Clinical Trials Commons^™

Do Firms Respond To Peer Disclosures? Evidence From Clinical Trial Disclosures, Vedran Capkun, Yun Lou, Clemens A. Otto, Yin Wang

Research Collection School Of Accountancy

We examine whether a firm’s decision to disclose non-financial proprietary information depends on peer disclosures of similar information. Using a sample of 5,035 unique clinical trials by U.S. pharmaceutical firms over the 2007-2014 period, we find that the firm is less likely to disclose its own clinical trial results if peers have published clinical trial results pertaining to the same medical condition. Conditional on disclosing clinical trial results, the firm is also less likely to disclose the trial results on time when peers have disclosed their clinical trial results. Our cross-sectional tests suggest that proprietary costs of disclosure play an …

Cognitive Effects Of The Bet Protein Inhibitor Apabetalone: A Prespecified Montreal Cognitive Assessment Analysis Nested In The Betonmace Randomized Controlled Trial, Jeffrey Cummings, Gregory G. Schwartz, Stephen J. Nicholls, Aziz Khan, Chris Halliday, Peter P. Toth, Michael Sweeney, Jan O. Johansson, Norman C.W. Wong, Ewelina Kulikowski, Kamyar Kalantar-Zadeh, Kenneth Lebioda, Henry N. Ginsberg, Bengt Winblad, Henrik Zetterberg, Kausik K. Ray

School of Medicine Faculty Research

Background: Epigenetic changes may contribute importantly to cognitive decline in late life including Alzheimer's disease (AD) and vascular dementia (VaD). Bromodomain and extra-terminal (BET) proteins are epigenetic 'readers' that may distort normal gene expression and contribute to chronic disorders. Objective: To assess the effects of apabetalone, a small molecule BET protein inhibitor, on cognitive performance of patients 70 years or older participating in a randomized trial of patients at high risk for major cardiovascular events (MACE). Methods: The Montreal Cognitive Assessment (MoCA) was performed on all patients 70 years or older at the time of randomization. 464 participants were randomized …

Tocilizumab And Covid-19: A Meta-Analysis Of 2120 Patients With Severe Disease And Implications For Clinical Trial Methodologies, Azza Sarfraz, Zouina Sarfraz, Muzna Sarfraz, Hinna Aftab, Zainab Pervaiz

Department of Paediatrics and Child Health

Background/aim: Since the outbreak of the COVID-19, numerous therapies to counteract this severe disease have emerged. The benefits of Tocilizumab for severely infected COVID-19 patients and the methodologies of ongoing clinical trials are explored.
Materials and methods: A systematic search adhering to PRISMA guidelines was conducted in PubMed, Cochrane Central, medRxiv, and bioRxiv using the following keywords: “Tocilizumab,” “Actemra,” “COVID-19.” An additional subsearch was conducted on Clinicaltrials.gov to locate ongoing tocilizumab trials.
Results: A total of 13 studies were included in the meta-analysis comprising 2120 patients. The treatment group had lower mortality compared to the control group (OR = 0.42, …

Innovative Statistical Models In Cancer Immunotherapy Trial Design, Jing Wei

Theses and Dissertations--Statistics

A challenge arising in cancer immunotherapy trial design is the presence of non-proportional hazards (NPH) patterns in survival curves. We considered three different NPH patterns caused by delayed treatment effect, cure rate and responder rate of treatment group in this dissertation. These three NPH patterns would violate the proportional hazard model assumption and ignoring any of them in an immunotherapy trial design will result in substantial loss of statistical power.

In this dissertation, four models to deal with NPH patterns are discussed. First, a piecewise proportional hazards model is proposed to incorporate delayed treatment effect into the trial design consideration. …

Integrated Multiple Adaptive Design Involving Sample Size Re-Estimation And (Covariate-Adjusted) Response-Adaptive Randomization For Continuous And Binary Outcomes, Christine M. Orndahl

Theses and Dissertations

Historically, clinical trials have been performed based on decisions made prior to the start of the trial. Adaptive designs have been developed to provide increased flexibility, allowing pre-specified changes to occur based on interim data. Each adaptive design addresses a unique pitfall of a non-adaptive design, such as minimizing the chance of an under- or over-powered study by utilizing interim data to update the sample size estimate (sample size re-estimation) or increasing the ethical benefit of a trial by allocating more participants to the better performing treatment group ([covariate-adjusted] response-adaptive randomization). Additional benefit is attainable by combining more than one …

Responsible Translation Of Stem Cell Research: An Assessment Of Clinical Trial Registration And Publications, Moses Fung, Yan Yuan, Harold Atkins, Qian Shi, Tania M. Bubela

Office of the Provost

We assessed the extent to which the publication of clinical trial results of innovative cell-based interventions reflects International Society for Stem Cell Research best practice guidelines. We assessed: (1) characteristics and time to publication of completed trials; (2) quality of reported trials; and (3) results of published trials. We identified and analyzed publications from 1,052 novel stem cell clinical trials: 179 (45.4%) of 393 completed trials had published results; 48 trials were registered by known stem cell tourism clinics, none of which reported results. Completed non-industry-sponsored trials initially published more rapidly, but differences with industry-sponsored trials decreased over time. Most …

Clinical Trials And Late-Stage Drug Development In Alzheimer’S Disease: An Appraisal From 1984 To 2014, L. S. Schneider, F. Mangialasche, S. Andreasen, H. Feldman, E. Giacobini, R. Jones, V. Mantua, P. Mecocci, L. Pani, B. Winblad, M. Kivipelto

Human Clinical Trials Collection

The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, …

Adaptive Randomization Designs, Jenna Colavincenzo

Statistics

Adaptive design methodologies use prior information to develop a clinical trial design. The goal of an adaptive design is to maintain the integrity and validity of the study while giving the researcher flexibility in identifying the optimal treatment. An example of an adaptive design can be seen in a basic pharmaceutical trial. There are three phases of the overall trial to compare treatments and experimenters use the information from the previous phase to make changes to the subsequent phase before it begins.

Adaptive design methods have been in practice since the 1970s, but have become increasingly complex ever since. One …

Constrained Boundary Monitoring For Group Sequential Clinical Trials, Bart E. Burington, Scott S. Emerson

UW Biostatistics Working Paper Series

Group sequential stopping rules are often used during the conduct of clinical trials in order to attain more ethical treatment of patients and to better address efficiency concerns. Because the use of such stopping rules materially affects the frequentist operating characteristics of the hypothesis test, it is necessary to choose an appropriate stopping rule during the planning of the study. It is often the case, however, that the number and timing of interim analyses are not precisely known at the time of trial design, and thus the implementation of a particular stopping rule must allow for flexible determination of the …

Mixture Hazards Models With Additive Random Effects Accounting For Treatment Effectiveness Lag Time, Ying Qing Chen, C. A. Rohde, M.-C. Wang

U.C. Berkeley Division of Biostatistics Working Paper Series

In many clinical trials to evaluate treatment efficacy, it is believed that there may exist latent treatment effectiveness lag times after which medical treatment procedure or chemical compound would be in full effect. In this article, semiparametric regression models are proposed and studied for estimating the treatment effect accounting for such latent lag times. The new models take advantage of the invariance property of the additive hazards model in marginalising over an additive latent variable; parameters in the models are thus easily estimated and interpreted, while the flexibility of not having to specify the baseline hazard function is preserved. Monte …