Clinical genomics laboratories are increasingly looking to liquid biopsy cancer assays to complement their current solid tumor assays. Compared to their solid tumor assay counterparts, circulating tumor DNA (ctDNA) assays offer a different set of challenges to consider for clinical labs. One of the most important of which, is to develop a set of reagents that are appropriately validated to determine the critical performance of the assay across many parameters. The ctDNA targets of liquid biopsy assays are typically at much lower allelic frequencies and require a robust and reproducibly designed assay to consistently detect these important variants.
SeraCare’s new Seraseq™ Circulating Tumor Reference Materials
Insight from the 2017 Precision Medicine World Conference
Accuracy of NGS results is extremely critical for clinical genomic laboratories, when developing, validating or running an assay. At the 2017 Precision Medicine World Conference a panel discussion entitled ‘Achieving Accurate NGS Test Results’ featured Dr. Greg Tsongalis, Director of Clinical Genomics and Advanced Technology at Dartmouth Hitchcock Medical Center; Dr. Dara Aisner, Associate Professor of Pathology at University of Colorado Anschutz Medical Campus School of Medicine; and Dr. Russell Garlick,
Chief Scientific Officer of SeraCare Life Sciences.
iQ™ NGS QC Management software for easy assessment of assay performance
As a manager of a clinical genomics laboratory, how many times have you been faced with the following situations?
- You need to produce trending performance data over the past three months as a part of an internal audit
- You need to examine the last runs performed that used a particular piece of equipment that you suspect may be out of specification
- You need to produce a QC report for an upcoming regulatory inspection
- You need to find out root cause of an assay failure
The Chair of Molecular Diagnostics, Department of Pathology at Virginia Commonwealth University shares her success story
As a 25-year veteran of clinical molecular diagnostics, Dr. Andrea Ferreira-Gonzalez has seen many changes in genetic technologies used in the testing laboratory. With the advent of personalized medicine and using multi-gene NGS panels as a laboratory-developed test, Dr. Ferreira-Gonzalez and other experts have agreed to lend their expertise to the design of SeraCare’s reference materials.
She and other groups have participated in an interlaboratory test of standardized reference materials for detecting cancer somatic mutations, with results that will be published in the coming months.
A 0.1% measurement requires a reasonable amount of input material
The field of circulating tumor DNA analysis (ctDNA, also sometimes called in a larger context “liquid biopsy”) holds great promise for monitoring response to cancer treatment, assisting therapeutic choice, monitoring recurrence, and for pre-cancer screening. As such there is a great amount of assay development and ongoing clinical trials; at ClinicalTrials.gov searching for the term "Circulating DNA" you can find over 180 open clinical trials for a wide range of tumor types and interventions.
How do I know my NGS-based LDT is producing the right results? And how do my results compare with others running similar tests?
If you’re involved with complex diagnostic tests — in particular, next generation sequencing (NGS)-based laboratory-developed tests (LDTs) — producing the right results consistently can be a big concern. Your test equation has many different variables, each of which carries a chance of something going wrong:
- The multiple manual steps of the wet lab work.
- The vagaries and many parameters on the dry lab (bioinformatics) analyses.
- The challenge of interpretation (depending on the nature of the test).
When an LDT Goes Wrong
The recent high-profile fiasco at fingerstick microfluidics diagnostics company Theranos Incorporated is a case study on the genuine harm testing errors can inflict on patients.
The Wall Street Journal reports that the undue anxiety and other harm patients experienced from incorrect test results sparked at least 10 lawsuits against the company in California and Arizona.
“While inaccurate test results can occur at any laboratory, Theranos failed to maintain basic safeguards to ensure consistent results, according to regulators, independent lab directors and quality-control experts.”
Theranos may be one extreme example, but in late 2015, the U.S. Food and Drug Administration (FDA) published a report outlining 20 instances of harm from LDTs.
The acute dangers of false-positive and false-negative results from laboratory developed tests are real:
- When patients are told they have conditions they do not actually have, it can cause unneeded distress and unnecessary treatment.
- When life-threatening diseases go undetected, patients can suffer and die.
In our experience, NGS-based LDTs are error-prone for two main reasons:
- The inadequacy of “known positive” samples.
- The lack of peer review for comparing one lab’s results with another’s.
Here, we’ll take a closer look at each problem and suggest a solution.
For clinical genomics testing laboratories, validation — and to a certain extent, revalidation — is a fact of life.
For clinical genomics testing laboratories, validation — and to a certain extent, revalidation — is a fact of life. It’s written into the CAP/CLIA regulations.
The regulations say you must validate:
- Any new FDA-cleared test your lab introduces.
- Any modifications you make to an FDA-cleared test.
- Any laboratory-developed (LDT) test not subject to FDA regulation.
In the case of the first one, validation means you can replicate the performance specifications determined by the manufacturer of the test. In the second two, however, validation involves determining the performance specifications yourself (in seven areas, as outlined by CLIA).
How do you go about testing the accuracy of a test your lab purchased or determining the accuracy of a test your lab designed?
While clinical genomics labs (those running NGS-based laboratory developed tests) are not currently subject to FDA oversight, that doesn’t mean they won’t be someday. The question is, how soon will that day come and, when it does, will your lab be ready?
Topics: FDA Regualtions
When you’re in charge of quality control (QC) for a clinical genomics testing laboratory, you know that one word — quality — casts a wide net. For you, quality means (among many other things):
Topics: Lab Management
Do remnant patient samples perform well enough to train new laboratory personnel quickly and assess their proficiency?
Due to either staff turnover or increased testing demand, your clinical genomics laboratory is expanding. You need your new personnel trained and ready to perform at the same high level as the rest of your staff as soon as possible.
You know that the best training programs are guided ones, with samples and workflows similar to those your new staff members will encounter on a day-to-day basis.
Are your remnant patient samples up to the task?
Topics: Employee Training