Use of composite outcomes to assess risk-benefit in clinical trials

Clinical Trials : Journal of the Society for Clinical Trials
Pamela A Shaw

Abstract

Before a novel treatment can be deemed a clinical success, an assessment of its risk-benefit profile must be made. One of the inherent challenges for this assessment comes from the multiplicity that arises from comparing treatment groups across multiple outcomes. Composite outcomes that summarize a patient's clinical status, or severity, across a prioritized list of safety and efficacy outcomes have become increasing popular. In this article, we review these approaches and illustrate through examples some of the challenges and complexities of a composite derived from prioritized outcomes, such as the win ratio. These challenges include the difficult tension between the analytical validity that comes from choosing a pre-specified outcome and an evaluation that is responsive to unexpected safety events that arise during the course of a trial. Other challenges include a sensitivity of the resulting test statistic to the underlying censoring distribution and other nuisance parameters. Approaches that resolve some of the difficulties of the analytical challenges associated with prioritized outcomes are then discussed. Ultimately, a composite outcome of net clinical benefit is another decision tool, but one to be used alongside more ...Continue Reading

References

Aug 1, 1991·The New England Journal of Medicine·UNKNOWN SOLVD InvestigatorsJay N Cohn
May 30, 1997·Statistics in Medicine·L E Bjorling, J S Hodges
Jul 10, 1999·Statistics in Medicine·D M Finkelstein, D A Schoenfeld
Jul 19, 2002·JAMA : the Journal of the American Medical Association·Jacques E RossouwUNKNOWN Writing Group for the Women's Health Initiative Investigators
Oct 31, 2002·Statistics in Medicine·Dean A Follmann
Oct 25, 2003·Annals of Epidemiology·Jennifer HaysJacques E Rossouw
Apr 15, 2004·JAMA : the Journal of the American Medical Association·Garnet L AndersonUNKNOWN Women's Health Initiative Steering Committee
Oct 19, 2005·Journal of Cardiac Failure·James D NeatonMarvin A Konstam
Aug 24, 2007·Clinical Trials : Journal of the Society for Clinical Trials·Janet WittesSalim Yusuf
Aug 20, 2010·BMJ : British Medical Journal·Gloria CordobaPeter C Gøtzsche
Jun 1, 2011·Journal of the American Statistical Association·Aiyi LiuKai F Yu
Jan 26, 2012·Statistical Methods in Medical Research·Jeffrey A BakalPaul W Armstrong
Oct 15, 2013·Statistics in Medicine·Geraldine RauchMeinhard Kieser
Feb 7, 2014·Statistics in Medicine·Dianne M Finkelstein, David A Schoenfeld
Jun 27, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Scott R EvansHenry F Chambers
Apr 10, 2016·Statistics in Medicine·Pamela A Shaw, Michael P Fay
Jan 4, 2017·Journal of Clinical Tuberculosis and Other Mycobacterial Diseases·Grace MontepiedraScott R Evans
Mar 28, 2017·Statistics in Medicine·Xiaodong LuoHong Tian
Jun 7, 2017·Circulation·Paul W Armstrong, Cynthia M Westerhout
Dec 1, 2017·The Pediatric Infectious Disease Journal·Konstantia AngelidouUNKNOWN International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) P1060 Study Team

❮ Previous
Next ❯

Citations

Dec 30, 2018·Clinical Journal of the American Society of Nephrology : CJASN·Katherine G GarloKevin E Chan
Aug 8, 2019·Clinical Trials : Journal of the Society for Clinical Trials·Ales KotalikJames D Neaton

❮ Previous
Next ❯

Methods Mentioned

BETA
hormone replacement therapy

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.