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Accepted (AM)Open Access (License Unspecified), Open
Journal article
METHODOLOGIC ISSUES IN THE VALIDATION OF PUTATIVE BIOMARKERS AND SURROGATE ENDPOINTS IN TREATMENT EVALUATION FOR SYSTEMIC LUPUS ERYTHEMATOSUS
Endocrine, metabolic & immune disorders drug targets, v 9(1), pp 108-112
01 Mar 2009
PMID: 19275685
Abstract
No new drugs have been approved for the treatment of systemic lupus erythematosus (SLE) by the FDA for the last 30 years and one barrier has been the lack of validated of biomarkers and surrogate endpoints. Validation of SLE biomarkers in the past have been methodologically flawed. We put forth a conceptual framework and the five critical criterion for validating putative biomarkers and bio-surrogates in this heterogeneous multi-system disease with protean manifestations. Using the example of a putative biomarker for end-stage renal disease from lupus nephritis, we also performed computer simulations for planning a biomarker bio-repository to support the validation process. “Random time window” sampling where a biomarker is obtained in an interval randomly selected from the total follow-up time for that subject yields serious ‘survival bias’. This can be avoided by the “fixed calendar window” design, in which biomarkers are measured within the same, pre-specified period for all cohort members who remain at risk during that period. In lupus nephritis where the incidence rate of end-stage renal disease is relatively low, to accumulate 300 instances of end-stage renal disease, at risk patients would have to be followed for about 5,000 person-years, implying 500 subjects followed, on average, for about 10 years. Increasing the number of biomarker determinations per subject from one to five reduces the required number of subjects by 10-15%, while further increases of the number of observations per subject yielded much smaller gains. The large numbers of subjects required for a bio-repository, makes it essential to maximize the efficiency of study designs and analyses and provides the strongest rationale for collaboration and the use of standardized measures to ensure comparability.
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9 citations in Scopus
Details
- Title
- METHODOLOGIC ISSUES IN THE VALIDATION OF PUTATIVE BIOMARKERS AND SURROGATE ENDPOINTS IN TREATMENT EVALUATION FOR SYSTEMIC LUPUS ERYTHEMATOSUS
- Creators
- Matthew H. Liang - Brigham and Women's HospitalJulia F. SimardKaren CostenbaderBenjamin T. DoreMichael WardPaul R. FortinGabor G. IlleiSusan ManziBarbara MittlemanJill BuyonSamardeep GuptaMichal Abrahamowicz
- Publication Details
- Endocrine, metabolic & immune disorders drug targets, v 9(1), pp 108-112
- Publisher
- Bentham
- Number of pages
- 5
- Grant note
- Z01 AR041153-03 || AR / National Institute of Arthritis and Musculoskeletal and Skin Diseases : NIAMS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Scopus ID
- 2-s2.0-65549161447
- Other Identifier
- 991021934006904721