Both diagnostics and pharmaceuticals companies are gradually realizing that in many complex diseases, a simple single biomarker is unlikely to be adequate for either prognosis or diagnosis. In response to this trend, the FDA issued draft guidance for industry, clinical laboratories, and FDA staff on what has been termed IVDMIA (In Vitro Diagnostic Multivariate Index Assays). The excerpt from the article provides a good definition:
An IVDMIA is a device that:
1) Combines the values of multiple variables using an interpretation function to yield a single, patient-specific result (e.g., a “classification,” “score,” “index,” etc.), that is
intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment or prevention of disease, and
2) Provides a result whose derivation is non-transparent and cannot be independently derived or verified by the end user.
Three specific examples are given in the draft guidance, including:
a) gene expression profiling devices for breast cancer recurrence classed under classified under 21 CFR 866.6040 (e.g. Genomic Health’s OncoType DX and Agendia’s MammaPrint),
b) device that integrates quantitative results from multiple immunoassays to obtain a qualitative “score” that predicts a person’s risk of developing a disease or condition.
c) device that integrates a patient’s age, sex, and genotype of multiple genes to predict risk of or diagnose a disease or condition.
At Flagship, we are most interested in the second example, and specifically the integration of multiple immunoassay-based biomarkers in tissue (a.k.a. IHC) to determine a score used in prognosis. We have spent many years working on improving reproducibility in IHCs within pharmaceutical drug development. Much of this predates new computer analysis approaches, and includes both common-sense and good histopathology practices. With computer analysis, improving the reproducibility of a single IHC measurement is the first step in then looking at a combined scoring approach.
We have resources in-house and through collaboration for both improving a single IHC measurement in tissue, as well as biostatistical and bioinformatics approaches for how multiple proteins are combined to form a single score. Please contact us to discuss your particular application.