Is Your Biomedical Research Accurate and Precise?
In biomedical research, scientists need the ability to accurately and precisely measure a biomarker or set of biomarkers in some disease vs. healthy experimental design. The ability to measure something depends on the ability of the measurement methodology, including analytical tools, to accurately and precisely quantify the true value for the object of interest.
- Accuracy: How close is the measurement to the actual quantity?
- Precision: How reproducible is the measurement?
In some cases, greater than 70% of research is irreproducible and carries a staggering cost of $28B/year in wasted funding in the U.S. alone.
Neither accurate nor precise
In recent months, the significant problem of irreproducibility in biomedical research has come to light. The issue has created such a storm that the NIH has established new guidelines and requirements around “Rigor and Reproducibility” in all grant applications moving forward. To further compound the issue, more than 75 high-impact journals have endorsed the new NIH requirements and anticipate that researchers will be submitting data in adherence to the new requirements.
One fundamental cause
The single largest contributor to the problem of irreproducibility in biomedical research is biological reagents and reference materials. In combination, these factors account for over 36% of the $28B of wasted U.S. research funding, costing our industry over $10B annually.
The call for improved cell lines and antibodies has been wide-spread and convicting. Issues of non-specificity and lot-to-lot variability in antibody-based technologies have been painfully portrayed in a number of high-profile articles and cited as the reason for high impact retractions. One in Nature commentary went so far as to claim that “antibodies are the workhorse of biomedical research and they are littering the landscape with false findings” (Baker, 2015).
An expensive requirement
In a drive to reduce these sources of irreproducibility and as part of the new guidelines for “Rigor and Reproducibility,” NIH now requires an authentication plan for all key biological and chemical resources in all grant applications. In short, researchers will need to detail how their lab will validate any of the biological or chemical resources to be used in the proposed study. The requirement extends to reagents purchased from third-party vendors including antibody-based kit manufacturers.
One outcome will be the addition of significant cost and time burdens to new research projects.
A powerful alternative
Liquid chromatography and mass spectrometry-based technologies (LC-MS) offer an attractive alternative to antibody-based technologies. Measuring a wide range of small and large biomarkers without the need for antibodies, LC-MS systems provide an analytical platform that can accurately and precisely quantify biomarkers in a variety of matrices.
Working off of principles of mass detection and quantitation, LC-MS separates and “weighs” each of the components of a sample leading to the identification of compounds of interest. Importantly, LCMS provides a direct measurement of the molecules of interest; there are no surrogates such as antibodies or florescence. A significant benefit of LC-MS is the ability to quantitatively measure multiple biomarkers in a single sample.
The analytical capability to reproducibly quantitate complete biological pathways accurately and precisely provides biomedical researchers unprecedented visibility into mechanisms of biology and disease that promises to accelerate novel discoveries.