Holger Schünemann Yngve Falck-Ytter AHRQ Annual Conference Washington, September 8, 2008. GRADE Introduction. Disclosure.
In the past three years, Dr. Schünemann received no personal payments for service from the pharmaceutical industry. His research group received research grants and - until April 2008 - fees and/or honoraria that were deposited into research accounts from Chiesi Foundation and Lily, as lecture fees related to research methodology. He is documents editor for the American Thoracic Society. Institutions or organizations that he is affiliated with likely receive funding from for-profit sponsors that are supporting infrastructure and research that may serve his work.
GRADE working group. BMJ. 2004 & 2008
CMAJ 2003, BMJ 2004, BMC 2004, BMC 2005, AJRCCM 2006, Chest 2006, BMJ 2008
Dana Best, assistant professorb
Martin Eccles, professord
Francoise Cluzeau, lecturerx
Yngve Falck-Ytter, associate directore
Signe Flottorp, researcherf
Gordon H Guyatt, professorg
Robin T Harbour, quality and information director h
Margaret C Haugh, methodologisti
David Henry, professorj
Suzanne Hill, senior lecturerj
Roman Jaeschke, clinical professork
Regina Kunx, Associate Professor
Gillian Leng, guidelines programme directorl
Alessandro Liberati, professorm
Nicola Magrini, directorn
James Mason, professord
Philippa Middleton, honorary research fellowo
Jacek Mrukowicz, executive directorp
Dianne O’Connell, senior epidemiologistq
Andrew D Oxman, directorf
Bob Phillips, associate fellowr
Holger J Schünemann, professorg,s
Tessa Tan-Torres Edejer, medical officert
David Tovey, Editory
Jane Thomas, Lecturer, UK
Helena Varonen, associate editoru
Gunn E Vist, researcherf
John W Williams Jr, professorv
Stephanie Zaza, project directorw
a) Agency for Healthcare Research and Quality,USA
b) Children's National Medical Center, USA
c) Centers for Disease Control and Prevention, USA
d) University of Newcastle upon Tyne, UK
e) German Cochrane Centre, Germany
f) Norwegian Centre for Health Services, Norway
g) McMaster University, Canada
h) Scottish Intercollegiate Guidelines Network, UK
i) Fédération Nationale des Centres de Lutte Contre le Cancer, France
j) University of Newcastle, Australia
k) McMaster University, Canada
l) National Institute for Clinical Excellence, UK
m) Università di Modena e Reggio Emilia, Italy
n) Centro per la Valutazione della Efficacia della Assistenza Sanitaria, Italy
o) Australasian Cochrane Centre, Australia
p) Polish Institute for Evidence Based Medicine, Poland
q) The Cancer Council, Australia
r) Centre for Evidence-based Medicine, UK
s) National Cancer Institute, Italy
t) World Health Organisation, Switzerland
u) Finnish Medical Society Duodecim, Finland
v) Duke University Medical Center, USA
w) Centers for Disease Control and Prevention, USA
x) University of London, UK
Y) BMJ Clinical Evidence, UKGRADE Working Group
Clear separation of 2 issues:
1) 4 categories of quality of evidence: very low, low, moderate, or high quality?
2) Recommendation: 2 grades - weak or strong (for or against)?
“Extent to which confidence in estimate of effect adequate to support decision”
Overall judgment required
Example: a systematic review of topical treatments for seasonal allergic conjunctivitis showed that patients using topical sodium cromoglycate were more likely to perceive benefit than those using placebo. However, only small trials reported clinically and statistically significant benefits of active treatment, while a larger trial showed a much smaller and a statistically not significant effect (Owen 2004 ). These findings suggest that smaller studies demonstrating smaller effects might not have been published.
(higher INR – increased bleeding)
Summary of Findings
A 68 year old male long-term patient of yours. He suffers from COPD but is unable to stop smoking after over 30 years of tobacco use. He has been taking beta-carotene supplements for several months because someone in the “healthy food” store recommended it to prevent cancer.
He wants to know whether this will prevent him from getting cancer and whether he should use beta-carotene.
Population: In smokers with COPD
Intervention: does beta-carotene suppl
Comparison: compared to no suppl.
Outcomes: reduce the risk of COPD symptoms, lung cancer
and death and improve PFTs?
1) The Alpha-Tocopherol Beta-Carotene (ATBC) trial randomly assigned 29,133 people to receive beta carotene, tocopherol, both, or placebo.
Study participants averaged 57.2 years of age, 20.4 cigarettes per day, and 35.9 years of smoking. They were followed up for 5 to 8 years.
RR for lung cancer = 1.16 (95% CI 1.02-1.33)
Albanes et al, JNCI, 1996
2) The Beta-Carotene and Retinol Efficacy Trial (CARET) evaluated high-risk current and former smokers with a 20–pack-year history of smoking (n = 14,254), ~ 60 years old.
The participants were randomly assigned to receive either a combination of beta carotene and vitamin A or placebo. Mean length of follow up: 4 years.
RR for lung cancer = 1.28 (95% CI 1.04-1.57)
Table. Decisions about the strength of a recommendation
Frequent “yes” answers will increase the likelihood of a weak recommendation
In patients with COPD who continue to smoke, we recommend stopping beta-carotene supplementation.
In patients with COPD who continue to smoke, clinicians should stop beta-carotene supplementation.