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Special Communication |

Clinical Epidemiological Quality in Molecular Genetic Research:  The Need for Methodological Standards

Sidney T. Bogardus, Jr, MD; John Concato, MD, MS, MPH; Alvan R. Feinstein, MD, MS
JAMA. 1999;281(20):1919-1926. doi:10.1001/jama.281.20.1919.
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Context  A genetic basis has been identified for many medical conditions and some molecular tests have been commercialized. However, little attention has been given to the quality of clinical epidemiology in molecular studies.

Objective  To examine the clinical epidemiological quality of recent publications on molecular genetic analysis.

Design  Cross-sectional study of original research articles published in 1995, identified by manually searching 4 general clinical journals. Of 83 articles identified, 40 were selected for analysis; these 40 discussed molecular genetic techniques, studied 10 or more patients, and had inferential conclusions.

Main Outcome Measure  Compliance of the selected articles with 7 methodological standards for clinical epidemiological science (reproducibility, objectivity, delineation of case group, adequacy of spectrum in case group, delineation of comparison group, adequacy of comparison group, and quantitative summary of results).

Results  Among the 40 inferential articles that studied 10 or more patients, only 5 (12.5%) complied with all 7 applicable standards, and 10 (25.0%) complied with all but 1 standard, whereas 25 articles (62.5%) failed to comply with 2 or more standards and 9 (22.5%) failed 4 or 5 standards. Most articles did not comply with standards for reproducibility (n=25, 62.5%) or objectivity (n=27, 67.5%); however, the majority of articles did comply with standards for adequacy of case group (n=35, 87.5%), adequacy of comparison group (n=35, 87.5%), and quantitative summary of results (n=36, 90%).

Conclusions  Despite major laboratory advances in molecular genetic analysis, our data suggest that reported applications in clinical journals often have troubling omissions, deficiencies, and lack of attention to the different, but necessary, principles of clinical epidemiological science. Without suitable attention to fundamental methodological standards, the expected benefits of molecular genetic testing may not be achieved.

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