Advertisement
Search for

Volume 7, Issue 11, Pages 1156-1163 (November 2009)


View previous. 21 of 41 View next.

Editorial Accompanies ArticleEvidence for Endoscopic Ulcers as Meaningful Surrogate Endpoint for Clinically Significant Upper Gastrointestinal Harm

Andrew MooreCorresponding Author Informationemail address, Ingvar Bjarnason, Byron Cryer§, Luis Garcia–Rodriguez, Larry Goldkind, Angel Lanas#, Lee Simon⁎⁎

published online 13 April 2009.

Refers to article:
Endoscopic Ulcers Are Neither Meaningful Nor Validated as a Surrogate for Clinically Significant Upper Gastrointestinal Harm , 26 June 2009
David Y. Graham
Clinical Gastroenterology and Hepatology
November 2009 (Vol. 7, Issue 11, Pages 1147-1150)
Full Text | Full-Text PDF (208 KB)
Background & Aims

Surrogate endpoints are biomarkers intended to substitute for a clinical endpoint. Are endoscopic ulcers a useful surrogate endpoint for a biological progression to clinical endpoints of ulcer complications (perforation, ulcers, and bleeds), hospital admission, or death?

Methods

Review of randomized trials, meta-analyses, clinical outcomes trials, and observational studies.

Results

No large study examined both endoscopic and clinical endpoints. Endoscopic ulcers and clinically significant ulcer complications were affected in the same direction and to about the same extent in 4 distinct circumstances: (1) by risk factors—age, previous history of symptomatic ulcer or bleeding, Helicobacter pylori, aspirin; (2) in studies of antiulcer treatments with differing modes of action, especially in relation to nonsteroidal anti-inflammatory drug toxicity, and Helicobacter pylori infection; (3) in studies evaluating ulcer complications with Cox-2 selective drugs and nonsteroidal anti-inflammatory drugs; and (4) in studies of interventions in patients with high risk of recurrent ulcer bleed needing nonsteroidal anti-inflammatory drug therapy. All study designs showed consistent and reproducible effects on gastrointestinal ulcer complications paralleling endoscopy.

Conclusions

Consistent and plausible findings from disparate populations and designs make endoscopic ulcers a strong candidate for surrogacy, though direct progression from endoscopic ulcers to ulcer complications cannot be demonstrated. Large outcome studies are needed to establish the power of the surrogacy, absolute risk of clinical outcomes, and to identify the totality of risks and benefits of new pharmacologic therapies.

 Pain Research and Nuffield Department of Anaesthetics, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom

 Department of Medicine, King's College Hospital, Denmark Hill, London, United Kingdom

§ Medical Service, Department of Veterans Affairs Medical Center, Dallas, Texas

 Spanish Centre for Pharmacoepidemiological Research (CEIFE), Madrid, Spain

 Uniformed Services University of Health Sciences, School of Medicine, Bethesda, Maryland

# Department of Gastroenterology, University Hospital, Institute of Health Sciences of Aragon, Zaragoza, Spain

⁎⁎ Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Corresponding Author InformationReprint requests Address requests for reprints to: Dr Andrew Moore, Pain Research and Nuffield Department of Anaesthetics, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom, OX3 9DU. fax: (44) 1865 234539

 Conflicts of interest The authors disclose the following: All the authors have received research grants, consulting, or lecture fees from pharmaceutical companies, charities, and government sources at various times. The authors were involved in discussions concerning a review, supported by Pfizer Inc, for the creation of a white paper for presentation to regulatory authorities. The decision to write this paper was the decision of the authors. Pfizer and its agents had no role in the interpretation of data or writing of the paper, or in the decision to publish. The authors had the absolute right to publish the results of their research regardless of any conclusions reached. No payments were received for preparing this manuscript.

PII: S1542-3565(09)00316-4

doi:10.1016/j.cgh.2009.03.032


View previous. 21 of 41 View next.

Advertisement