US Stem Cell Inc (USRM)

[Dragon Lady]

For example- kinda left out 4.3: (further, these sections being cited, are "recommendations" and are "non-binding") they're part of a much, much bigger set of rules/regulations the FDA relies on, IMO and as far as I'm aware of. 3.1, 4.3, etc are just one, of many "recommendation" of process/procedure.

Also, If I'm not mistaken, it's the "CFR" (Code of Federal Regulations) sections that are the actual "law" as codified, passed by congress, etc. The area you cited is equivalent to FDA internal "guidelines" as far as I am aware and reference back to the relevant "CFR" actual law/regulations which are book-thick as far as I am aware. My opinion. Example:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?FR=860.7

That's the actual "law" portion- and it's long, complicated and goes into sub, sub, sub categories, etc

4.3 Additional Factors in the Assessment of the Probable Benefits and
Risks of Devices
Uncertainty – there is never 100% certainty when determining reasonable assurance of
safety and effectiveness of a device. However, the degree of certainty of the benefits and
risks of a device is a factor we consider when making benefit-risk determinations.
Factors such as poor design or poor conduct of clinical trials, or inadequate analysis of
data, can render the outcomes of the study unreliable. Additionally, for certain device
types, it is sometimes difficult to distinguish between a real effect and a placebo effect in
the absence of a trial design that is capable of blinding investigators and subjects.
Furthermore, the repeatability of the study results, the validation of the analytical
approach, and the results of other similar studies and whether the study is the first of its
kind or a standalone investigation can all influence the level of certainty. In addition, the
generalizability of the trial results to the intended treatment and user population is
important. For example, if the device requires in-depth user training or specialization, the
results of the clinical study may not be generalizable to a wider physician population.
Likewise, if the device is intended to diagnose a disease in a subpopulation, it may not be
useful in the general population. In general, it is important to consider the degree to
which a clinical trial population is representative of the intended marketing or target
population.
Characterization of the disease – the treated or diagnosed condition, its clinical
manifestation, how it affects the patients who have it, how and whether a diagnosed
condition is treated, and the condition’s natural history and progression (i.e., does it get
progressively better or worse for the patient and at what expected rate) are all important
factors that FDA considers when characterizing disease and determining benefits and
risks.
Patient tolerance for risk and perspective on benefit – if the risks are identifiable and
definable, risk tolerance will vary among patients, and this will affect individual patient
decisions as to whether the risks are acceptable15
in exchange for a probable benefit.
When making a benefit-risk determination at the time of approval or de novo
classification, FDA recognizes that patient tolerance for risk and a patient-centric
assessment of risk may reveal reasonable patients who are willing to tolerate a very high
level of risk to achieve a probable benefit, especially if that benefit results in an
improvement in quality of life. How data concerning patient risk tolerance and other
patient-centered metrics are developed will vary depending on a number of factors,
including the nature of the disease or condition and the availability of existing treatments,
as well as the risks and benefits they present. FDA encourages any sponsor that is

15
21 CFR 860.7(d)(1) states that “The valid scientific evidence used to determine the safety of a device
shall adequately demonstrate the absence of unreasonable risk of illness or injury associated with the use of
the device for its intended uses and conditions of use.”