Far, far away….the Association of Molecular Pathology (AMP) has a bad feeling about the FDA’s recent report….
After reviewing the case studies, the Association for Molecular Pathology (AMP) concluded that Han Solo of the 20 tests identified by the FDA could cause patient harms that FDA oversight might have prevented. “This is a story about the facts the FDA Ignored: An analysis of the FDA report.”
- AMP has a bad feeling about this
- Of the 20 case studies, if you’re Wookie only a few would have been prevented with FDA oversight
- CMS reimbursement code ‘C3PO’ doesn’t exist
“Don’t be a (Storm) trooper” states AMP, “…the report fails to acknowledge that even if all of the case studies presented had concerns that might have been addressed by FDA oversight (although, this is clearly not the case), these tests are a miniscule fraction of the thousands of LDPs that are designed, developed, validated, and interpreted by appropriately trained and qualified health care professionals.”
If you Luke further, AMP puts a good argument across. Focusing on the BRAF V600E Genetic Mutation Test to Guide Melanoma Treatment, they pick out 4 key points.
death star star killer base only has a single use
The only FDA approved test on the market, tests for a single BRAF V600E. Whilst this is the biggest biomarker to test for (see table below) with over 80% of patients having genotype, it is only a single use. Much like the death star, yes it’s great and it will destroy a planet, but that’s all it does (and we all know there’s always a conveniently placed hole to blow it up).
The drug, Vemurafenib, prolongs both progression-free and overall survival in melanoma patients whose tumors contain a V600 mutation. So what about V600G/K/M/R?
Real point 1: “The FDA approved test reliably only detects a single codon 600 mutation: V600E”
2. Snoke no further, we’ve already found the Jedi temple
In August 2011, FDA approved the in vitro diagnostic Roche Cobas® 4800 test as a commercially distributed companion diagnostic to detect the BRAF V600 mutation, whereupon at least nine laboratories announced that they were offering their own LDT version of the BRAF test for the same intended use.
Real point 2: “BRAF testing has been effectively performed as an LDP for over 10 years, most commonly for patients with colon cancer and thyroid cancer. Therefore, it is disingenuous and misleading for FDA to imply that the manufacturer it cited discovered the BRAF marker or invented BRAF testing.”
3. The droid’s name is R2D2… not R1D1
Responses (R) to Drugs (D) are no longer a 1:1 ratio. The advances in NGS and genomics has led to a greater understanding of the driving force behind cancerous mutations and how to stop them. Within a single pathway, multiple biomarkers now drive drug responses. If you followed the reasoning, it would mean that the FDA would force laboratories to maintain multiple tests for the identical marker…?
Real point 3: “The logical conclusion to which FDA’s reasoning leads, is that laboratories would need to order the particular FDA approved test for each drug that is directed toward any given molecular maker. This impractical and unnecessary reasoning means that FDA would force laboratories to maintain multiple tests for the identical marker, with the use of each test solely dependent on the specific drug the physician would want to give. “
4. Why use a gun when you have a lightsaber?
and even a cleaner can use a lightsaber….
AMP’s fourth and final point on FDA-regulated tests is that they are just not as good as LDPs. Take the FDA approved test for KRAS that looks at codons 12 & 13 in exon 2. Now look at NCCN/ASCO guidelines and you can quite quickly find that you should probably be looking at exons 3 and 4 as well, ergo….lightsaber beats a gun?
Real point 4: “The deficiencies in FDA’s position are well-illustrated by the FDA approved test for KRAS-mutation testing in metastatic colorectal cancer. KRAS testing is used in this setting to identify patients who will not benefit from antibody therapies directed toward the epidermal growth factor receptor. The FDA approved KRAS test only assesses for a limited number of KRAS mutations, those in codons 12 and 13 in exon 2. By contrast, medical guidelines such as those promulgated by the National Comprehensive Cancer Network (NCCN) and the American Society for Clinical Oncology (ASCO) both recommend extended KRAS testing including additional mutations in exons 3 and 4. Thus, the FDA approved KRAS test has rapidly become obsolete. All extended KRAS testing is performed using laboratory developed procedures. Forced use of the FDA approved KRAS test would overtly conflict with recommended medical practice and would severely compromise patient care.”