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Written on: 26. 05. 2009 [11:04]
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Boutros
Nashaat Boutros
registered since: 01.01.1970
Posts: 0
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 The recent emphasis on developing endophenotypes has, to a significant degree, deemphasized the complete lack of and the serious needs for developing objective laboratory-based diagnostic disease markers. There are a number of such candidates. For example P300 decreased amplitude in schizophrenia is foremost among these measures. Other candidates include sensory gating in schizophrenia, REM sleep changes in major depression, and lactate infusion in panic attacks.
The clinical applications of a biological finding in psychiatry is difficult and must be approached with great caution. While criteria for endophenotypes are reasonably widely accepted, criteria for diagnostic markers are much less developed.
The development of ancillary diagnostic procedures is important to help the field
move forward as diagnosis in psychiatry remains the major limiting step in biological research and treatment studies. In order to promote a standard approach we have proposed a four-step process for developing laboratory-based diagnostic tests for use in aiding the diagnostic process in psychiatry (Boutros and Arfken, 2007). The Four-Step approach proposed is based on the guidelines for deciding the clinical usefulness of diagnostic tests recently published as the Standard for Reporting Diagnostic tests (STARD) (Bossuyt et al., 2003).
For Step 1, a biological variable is observed to be deviant from healthy controls in a particular patient population. The demonstration of test-retest reliability and replication and confirmation by independent groups is essential for this particular test to move into the next step. Step 2 involves demonstrating the potential clinical usefulness of the specific finding. The objectives at this step are demonstration of difference between the target patient population and appropriate comparison groups. Abnormalities with significant differential prevalence among disorders to be differentiated are likely to be able to significantly contribute to the differential diagnostic process and should progress to Step 3. Estimation of the effect size of the finding could be a reasonable guide to which findings should be considered good candidates for Step 3 studies.
During Step 3 the performance characteristics of the test should be established. Specifically, the sensitivity, specificity, positive and negative predictive values of the biological marker should be examined. These data should allow the estimation of the added diagnostic value resulting from incorporating the test into the work-up of a particular patient. The choice of the “gold standard” or reference test is an essential component of this step. This is the standard against which the test being developed will be measured. The currently accepted gold standard in psychiatric diagnosis is the “Best Estimate Diagnosis”. Best Estimate Diagnosis is reached by agreement among a number of experts relying on multiple sources of information and with a standardized scale with demonstrated validity and reliability. At this step, the clinical characteristics of the patient group identified by the test are usually further delineated. Step 4 defines the clinical application of the test and helps standardize the technique used in large and multicenter clinical trials. Multicenter trials should pave the road towards standardization of laboratory procedures used to conduct the test as well as providing data regarding cost effectiveness and impact on both short-term and long-term clinical outcomes. Step 4 studies should begin to develop larger normative databases that can eventually be used to examine an individual’s data. Development of such databases can be challenging and will require collaboration among research groups concerned with the specific test being developed. The required standardization must precisely define the stimuli, the task parameters, the instructions set, and the testing environment, as well as the methods used to quantify and analyze the data.
While advancing science requires “innovation”, developing diagnostic testing requires standardization. Studies wishing to contribute to the development of diagnostic testing should thus adhere to the methodology that yields maximal differentiation of the target group from groups of patients frequently appearing on the same differential diagnostic tests.
Boutros NN, Arfken CL. A four-step approach to developing diagnostic testing in psychiatry. Clin EEG and Neuroscience 38 (2); 62-65, 2007
Bussuyt PM, Reitsma JB, Bruns DE: Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD initiative. Clin Chem 2003; 49:1-6.
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