"Science is facts; just as houses are made of stones, so is science
made of facts; but a pile of stones is not a house and a collection
of facts is not necessarily science.” - Henri Poincaré
Scientific evidence is gathered through observation and
repetition. The evidence and the ways of making it are closely
scrutinized. One must always remember that the burden of proof
is on the person making a contentious claim (i.e., presenters of a
paper), in which the presenters argue for their specific findings.
In an attempt to avoid the bias inherent to anecdotal data,
scientific evidence must be collected through a system, such as
the hypothetico-deductive scientific method: induction
(formulating a hypothesis based on existing data), deduction
(making specific predictions based on the hypothesis),
observation (gathering data, driven by the hypothesis) and
verification (testing the predictions against further observations
to confirm or falsify the initial hypothesis).
While in clinical practice, formulating a benefit/risk
hypothesis is an intuitive and implicit process based on expert
judgment, the Hippocratic Oath includes the promise "to abstain
from doing harm" or that "given an existing problem, it may be
better not to do something, or even to do nothing, than to risk
causing more harm than good"1. Good clinical practice and the
best interests of the patient require that physicians use legally
available therapies according to their best knowledge and
judgement, to base its use on firm scientific evidence, and to
maintain records of its use and effects.
The possibility of loss, injury, or other adverse or unwelcome
circumstance is known a risk (Oxford English Dictionary).
Unsurprisingly, there are no uniform definitions or unvarying
concepts for benefit and risk in medical practice, or accurate and
precise guidance on the process of their balancing. Most notably,
complications or just the uncertainty of realizing a benefit from
the use of a pharmaceutical product or medical/surgical
procedure are frequently mentioned as a risk. Perhaps one of the
most challenging situations is that in which the effects, positive
or negative, of a given treatment are mostly unproven or simply
unknown. There is a great variance of opinion amongst
stakeholders, and in particular people living with multiple
sclerosis (MS) and their physicians not always share the same
view on the meaning of benefits and risks, and on their
weighing2.
In this issue of CJNS, Burton and colleagues from the
University of Calgary raise a very important and timely issue for
people living with MS and their physicians3. They report on a
range of moderate to severe complications associated with
endovascular vein dilation procedures and stent placement in
internal jugular and azygous veins performed on people with MS
who have sought treatment abroad. Local follow-up by the
treating physician is not typically provided and complications
may go under-reported or misclassified, so the risk/benefit profile of endovascular procedures for presumed venous stenosis
in MS patients remains unknown. Interestingly, as Burton et al
point out, Zamboni et al4 reported that no operative or
postoperative complications occurred in their trial, however
bleeding from vascular access sites happened “occasionally”
while the acute post-procedure monitoring time was only four
hours. Fatal consequences, albeit rare, have also been reported5.
A review of 344 endovascular interventions in Poland reported
minor complications with virtually no clinical consequences,
while there were in fact two thrombosed stents, five
hospitalizations including one gastrointestinal hemorrhage, two
cases of atrial fibrillation, four cases of stent migration requiring
additional stenting, pseudoaneurysm development and surgical
intervention to remove an angioplastic balloon6. Another review
of 495 endovascular procedures in Bulgaria concluded “there
were no major adverse events during the hospital stay”.
However, complications included four groin hematomas, one AV
malformation ruptured, six cardiac arrhythmias (1 ventricular
tachycardia associated with ST elevation), 2 azygos veins
ruptured, 15 vein wall dissections, 8 acute thrombosis,
recanalized by selective fibrinolysis, mechanical thromboaspiration,
and additional balloon angioplasty7. Remarkably,
some of these events would meet widely accepted international
definitions for reportable Serious Adverse Events8.
Amidst controversy and without independent confirmation or
scientific evidence, it has been hypothesized, but not proven, that
abnormal venous drainage of the brain is strongly associated to
MS, and also that dilation or stenting of the abnormal veins can
improve symptoms of MS. Such procedures are not approved for
the treatment of MS in Canada, but principles for the
management of complications in patients with MS who have had
endovascular procedures in other countries are being developed
by experts consensus opinion. Can medical decisions be wisely
made without supportive data? Can experimental procedures
with unknown risk/benefit profiles be systematically offered to
patients? Is it justifiable to seek benefits despite the risks
involved, and when the benefits should be foregone because of
the risks? Can pressure from vulnerable patients with unmet
needs and their opportunistic advocates lead science in the
absence of convincing scientific evidence? While the debate
continues, and science runs its course, Burton et al3 remind us
that these procedures are not without risk, and that follow-up
care should focus on identification of potential complications, as
it is the duty of the treating physician to identify, investigate, and
mitigate such risks while maximizing benefits. As Aldous
Huxley famously said “facts do not cease to exist because they
are ignored."
Marcelo Kremenchutzky
London Health Sciences Centre
London, Ontario, Canada
http://cjns.metapress.com/index/M4167RL6464M1683.pdf