Biology Reference
In-Depth Information
assays to optimize the number of samples that can be run on a single plate may not be nec-
essary. However, if the disease of interest is highly prevalent, and research indicates that
the majority of patients will be tested, then the assay format would need to be adjusted to
optimize the number of samples that can be evaluated on each run. The volume of testing
may also dictate whether the test is available in all clinical testing laboratories throughout
the region of interest, or if specific laboratories are targeted to run the companion diagnos-
tic device. It is wise to have multiple parties conduct similar research in this effort to ensure
an accurate assessment of test volume, as it has been noted that test volume alone can be a
major contributor to assay format and development.
7.4.2.8 Ease of Use
Regardless of the number of sites necessary to handle testing volume, the ease of use and
result is a key to a successful companion diagnostic implementation. Complex assays that
require a great deal of manipulation increase the possibility of user error. For this reason it is
imperative that the device, including everything from analyte isolation through to final result,
be as user friendly as possible. There are a number of strategies to improve ease of use. These
strategies generally fall into one of two categories - automation or assay simplification. While
automation may be considered a viable option for a number of devices, the investigator must
remember to consider the clearance status of the automation equipment being utilized. There
are only a few pieces of automation instrumentation and associated protocols that have been
cleared. The advantage of automation is that it significantly decreases the opportunity for
user error leading to test failure. Automation is best applied to repetitive tasks, freeing techni-
cians to perform other steps requiring more user input. Automation can be applied through-
out the process from analyte isolation through plate or assay set up, and perhaps is best
applied in terms of analysis. Software including automated pass
/
fail, and subsequent genera-
tion of results, removes the user from performing any calculations and provides consistency
to the analysis. Assay simplification is another key component of ease of use. This includes
aspects of the device process, such as multiplexing for multiple targets, combining steps if
possible (i.e., one step polymerase chain reaction (PCR) instead of a separate reverse tran-
scription reaction and quantitative PCR steps), and minimizing the number of pipetting steps.
While alterations to the assay such as these may seem trivial, they must be incorporated early
in the development of an assay to ensure there are no additional technical hurdles created.
In addition, later incorporation of these changes may require additional validation work that
will cost both time and resources. The investigator needs to be aware of the risk and benefit of
the addition of these measures in the assay processes and decide which aspects are necessary
for the particular assay in question. In general, the more simple and user friendly an assay
can be, the better, as this will ease the transition of the device into the clinical testing setting.
7.4.2.9 Number of Analytes
The number of analytes assayed can be quite relevant to the development of a compan-
ion diagnostic device. From a validation standpoint, draft guidance has suggested that a test
featuring two to 10 analytes must be individually validated, while larger numbers of ana-
lytes dictate validation of the system as a whole rather than the individual components
[3]
.
There are also considerations of assay configuration based on proposed sample throughput.
As discussed in the testing volume section above, a large number of analytes may limit the
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