Biomedical Engineering Reference
In-Depth Information
frequent occurrence of all AEs, rather than just for the rarer SAEs, PIs and
other personnel may become more familiar with it and use it more frequently.
In addition, if the system were to be more evidence based, using previous
information to guide researchers in not just reporting AEs but also deploying
clinical studies with inclusion and exclusion criteria that would be inherently
more protective of vulnerable subjects, the system may be even more useful
[20]. Thus, even within centers within the NIH, the silo mentality exists.
An additional area beyond formal reporting that has barely been explored
is the potential of patient advocacy websites and communities to be valuable
sources of information on AEs. Patients are likely to represent the most
willing and richest source of information on adverse drug reactions, drug
interactions, and environmental effects. Increasingly these communities are
driving, funding, and even directing the drug discovery process and the devel-
opment of treatment regimens. While there are obvious potential issues with
reporting consistency and precision, this represents a vast untapped reserve
of information on drug performance. In our modern connected age, failing
to connect with the end user and to take on board their feedback has badly
damaged many organizations. There is no reason to expect drug discovery
and validation processes and organizations to be any different.
It is our opinion that AE systems could be developed that are more col-
laborative in nature such that they are in line with the other collaborative
tools described above. It is also possible that such efforts could also be com-
bined with the creation of drug safety databases and used as a crowdsourcing
initiative, whereby anyone can contribute observations and data for a par-
ticular approved drug. Obviously there would need to be fi lters implemented
for spurious data. Such systems should be harmonized throughout the drug
approval process such that the structure-activity relationship (SAR) of the
compound indicates the likelihood of an agent exhibiting a particular AE,
the preapproval clinical trials track it, and the postmarketing surveillance
quantifi es it. This may be particularly important to capture information on
molecules associated with idiosyncratic toxicity that may not be observed
in relatively small clinical trials [29-31]. For example, the liver is a frequent
site of toxicity of pharmaceuticals in humans, [32, 33] likely because of the
physiological location and drug clearance function of the liver leading to
higher exposure to drug than that being measured systemically [34]. Drug
metabolism in the liver can also convert some drugs into highly reactive
intermediates which, in turn, can adversely affect the structure and functions
of the liver [35-38]. Drug-induced liver injury (DILI) is a major reason why
drugs are not approved and why some of them were withdrawn from the
market after approval [39]. Postmarketing data may help fi nd additional mol-
ecules with this issue and help in alerting authorities to new drugs displaying
such toxicities. The real issue here is providing a mechanism for patients and
health practitioners to alert the FDA and other health authorities in a timely
manner.
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