: a comparative analysis.

Journal article Lancet Reg Health West Pac · March 2023 BACKGROUND: Affordability to novel anticancer drugs has become a major health issue in China. It is encouraging to note that China initiated its drug regulatory reform and national price negotiation policies since 2015. As a growing number of domestic with ... Full text Link to item Cite

Statistical tests for detecting reference product change in biosimilar studies

Journal article Gabi Journal · January 1, 2023 For the biosimilarity assessment between a test product and a reference product, the US Food and Drug Administration (FDA) recommends a stepwise approach for obtaining totality-of-the-evidence in support of regulatory approval of the submission. The stepwi ... Full text Cite

Acupuncture for acute musculoskeletal pain management in the emergency department and continuity clinic: a protocol for an adaptive pragmatic randomised controlled trial.

Journal article BMJ Open · September 23, 2022 INTRODUCTION: Chronic musculoskeletal pain causes a significant burden on health and quality of life and may result from inadequate treatment of acute musculoskeletal pain. The emergency department (ED) represents a novel setting in which to test non-pharm ... Full text Link to item Cite

Efficacy of Transcendental Meditation to Reduce Stress Among Health Care Workers: A Randomized Clinical Trial.

Journal article JAMA Netw Open · September 1, 2022 IMPORTANCE: Health care workers (HCWs) have been experiencing substantial stress and burnout, and evidence-based mitigation strategies are needed. Transcendental Meditation (TM) is a mantra meditation practice with potential efficacy in reducing stress. OB ... Full text Open Access Link to item Cite

Statistical Evaluation of Absolute Change versus Responder Analysis in Clinical Trials.

Journal article Acta Mater Med · July 21, 2022 In clinical trials, the primary analysis is often either a test of absolute/relative change in a measured outcome or a corresponding responder analysis. Though each of these tests may be reasonable, determining which test is most suitable for a particular ... Full text Link to item Cite

A Time-response Measure to Assess Clinical Equivalence in Rheumatoid Arthritis: an Assessment Using Data From Clinical Trials of Biosimilars

Journal article Statistics in Biopharmaceutical Research · January 1, 2022 Because of structural complexity, a “biosimilar” will not be exactly the same as its reference biologic treatment, but is required to be equivalent in all relevant attributes, including efficacy. Therapeutic equivalence is often assessed at a single time p ... Full text Cite

On statistical evaluation for interchangeability of biosimilar products

Journal article Gabi Journal · January 1, 2022 Abiosimilar product is a biological product which is highly similar to an existing reference product in structure and function and has no clinically meaningful difference in terms of safety, purity or potency. Under the Biologics Price Competition and Inno ... Full text Cite

Sample size re-estimation in clinical trials.

Journal article Stat Med · November 30, 2021 In clinical trials, sample size re-estimation is often conducted at interim. The purpose is to determine whether the study will achieve study objectives if the observed treatment effect at interim preserves till end of the study. A traditional approach is ... Full text Link to item Cite

Innovative Design and Analysis for PK/PD Biosimilar Bridging Studies with Multiple References.

Journal article AAPS J · November 30, 2021 When there are multiple reference products, (e.g., EU-approved product and US-licensed product), a pharmacokinetic/pharmacodynamic (PK/PD) bridging study is often conducted in order to bridge the clinical data from the original region (e.g., Europe) to the ... Full text Link to item Cite

Review of current controversial issues in clinical trials

Journal article General Psychiatry · October 27, 2021 In clinical development, adequate and well-controlled randomised clinical trials are usually conducted to evaluate the safety and efficacy of test treatment under investigation. The purpose is to ensure that there is an accurate and reliable assessment of ... Full text Open Access Cite

The use of real-world data/evidence in regulatory submissions.

Journal article Contemp Clin Trials · October 2021 The 21st Century Cures Act passed by the United States (US) Congress in December 2016 requires the US Food and Drug Administration (FDA) shall establish a program to evaluate the potential use of real-world evidence (RWE) which is generated from real-world ... Full text Link to item Cite

Sex and Menopause Modify the Effect of Single Nucleotide Polymorphism Genotypes on Fibrosis in NAFLD.

Journal article Hepatol Commun · April 2021 The development of fibrosis in nonalcoholic fatty liver disease (NAFLD) is influenced by genetics, sex, and menopausal status, but whether genetic susceptibility to fibrosis is influenced by sex and reproductive status is unclear. Our aim was to identify m ... Full text Link to item Cite

Current Issues in Analytical Similarity Assessment

Journal article Statistics in Biopharmaceutical Research · January 1, 2021 In 2017, Food and Drug Administration (FDA) circulated a draft guidance on analytical similarity assessment to assist the sponsors for providing totality-of-the-evidence in support of the demonstration of biosimilarity between a proposed biosimilar product ... Full text Cite

Statistical Evaluation of Clinical Trials Under COVID-19 Pandemic.

Journal article Ther Innov Regul Sci · November 2020 When conducting clinical trials under COVID-19 pandemic, protocol deviations and/or protocol violations are inevitably encountered due to possible environment change which may have an impact on the accuracy and reliability of clinical evaluation of the tes ... Full text Link to item Cite

Innovative design and analysis for rare disease drug development.

Journal article J Biopharm Stat · May 3, 2020 One of the most challenges for rare diseases drug development is probably the availability of subjects with the diseases under a small patient population. It is then a great concern how to conduct clinical trials with the limited number of subjects availab ... Full text Link to item Cite

Unified approaches to assessing treatment effect of traditional Chinese medicine based on health profiles.

Journal article J Biopharm Stat · May 3, 2020 Two dissimilarity indices are introduced to measure the disharmony of a human body system by mimicking the population bioequivalence and the individual bioequivalence concepts. Hypotheses for the treatment effect of a traditional Chinese medicine are formu ... Full text Link to item Cite

Some thoughts on the QR method for analytical similarity evaluation.

Journal article J Biopharm Stat · May 3, 2020 As indicated in a recent published draft guidance on comparative analytical assessment, the United States (US) Food and Drug Administration (FDA) seems to suggest the use of quality range (QR) method for analytical similarity evaluation. It is a concern th ... Full text Link to item Cite

Use of left atrial appendage occlusion among older cardiac surgery patients with preoperative atrial fibrillation: a national cohort study.

Journal article J Interv Card Electrophysiol · April 2020 PURPOSE: Patients with atrial fibrillation (AF) undergoing cardiac surgery are at substantially increased risk for stroke. Increasing evidence has suggested that surgical left atrial appendage occlusion (S-LAAO) may have the potential to substantially miti ... Full text Link to item Cite

Tenofovir versus entecavir in lowering the risk of hepatocellular carcinoma development in patients with chronic hepatitis B: a critical systematic review and meta-analysis.

Journal article Hepatol Int · January 2020 BACKGROUND: Controversy exists on whether tenofovir disoproxil fumarate (TDF) is superior to entecavir (ETV) in lowering the risk of hepatocellular carcinoma (HCC) development. This meta-analysis was performed to clarify this issue with critical clinical a ... Full text Link to item Cite

Prior tonsillectomy is associated with an increased risk of esophageal adenocarcinoma.

Journal article PLoS One · 2020 BACKGROUND: Esophageal cancer is a deadly cancer with 5-year survival <20%. Although multiple risk factors for esophageal adenocarcinoma (EAC) including obesity, GERD and smoking have been identified, these risk factors do not fully explain the rising inci ... Full text Link to item Cite

Design and Analysis of Biosimilar Switching Studies.

Journal article Pharmaceut Med · October 2019 Under the US Biologics Price Competition and Innovation Act of 2009 (BPCI), the development of biosimilar (test) products provides affordable alternatives to innovative biological (reference) products for the general patient population. However, in practic ... Full text Link to item Cite

Practical Issues in Clinical Inspection Process.

Journal article Ther Innov Regul Sci · May 2019 Regulatory inspection of clinical trial is necessary in order for (1) assessing compliance with statutory requirements and regulatory requirement governing the conduct of clinical trials and (2) verifying the accuracy and reliability of clinical trial data ... Full text Link to item Cite

Inconsistencies in Colonic Tattooing Practice: Differences in Reported and Actual Practices at a Tertiary Medical Center.

Journal article South Med J · April 2019 OBJECTIVES: Accurate localization of a colonic lesion is crucial to successful resection. Although colonic tattooing is a widely accepted technique to mark lesions for future identification surgery or repeat colonoscopy, no consensus guidelines exist. The ... Full text Open Access Link to item Cite

Interim analysis of binary outcome data in clinical trials: a comparison of five estimators.

Journal article J Biopharm Stat · 2019 In clinical trials, where the outcome of interest is the occurrence of an event over a fixed time period, estimation of the event proportion at interim analysis can form a basis for decision-making such as early trial termination, sample size re-estimation ... Full text Open Access Link to item Cite

Innovative Thinking on Endpoint Selection in Clinical Trials.

Journal article J Biopharm Stat · 2019 In clinical trials, selection of appropriate study endpoints is critical for an accurate and reliable evaluation of safety and effectiveness of a test treatment under investigation. In practice, however, there are usually multiple endpoints available for m ... Full text Link to item Cite

Statistical considerations for rare diseases drug development.

Journal article J Biopharm Stat · 2019 One of the most challenges for rare disease clinical trials is probably the availability of a small patient population. It is then a great concern on how to conduct clinical trials with a small number of subjects available for obtaining substantial evidenc ... Full text Link to item Cite

Probability monitoring procedures for sample size determination.

Journal article J Biopharm Stat · 2019 In clinical research, power analysis is often performed for sample size calculation. The purpose is to achieve a desired power of correctly detecting a clinically meaningful difference at a pre-specified level of significance if such a difference truly exi ... Full text Link to item Cite

The use of 95% CI or 90% CI for drug product development - a controversial issue?

Journal article J Biopharm Stat · 2019 For review and approval of drug products, a 95% confidence interval approach for evaluation of new drugs is commonly used, while a 90% confidence interval approach is considered for assessment of generic drugs and biosimilar products. In the past decade, F ... Full text Link to item Cite

Demonstrating effectiveness or demonstrating not ineffectiveness - A potential solution for rare disease drug product development?

Journal article J Biopharm Stat · 2019 For review and approval of new drug products, substantial evidence regarding safety and effectiveness of the drug products under investigation are necessarily provided. A traditional approach is to test a null hypothesis of ineffectiveness against an alter ... Full text Link to item Cite

Criteria for dose-finding in two-stage seamless adaptive design.

Journal article J Biopharm Stat · 2019 In pharmaceutical/clinical development, two-stage seamless adaptive designs are commonly considered. Such designs include a two-stage phase I/II or phase II/III adaptive trial that combines one phase IIb study for dose-finding or treatment selection and on ... Full text Link to item Cite

Simultaneous confidence interval methods for analytical similarity assessment.

Journal article J Biopharm Stat · 2019 In analytical similarity assessment of a biosimilar product, key quality attributes of the test and reference products need to be shown statistically similar. When there were multiple references, similarity among the reference products is also required. We ... Full text Link to item Cite

Helicobacter pylori-associated peptic ulcer disease: A retrospective analysis of post-treatment testing practices.

Journal article Helicobacter · December 2018 BACKGROUND & AIMS: Guidelines recommend that patients with Helicobacter pylori (H. pylori)-associated peptic ulcer disease (PUD) receive H. pylori eradication therapy followed by post-treatment testing to prove eradication; however, post-treatment testing ... Full text Link to item Cite

The impact of human leukocyte antigen donor and recipient serotyping and matching on liver transplant graft failure in primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cholangitis.

Journal article Clin Transplant · October 2018 Human leukocyte antigen (HLA) serotyping is not considered to have significant impact on liver graft survival and does not factor into U.S. organ allocation. Immune-related liver diseases such as primary sclerosing cholangitis (PSC), autoimmune hepatitis ( ... Full text Link to item Cite

A visual analysis of network pharmacology research trends

Journal article World Journal of Traditional Chinese Medicine · October 1, 2018 To understand the current situation of network pharmacology, and to analyze external and internal characteristics of literature, is of great significance for the development of network pharmacology in the future and its application in the modernization of ... Full text Cite

Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.

Journal article JAMA · September 25, 2018 IMPORTANCE: The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. OBJECTIVE: To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without in ... Full text Open Access Link to item Cite

Gastroesophageal reflux symptoms are not sufficient to guide esophageal function testing in lung transplant candidates.

Journal article Dis Esophagus · May 1, 2018 Gastroesophageal reflux disease and esophageal dysmotility are prevalent in patients with advanced lung disease and are associated with graft dysfunction following lung transplantation. As a result, many transplant centers perform esophageal function testi ... Full text Open Access Link to item Cite

Association Between Left Atrial Appendage Occlusion and Readmission for Thromboembolism Among Patients With Atrial Fibrillation Undergoing Concomitant Cardiac Surgery.

Journal article JAMA · January 23, 2018 IMPORTANCE: The left atrial appendage is a key site of thrombus formation in atrial fibrillation (AF) and can be occluded or removed at the time of cardiac surgery. There is limited evidence regarding the effectiveness of surgical left atrial appendage occ ... Full text Link to item Cite

On evaluation of consistency in multi-regional clinical trials.

Journal article J Biopharm Stat · 2018 In recent years, multi-regional clinical trials (MRCT) that conduct clinical trials simultaneously in Asian Pacific region, Europe, and the United States have become very popular for global pharmaceutical development. The main purpose of multi-regional cli ... Full text Link to item Cite

Direct-Acting Antivirals Improve Access to Care and Cure for Patients With HIV and Chronic HCV Infection.

Journal article Open Forum Infect Dis · January 2018 BACKGROUND: Direct-acting antivirals (DAA) as curative therapy for hepatitis C virus (HCV) infection offer >95% sustained virologic response (SVR), including in patients with human immunodeficiency virus (HIV) infection. Despite improved safety and efficac ... Full text Open Access Link to item Cite

On sample size requirement for analytical similarity assessment.

Journal article J Biopharm Stat · 2018 For approval of biosimilar products, the U.S. Food and Drug Administration (FDA) recommends a stepwise approach for obtaining the totality-of-the-evidence for assessing biosimilarirty between a proposed biosimilar product and its corresponding innovative ( ... Full text Link to item Cite

Statistical Methods for Conditional Survival Analysis.

Journal article J Biopharm Stat · 2018 We investigate the survival distribution of the patients who have survived over a certain time period. This is called a conditional survival distribution. In this paper, we show that one-sample estimation, two-sample comparison and regression analysis of c ... Full text Link to item Cite

Differences in Phenotypes and Liver Transplantation Outcomes by Age Group in Patients with Primary Sclerosing Cholangitis.

Journal article Dig Dis Sci · November 2017 BACKGROUND: There is increasing evidence for a heterogeneity of phenotypes in primary sclerosing cholangitis (PSC), but differences across the age spectrum in adults with PSC have not been well characterized. AIMS: To characterize phenotypic variations and ... Full text Link to item Cite

Analytical similarity assessment

Journal article Wiley Interdisciplinary Reviews Computational Statistics · November 1, 2017 For regulatory review and approval of biosimilar products, the United States (US) Food and Drug Administration (FDA) recommended a stepwise approach for demonstrating biosimilarity between a proposed biosimilar product and an innovative (reference) biologi ... Full text Cite

Clinical endpoints and adaptive clinical trials in precirrhotic nonalcoholic steatohepatitis: Facilitating development approaches for an emerging epidemic.

Journal article Hepatol Commun · September 2017 Due to the increasing prevalence of nonalcoholic steatohepatitis (NASH) and its associated health burden, there is a high need to develop therapeutic strategies for patients with this disease. Unfortunately, its long and asymptomatic natural history, the u ... Full text Link to item Cite

On assessing bioequivalence and interchangeability between generics based on indirect comparisons.

Journal article Stat Med · August 30, 2017 As more and more generics become available in the market place, the safety/efficacy concerns may arise as the result of interchangeably use of approved generics. However, bioequivalence assessment for regulatory approval among generics of the innovative dr ... Full text Link to item Cite

Complementary and Alternative Medicine Use in United States Adults With Liver Disease.

Journal article J Clin Gastroenterol · July 2017 GOALS: To describe the complementary and alternative medicine (CAM) use in US adults with liver disease. BACKGROUND: The prevalence and patterns of CAM use among US adults with liver disease have not been well characterized. The 2012 National Health Interv ... Full text Link to item Cite

Outcomes of liver retransplantation in patients with primary sclerosing cholangitis.

Journal article Liver Transpl · June 2017 Liver retransplantation in patients with primary sclerosing cholangitis (PSC) has not been well studied. The aims of this study were to characterize patients with PSC listed for and undergoing retransplantation and to describe the outcomes in these patient ... Full text Link to item Cite

Assessing bioequivalence and drug interchangeability.

Journal article J Biopharm Stat · 2017 As indicated by the US Food and Drug Administration (FDA), approved generic drug products can be used as substitutes for their respective innovative drug products. The FDA, however, does not indicate that two generic copies of the same innovative drug can ... Full text Link to item Cite

On the establishment of equivalence acceptance criterion in analytical similarity assessment.

Journal article J Biopharm Stat · 2017 For the assessment of biosimilarity of biosimilar products, the United States (US) Food and Drug Administration (FDA) proposed a stepwise approach for providing the totality-of-the-evidence of similarity between a proposed biosimilar product and a US-licen ... Full text Link to item Cite

On the evaluation of reliability, repeatability, and reproducibility of instrumental evaluation methods and measurement systems.

Journal article J Biopharm Stat · 2017 Validation of instrumental evaluation methods or measurement systems plays an important role in both pharmaceutical and cosmetic research and development. In practice, it is suggested that validation should be performed according to performance characteris ... Full text Link to item Cite

On safety margin for drug interchangeability.

Journal article J Biopharm Stat · 2017 As more and more generic (or biosimilar) drug products become available in the market place, it is a concern whether the approved generic (or biosimilar) drug products are safe and efficacious and hence can be used interchangeably. According to current reg ... Full text Link to item Cite

Sample size requirement in analytical studies for similarity assessment.

Journal article J Biopharm Stat · 2017 For the assessment of biosimilar products, the FDA recommends a stepwise approach for obtaining the totality-of-the-evidence for assessing biosimilarity between a proposed biosimilar product and its corresponding innovative biologic product. The stepwise a ... Full text Link to item Cite

On hybrid parallel-crossover designs for assessing drug interchangeability of biosimilar products.

Journal article J Biopharm Stat · 2017 In recent years, a specific hybrid parallel-crossover design that consists of two sequences of treatments, namely R-R-R-R and R-T-R-T, where T and R is a proposed biosimilar product and an innovative biological product, respectively, have been proposed and ... Full text Link to item Cite

Statistical evaluation of the scaled criterion for drug interchangeability.

Journal article J Biopharm Stat · 2017 As more and more generic drug products become available in the marketplace, it is a concern whether these generic drug products can be used interchangeably in terms of their quality, safety, and efficacy. The United States Food and Drug Administration (FDA ... Full text Link to item Cite

Clinical Performance of Prediction Rules and Nasogastric Lavage for the Evaluation of Upper Gastrointestinal Bleeding: A Retrospective Observational Study.

Journal article Gastroenterol Res Pract · 2017 Introduction. The majority of patients with acute upper gastrointestinal bleeding (UGIB) are admitted for urgent endoscopy as it can be difficult to determine who can be safely managed as an outpatient. Our objective was to compare four clinical prediction ... Full text Link to item Cite

Female gender lost protective effect against disease progression in elderly patients with chronic hepatitis B.

Journal article Sci Rep · November 28, 2016 Female gender and younger age are protective factors against disease progression in chronic hepatitis B (CHB). However, it is not clear whether the disease progression still remains slow in elderly females. This study investigated the interaction of female ... Full text Link to item Cite

Characterization of Simian Immunodeficiency Virus Variants Anatomically Compartmentalized in Plasma and Milk in Chronically Infected African Green Monkeys.

Journal article J Virol · October 1, 2016 UNLABELLED: Unlike human immunodeficiency virus type 1 (HIV-1)-infected humans, African-origin, natural simian immunodeficiency virus (SIV) hosts, such as African green monkeys (AGMs), sustain nonpathogenic SIV infections and rarely vertically transmit SIV ... Full text Link to item Cite

The Diagnostic Yield of Repeated Endoscopic Evaluation in Patients with Gastrointestinal Bleeding and Left Ventricular Assist Devices.

Journal article Dig Dis Sci · June 2016 INTRODUCTION: Left ventricular assist devices (LVADs) are increasingly common in patients with advanced heart failure. GI bleeding (GIB) occurs in 20-30 % of these patients and can arise anywhere in the GI tract. Given the high rates of GIB in this populat ... Full text Link to item Cite

Analytical Similarity Assessment in Biosimilar Studies.

Journal article AAPS J · May 2016 For assessment of biosimilarity, the US Food and Drug Administration (FDA) recommends a stepwise approach for obtaining the totality-of-the-evidence for demonstrating biosimilarity between a proposed biosimilar product and an innovative (reference) biologi ... Full text Link to item Cite

On sample size estimation and re-estimation adjusting for variability in confirmatory trials.

Journal article J Biopharm Stat · 2016 Sample size estimation (SSE) is an important issue in the planning of clinical studies. While larger studies are likely to have sufficient power, it may be unethical to expose more patients than necessary to answer a scientific question. Budget considerati ... Full text Link to item Cite

Coronary artery disease risk reduction in HIV-infected persons: a comparative analysis.

Journal article AIDS Care · 2016 Despite an increased risk of coronary artery disease (CAD) in persons infected with human immunodeficiency virus (HIV), few data are available on primary prevention of CAD in this population. In this retrospective cohort study, HIV-infected patients treate ... Full text Link to item Cite

Some thoughts on drug interchangeability.

Journal article J Biopharm Stat · 2016 Current regulation for generic approval is based on the assessment of average bioequivalence. As indicated by the United States Food and Drug Administration (FDA), an approved generic drug can be used as a substitute for the innovative drug. FDA does not i ... Full text Link to item Cite

On controversial statistical issues in clinical research

Journal article Open Access Journal of Clinical Trials · May 2, 2015 In clinical development of a test treatment under investigation, clinical trials are often conducted for evaluation of safety and efficacy of the test treatment. To provide an accurate and reliable assessment, adequate and well-controlled clinical trials u ... Full text Cite

Antiretroviral Effects on Host Lipoproteins Are Associated With Changes in Hepatitis C Virus (HCV) RNA Levels in Human Immunodeficiency Virus/HCV Coinfected Individuals.

Journal article Open Forum Infect Dis · April 2015 We evaluated the impact of antiretroviral-induced dyslipidemia on hepatitis C virus (HCV) biogenesis in human immunodeficiency virus (HIV)/HCV coinfected patients. This study used serum samples from antiretroviral-naive HIV/HCV patients initiating their fi ... Full text Open Access Link to item Cite

On statistical tests for homogeneity of two bivariate zero-inflated Poisson populations.

Journal article J Biopharm Stat · 2015 The problem of testing treatment difference in the occurrence of a study endpoint in a randomized parallel-group comparative clinical trial with repeated responses under the assumption that the responses follow a bivariate zero-inflated Poisson (ZIP) distr ... Full text Link to item Cite

Confidence region approach for assessing bioequivalence and biosimilarity accounting for heterogeneity of variability

Journal article Journal of Probability and Statistics · January 1, 2015 For approval of generic drugs, the FDA requires that evidence of bioequivalence in average bioequivalence in terms of drug absorption be provided through the conduct of a bioequivalence study. A test product is said to be average bioequivalent to a referen ... Full text Cite

Independent data monitoring committees: preparing a path for the future.

Journal article Am Heart J · August 2014 Independent data monitoring committees (IDMCs) were introduced to monitor patient safety and study conduct in randomized clinical trials (RCTs), but certain challenges regarding the utilization of IDMCs have developed. First, the roles and responsibilities ... Full text Link to item Cite

Statistical and regulatory considerations in assessments of interchangeability of biological drug products.

Journal article Eur J Health Econ · May 2014 When the patent of a brand-name, marketed drug expires, new, generic products are usually offered. Small-molecule generic and originator drug products are expected to be chemically identical. Their pharmaceutical similarity can be typically assessed by sim ... Full text Link to item Cite

A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania.

Journal article BMC Infect Dis · February 20, 2014 BACKGROUND: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] o ... Full text Open Access Link to item Cite

A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania

Journal article BMC Infectious Diseases · February 20, 2014 Background: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] o ... Full text Cite

Sample size estimation of multiregional clinical trials with heterogeneous variability across regions.

Journal article J Biopharm Stat · 2014 In recent years, global collaboration has become a conventional strategy for new drug development. To accelerate the development process and shorten approval time, the design of multiregional clinical trials (MRCTs) incorporates subjects from many countrie ... Full text Link to item Cite

In vivo and in vitro bioequivalence testing

Journal article Journal of Bioequivalence and Bioavailability · January 1, 2014 For approval of generic drug products, the FDA requires that evidence of average bioequivalence in drug absorption be provided through the conduct of bioequivalence studies. As indicated in 21CFR320.24, bioequivalence may be established by in vivo (e.g., p ... Full text Cite

Bioavailability and bioequivalence in drug development

Journal article Wiley Interdisciplinary Reviews: Computational Statistics · 2014 Cite

Adaptive clinical trial design.

Journal article Annu Rev Med · 2014 In recent years, the use of adaptive design methods in clinical trials based on accumulated data at interim has received much attention because of its flexibility and efficiency in pharmaceutical/clinical development. In practice, adaptive design may provi ... Full text Link to item Cite

Bioavailability and bioequivalence in drug development

Journal article Wiley Interdisciplinary Reviews Computational Statistics · January 1, 2014 Bioavailability is referred to as the extent and rate to which the active drug ingredient or active moiety from the drug product is absorbed and becomes available at the site of drug action. The relative bioavailability in terms of the rate and extent of d ... Full text Cite

Applications of the bayesian prior information to evaluation of equivalence of similar biological medicinal products.

Journal article J Biopharm Stat · 2014 In 2014, there are a number of patents of best-selling biotech drugs around the world about to expire. Large commercial interests will inevitably set off international competition among major pharmaceutical companies. The European Union, the United States, ... Full text Link to item Cite

Nonparametric tests for evaluation of biosimilarity in variability of follow-on biologics.

Journal article J Biopharm Stat · 2014 As more biologic products are going off patent protection, the development of follow-on biologic products (also known as biosimilars) has gained much attention from both the biotechnology industry and regulatory agencies. Unlike small molecules, the develo ... Full text Link to item Cite

Frequency estimator for assessing of follow-on biologics.

Journal article J Biopharm Stat · 2014 For approval of generic drugs, the U.S. Food and Drug Administration (FDA) requires the evidence of bioequivalence in average bioavailability be provided. This is based on the Fundmental Bioequivalence Assumption from FDA that if two drug products are show ... Full text Link to item Cite

Scientific factors and current issues in biosimilar studies.

Journal article J Biopharm Stat · 2014 Biological drugs are much more complicated than chemically synthesized, small-molecule drugs; for instance, their size is much larger, their structure is more complicated, they can be sensitive to environmental conditions such as temperature or pressure, a ... Full text Link to item Cite

Use of Random Effect Models in the Design and Analysis of Multi-regional Clinical Trials

Journal article Springer Proceedings in Mathematics and Statistics · October 28, 2013 In recent years, global collaboration has become a commonly used strategy for new drug development. To accelerate the development process and shorten the approval time, the design of multi-regional clinical trials (MRCTs) incorporates subjects from many co ... Full text Cite

Statistical considerations in biosimilar assessment using biosimilarity index.

Journal article J Bioequivalence Bioavailab · September 2, 2013 When an innovative biologic product goes off patent, biopharmaceutical or biotechnological companies may file an application for regulatory approval of biosimilar products. Unlike small molecule drug products, biosimilars are not exact copies of their bran ... Full text Link to item Cite

Short communication: from wasting to obesity: initial antiretroviral therapy and weight gain in HIV-infected persons.

Journal article AIDS Res Hum Retroviruses · March 2013 Data on weight gain and the progression to overweight/obesity in HIV-infected persons during initial combination antiretroviral therapy (cART) are limited, and comparisons to the general population are inconclusive. Weight and body mass index (BMI) changes ... Full text Link to item Cite

Statistical assessment of biosimilarity based on relative distance between follow-on biologics.

Journal article Stat Med · February 10, 2013 In this paper, we propose a new three-arm parallel design to investigate biosimilarity between a biosimilar product and an innovator biological product by using relative distance based on the absolute mean differences. In the proposed design, one arm is fo ... Full text Link to item Cite

An adapted F-test for homogeneity of variability in follow-on biological products.

Journal article Stat Med · February 10, 2013 In recent years, follow-on biological products (biosimilars) have received much attention from both the biotechnology industry and the regulatory agencies, especially after the passage of the 2010 healthcare reform bill. Unlike the traditional small-molecu ... Full text Link to item Cite

Impact of variability on the choice of biosimilarity limits in assessing follow-on biologics.

Journal article Stat Med · February 10, 2013 With larger variation in biological products compared with small molecular drugs, it is suggested that the assessment of biosimilarity of follow-on biologics (FOBs) should take variability into consideration in addition to average as standard in bioequival ... Full text Link to item Cite

Scientific considerations for assessing biosimilar products.

Journal article Stat Med · February 10, 2013 The problem for assessing biosimilarity and drug interchangeability of follow-on biologics (biosimilar products) is studied. Unlike the generic products, the development of biosimilar products is much more complicated because of fundamental differences in ... Full text Link to item Cite

On the interchangeability of biologic drug products.

Journal article Stat Med · February 10, 2013 Interchangeability of drug products has very different features with small molecules and with biologicals. With small-molecule drugs, a statement of bioequivalence generally indicates therapeutic equivalence and interchangeability. In contrast, with the mu ... Full text Link to item Cite

Application of the parallel line assay to assessment of biosimilar products based on binary endpoints.

Journal article Stat Med · February 10, 2013 Biological drug products are therapeutic moieties manufactured by a living system or organisms. These are important life-saving drug products for patients with unmet medical needs. Because of expensive cost, only a few patients have access to life-saving b ... Full text Link to item Cite

Comments on the FDA draft guidance on biosimilar products.

Journal article Stat Med · February 10, 2013 The Food and Drug Administration issued on February 9, 2012, drafts of three new guidance documents about the demonstration of biosimilarity. One of these deals with scientific considerations. It suggests, among others, that demonstration of biosimilarity ... Full text Link to item Cite

The evaluation of biosimilarity index based on reproducibility probability for assessing follow-on biologics.

Journal article Stat Med · February 10, 2013 Unlike small molecule drug products, biological products are therapeutic agents producted using of a living system or organism. Thus, the development of biologic products is a very different and complicated process that is sensitive to environmental factor ... Full text Link to item Cite

Statistical methods for assessing interchangeability of biosimilars.

Journal article Stat Med · February 10, 2013 Unlike traditional small molecule (chemical) drug products, the development of biologic products is very different and variable with respect to the manufacturing process and environmental factors such as light and temperature. The complexity and heterogene ... Full text Link to item Cite

Advancing clinical trial design in pulmonary hypertension

Journal article Pulmonary Circulation · January 1, 2013 In pulmonary hypertension, as in many other diseases, there is a need for a smarter approach to evaluating new treatments. The traditional randomized controlled trial has served medical science well, but constrains the development of treatments for rare di ... Full text Cite

Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.

Journal article Drug Des Devel Ther · 2013 OBJECTIVE: MAP0004 is an investigational product which delivers dihydroergotamine (DHE) through the lung via a breath-synchronized metered dose inhaler. The objective of this study was to compare the acute effects of orally inhaled and intravenous (IV) DHE ... Full text Open Access Link to item Cite

Sample Size and Data Monitoring for Clinical Trials With Extremely Low Incidence Rates

Journal article Therapeutic Innovation and Regulatory Science · January 1, 2013 In clinical trials, statistical analyses on incidence rates detect significant differences between the responses from groups. Sample size estimation is always one of the key aspects in clinical trials that have limited budgets. A prestudy power analysis fo ... Full text Cite

Statistical methods for bridging studies.

Journal article J Biopharm Stat · September 2012 In 1998, the International Conference on Harmonization (ICH) published a guidance to facilitate the registration of medicines among ICH regions including the European Union, the United States, and Japan by recommending a framework for evaluating the impact ... Full text Link to item Cite

Bacteremic disseminated tuberculosis in sub-saharan Africa: a prospective cohort study.

Journal article Clin Infect Dis · July 2012 BACKGROUND: Disseminated tuberculosis is a major health problem in countries where generalized human immunodeficiency virus (HIV) infection epidemics coincide with high tuberculosis incidence rates; data are limited on patient outcomes beyond the inpatient ... Full text Open Access Link to item Cite

Authors reply to the letter to the editor by L. Chen and Y. X. Liu

Journal article Pharmaceutical Statistics · July 1, 2012 Full text Cite

On the regulatory approval pathway of biosimilar products.

Journal article Pharmaceuticals (Basel) · March 30, 2012 Biosimilars (or follow-on biologics) are a new class of medicine which enters the market subsequent to a previously approved version. They have demonstrated similarity to innovator biologic products in terms of quality, safety, and efficacy. The EMA has ta ... Full text Link to item Cite

On sample size calculation for comparing survival curves under general hypothesis testing.

Journal article J Biopharm Stat · 2012 The log-rank test is commonly used to test the equivalence of two survival distributions under right censoring. Jung et al. (2005) proposed a modified log-rank test for noninferiority trials and its corresponding sample size calculation. In this article, w ... Full text Link to item Cite

On the independence of data monitoring committee in adaptive design clinical trials.

Journal article J Biopharm Stat · 2012 In clinical trials, an independent data monitoring committee (DMC) is often established to perform both ongoing safety data monitoring and interim efficacy analysis. These evaluations are performed in a blinded fashion in order to avoid possible operationa ... Full text Link to item Cite

Analysis of time-to-event data with nonuniform patient entry and loss to follow-up under a two-stage seamless adaptive design with weibull distribution.

Journal article J Biopharm Stat · 2012 In the pharmaceutical industry, a two-stage seamless adaptive design that combines two separate independent clinical trials into a single clinical study is commonly employed in clinical research and development. In practice, in the interest of shortening t ... Full text Link to item Cite

Ovarian reserve diminished by oral cyclophosphamide therapy for granulomatosis with polyangiitis (Wegener's).

Journal article Arthritis Care Res (Hoboken) · December 2011 OBJECTIVE: Standard treatment for severe granulomatosis with polyangiitis (Wegener's) (GPA) is daily oral cyclophosphamide (CYC), a cytotoxic agent associated with ovarian failure. In this study, we assessed the rate of diminished ovarian reserve in women ... Full text Link to item Cite

Benefits, challenges and obstacles of adaptive clinical trial designs.

Journal article Orphanet J Rare Dis · November 30, 2011 In recent years, the use of adaptive design methods in pharmaceutical/clinical research and development has become popular due to its flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation ... Full text Link to item Cite

Sample size calculations for clinical trials

Journal article Wiley Interdisciplinary Reviews Computational Statistics · September 1, 2011 Sample size calculation plays an important role in clinical research. It is not only to identify signals or trends (with certain statistical assurance) of any (preferably optimal or best) clinical benefits to the patient population under study, but also to ... Full text Cite

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected children and infants in northern Tanzania.

Journal article Trop Med Int Health · July 2011 OBJECTIVE: To describe the contribution of paediatric HIV and of HIV co-infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods. METHODS: During 1 year, we enrolled consecutively admitted patients aged ≥2 months and ... Full text Link to item Cite

Spot the difference

Journal article EBR European Biopharmaceutical Review · June 1, 2011 Cite

Statistical inference for clinical trials with binary responses when there is a shift in patient population.

Journal article J Biopharm Stat · May 2011 In clinical research, it is not uncommon to modify a trial procedure and/or statistical methods of ongoing clinical trials through protocol amendments. A major modification to the study protocol could result in a shift in target patient population. In addi ... Full text Link to item Cite

Imputation method adjusted for covariates for nonrespondents in instruments with applications.

Journal article J Biopharm Stat · March 2011 In clinical research, measurement instruments (or questionnaires) consisting of a number of items (questions) are often used to assess treatment effect, e.g., quality-of-life assessment, and clinical disease activity index. In many situations, instead of a ... Full text Link to item Cite

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected adults and adolescents in northern Tanzania.

Journal article Clin Infect Dis · February 1, 2011 BACKGROUND: few studies describe patterns of human immunodeficiency virus (HIV) co-infections in African hospitals in the antiretroviral therapy (ART) era. METHODS: we enrolled consecutive admitted patients aged ≥ 13 years with oral temperature of ≥ 38.0°C ... Full text Link to item Cite

Some controversial issues in clinical trials

Journal article Drug Information Journal · 2011 In clinical development of a test treatment, clinical trials are usually conducted to collect data for evaluation of safety and efficacy of the test treatment under investigation. To provide accurate and reliable assessment, wellcontrolled clinical trials ... Cite

Assessing departure from dose linearity under a repeated measures incomplete block design.

Journal article Pharm Stat · 2011 Dose proportionality/linearity is a desirable property in pharmacokinetic studies. Various methods have been proposed for its assessment. When dose proportionality is not established, it is of interest to evaluate the degree of departure from dose linearit ... Full text Link to item Cite

On flexibility of adaptive designs and criteria for choosing a good one--a discussion of FDA draft guidance.

Journal article J Biopharm Stat · November 2010 In recent years, the use of adaptive design methods in clinical trials has attracted much attention due to its flexibility in identifying the best clinical benefit of the test treatment under investigation. The flexibility, however, comes at the price of d ... Full text Link to item Cite

Changing with the times

Journal article EBR European Biopharmaceutical Review · September 1, 2010 In early 2000, when the US FDA recognised that increased spending on biomedical research does not necessarily reflect an increase of the success rate of pharmaceutical development, the organisation kicked off the Critical Path Initiative to assist sponsors ... Cite

The use of complementary and alternative medicine by patients with chronic hepatitis C.

Journal article Complement Ther Clin Pract · August 2010 BACKGROUND: The use of complementary and alternative medicine (CAM) is expanding globally. However, prevalence of its use by patients with chronic hepatitis C (CHC) remains unclear. METHODS: An exploratory, descriptive study was conducted using a questionn ... Full text Link to item Cite

Analysis of time-to-event data under a two-stage survival adaptive design in clinical trials.

Journal article J Biopharm Stat · July 2010 In recent years, the use of a two-stage seamless design in clinical trials has attracted much attention. A two-stage seamless trial design is referred to as a study design that combines two separate clinical studies that are normally conducted to achieve s ... Full text Link to item Cite

Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial.

Journal article Ann Intern Med · June 15, 2010 BACKGROUND: Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients. OBJECTIVE: To determine whether extending prophylaxis with oral valganciclovir from ... Full text Link to item Cite

Proposals of statistical consideration to evaluation of results for a specific region in multi-regional trials--Asian perspective.

Journal article Pharm Stat · 2010 In recent years, global collaboration has become a conventional strategy for new drug development. To accelerate the development process and to shorten approval time, the design of multi-regional trials incorporates subjects from many countries around the ... Full text Link to item Cite

Bridging diversity: Extrapolating foreign data to a new region

Journal article Pharmaceutical Medicine · January 1, 2010 In recent years, global collaboration has led to a new strategy for drug development. However, clinical outcomes may be influenced by geographic variations in efficacy and safety; significant ethnic differences seem to exist in the enzymatic activity of se ... Full text Cite

Statistical assessment of biosimilar products.

Journal article J Biopharm Stat · January 2010 Biological products or medicines are therapeutic agents that are produced using a living system or organism. Access to these life-saving biological products is limited because of their expensive costs. Patents on the early biological products will soon exp ... Full text Link to item Cite

A comparison of moment-based and probability-based criteria for assessment of follow-on biologics.

Journal article J Biopharm Stat · January 2010 For approval of generic drugs, the U.S. Food and Drug Administration (FDA) requires the evidence of bioequivalence in average bioavailability from the bioavailability/bioequivalence studies. The criterion for assessment of bioequivalence adopted by the FDA ... Full text Link to item Cite

Statistical methods for assessment of biosimilarity using biomarker data.

Journal article J Biopharm Stat · January 2010 The problem for assessing biosimilarity between biologic products is studied. For approval of follow-on biologic products, the U.S. Food and Drug Administration (FDA) indicated that the follow-on biologic products can be approved under an abbreviated new d ... Full text Link to item Cite

Statistical test for evaluation of biosimilarity in variability of follow-on biologics.

Journal article J Biopharm Stat · January 2010 As more biologic products are going off patent protection, the development of follow-on biologics products has received much attention from both biotechnology industry and the regulatory agencies. Unlike small-molecule drug products, the development of bio ... Full text Link to item Cite

On assessing bioequivalence using genomic data with model misspecification.

Journal article J Biopharm Stat · July 2009 This study considers the effect of a nonlinear relationship between pharmacokinetic (PK) and genomic data on bioequivalence assessment using genomic data. A true relationship between PK and genomic data is assumed to be quadratic, but a linear relationship ... Full text Link to item Cite

Testing homogeneity of two zero-inflated Poisson populations.

Journal article Biom J · February 2009 The problem of testing treatment difference in the occurrence of a safety parameter in a randomized parallel-group comparative clinical trial under the assumption that the number of occurrence follows a zero-inflated Poisson (ZIP) distribution is considere ... Full text Link to item Cite

Statistical validation of traditional Chinese diagnostic procedures

Journal article Drug Information Journal · 2009 In recent years, the modernization of traditional Chinese medicine (TCM) for treatment of patients with critical and life-threatening diseases has attracted much attention in the pharmaceutical industry. The modernization of TCM is based on a scientific ev ... Cite

Inference on treatment effects for targeted clinical trials under enrichment design.

Journal article Pharm Stat · 2009 After completion of a human genome project, the disease targets at molecular level can be identified. As a result, treatment modality for molecular targets can be developed. In practice, targeted clinical trials are usually conducted for evaluation of the ... Full text Link to item Cite

Deviations from linearity in statistical evaluation of linearity in assay validation

Journal article Journal of Chemometrics · January 1, 2009 Linearity and linear range are the key evaluations of the accuracy in assay validation. The average deviation from linearity (ADL) and the sum of squares of deviations from linearity (SSDL) have been proposed for assessment of the linearity. However, both ... Full text Cite

Sample size estimation based on event data for a two-stage survival adaptive trial with different durations.

Journal article J Biopharm Stat · 2009 In clinical development, an adaptive design combining results from two separate studies (e.g., a seamless adaptive design with a dose finding study phase and a confirmatory study phase) is commonly considered. The purpose of an adaptive design is not only ... Full text Link to item Cite

On Two-stage Seamless Adaptive Design in Clinical Trials.

Journal article J Formos Med Assoc · December 2008 In recent years, the use of adaptive design methods in clinical research and development based on accrued data has become very popular because of its efficiency and flexibility in modifying trial and/or statistical procedures of ongoing clinical trials. On ... Full text Link to item Cite

Statistical tests for one-way/two-way translation in translational medicine.

Journal article J Formos Med Assoc · December 2008 Translational medicine has been defined as bench-to-bedside research, where a basic laboratory discovery becomes applicable to the diagnosis, treatment or prevention of a specific disease, and is brought forth by either a physician/scientist who works at t ... Full text Link to item Cite

Statistical methods in translational medicine.

Journal article J Formos Med Assoc · December 2008 This study focuses on strategies and statistical considerations for assessment of translation in language (e.g. translation of case report forms in multinational clinical trials), information (e.g. translation of basic discoveries to the clinic) and techno ... Full text Link to item Cite

Adaptive design methods in clinical trials - a review.

Journal article Orphanet J Rare Dis · May 2, 2008 In recent years, the use of adaptive design methods in clinical research and development based on accrued data has become very popular due to its flexibility and efficiency. Based on adaptations applied, adaptive designs can be classified into three catego ... Full text Link to item Cite

Sample size calculation for the log-rank tests for multi-arm trials with a control

Journal article Journal of the Korean Statistical Society · March 1, 2008 Suppose that there are K experimental arms and a control arm in a study with survival as the primary endpoint. We consider a Dunnett-type testing procedure to discover the experimental arms that have longer survival distributions than the control arm using ... Full text Cite

Statistical test for ordered categorical data in clinical trials

Journal article Drug Information Journal · 2008 In clinical trials, subjects are often classified into ordered categories (eg, worsening, no change, and improvement) based on their post-treatment clinical response changes from baseline. The usual approach in using a multinomial model for assessing treat ... Cite

A two-stage design for drug screening trials based on continuous endpoints

Journal article Drug Information Journal · 2008 Pharmaceutical development is a risky, complex, costly, and time-consuming endeavor. More than half of development duration is spent in clinical trials. Despite the large number of potential candidates available and the lengthy process of clinical developm ... Cite

Statistical assessment of QT/QTc prolongation based on maximum of correlated normal random variables.

Journal article J Biopharm Stat · 2008 To establish noninferiority in QT/QTc prolongation of a test drug with respect to either a placebo or an active control, a thorough QT/QTc study is recommended by ICH (ICH E14, ICH 2005) which concerns statistical inference on the maximal time-matched drug ... Full text Link to item Cite

On power and sample size calculation for QT studies with recording replicates at given time point.

Journal article J Biopharm Stat · 2008 The problem of the impact on power and sample size calculation for routine QT studies with ECG recording replicates under a parallel-group design and a crossover design is examined. Replicate ECGs are defined as single ECG recorded within several minutes o ... Full text Link to item Cite

Statistical issues on the diagnostic multivariate index assay for targeted clinical trials.

Journal article J Biopharm Stat · 2008 In the past decade, pharmacogenomics and microarrays are considered two of the most important scientific breakthroughs for detection and treatment of diseases with many other applications. After completion of the Human Genome Project (HGP), the importance ... Full text Link to item Cite

Variable screening in predicting clinical outcome with high-dimensional microarrays

Journal article Journal of Multivariate Analysis · September 1, 2007 Statistical modeling is an important area of biomarker research of important genes for new drug targets, drug candidate validation, disease diagnoses, personalized treatment, and prediction of clinical outcome of a treatment. A widely adopted technology is ... Full text Cite

Stability analysis for drugs with multiple active ingredients.

Journal article Stat Med · March 30, 2007 For every drug product on the market, the United States Food and Drug Administration (FDA) requires that an expiration dating period (shelf-life) must be indicated on the immediate container label. For determination of the expiration dating period of a dru ... Full text Link to item Cite

Series introduction

Journal article Computational Methods in Biomedical Research · January 1, 2007 Cite

Analysis strategies for adaptive designs with multiple endpoints.

Journal article J Biopharm Stat · 2007 The problem of analysis strategies for adaptive designs with multiple endpoints is considered. We first provide a review of the commonly used methods for addressing the issue of multiplicity in classical designs, followed by the gatekeeper procedure and th ... Full text Link to item Cite

Adaptive group sequential test for clinical trials with changing patient population.

Journal article J Biopharm Stat · 2007 In clinical trials, a standard group sequential test with a fixed number of planned interim analyses is usually considered to assess the effect of a test treatment under study. The standard group sequential test is statistically valid under the assumption ... Full text Link to item Cite

Statistical analysis for two-stage seamless design with different study endpoints.

Journal article J Biopharm Stat · 2007 In the pharmaceutical industry, it is desirable to apply an adaptive seamless trial design to combine two separate clinical studies that are normally conducted for achieving separate objectives such as a Phase II study for dose finding and a Phase III conf ... Full text Link to item Cite

Assessing the consistency of traditional Chinese medicine with multiple correlative active components.

Journal article J Biopharm Stat · 2007 The problem of controlling the quality of raw materials and/or final product of traditional Chinese medicine (TCM) has been studied. Earlier proposed consistency index to assess the consistency of quality of raw materials and/or final product processed or ... Full text Link to item Cite

Mixed noninferiority margin and statistical tests in active controlled trials.

Journal article J Biopharm Stat · 2007 In an active controlled noninferiority trial without a placebo arm, one of the major considerations is the selection of the noninferiority margin. Although the ICH E10 guideline provides general principles for the selection of appropriate noninferiority ma ... Full text Link to item Cite

A note on sample size calculation based on propensity analysis in nonrandomized trials.

Journal article J Biopharm Stat · 2007 In nonrandomized trials, patients are not randomly assigned to treatment groups with equal probability. Instead, the probability of assignment varies from patient to patient depending on patients baseline covariates. This often results in a non-comparable ... Full text Link to item Cite

Adaptive design in clinical research: issues, opportunities, and recommendations.

Journal article J Biopharm Stat · May 2006 The issues and opportunities of adaptive designs are discussed. Starting with the definitions of an adaptive design, its validity and integrity are discussed. The three key components of an adaptive design, i.e., Type I error control, p-value adjustment, a ... Full text Link to item Cite

On the assessment of dose proportionality: a comparison of two slope approaches.

Journal article J Biopharm Stat · May 2006 The problem for assessment of dose proportionality (or linearity) is studied. Various methods for assessment of dose proportionality (or linearity) such as ANOVA type F-test have been proposed. Cheng et al. (2006) proposed an alternative approach based on ... Full text Link to item Cite

Editor's note - JBS is now an SCI journal

Journal article Journal of Biopharmaceutical Statistics · May 1, 2006 Full text Cite

Author's reply [4]

Journal article Statistics in Medicine · April 30, 2006 Full text Cite

On non-inferiority margin and statistical tests in active control trials.

Journal article Stat Med · April 15, 2006 Featured Publication The problem of selecting a non-inferiority margin and the corresponding statistical test for non-inferiority in active control trials is considered. For selection of non-inferiority margin, the guideline by the International Conference on Harmonization (IC ... Full text Link to item Cite

Statistical quality control process for traditional Chinese medicine.

Journal article J Biopharm Stat · 2006 The statistical quality control process on raw materials and/or the final product of traditional Chinese medicine (TCM) is examined. We develop a statistical quality control (QC) method to assess a proposed consistency index of raw materials from different ... Full text Link to item Cite

On traditional Chinese medicine clinical trials

Journal article Drug Information Journal · January 1, 2006 In recent years, the Westernization of traditional Chinese medicine (TCM) has attracted much attention in pharmaceutical research and development. One of the key issues in Westernization of TCM is how to conduct a scientifically valid clinical trial to eva ... Full text Cite

Statistical inference for cancer trials with treatment switching.

Journal article Stat Med · June 30, 2005 Featured Publication In cancer clinical trials, it is not uncommon that some patients switched their treatments due to lack of efficacy and/or disease progression under ethical consideration. This treatment switch makes it difficult for the evaluation of the efficacy of the tr ... Full text Link to item Cite

Journal of Biopharmaceutical Statistics: Editor's note

Journal article Journal of Biopharmaceutical Statistics · January 31, 2005 Full text Cite

Statistical consideration of adaptive methods in clinical development.

Journal article J Biopharm Stat · 2005 Featured Publication In recent years, the use of adaptive methods in clinical development based on accrued data has become very popular due to its flexibility in modifying trial procedures and/or statistical procedures of on-going clinical trials. However, it is a concern that ... Full text Link to item Cite

Inference for clinical trials with some protocol amendments.

Journal article J Biopharm Stat · 2005 Featured Publication The use of adaptive methods in clinical development has become very popular in recent years due to its flexibility in modifying trial procedures and/or statistical procedures of on-going clinical trials. Modifications to trial procedures are usually docume ... Full text Link to item Cite

A hybrid Bayesian adaptive design for dose response trials.

Journal article J Biopharm Stat · 2005 Featured Publication In recent years, the use of adaptive design methods based on accrued data of on-going trials have become very popular for dose response trials in early clinical development due to their flexibility (EMEA, 2002). In this paper, we developed a hybrid frequen ... Full text Link to item Cite

A Bayesian approach on sample size calculation for comparing means.

Journal article J Biopharm Stat · 2005 Featured Publication In clinical research, parameters required for sample size calculation are usually unknown. A typical approach is to use estimates from some pilot studies as the true parameters in the calculation. This approach, however, does not take into consideration sa ... Full text Link to item Cite

Assessing bioequivalence using genomic data.

Journal article J Biopharm Stat · November 2004 Featured Publication For approval of a generic drug product, the assessment of bioequivalence in drug absorption is usually considered as a surrogate for evaluation of drug efficacy and safety in clinical studies. For some drug products, the United States Food and Drug Adminis ... Full text Link to item Cite

Cross-validation for linear model with unequal variances in genomic analysis.

Journal article J Biopharm Stat · August 2004 Featured Publication In recent years, genomic studies are usually conducted to identify genes that may have an impact on clinical outcomes. The identified genes are then used to establish a predictive model for identifying subjects who are most likely to respond to the test tr ... Full text Link to item Cite

Modified large-sample confidence intervals for linear combinations of variance components: Extension, theory, and application

Journal article Journal of the American Statistical Association · June 1, 2004 We consider the problem of setting a confidence interval or bound for a linear combination of variance components related to a multivariate normal distribution, which includes important applications such as comparing variance components and testing the bio ... Full text Cite

Analysis of clinical data with breached blindness.

Journal article Stat Med · April 30, 2004 Featured Publication In clinical trials, blinding is usually employed to prevent bias that may be introduced due to the knowledge of the identity of the treatment codes. This bias could alter the conclusion of statistical inference on the treatment effect. The purpose of this ... Full text Link to item Cite

Sample size determination based on rank tests in clinical trials.

Journal article J Biopharm Stat · November 2003 Featured Publication The problem of sample size determination based on three commonly used non-parametric rank based tests, namely, one-sample Wilcoxon's rank sum test, two-sample's Wilcoxon's rank sum test, and the rank-based test for independence is studied. Explicit formula ... Full text Link to item Cite

Stability analysis with discrete responses.

Journal article J Biopharm Stat · August 2003 Featured Publication We consider the estimation of shelf life of a drug product when the stability data are discrete. When there is no batch-to-batch variation, the proposed shelf life estimator is an approximate 95% lower confidence bound of the true shelf life. In the presen ... Full text Link to item Cite

Statistical tests for population bioequivalence

Journal article Statistica Sinica · April 1, 2003 In its 2001 guidance, the U.S. Food and Drug Administration (FDA) recommends that population bioequivalence (PBE) and individual bioequivalence (IBE) be assessed to address respectively the prescribability and switchability between a brand-name drug produc ... Cite

Pharmacokinetics of doxorubicin administered i.v. as Myocet (TLC D-99; liposome-encapsulated doxorubicin citrate) compared with conventional doxorubicin when given in combination with cyclophosphamide in patients with metastatic breast cancer.

Journal article Anticancer Drugs · March 2003 Myocet (TLC D-99) is a liposomal formulation of the anti-neoplastic drug doxorubicin with an improved therapeutic index compared with conventional doxorubicin. The objective of this study was to assess the plasma disposition of doxorubicin when administere ... Full text Link to item Cite

Examining outlying subjects and outlying records in bioequivalence trials.

Journal article J Biopharm Stat · February 2003 Featured Publication The problem of detecting outliers in bioequivalence trials is considered. We formulate the problem as a hypothesis-testing problem under a mean-shift model and propose a test procedure based on the likelihood function. The test statistic has two components ... Full text Link to item Cite

In vitro bioequivalence testing.

Journal article Stat Med · January 15, 2003 Featured Publication A statistical test is proposed for in vitro bioequivalence testing between drug products such as nasal aerosols and nasal sprays. The proposed test generalizes the one recommended in the FDA 1999 guidance to the situation where replicated observations obta ... Full text Link to item Cite

On sample size calculation based on odds ratio in clinical trials.

Journal article J Biopharm Stat · November 2002 Featured Publication Sample size calculation formulas for testing equality, noninferiority, superiority, and equivalence based on odds ratio were derived under both parallel and one-arm crossover designs. An example concerning the study of odds ratio between a test compound (t ... Full text Link to item Cite

Tests for inter-subject and total variabilities under crossover designs.

Journal article J Biopharm Stat · November 2002 Featured Publication In this paper, we consider statistical tests for inter-subject and total variabilities between treatments under crossover designs. Since estimators of variance components for inter-subject variability and total variability in crossover design are not indep ... Full text Link to item Cite

A note on sample size calculation for mean comparisons based on noncentral t-statistics.

Journal article J Biopharm Stat · November 2002 Featured Publication One-sample and two-sample t-tests are commonly used in analyzing data from clinical trials in comparing mean responses from two drug products. During the planning stage of a clinical study, a crucial step is the sample size calculation, i.e., the determina ... Full text Link to item Cite

A practical approach for comparing means of two groups without equal variance assumption.

Journal article Stat Med · October 30, 2002 Featured Publication In this paper we consider two-groups of i.i.d. normally distributed random variables (N(mu(x),sigma(x) (2)) and N(mu(y),sigma(y) (2))) without assuming equal variance (sigma(x) (2) = sigma(y) (2)). We propose a simple method for constructing confidence bou ... Full text Link to item Cite

A note on statistical methods for assessing therapeutic equivalence.

Journal article Control Clin Trials · October 2002 Featured Publication The two one-sided tests procedure and the confidence interval approach are two commonly used statistical approaches for testing therapeutic equivalence or assessing bioequivalence. However, some confusion arises. For example, what is the difference between ... Full text Link to item Cite

Bridging studies in clinical development.

Journal article J Biopharm Stat · August 2002 Featured Publication Global development of pharmaceutical products has become the key to the success of any pharmaceutical sponsors. It is therefore crucial to address the efficacy and safety variations of a new test pharmaceutical product among different geographic regions du ... Full text Link to item Cite

On the assessment of similarity for dissolution profiles of two drug products.

Journal article J Biopharm Stat · August 2002 Featured Publication The assessment of similarity between dissolution profiles of two drug products is considered. After reviewing some existing approaches, we propose a statistical method of assessing local and global similarities based on a time series model for the ratio of ... Full text Link to item Cite

Assessing sensitivity and similarity in bridging studies.

Journal article J Biopharm Stat · August 2002 Featured Publication In pharmaceutical industry, the sponsors are interested in bringing their drug products from one region (e.g., the United States of America) to another region (e.g., Asian Pacific) to increase the exclusivity of the drug products in the marketplace. Howeve ... Full text Link to item Cite

On statistical power for average bioequivalence testing under replicated crossover designs.

Journal article J Biopharm Stat · August 2002 Featured Publication In its recent guidance on bioequivalence, the U.S. Food and Drug Administration (FDA) recommends a two-sequence, four-period (2 x 4) replicated crossover design be used for assessment of population and individual bioequivalence [FDA. Guidance for Industry ... Full text Link to item Cite

Reproducibility probability in clinical trials.

Journal article Stat Med · June 30, 2002 Featured Publication For marketing approval of a new drug product, the United States Food and Drug Administration (FDA) requires that substantial evidence of the effectiveness of the drug product be provided through the conduct of at least two adequate and well-controlled clin ... Full text Link to item Cite

Individual bioequivalence testing under 2x3 designs.

Journal article Stat Med · March 15, 2002 Featured Publication In recent years, as more generic drug products become available, it is a concern not only whether generic drug products that have been approved based on the regulation of average bioequivalence will have the same quality, safety and efficacy as that of the ... Full text Link to item Cite

Probability lower bounds for USP/NF tests.

Journal article J Biopharm Stat · February 2002 Featured Publication In the pharmaceutical industry, a number of tests such as content uniformity and dissolution testing are usually performed at various stages of drug manufacturing process to ensure that the drug product meets standards for identity, strength, quality, puri ... Full text Link to item Cite

Sample size calculation in bioequivalence trials.

Journal article J Pharmacokinet Pharmacodyn · February 2002 Full text Link to item Cite

Journal of Biopharmaceutical Statistics: Editor's note

Journal article Journal of Biopharmaceutical Statistics · January 1, 2002 Cite

Drug shelf-life estimation

Journal article Statistica Sinica · July 1, 2001 The shelf-life of a drug product is the time that the average drug characteristic (e.g., potency) remains within an approved specification after manufacture. The United States Food and Drug Administration (FDA) requires indication for every drug product of ... Cite

Two-phase shelf-life estimation.

Journal article Stat Med · April 30, 2001 Featured Publication Unlike most drug products, some drug products must be stored at several temperatures, such as -20 degrees C, 5 degrees C and 25 degrees C, in order to maintain the stability of the drug products. Drug products of this kind are usually referred to as frozen ... Full text Link to item Cite

On sample size calculation in bioequivalence trials.

Journal article J Pharmacokinet Pharmacodyn · April 2001 Featured Publication Sample size calculation plays an important role in bioequivalence trials. In practice, a bioequivalence study is usually conducted under a crossover design or a parallel design with raw data or log-transformed data. In this paper, we discuss the difference ... Full text Link to item Cite

The bootstrap procedure in individual bioequivalence.

Journal article Stat Med · October 30, 2000 Featured Publication A bootstrap-type hypothesis test procedure for assessing individual (or population) bioequivalence between two drug formulations is suggested in a draft guidance from the United States Food and Drug Administration (FDA). The purpose of this article is to s ... Full text Link to item Cite

Preface. Bioequilavence measures.

Journal article Stat Med · October 30, 2000 Full text Link to item Cite

On statistical analysis for placebo-challenging designs in clinical trials.

Journal article Stat Med · April 30, 2000 Featured Publication In clinical trials, appropriate designs are often chosen to address scientific/medical questions of particular interest to the investigator. For a chosen statistical design, however, standard statistical procedures may not be applicable owing to the nature ... Full text Link to item Cite

Assessing distributions of estimated drug shelf lives in stability analysis.

Journal article Biometrics · September 1999 A stability study is usually conducted to ensure that a drug product can meet the approved specifications prior to its expiration dating period (shelf life). Several approaches for determination of drug shelf life assuming random batches have been proposed ... Full text Link to item Cite

Bioequivalence review for drug interchangeability.

Journal article J Biopharm Stat · August 1999 To monitor the performance of the approved generic copies of a brand-name drug, we propose some methods in assessing bioequivalence among generic copies and the brand-name drug, and among generic copies themselves, using data from several bioequivalence st ... Full text Link to item Cite

Individual bioequivalence - A review of the FDA draft guidance

Journal article Drug Information Journal · 1999 As more generic drugs become available in the marketplace, it is a public concern whether the quality, safety, and efficacy of generic drugs are the same as the brand name drug. Under current regulation, the United States Food and Drug Administration (FDA) ... Cite

Design and analysis of multinational clinical trials

Journal article Drug Information Journal · January 1, 1998 In recent years, multinational multicenter trials have become increasingly popular for evaluation of the generalizability of clinical results across different countries. With the implementation of the International Conference on Harmonization (ICH) Good Cl ... Full text Cite

An overview of the regulatory approval process in drug development

Journal article Drug Information Journal · January 1, 1998 This paper provides a brief history and an overview of the regulatory process for drug approval in the United States through illustrations of Investigational New Drug (INDs) Applications and New Drug Applications (NDAs). For INDs, the regulatory requiremen ... Full text Cite

A note on sample size determination for bioequivalence studies with high-order crossover designs.

Journal article J Pharmacokinet Biopharm · December 1997 Similar to Liu and Chow, approximate formulas for sample size determination are derived based on Schuirmann's two one-sided tests procedure for bioequivalence studies for the additive and the multiplicative models under various higher order crossover desig ... Full text Link to item Cite

Statistical methods for two-sequence three-period cross-over designs with incomplete data.

Journal article Stat Med · May 15, 1997 In clinical trials, and in bioavailability and bioequivalence studies, one often encounters replicate cross-over designs such as a two-sequence three-period cross-over design to assess treatment and carry-over effects of two formulations of a drug product. ... Full text Link to item Cite

Statistical comparison between dissolution profiles of drug products.

Journal article J Biopharm Stat · May 1997 The problem for assessment of similarity between dissolution profiles of two drug products is considered. The commonly used classical methods including model-dependent and model-independent approaches are reviewed. Most methods encountered the difficulties ... Full text Link to item Cite

A two one-sided tests procedure for assessment of individual bioequivalence.

Journal article J Biopharm Stat · March 1997 In this paper we propose a two one-sided tests procedure for assessment of individual bioequivalence based on the concept of individual equivalence ratios proposed by Anderson and Hauck. The proposed procedure is derived under the normality assumption for ... Full text Link to item Cite

Some thoughts on individual bioequivalence.

Journal article J Biopharm Stat · March 1997 Full text Link to item Cite

Meta-analysis for bioequivalence review.

Journal article J Biopharm Stat · March 1997 The problem of drug interchangeability among a brand-name drug and its generic copies is considered. Under current Food and Drug Administration (FDA) regulation, a patient may switch from the brand-name drug to a generic drug if the generic drug is shown t ... Full text Link to item Cite

An adjusted two one-sided t-test for the assessment of bioequivalence with multiple doses.

Journal article J Biopharm Stat · March 1997 In medical practice, it has been realized that noncompliance may have an impact on the therapeutic effect of a drug therapy, regardless of race, gender, and education of patients. Therefore, it is of interest to study the impact of noncompliance on drug ab ... Full text Link to item Cite

Statistical/practical issues in clinical trials

Journal article Therapeutic Innovation Regulatory Science · January 1, 1997 For approval of a drug product, the United States Food and Drug Administration (FDA) requires that substantial evidence of the effectiveness and safety of the drug product be provided through the conduct of two adequate, well-controlled clinical trials. To ... Full text Cite

Interval estimation for ratios in bioequivalence trials

Journal article Biometrical Journal · January 1, 1997 The problem for assessment of equivalence in variability of bioavailability between two drug products is considered. An exact confidence region for the ratio between intrasubject variabilities is derived when the intersubject variance is known. When the in ... Full text Cite

On the test of Liu and Chow's procedure for assessing equivalence in variability of bioavailability

Journal article Communications in Statistics Part B Simulation and Computation · January 1, 1997 Similar to Schuirmann's two one-sided tests procedure for assessment of bioequivalence in average bioavailability (Schuirmann, 1987), Liu and Chow (1992) proposed a two one-sided tests procedure for assessment of equivalence of variability of bioavailabili ... Full text Cite

Good statistics practice in the drug development and regulatory approval process

Journal article Therapeutic Innovation Regulatory Science · January 1, 1997 During the development and approval process of a new drug, the concept of good statistics practice (GSP) is necessarily implemented. GSP is a set of principles which assures the validity of the design and analysis of the intended studies conducted at vario ... Full text Cite

Pharmaceutical validation and process controls in drug development

Journal article Therapeutic Innovation Regulatory Science · January 1, 1997 In drug development, pharmaceutical validation and process controls are important to assure that the drug product can meet standards for the identity, strength, quality, purity, and stability of the drug product. Pharmaceutical validation includes analytic ... Full text Cite

The impact of patient compliance on drug concentration profile in multiple doses.

Journal article Stat Med · March 30, 1996 Physicians commonly prescribe drugs in a multiple dosage regimen for prolonged therapeutic activity. To study the effect of multiple dosing on drug concentration in blood, researchers often use deterministic models with the assumption that drugs are admini ... Full text Link to item Cite

A procedure for weight and model selection in assay development

Journal article Journal of Food and Drug Analysis · March 1, 1996 The problem of weight and model selection for standard curve in the calibration of an instrument for assay development is considered. An instrument is usually calibrated by studying the relationship between a number of known standards and their correspondi ... Cite

Bioequivalence of two tablet formulations of nadolol using single and multiple dose data: assessment using stereospecific and nonstereospecific assays.

Journal article J Pharm Sci · March 1996 Nadolol, a nonspecific beta-blocker, is a racemate composed of equal amounts of four stereoisomers, namely, SQ-12148, SQ-12149, SQ-12150, and SQ-12151. In an open-label, randomized, four-period crossover study, the pharmacokinetics of nadolol and its stere ... Full text Link to item Cite

Statistical issues in quality-of-life assessment.

Journal article J Biopharm Stat · March 1996 In recent years, the assessment of drug effects on quality of life (QOL) has become very popular in clinical trials. QOL assessment quantifies the ability of a person to function normally in society. It may be used to distinguish between therapies that app ... Full text Link to item Cite

Statistical issues on the FDA conjugated estrogen tablets bioequivalence guidance

Journal article Drug Information Journal · 1996 This paper considers some key statistical issues embedded in the Guidance on Conjugated Estrogen Tablets - In Vivo Bioequivalence and In Vitro Drug Release issued by the United States Form and Drug Administration in 1991. These statistical issues are addre ... Cite

Comment

Journal article Statistical Science · January 1, 1996 Cite

An overview of stability studies

Journal article Journal of Food and Drug Analysis · January 1, 1996 Before any drug products are marketed, it is required by the government regulatory agencies that stability studies to be conducted. The objective of the stability studies is not only to characterize the degradation curve but also to estimate the shelf-life ... Full text Cite

A confidence region approach for assessing equivalence in variability of bioavailability

Journal article Biometrical Journal · January 1, 1996 The problem for assessment of equivalence in variability of bioavailability between two drug products is considered. Similar to the method for assessing bioequivalence in average bioavailability proposed by CHOW and SHAO (1990), an exact confidence region ... Full text Cite

On likelihood distance for outliers detection.

Journal article J Biopharm Stat · November 1995 The likelihood distance has been widely used to detect outlying observations in data analysis. Cook and Weisberg (5) suggested that the likelihood distance may be compared to a chi 2 distribution for large samples. In this paper, we show that use of the ch ... Full text Link to item Cite

On stability designs in drug shelf-life estimation.

Journal article J Biopharm Stat · July 1995 In this paper, various stability designs, including matrixing and bracketing designs for determining drug shelf-life, are considered. We propose a criterion for design selection based on the precision of drug shelf-life estimates. For a fixed sample size, ... Full text Link to item Cite

The impact of outlying subjects on decision of bioequivalence.

Journal article J Biopharm Stat · March 1995 As a consequence of a hearing on bioequivalence conducted by the Food and Drug Administration in 1986, the identification and the treatment of a potential outlier in bioequivalence trials has become an important issue in the assessment of bioequivalence be ... Full text Link to item Cite

Application of Williams' design for bioequivalence trials

Journal article Drug Information Journal · 1995 This paper illustrates the application of Williams' design to bioequivalence trials. The replicated and variance-balanced crossover design is briefly outlined. Statistical methods for analysis of a Williams' design are discussed. Results are presented from ... Cite

Replicated crossover designs in bioavailability and bioequivalence trials

Journal article Drug Information Journal · 1995 The concept of bioequivalence is illustrated in terms of prescribability for population bioequivalence and switchability for individual bioequivalence. Population bioequivalence or prescribability examines closeness of the distributions of the pharmacokine ... Cite

Current issues in bioequivalence trials

Journal article Drug Information Journal · 1995 In recent years, as more generic drug products became available, the quality, safety, and efficacy of generic drugs became a great concern. As a result, the assessment of bioequivalence between the generic drug products and the innovator product has become ... Cite

Guest editor's note: Bioavailability and bioequivalence

Journal article Therapeutic Innovation Regulatory Science · January 1, 1995 Full text Cite

On model selection for standard curve in assay development

Journal article Journal of Biopharmaceutical Statistics · 1995 This paper discusses the selection of an appropriate statistical model for representing standard curve in assay development. This is an important issue in assay validation because the accuracy and reliability of the assay result depend on the selected stan ... Cite

On ordinary least-squares methods for sample surveys

Journal article Statistics and Probability Letters · June 22, 1994 The performance of the ordinary least-squares (LS) method for two-stage sampling in regression analysis is studied. It is shown that the best linear unbiased estimator (BLUE) can be approximated by a polynomial in intracluster correlation. In particular, t ... Full text Cite

On statistical characteristics of quality of life assessment.

Journal article J Biopharm Stat · March 1994 In recent years, the assessment of drug effects on quality of life (QOL), which is the ability of a person to function normally in society as perceived by the patient, has become a popular issue in clinical trials. Since the response may vary widely from p ... Full text Link to item Cite

On the estimation of variance components in stability analysis

Journal article Communications in Statistics Theory and Methods · January 1, 1994 Chow and Shao (1989, 1991) indicated that the presence of batch-to-batch variation has an impact on the determination of drug shelf-life in stability studies. In this paper, we propose two unbiased estmators for batch-to-batch variation. The proposed estim ... Full text Cite

Statistical considerations in bioequivalence trials

Journal article Communications in Statistics Theory and Methods · January 1, 1994 We discuss the statistical issues in evaluation of bioequivalence addressed by the FDA Bioequivalence Hearing (1986) and Guidance on Statistical Procedures for Bioequivalence Studies released by the Division of Bioequivalence, Office of Generic Drugs of FD ... Full text Cite

Statistical inference in stability analysis

Journal article Biometrics · January 1, 1994 Statistical inference for drug shelf-life in stability analysis is considered. We propose a model that takes into account the batch-to-batch variation in assay results. Tests for batch-to-batch variation as well as the effects of some covariates such as ti ... Full text Cite

Recent statistical developments in bioequivalence trials - A review of the FDA guidance

Journal article Drug Information Journal · January 1, 1994 This paper provides an overview of recent statistical developments in bioavailability and bioequivalence studies, including background, the fundamental bioequivalence concept, decision rules, and statistical methods for assessment of bioequivalence. Statis ... Full text Cite

Two-stage sampling in pharmaceutical applications.

Journal article Stat Med · November 15, 1993 In the pharmaceutical industry, some tests for quality assurance before, during and after the manufacture of a drug product involve a two-stage sampling technique. We propose statistical testing procedures in a two-stage sampling problem with large within- ... Full text Link to item Cite

On Assessment of Bioequivalence for Drugs with Negligible Plasma Levels

Journal article Biometrical Journal · January 1, 1993 In bioavailability studies, bioequivalence between drug products is usually determined based on some pharmacokinetic responses such as area under the blood or plasma concentration‐time curve and maximum concentration. For some drug products, however, we ma ... Full text Cite

On the assessment of variability in bioavailability/bioequivalence studies

Journal article Communications in Statistics Theory and Methods · January 1, 1992 A procedure is proposed for the assessment of bioequivalence of variabilities between two formulations in bioavailability/bioequivalence studies. This procedure is essentially a two one-sided Pitman-Morgan's tests procedure which is based on the correlatio ... Full text Cite

On assessment of bioequivalence under a higher-order crossover design.

Journal article J Biopharm Stat · 1992 In bioavailability studies of two formulations of a drug, the standard two-sequence, two-period crossover design is usually considered to assess bioequivalence. The standard two-sequence, two-period crossover design, however, may not be useful when differe ... Full text Link to item Cite

Therapy for pharyngitis and tonsillitis caused by group A beta-hemolytic streptococci: a meta-analysis comparing the efficacy and safety of cefadroxil monohydrate versus oral penicillin V.

Journal article Clin Ther · 1992 A meta-analysis was conducted to compare the efficacy and safety of oral cefadroxil monohydrate (30 mg/kg QD or 15 mg/kg BID) with that of oral penicillin V (8, 10, or 15 mg/kg BID, TID, or QID) in the treatment of group A beta-hemolytic streptococcal (GAB ... Link to item Cite

On the estimation of total variability in assay validation.

Journal article Stat Med · October 1991 In the pharmaceutical industry, an assay method is considered validated if the accuracy and precision for an assay meet some acceptable limits. This paper discusses the assessment of assay precision in terms of the estimation of total variability of an ass ... Full text Link to item Cite

Estimating drug shelf-life with random batches.

Journal article Biometrics · September 1991 The problem of assessing the shelf-lives of drug products in the market is considered. We focus on the situation where the drug characteristic of interest has a linear relationship over time and batch-to-batch variation is present. Two methods for assessin ... Link to item Cite

The estimation of parameters from bulked samples.

Journal article J Biopharm Stat · 1991 An estimation procedure has been developed for the estimation of parameters from bulked sample using the parametric bootstrap and density estimation in conjunction with the one-step maximum-likelihood estimator. It is shown that the proposed estimation pro ... Full text Link to item Cite

Assessment of bioequivalence using a multiplicative model.

Journal article J Biopharm Stat · 1991 In many bioavailability/bioequivalence studies, the distributions of responses such as AUC and Cmax are often positively skewed and exhibit a lack of homogeneity of variances. In this situation, a logarithmic transformation is usually considered for reduct ... Full text Link to item Cite

Outlier detection in bioavailability/bioequivalence studies.

Journal article Stat Med · May 1990 This paper concerns techniques for detection of a potential outlier or extreme observation in a bioavailability/bioequivalence study. A bioavailability analysis that includes possible outlying values may affect the decision on bioequivalence. We consider a ... Full text Link to item Cite

TEST FOR TREATMENT EFFECT BASED ON BINARY DATA WITH RANDOM SAMPLE SIZES

Journal article Australian Journal of Statistics · January 1, 1990 The problem of testing for treatment effect based on binary response data is considered, assuming that the sample size for each experimental unit and treatment combination is random. It is assumed that the sample size follows a distribution that belongs to ... Full text Cite

An Alternative Approach for the Assessment of Bioequivalence Between Two Formulations of a Drug

Journal article Biometrical Journal · January 1, 1990 The problem of the assessment of bioequivalence between a test formulation (T) and a reference formulation (R) of a drug using a two‐way crossover experiment is considered. To claim bioequivalence between two formulations, it is required by the United Stat ... Full text Cite

A Related Problem in Bioavailability/Bioequivalence Studies — Estimation of the Intrasubject Variability With a Common CV

Journal article Biometrical Journal · January 1, 1990 The problem of characterizing the intrasubject variability in bioavailability/bioequivalence studies when the intrasubject variability differs from subject to subject is considered. To account for the heterogeneity of the intrasubject variability, a condit ... Full text Cite

On the measures of multicollinearity in least squares regression

Journal article Statistics and Probability Letters · January 1, 1990 For a general regression model y = Xβ + e, E(e) = 0, Cov(e) = σ2V-1, some results on the relationship between two measures of multicollinearity, the eigenvalues and the condition numbers of X′X and X′VX, are obtained. These results ar ... Full text Cite

A note on adaptive generalized ridge regression estimator

Journal article Statistics and Probability Letters · January 1, 1990 The problem of estimating parameters in a linear regression model is considered. A class of adaptive generalized ridge estimator is proposed. It is shown that the proposed estimator has smaller mean squared error than the least squares estimator under some ... Full text Cite

Alternative approaches for assessing bioequivalence regarding normality assumptions

Journal article Drug Information Journal · January 1, 1990 This paper concerns several alternative approaches for the assessment of bioequivalence between two formulations (a test formulation and a reference formulation) of a drug with respect to various situations depending upon whether the normality assumptions ... Full text Cite

Test for batch-to-batch variation in stability analysis.

Journal article Stat Med · July 1989 We propose several statistical tests for batch-to-batch variation in the stability analysis of a drug product and present applications with data from new drug application stability and marketing stability analyses. ... Full text Link to item Cite

A new procedure for the estimation of variance components

Journal article Statistics and Probability Letters · January 1, 1988 For the estimation of variance components in the one way random effects models, we propose some estimators which avoid negative and zero estimates of the variance component, a well-known problem with customary estimators such as the maximum likelihood or t ... Full text Cite