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Horvath AR. PL3-1: Evidence Based Laboratory Medicine - What study design answers my question best? Biochemia Medica 2009;19(Suppl 1):S11-S12.
Department of Laboratory Medicine, University of Szeged, Medical Faculty, Albert Szent-Györgyi Clinical Centre, Szeged, Hungary
*Corresponding author: ahorvath [at] clab [dot] szote [dot] u-szeged [dot] hu
 
Abstract
 
A test is a procedure that makes use of an assay in the context of a particular disease, in a particular population, for a particular purpose, followed by specific action(s). Laboratory tests have clinical value only if they provide benefit to patients at acceptable costs. Translational research aims to decrease the gap between the identification of new biomarkers and proving that these are clinically effective and improve patient-centred, or organizational or economic outcomes. Nevertheless, new laboratory tests are often released to market with little evidence supporting their value or impact in clinical practice. Since resources are finite, evidence-based decisions about the use of diagnostic interventions should depend on well-designed and conducted test evaluation studies and technology appraisals. It has been shown, however, that studies of the same test can produce varying estimates of diagnostic accuracy depending on choices and conduct of study design.
After initial discovery of new biomarkers, careful consideration should be given to its purpose, the context and the clinical pathway for its application, the population and healthcare setting in which the test is intended to be used, and its potential consequences in clinical practice. No new test should be subjected to tedious evaluation if the test is unlikely to result in improved clinical actions or measurable outcomes. Test evaluation should be carried out with carefully planned study designs appropriate for the questions addressed at each stage of development. The rigour and depth of evaluation should be proportionate to the questions and expected outcomes being addressed. The below steps are proposed when investigating the value of testing:
Phase I: Basic research into the association of disease with the new biomarker: i.e., Do patients with the target disorder have different test results from normal individuals? This question is best addressed by case-control designs.
Phase II: Clinical research into the validity of tests: i.e., In patients suspected of having the target condition will the test distinguish those with and without the disorder? This question should be investigated in cross-sectional diagnostic accuracy studies in a representative spectrum of consecutively enrolled patients.
Phase III: Clinical application/utility of tests: i.e., Do patients who undergo the test fare better (in terms of health outcomes) than those who do not? The most suitable study design for this type of question is an RCT or meta-analysis of multiple RCTs.
Phase IV: Impact of testing in practice: i.e., What are the ethical, legal, financial or social implications of testing? This is best explored by heath technology assessment.
The evidence-based methodology of these steps is reviewed and the pitfalls and potential biases in test evaluation studies are highlighted with practical examples.

In conclusion, clinical utilization and reimbursement for laboratory tests should move from a cost-based towards a value- and evidence-based approach. A multidisciplinary, more responsive and proportionate risk assessment during pre-market approval of new tests is needed to ensure patient safety.