Diagnosis: toxic!--trying to apply approaches of clinical diagnostics and prevalence in toxicology considerations.

The assessment of relevance of toxicological testing was compared with approaches of diagnostic medicine, a discipline that faces a comparable situation. Considering the work of a toxicologist as setting a diagnosis for compounds, assessment tools for diagnostic tests were transferred to toxicological tests. In clinical diagnostics, test uncertainty is well accepted and incorporated in this assessment. Furthermore, prevalence information is considered to evaluate the gain in information resulting from the application of a test. Several common toxicological scenarios, in which test uncertainty and prevalence are combined, are discussed including the interdependence of test accuracy, prevalence and predictive values or the sequential application of a screening and a confirmatory test. In addition, real prevalences derived from prevalences determined by an imperfect test are presented. We conclude that information on prevalences of toxic health effects is required to allow a complete assessment of the relevance of toxicological test. In this process, lessons can be learned from evidence-based approaches in clinical diagnostics.

[1]  Allen F. Shaughnessy,et al.  Clinical Epidemiology: A Basic Science for Clinical Medicine , 2007, BMJ : British Medical Journal.

[2]  E. Murray.  Decision making in health and medicine: integrating evidence and values (with CD). Myriam Hunink, Paul Glasziou, Joanna Siegel, Jane Weeks, Joseph Pliskin, Arthur Elstein, Milton Weinstein. (400 pages, £34.95, US$49.95.) Cambridge University Press, 2001. ISBN 0-521-77029-7. , 2002 .

[3]  A. Baron,et al.  Reference test errors bias the evaluation of diagnostic tests for ischemic heart disease , 1988, Journal of General Internal Medicine.

[4]  J J Gart,et al.  Comparison of a screening test and a reference test in epidemiologic studies. I. Indices of agreement and their relation to prevalence. , 1966, American journal of epidemiology.

[5]  Ebm Notebook,et al.  Transferring evidence from research into practice: 1. The role of clinical care research evidence in clinical decisions , 1996, ACP Journal Club.

[6]  M Liebsch,et al.  The ECVAM International Validation Study on In Vitro Tests for Skin Corrosivity. 2. Results and Evaluation by the Management Team. , 1998, Toxicology in vitro : an international journal published in association with BIBRA.

[7]  S C Weller,et al.  Assessing Rater Performance without a "Gold Standard" Using Consensus Theory , 1997, Medical decision making : an international journal of the Society for Medical Decision Making.

[8]  R. Marshall,et al.  The Predictive Value of Simple Rules for Combining Two Diagnostic Tests , 1989 .

[9]  C. Gatsonis,et al.  Designing studies to ensure that estimates of test accuracy are transferable , 2002, BMJ : British Medical Journal.

[10]  Rodger Curren,et al.  No Prediction Model, No Validation Study , 1996 .

[11]  A P Worth,et al.  The Importance of the Prediction Model in the Validation of Alternative Tests , 2001, Alternatives to laboratory animals : ATLA.

[12]  F. Drudi,et al.  Assessment of the accuracy of diagnostic chest CT scanning. Impact on lung cancer management. , 1996, International surgery.

[13]  Allanou Remi,et al.  Public Availability of Data on EU High Production Volume Chemicals. Part 1. , 2003 .

[14]  K. Schulz,et al.  Uses and abuses of screening tests , 2002, The Lancet.

[15]  U. Epa,et al.  Office of Pollution Prevention and Toxics , 2000 .

[16]  L. Dopson.  Clinical Expertise , 2007, Nursing times.

[17]  B. Ames,et al.  Chemical carcinogenesis: too many rodent carcinogens. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[18]  D. Sackett,et al.  The architecture of diagnostic research , 2002, BMJ : British Medical Journal.

[19]  Sac-fry Stages,et al.  OECD GUIDELINE FOR TESTING OF CHEMICALS , 2002 .

[20]  S D Walter,et al.  Meta-analysis of diagnostic tests with imperfect reference standards. , 1999, Journal of clinical epidemiology.

[21]  J André Knottnerus,et al.  Evaluation of diagnostic procedures , 2002, BMJ : British Medical Journal.

[22]  G J Carr,et al.  An investigation of new toxicity test method performance in validation studies: 3. sensitivity and specificity are not independent of prevalence or distribution of toxicity , 2002, Human & experimental toxicology.

[23]  P. Bossuyt,et al.  BMC Medical Research Methodology , 2002 .

[24]  Spielmann Horst,et al.  Practical Aspects of the Validation of Toxicity Test Procedures , 1995 .

[25]  Gordon H Guyatt,et al.  Clinical expertise in the era of evidence-based medicine and patient choice , 2002, ACP journal club.

[26]  Sebastian Hoffmann,et al.  Skin irritation: prevalence, variability, and regulatory classification of existing in vivo data from industrial chemicals. , 2005, Regulatory toxicology and pharmacology : RTP.

[27]  L. Bruner,et al.  An investigation of new toxicity test method performance in validation studies: 2. comparison of three measures of toxicity test performance , 2002, Human & experimental toxicology.

[28]  Michael Balls,et al.  Report and Recommendations of the CAAT 1 /ERGATT 2 Workshop on the Validation of Toxicity Test Procedures 3 , 1990 .

[29]  M. Weinstein,et al.  Decision Making in Health and Medicine , 2001 .

[30]  E. Keeler,et al.  Primer on certain elements of medical decision making. , 1975, The New England journal of medicine.

[31]  G. Guyatt,et al.  Clinical expertise in the era of evidence-based medicine and patient choice. , 2002, Vox sanguinis.

[32]  J. Knottnerus,et al.  Assessment of the accuracy of diagnostic tests: the cross-sectional study. , 2003, Journal of clinical epidemiology.

[33]  G. Gigerenzer,et al.  AIDS counselling for low-risk clients. , 1998, AIDS care.

[34]  B. Ames,et al.  What do animal cancer tests tell us about human cancer risk?: Overview of analyses of the carcinogenic potency database. , 1998, Drug metabolism reviews.

[35]  Y. T. van der Schouw,et al.  Guidelines for the Assessment of New Diagnostic Tests , 1995, Investigative radiology.

[36]  H Brenner,et al.  Variation of sensitivity, specificity, likelihood ratios and predictive values with disease prevalence. , 1997, Statistics in medicine.

[37]  K. Linnet,et al.  A review on the methodology for assessing diagnostic tests. , 1988, Clinical chemistry.