Cell Culture Drug Resistance Testing (CCDRT) Cell Death Assays:
Misconceptions Versus Objective Data
What the critics say (continued): B. The AMA "Tech Review"
A brief critique of the 1996 AMA "Tech Brief" on CCDRT:
This "Tech Brief" has a summary statement which reads as follows:
"The effectiveness of the Thymidine Incorporation Assay and the Differential Staining Cytotoxicity (DISC) Assay to predict in vivo sensitivity of human tumors to chemotherapy were considered to be investigational at best by the expert panel. These procedures were considered to be promising or investigational to predict extreme drug resistance by a majority of the panel."
In the first place, this was NOT a true "panel" which met and had a back and forth discussion of the pros and cons, after considering evidence and hearing testimony representing all points of view from the true experts in the field in open meetings. This is how California Blue Shield did it. Rather, this "panel" was nothing more than a mailed popular opinion questionnaire sent to 93 "panelists" (really just individual physicians) "with a stated interest in cancer, tumors, or oncology" selected from an electronic database. Of the 93 "panelists," one third did not respond to either the primary or follow-up questionnaire.
These panelists are represented as "experts." This is peculiar, as this is a very complex field, and I have seldom met a practicing oncologist or a university oncologist, for that matter, that can carry on an intelligent discussion concerning either the technology or the supporting data relating to this field.
So were they experts?
The first thing that struck me was how closely the percentages in each category matched for both the thymidine incorporation assay and for the DISC assay. These are two very different technologies, each with its own strengths and weaknesses. Responses for the technologies should have been different for the different questions asked. But they weren't different. They were virtually identical. This indicates that the so-called "expert panel" knew nothing at all about the technologies that they were supposedly reviewing and on which they were passing judgment.
To take only one particularly egregious example, look at questions 6.f. and 7.f. The question asks: "Is the DISC/Thymidine assay an effective method to predict in vivo sensitivity of specific tumors?"
Now, if you look at the percentage distribution of the answers for question 6.f. and 7.f., you will see that they are virtually identical, indicating that the assays are equivalent regarding their utility or potential utility in hematologic neoplasms. Yet there are numerous peer-reviewed, published clinical papers, reporting hundreds of clinical correlations, in good journals, reporting results of the DISC assay in hematologic tumors and not a single publication describing results of the thymidine assay in hematologic tumors! Furthermore, no investigator or company I know is even doing research on the use of the thymidine assay in hematologic tumors! Furthermore, there are obvious technical reasons why the thymidine assay cannot be applied to hematologic neoplasms, such as leukemia, while there are voluminous data showing the accuracy and utility of the DISC assay in this area.
The above constitutes prima facie proof of the incompetence of the so-called "experts."
A major problem with this field, once again, is that there are no true "experts" regarding CCDRT within the academic environment, which abandoned serious research into this field more than a dozen years ago, save for Drs. Salmon and Von Hoff, who stubbornly clung to a single outmoded technology, which they personally originated and developed.
And, with the exception of California Blue Shield, the organizers of the other (utterly naive and erroneous) reviews did not seek input and rebuttal from the true experts in this field, which are the private sector physicians and laboratories who have been working in this field for more than 15 years and providing real-world services in this field for more than 10 years, as a full-time effort.