Optimal group-sequential designs for simultaneous testing of superiority and non-inferiority

Statistics in Medicine
Fredrik Ohrn, Christopher Jennison

Abstract

Confirmatory clinical trials comparing the efficacy of a new treatment with an active control typically aim at demonstrating either superiority or non-inferiority. In the latter case, the objective is to show that the experimental treatment is not worse than the active control by more than a pre-specified non-inferiority margin. We consider two classes of group-sequential designs that combine the superiority and non-inferiority objectives: non-adaptive designs with fixed group sizes and adaptive designs where future group sizes may be based on the observed treatment effect. For both classes, we derive group-sequential designs meeting error probability constraints that have the lowest possible expected sample size averaged over a set of values of the treatment effect. These optimized designs provide an efficient means of reducing expected sample size under a range of treatment effects, even when the separate objectives of proving superiority and non-inferiority would require quite different fixed sample sizes. We also present error spending versions of group-sequential designs that are easily implementable and can handle unpredictable group sizes or information levels. We find the adaptive choice of group sizes to yield some mod...Continue Reading

References

Nov 1, 1995·Journal of Biopharmaceutical Statistics·T Morikawa, M Yoshida
Feb 24, 2001·Statistical Methods in Medical Research·B SpiessensD L DeMets
Mar 11, 2003·Statistics in Medicine·Christopher Jennison, Bruce W Turnbull
May 24, 2003·Biometrics·W BrannathM Posch
Oct 13, 2005·Statistics in Medicine·Christopher Jennison, Bruce W Turnbull
May 23, 2007·Diabetic Medicine : a Journal of the British Diabetic Association·P D HomeUNKNOWN RECORD Study Group
Oct 2, 2007·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Burkhard GökeUNKNOWN GALLANT 8 Study Group

❮ Previous
Next ❯

Citations

Nov 6, 2014·Journal of Biopharmaceutical Statistics·Toshifumi SugitaniWilli Maurer
Mar 23, 2012·Statistics in Medicine·Y H Joshua Chen, Cong Chen
Oct 16, 2014·Statistics in Medicine·Lisa V Hampson, Christopher Jennison
Sep 17, 2011·Clinical Trials : Journal of the Society for Clinical Trials·Valerie DurkalskiDaniel Lowenstein
Feb 10, 2017·Clinical Trials : Journal of the Society for Clinical Trials·Bruce W Turnbull
Sep 21, 2016·Statistical Methods in Medical Research·Junjiang ZhongSiu Hung Cheung
Oct 22, 2014·World Journal of Methodology·Charles F Babbs
Jan 22, 2013·Journal of Biopharmaceutical Statistics·Hui QuanYujun Wu

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.