PMID: 9160496May 15, 1997Paper

Adjusting for non-compliance and contamination in randomized clinical trials

Statistics in Medicine
J CuzickN Segnan

Abstract

A method of analysis is presented for estimating the magnitude of a treatment effect among compliers in a clinical trial which is asymptotically unbiased and respects the randomization. The approach is valid even when compliers have a different baseline risk than non-compliers. Adjustments for contamination (use of the treatment by individuals in the control arm) are also developed. When the baseline failure rates in non-compliers and contaminators are the same as those who accept their allocated treatment, the method produces larger treatment effects than an 'intent-to-treat' analysis, but the confidence limits are also wider, and (even without this assumption) asymptotically the efficiencies are the same. In addition to providing a better estimate of the true effect of a treatment in compliers, the method also provides a more realistic confidence interval, which can be especially important for trials aimed at showing the equivalence of two treatments. In this case the intent-to-treat analysis can give unrealistically narrow confidence intervals if substantial numbers of patients elect to have the treatment they were not randomized to receive.

Citations

Sep 10, 1999·BMJ : British Medical Journal·S Hollis, F Campbell
Jun 18, 2003·BMC Medical Research Methodology·Stuart G Baker, Barnett S Kramer
Aug 16, 2006·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·Catherine E HewittJeremy N V Miles
Oct 18, 2008·Journal of Medical Screening·Stuart G BakerPhilip C Prorok
Jul 4, 2009·Journal of the National Cancer Institute·Stuart G Baker
Sep 8, 2010·Clinical Trials : Journal of the Society for Clinical Trials·Simon J Bond, Ian R White
Sep 11, 2010·AIDS·Keri N AlthoffUNKNOWN North American AIDS Cohorts Collaboration on Research, Design (NA-ACCORD)
Nov 3, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·E David CrawfordAnthony V D'Amico
Oct 20, 2006·The Gerontologist·Tamara L Smith, Ronald W Toseland
Aug 25, 2005·Acta Oncologica·Matti HakamaLars Påhlman
May 27, 2011·Acta Oncologica·Meelan Bul, Fritz H Schröder
Mar 30, 2005·Expert Opinion on Pharmacotherapy·Calogero CammàAntonio Craxì
Aug 5, 2015·Statistics in Medicine·Stuart G BakerKaren S Lindeman
Mar 24, 2015·Journal of Pediatric Psychology·Chad E ShenkHeather E Bensman
Nov 5, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S J OttoH J de Koning
Nov 5, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Fritz H SchröderMonique J Roobol
Sep 14, 2010·Lancet·V Paul Doria-RosePhilip C Prorok
May 1, 2010·Lancet·Wendy S AtkinUNKNOWN UK Flexible Sigmoidoscopy Trial Investigators
Apr 7, 2010·European Urology·Fritz H Schröder, Monique J Roobol
Apr 29, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Doris Schopper, Chris de Wolf
Sep 2, 2005·Biometrics·Shigeyuki Matsui
Oct 1, 2003·Statistics in Medicine·Michael Branson, John Whitehead
Apr 11, 2003·Statistics in Medicine·Marshall M Joffe, Colleen Brensinger
Jan 13, 2006·Biometrics·Ross L PrenticeGarnet L Anderson
Nov 16, 2005·Statistics in Medicine·Xiao-Hua Zhou, Sierra M Li
Oct 13, 2005·Statistics in Medicine·Dan Sheng, Mimi Y Kim

❮ 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.