Monday, August 24, 2015
FFPE Sample Availability and US Standard Care
Researchers who work with human FFPE samples and other human biospecimens can sometimes lose track of the fact that the material they work with really does come from either living or dead human beings. As such, the availability of ethically collected samples in academic and commercial biorepositories is closely tied to the practical details of prevalence within the population of that disease indication, and US standard care procedures in clinical environments. Researchers who don’t remember this when they design their studies are setting themselves up for failure. It’s also important to be realistic about the availability of normal samples. In many cases, normal control samples of human tissue are harder and more expensive to procure than diseased samples. Why? Because normal tissue is not typically removed from living donors. This may sound obvious, but it’s amazing how many researchers forget this. For some types of tissue, fully consented postmortem samples may be the only way to procure “normal” examples, and for these samples it’s important to recognize that biobanks must rely on generous donations by donors or their families and that the average age of people who die tends to be much higher than the population at large. Additionally, and sometimes crucially, researchers need to also be realistic about postmortem Interval (PMI) times and the possible affects of agonal state and sparse clinical information for non-lethal diseases in postmortem donors.
To minimize procurement times and maximize the number of cases received, researchers need to “do their homework” when it comes to placing realistic requests. There is no point in asking a biobank for >100 cases of an indication that only occurs in 1 in 1,000,000 individuals, and similarly there is no point in asking for whole tumor samples for cancer indications that are not treated surgically as part of US standard care. How can researcher’s find out what currently constitutes standard care? Actually the answer to this question is not as simple as it sounds, especially since a) standard care is always changing, b) not all clinics follow exactly the same guidelines, c) many biobanks contain “CAP graduated” archival specimens that were collected more than 10 years ago and therefore have the characteristics and attached data associated with standard care as it was at the time of collection, and d) it’s often surprisingly difficult for qualified life scientists who are not themselves medical doctors to be able to locate a succinct description of standard care, written in a way that makes sense to them.
My advice to researchers who may not necessarily be medical doctors is to ALWAYS partner with a medical specialist or pathologist, and talk to them to get a clear idea of what constitutes standard care for the indication you are interested in. If for example, your medical partner tells you that Fine Needle Aspirates (FNAs) are ALWAYS used for that indication, but the indication is never treated surgically, then FNAs might be your best for acquiring samples. If you are interested in only acquiring samples that have a particular biomarker, but this biomarker is not tested for as part of standard care, then you are going to have to make sure that your budget includes the cost of paying for , or performing your OWN screening for ALL of your samples. Even worse news is that if the biomarker of interest only occurs in 10 percent of cases, then you are probably going to have to procure and pay to test at least 10 times as many samples as you actually need in order to find the ones of interest. Similarly, if chemotherapy ALWAYS precedes surgery for a particular indication, then you pretty much need to abandon any idea of procuring samples that were surgically excised before treatment. Remember that standard care, NOT your experimental interests will determine what samples are available.
If you are a life science researcher who is not lucky enough to have an experienced medical partner to help you predict sample availability based on standard care, you may have no choice other than to simply do a lot of googling to see what (or who) you can find to help you, but trust me, this is time well spent compared to the months or even years you might waste waiting for the procurement of sample types or numbers that are simply not compatible with the realities of what biobanks actually receive from clinics.
Lab-Ally maintains a growing list of descriptions of standard care, and we would certainly appreciate additions, corrections and updates to this list that will help researchers to make meaningful predictions about sample availability.