See the Editorial and the Response in this issue, p 1.

J Neurosurg 100:2–7, 2004

Surgical innovation or surgical evolution: an ethical and

practical guide to handling novel neurosurgical procedures

MARK BERNSTEIN, M.D., F.R.C.S.(C), M.H.SC., AND JOSEPH BAMPOE, M.B.CH.B., F.R.C.S.(I)
Division of Neurosurgery, Toronto Western Hospital, and Joint Center for Bioethics, University of
Toronto, Canada

Object. Surgical innovation is an important driver of improvements in technique and technology, which ultimately trans-
lates into improvements in patients’ outcomes. Nevertheless, patients may face new risks of morbidity and mortality when
surgical innovation is used, and well-intentioned surgical “experimentation” on patients must be regulated and monitored.
In this paper the authors examine the challenges of defining surgical innovation and briefly review the literature on this
challenging subject.
Methods. Using examples from the field of neurosurgery and in part from the personal experience of the senior author,
the authors develop a model of levels of experimental acuity of surgical procedures and offer recommendations on how
these procedures would best be regulated.
Conclusions. The authors propose guidelines for determining the need for regulation of innovation. The potential role
of institutional review boards in this process is highlighted.

KEY WORDS • institutional review board • novel therapy • surgical innovation

should be abundantly clear to every clinician that to fixation to the base ring must breach the drapes. Another

I
T
conduct research in humans investigators must obtain
approval of the protocol from the appropriate IRB. The
IRB review of a research protocol is primarily aimed at
minimizing risks to the patients from unproven therapies
and ensuring that the patients understand, as fully as possi-
ble, what their options and risks are. Requirement for IRB
approval is articulated clearly by institutions’ codes of re-
search conduct and in published frameworks guiding the
ethical conduct of biomedical research.9,17,36,37,54 What is not
so clear, however, is which surgical procedures require an
IRB examination or some other form of formal regulation.
Furthermore, there is mounting evidence that IRBs are un-
der significant strain, exhibiting inadequate levels of per-
formance,5 and are in need of significant reform.46
When the surgical procedure is part of an RCT in which
an experimental treatment is tested, such as high-activity
brachytherapy for malignant brain tumors, the requirement
of IRB approval would seem to be clear.29,44 Nevertheless,
most surgical innovation does not take place in the context
of an RCT.3,24 Some innovations represent variations in an
accepted procedure, such as the application of a stereotactic
frame to the placement of intraventricular catheters; this in-
novation is likely to facilitate a reduction in the number of
passes through the brain, thus decreasing the risk to the pa-
tient.30 On the other hand, the use of a stereotactic frame
may increase the possibility of infection by introducing
more opportunities for a breach of sterile technique as the
frame is moved in and out of a sterile field and the points of
Abbreviations used in this paper: IRB = institutional review
board; RCT = research clinical trial.
modification is introduced when a stereotactic frame is used
to drill the guide hole for the catheter, but is removed before
formal draping, thus avoiding breaches of sterile technique
and decreasing the risk of infection.2 Does a surgeon require
approval from the IRB or another committee or supervisor
for such procedures? Similarly, the increased use of min-
imally invasive surgery has led to a trend toward shorter
hospitalization stays, and certain procedures that previous-
ly were considered inappropriate for outpatient surgery are
now performed in that manner.7,11 Does a surgeon need ap-
proval from the IRB or another source for this type of inno-
vation or is this simply the natural evolution of the art and
science of surgical practice in action?
Much of the literature on surgical innovation is commen-
tary and/or focuses on specific cases. We propose a num-
ber of distinct scenarios of severity, or acuity, regarding the
need for regulation of novel surgical procedures (Table 1).
Using examples from the field of neurosurgery, and partly
from the personal experience of the senior author (M.B.),
we explore the need for IRB approval and other forms of
regulation in surgical innovation, from an ethical and prac-
tical perspective. We will attempt to construct a framework
that addresses essentially all situations in which surgical in-
novators could find themselves.
Practice, Innovation, or Research: Practical
Problems Associated With the Assessment of
Surgical Innovation
Consideration of widely accepted and binding interna-
tional agreements on bioethical principles governing hu-

2 J. Neurosurg. / Volume 100 / January, 2004

Surgical innovation
TABLE 1
Rating of surgical procedures according to their need for regulation*
Procedure Description
A new procedure (never performed previously)
elective
urgent
B fairly new procedure that is part of an RCT
C amendment to the technique
of an established op
D amendment to other features
of an established op
E new procedure to an individual surgeon
* MCA = middle cerebral artery.
† This maneuver was performed by the senior author circa 1990, but may have been performed by other surgeons as well.
man research helps shed some light on the ethical obliga-
tions of the clinician seeking innovation.36,37,54 The concept
of innovative care as it appears in these documents is dis-
tinct from clinical practice or research.36,54 This distinction
first appears in The Belmont Report,36 in which innovative
care is characterized as a “practice that departs significant-
ly from the standard or accepted.” Innovative care does not,
in itself, constitute research, even though the treatment may
be new, untested, or different. Nevertheless, it must be
made the object of formal research “at an early stage” to
determine its safety and efficacy if it is to be adopted as
conventional care. This gives rise to a new question: Who
defines what constitutes a significant departure from stan-
dard or accepted practice and, by inference, an innovation?
Every application of a surgical procedure may raise differ-
ent challenges, requiring an instant innovation. Drawing the
line between what would be an experimental form of care
and what is merely a slight alteration, which could be clas-
sified under the rubric of standard care, may be difficult.
According to The Belmont Report36 the responsibility for
incorporating an innovation into a formal research project
rests with the IRB; however, if the surgeon performs an
innovation in isolation, the IRB can have no knowledge that
a potentially innovative therapy has been undertaken.
The designation “research” implies the formal testing of
a hypothesis, which permits a conclusion to be drawn. This
activity is designed to contribute to generalizable knowl-
edge.36,54 Clinical practice refers to interventions designed
solely to enhance the well being of an individual patient
and ones that are associated with a reasonable expectation
of success.36 It is also recognized that research is required to
improve prophylactic, diagnostic, and therapeutic proce-
dures54 and may be combined with clinical practice to eval-
uate the safety and efficacy of an innovative therapy.5,36
The term “innovation” would apply to a novel therapy,
which eventually is shown to be effective and is something
that the public needs or wants.36,39 A useful definition of in-
novative surgery for our purposes is “a novel procedure, a
significant modification of a standard technique, a new ap-
plication of or new indication for an established technique,
or an alternative combination of an established technique
with another therapeutic modality that was developed and
tested for the first time.”40
Several suggestions for the regulation of innovative care
in medicine have been made.1,3,5,6,14,18,20,21,24,31,32,34,35,39–42,47,50
J. Neurosurg. / Volume 100 / January, 2004
Example Authors & Year
neuronal cell transplant Kondziolka, et al., 2000
MCA anastomosis Steiger, 2001
leaving pattie to stop bleeding no specific publication†
brachytherapy Laperriere, et al., 1998
microsurgical lumbar discectomy Williams, 1978
outpatient brain tumor surgery Bernstein, 2001
surgeonʼs first complex no specific publication
instrumented spinal fusion
One example with a legislative basis can be found in a para-
graph from the Civil Code of Quebec; it states: “care con-
sidered by the ethics committee to be innovative care re-
quired by the state of health of the person concerned does
not constitute an experiment” (Article 21, Paragraph 4, Civ-
il Code of Quebec).12
When innovative care does not constitute a formal re-
search protocol, the cost of care is covered by hospital bud-
gets.12,39 This has several implications. In an era of techno-
logical advances with an ever-increasing pressure on finite
health care resources, there is a growing demand to ra-
tionalize clinical practice.4,10,15,19,20,32,39,45,50 Apart from the
obvious obligation to apply the most scientifically sound
treatment available to the patient’s problem,18,24,35 public ac-
countability is an important consideration when resources
might be diverted from other worthy social causes.17 Mini-
mization of the potential impact of conflict of interest on the
part of the innovator (for example, potential publication or
financial gain) can be addressed by third-party adjudication
of outcome parameters3 and by rigorous peer review by
journal editors, reviewers, and members of the profession
while innovation is in the development stage.21 Confound-
ing factors at this stage include the tendencies for an in-
novative technology or technique to evolve, its applications
to be altered, and the experience of innovators to increase
with improved performance (progression along the learning
curve).3,38 Although undertaking a formal assessment at too
early a stage may give a distorted picture that is biased
against the new technology or technique,38 in the interest of
patient safety, the IRB should insist that the surgical inno-
vation be tested in a formal research study.36,54 The degree of
urgency should be determined by how radical the new pro-
cedure is.36.
It is useful to differentiate between an innovation in tech-
nology and one in technique.40,50 Before the former can be
introduced into surgical practice rigorous training is re-
quired, such as taking defined courses to study the equip-
ment, visiting a center where the equipment is currently
being used, acclimating oneself to the equipment with the
aid of a proctor, and finally independent operating with
review.26,32,33,34,53 The surgeon’s institution should require
any combination of the aforementioned training as a mini-
mum for an innovation in technology. Innovation of tech-
nique, when conducted by an experienced surgeon, prob-
ably does not require the same degree, rigor, or urgency
3

of institutional review.2,7,11,22,25,43,52 Nevertheless, it is the re-
sponsibility of the institution and the profession at large to
scrutinize the procedure in the interests of patient safety. In
a situation in which the innovation has achieved sufficient
success such that there is uncertainty as to which therapy
(novel or standard) constitutes the best treatment, an RCT
should be conducted to compare the two therapies.20,24
In certain instances the pressure to obtain institutional or
peer review of an innovative therapy is not as rigorous as it
should be. This may occur more often in privately funded
surgical practice than in publicly funded practice.40 Regula-
tion of innovative surgery and, as a result, patient protection
is then achieved only by the apparent necessity of avoiding
malpractice litigation.40 This is unsatisfactory because the
fiduciary relationship between a physician and patient is
damaged when avoidance of litigation rather than benefi-
cence is the motivator for regulation of innovation. Litiga-
tion tends to set only the minimum standards for acceptable
patient care.21
Possible Scenarios
A New Procedure (Procedure A)
This type of procedure is new to all surgeons (Table 1). It
is imperative to subdivide this scenario into elective and ur-
gent situations. In the first case, we must ask: Should IRB
approval be required for an elective novel procedure such as
transplantation of cultured human neuronal cells to treat pa-
tients with major stroke?27 The obvious answer would be
“yes.” The demonstration in preclinical studies that the pro-
cedure has potential value and a favorable risk/benefit ratio
and the assessment that the procedure is the sole therapeu-
tic option are all prerequisites for IRB approval.17,36,37,54 In
such a scenario the IRB would be placed in a position to
examine a novel and exciting treatment and contribute to
the initiative by ensuring an optimum risk/benefit ratio and
the best possible informed consent process, as well as pro-
viding ongoing monitoring.
Some could argue that an alternate approach would be
for respected peers of the surgeon to endorse the proposed
procedure and for formal permission to be obtained from
the surgeon-in-chief. Unfortunately, this approach could
certainly be associated with some bias depending on the
surgeon-in-chief’s attitude, level of conservatism, and trust
in the track record of the surgeon involved in the inno-
vation. Appropriate informed consent from each patient
would be a prerequisite and the IRB should be sent a copy
of this form. Oversight of the surgeon’s experience with the
new procedure by a committee or a respected individual
(perhaps a senior surgical innovator) would be necessary.
In an emergency situation, the decision to undertake
a novel neurosurgical procedure that involves significant
risk cannot wait for IRB approval because of the extreme-
ly short time lines available. Numerous examples exist in
everyday practice such as the first time a dental mirror was
introduced into the operative field so that the surgeon could
see around a corner deep in the brain, and stopping an in-
tractable hemorrhage from a hole on the side of an artery
with a cloth surgical pattie because it is the only thing that
worked. In the latter case the hole was created by an aneu-
rysm clip, which tore off a small but wide-based aneurysm
from the parent artery. The maneuver was performed some
4 J. Neurosurg. / Volume 100 / January, 2004
M. Bernstein and J. Bampoe
years ago by the senior author without any knowledge of
whether it had been performed previously. It would be con-
sidered unorthodox at minimum and definitely would intro-
duce some risk of infection due to a retained foreign body.
These innovations could not possibly be assessed by an
IRB because of the urgency of the situation. The recom-
mended course of action taken to address the problem
would be discussion with an experienced colleague if pos-
sible. Some objectivity and experience could be introduced
to help solve the problem, and the principles of nonmal-
feasance and beneficence would be honored, although in-
formed consent would not be possible. The procedure ul-
timately undertaken in the emergency case was, in the
surgeon’s judgment, the one least likely to be associated
with complications, even though there was a some risk in-
volved in its undertaking.
The surgeon’s mandate should be to do the best for the
patient, using the best clinical judgment tempered by clini-
cal experience and knowledge of one’s surgical limitations.
If time and opportunity allow, requesting feedback and sup-
port from an experienced colleague is highly desirable to
provide a more objective assessment of the problem and its
possible solutions.47
Arm of an RCT (Procedure B)
The surgical arm of an RCT represents the archetypal or
“paradigm” case requiring IRB approval (Table 1). In any
situation in which there is clinical uncertainty about which
of two or more treatments is superior and patients are ran-
domly assigned to treatment groups, the most rigorous safe-
guards must be in place to protect patient safety and au-
tonomy. The legitimacy of the RCT should be based on
evidence of systematic preclinical development, the perfor-
mance of phase I and II clinical studies, and the availability
of appropriate technology. Neurosurgical examples would
include the study of extracranial–intracranial arterial bypass
as a treatment for cerebral ischemia16,28 and the two ran-
domized studies of the use of interstitial brachytherapy as a
radiation “boost” for de novo malignant gliomas.23,29,44 The
IRB should fill an important role in addressing the ethics of
the standard therapy arm in an RCT, particularly vis-à-vis
the use of placebo controls.51
Eventually many novel procedures undergo proper sci-
entific testing in the setting of an RCT; however, many pro-
cedures do not, for a variety of reasons including the tre-
mendous difficulty and expenditure of time, energy, and
resources required for the proper conception and execution
of an RCT.
Amendment to the Technique of an Established Operation
(Procedure C)
Should IRB approval be required for an amendment to an
established operative technique (Table 1)? Common sense
would suggest that it would depend on how major or radi-
cal the amendment is.36 For example, the stereotactic tech-
nique is basic to neurosurgical practice. Its application to
the insertion of an Ommaya reservoir would be expected to
increase the accuracy of catheter placement with very little
additional risk to the patient, except, perhaps, the possible
increased risk of infection.30 The risk of infection can be
addressed by appropriate adjustments, that is, further tech-
nical amendments that ultimately remove the frame from
Surgical innovation
the operative field.2 No mandatory requirement for IRB ap-
proval is probably necessary if the innovations are not rad-
ical and are performed by a surgeon with established expe-
rience in stereotactic technique, thus resulting in a favorable
risk/benefit ratio for the patients.2,17 The same situation ap-
plies to the introduction of the operating microscope for
routine neurosurgical procedures, such as microsurgical
lumbar discectomy.52 What is required of such an innova-
tion is the surgeon’s demonstrable familiarity with the tech-
nology, which can be enhanced with a period of training,
proctoring, or supervision mandated and regulated by a pro-
fessional or local training body.28,31 This simple but elegant
innovation revolutionized the technique of an exceedingly
common procedure performed by neurosurgeons and ortho-
pedic surgeons.
Also within this category is the introduction of novel
technology to enhance a standard neurosurgical operation.
An example of this would be the introduction of open mag-
nets located within the operating room so that real-time
magnetic resonance imaging can help guide the removal of
a brain tumor.8 This novel technology is associated with ob-
vious surgical advantages for patients. It is beneficial for the
surgeons as well because it allows them to view changes in
real time that would be difficult with the naked eye, which
is such a crude tool for distinguishing the interface between
normal brain and intraaxial tumors. Nevertheless, IRB ap-
proval would likely be required, partly because of the pos-
sibility of risks and complications not previously encoun-
tered, such as a missile injury to the patient or staff if a
magnetic object is accidentally introduced into the field of
the magnet.
Amendment to Other Features of an Established Operation
(Procedure D)
An example in this category (Table 1) would be the com-
bination of a standard neurosurgical operation such as cra-
niotomy for tumor resection and a stereotactic brain tumor
biopsy performed on an outpatient basis.11 Is this surgi-
cal innovation or purely evolution of the art and science of
neurosurgery, and what should be the role of the IRB or
other formal regulation? In this case the senior author has
already demonstrated a remarkably low complication rate
when awake craniotomy is performed for tumor resec-
tion.13,48 With this operation, over an 8-year period he has
progressively reduced the median duration of the hospital
stay from 4 days in the first quartile of patients to 1 day in
the last quartile.48 Additional information from the literature
shows that the main complication of a craniotomy, postop-
erative hematoma, expresses itself clinically in essentially
all cases within 6 hours.49 Therefore, patients undergoing
outpatient craniotomy would only be discharged home if
they were stable 6 hours postoperatively; all would have
quick access to the hospital in the event of a complication
and stay in the company of a responsible adult; and an even-
ing visit by a home-care nurse would be arranged in all cas-
es.7 The importance of patient autonomy must be recog-
nized; that is, the patient must receive a detailed explanation
of the procedure in which its possible outcomes and com-
plications are stressed. Importantly, patients should never
be treated as outpatients against their will—it should be
completely voluntary. With all these precautions in place
and with the personal experience of the author48 and others49
J. Neurosurg. / Volume 100 / January, 2004
as an experiential foundation, the evolution to a 0-night stay
in the hospital (or outpatient brain tumor surgery) does not
seem as radical as it did at first glance.
This type of innovation might simply be viewed as an
evolution in modern surgical practice; the median duration
of stay is decreasing for most surgical procedures and, in
this case, it evolutionally decreased to zero. One could ar-
gue that such an innovation, even though it sounds quite
extreme, does not require IRB approval. Furthermore, it is
entirely possible that IRB approval would be impossible to
obtain for such a protocol, thus blocking an innovation that
has been demonstrated to represent a safe and viable treat-
ment alternative.7,11 An alternative approach to appropriate
regulation of such an amendment might be the use of local
peer review and permission from the surgeon-in-chief, as
described earlier in Procedure A, Elective.
New Procedure to an Individual Surgeon (Procedure E)
Once neurosurgeons have been licensed by fulfilling the
requirements of a recognized residency training program
and passing the requisite examinations, they are qualified to
function independently in the jurisdiction covered by their
licensing body. Does this imply that the neurosurgeon is
qualified to undertake all neurosurgical procedures? Neuro-
surgery is becoming increasingly specialized and complex,
and not every training program exposes neurosurgical train-
ees to every surgical procedure. Many residents who have
recently completed their training are not competent to deal
with certain complex neurosurgery cases independently. A
resident may not have performed a particular procedure a
sufficient number of times to achieve competency and/or
the procedure may be so complex that it is primarily per-
formed by staff neurosurgeons alone or in teams. Examples
would include removal of a complex arteriovenous mal-
formation, major brachial plexus reconstruction, odontoid
screw placement, and endoscopic third ventriculostomy.
For general neurosurgeons who are not fully comfortable
with such an unfamiliar procedure, it would be unethical to
perform it and expose the patient to unnecessary risk.31,32
The same argument would hold for a situation in which a
resident, who is supervised by a staff surgeon, undertakes
a procedure with which he or she is not yet comfortable.
There would be no role for an IRB in sorting out this issue;
the problem is one of surgical qualification and not inno-
vation or research. Additional training, such as a clinical
fellowship with recognized experts may be required for
some procedures, and for others tutelage by an experienced
colleague on a number of cases might suffice. Ultimately
permission could be obtained from one’s senior peers and
the surgeon-in-chief as described earlier in Procedure A,
Elective.
Recommendations
When considering surgical innovation the verdict of his-
tory would argue against initial rigid control. Nevertheless,
the great benefits of heart surgery, total hip replacement,
transplant surgery, and numerous neurosurgical examples
have not been achieved without the costs of patient morbid-
ity and mortality. Many previous innovations would pos-
sibly not be acceptable to today’s IRBs. The benefits of
increased scientific knowledge and technology should and
5

can be extended to patients with minimal risk, a require-
ment consistent with the frameworks guiding the ethical
conduct of biomedical research.
The surgeon’s mission is to achieve the best results for
the patients, and common sense and knowledge of one’s
own surgical limitations are paramount for safe surgery. In-
novation is a normal part of human nature, especially for
academically and technically driven people such as neuro-
surgeons, and innovation is essential as new situations and
challenges arise. Many innovative techniques and technol-
ogy are born of immediate necessity, but many others can
be developed with the luxury of planning and preparation.
Recommendations for the Surgical Innovator
We make the following recommendations. 1) All pro-
cedures that are performed as part of an RCT should be
scrutinized by the IRB. 2) A brand new procedure that is
scheduled to be performed electively should probably be
reviewed by the IRB and sanctioned by one’s senior peers
and the surgeon-in-chief. 3) Procedures that represent major
modifications to accepted surgical procedures should sim-
ilarly be examined by the IRB and sanctioned by one’s
senior peers and the surgeon-in-chief. 4) Minor or evolu-
tionary modifications may be exempt from IRB approval.
One can never be too careful, however, and if there is any
question, sending a brief protocol to the IRB does not rep-
resent a great expenditure of resources or time. Sanction by
one’s peers and the surgeon-in-chief might be appropri-
ate in these cases. 5) Finally, for procedures which represent
personal innovation for a surgeon in doing a standard but
complex procedure for the first time, the IRB has no role.
Other institutional bodies such as the quality committee,
medical advisory committee, and/or the surgeon’s senior
peers and surgeon-in-chief would have a responsibility to
monitor this situation.
These recommendations are subjective; there is no gold
standard to assess their validity. We offer them to stimulate
debate and to provide a basic framework for surgeons to
grapple with this intriguing and challenging area. The ob-
jective is for no obstacle to stand in the way of surgical in-
novation. Surgeons are problem-solvers by nature and en-
couragement of technical and technological innovation will
benefit the patients not only of today but of tomorrow as
well. Nevertheless, the best intentions of well-meaning sur-
geon innovators must be regulated to the degree that the
maximal benefit is achieved for patients with the minimal
risk, without stultifying the innovative ingenuity and spirit
of surgeons.
Acknowledgments
We thank Trudo Lemmens, Alex Levin, Martin McKneally, and
Randi Zlotnik-Shaul for helpful comments.
References
1. Agich GJ: Ethics and innovation in medicine. J Med Ethics 27:
295–296, 2001
2. Al-Anazi A, Bernstein M: Modified stereotactic insertion of
Ommaya reservoir. Technical note. J Neurosurg 92:1050–1052,
2000
3. Awad IA: Innovation through minimalism: assessing emerging
technology in neurosurgery. Clin Neurosurg 43:303–316, 1996
6 J. Neurosurg. / Volume 100 / January, 2004
M. Bernstein and J. Bampoe
4. Bampoe J, Siomin V, Bernstein M: Quality-of-life assessment in
neurosurgical patients. Neurosurg Q 12:132–141, 2002
5. Beauchamp TL: IOM report on the system for protecting human
research participants. Kennedy Inst Ethics J 12:389–390, 2002
6. Beech R, Morgan M: Constraints on innovatory practice: the case
of day surgery in the NHS. Int J Health Plann Manage 7:
133–148, 1992
7. Bernstein M: Outpatient craniotomy for brain tumor: a pilot feasi-
bility study in 46 patients. Can J Neurol Sci 28:120–124, 2001
8. Bernstein M, Al-Anazi AR, Kucharczyk W, et al: Brain tumor
surgery with the Toronto open magnetic resonance imaging sys-
tem: preliminary results for 36 patients and analysis of advan-
tages, disadvantages, and future prospects. Neurosurgery 46:
900–909, 2000
9. Bernstein M, Upshur REG: Framework for bioethical assessing of
an article on therapy. J Neurosurg 98:485–490, 2003
10. Bernstein M, Walters BC: Introduction: Beyond survival: guide-
lines and outcomes in neurooncology. Neurosurg Focus 4(6):
1–2, 1998
11. Bhardwaj RD, Bernstein M: Prospective feasibility study of outpa-
tient stereotactic brain lesion biopsy. Neurosurgery 51:358–364,
2002
12. Blancquaert I, De Langavant GC, Bouchard L, et al: Oversight
mechanisms for technology transfer in molecular genetics. Can J
Policy Res 2:103–109, 2001
13. Blanshard HJ, Chung F, Manninen PH, et al: Awake craniotomy
for removal of intracranial tumor: considerations for early dis-
charge. Anesth Analg 92:89–94, 2001
14. Bunker JP, Hinkley D, McDermott WV: Surgical innovation and
its evaluation. Science 200:937–941, 1978
15. Duffner F, Freudenstein D, Hohenstein F, et al: Quality planning
for minimally invasive procedures in neurosurgery. Minim Inva-
sive Neurosurg 44:95–98, 2001
16. The EC/IC Bypass Study Group: Failure of extracranial-intra-
cranial arterial bypass to reduce the risk of ischemic stroke. Re-
sults of an international randomized trial. N Engl J Med 313:
1191–1200, 1985
17. Emanuel EJ, Wendler D, Grady C: What makes clinical research
ethical? JAMA 283:2701–2711, 2000
18. Frader JE, Flanagan-Klygis E: Innovation and research in pediatric
surgery. Semin Pediatr Surg 10:198–203, 2001
19. Gerszten PC: Outcomes research: a review. Neurosurgery 43:
1146–1156, 1998
20. Gillett G: Ethics of surgical innovation. Br J Surg 88:897–898,
2001
21. Grimmett MR, Sulmasy DP: The call of the sirens: ethically nav-
igating the sea of nonvalidated therapies. J Refract Surg 14:
559–566, 1998
22. Guerrissi JO: Innovation and surgical techniques: endoscopic re-
section of cervical branchiogenic cysts. J Craniofac Surg 13:
478–482, 2002
23. Gutin PH, Phillips TL, Wara WM, et al: Brachytherapy of recur-
rent malignant brain tumors with removable high-activity iodine-
125 sources. J Neurosurg 60:61–68, 1984
24. Haines SJ: Randomized clinical trials in the evaluation of surgical
innovation. J Neurosurg 51:5–11, 1979
25. Hashizume M, Shimada M, Tomikawa M, et al: Early experiences
of endoscopic procedures in general surgery assisted by a com-
puter-enhanced surgical system. Surg Endosc 16:1187–1191,
2002
26. Hoznek A, Zaki SK, Samadi DB, et al: Robotic assisted kidney
transplantation: an initial experience. J Urol 167:1604–1606,
2002
27. Kondziolka D, Wechsler L, Goldstein S, et al: Transplantation of
cultured human neuronal cells for patients with stroke. Neurology
55:565–569, 2000
28. Kriss TC, Kriss VM: History of the operating microscope: from
magnifying glass to microneurosurgery. Neurosurgery 42:
899–908, 1998
Surgical innovation
29. Laperriere NJ, Leung PMK, McKenzie S, et al: Randomized study
of brachytherapy in the initial management of patients with malig-
nant astrocytoma. Int J Radiat Oncol Biol Phys 41:1005–1011,
1998
30. McDermott MW, Ciricillo SF, Gutin PH, et al: Stereotactic inser-
tion of an Ommaya reservoir: technical note. Can J Neurol Sci
22:235–238, 1995
31. McKneally MF: Ethical problems in surgery: innovation leading
to unforeseen complications. World J Surg 23:786–788, 1999
32. Meakins JL: Innovation in surgery: the rules of evidence. Am J
Surg 183:399–405, 2002
33. Millesi W, Truppe M, Watzinger F, et al: Remote stereotactic
visualization for image-guided surgery: technical innovation. J
Craniomaxillofac Surg 25:136–138, 1997
34. Moore FD: Ethical problems special to surgery: surgical teaching,
surgical innovation, and the surgeon in managed care. Arch Surg
135:14–26, 2000
35. Mosteller F: Innovation and evaluation. Science 211:881–886,
1981
36. National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research: The Belmont Report:
Ethical Principles and Guidelines for the Protection of Hu-
man Subjects of Research. Washington, DC: US Government
Printing Office, 1978
37. Nuremberg Military Tribunal: The Nuremberg Code. JAMA 276:
1691, 1996
38. Ramsay CR, Grant AM, Wallace SA, et al: Assessment of the
learning curve in health technologies. A systematic review. Int J
Technol Assess Health Care 16:1095–1108, 2000
39. Reemtsma K, Gelijns AC, Sisk JE, et al: Supporting future surgi-
cal innovation. Lung transplantation as a case study. Ann Surg
218:465–475, 1993
40. Reitsma AM, Moreno JD: Ethical regulations for innovative sur-
gery: the last frontier? J Am Coll Surg 194:792–801, 2002
41. Richardson DA: Ethics in gynecologic surgical innovation. Am J
Obstet Gynecol 170:1–6, 1994
42. Roos LL, Sharp SM: Innovation, centralization, and growth. Coro-
nary artery bypass graft surgery in Manitoba. Med Care 27:
441–452, 1989
43. Ruit S, Paudyal G, Gurung R, et al: An innovation in developing
world cataract surgery: sutureless extracapsular cataract extraction
J. Neurosurg. / Volume 100 / January, 2004
with the intraocular lens implantation. Clin Exp Ophthalmol 28:
274–279, 2000
44. Selker RG, Shapiro WR, Burger P, et al: The Brain Tumor Co-
operative Group NIH Trial 87–01: a randomized comparison of
surgery, external radiotherapy, and carmustine versus surgery, in-
terstitial radiotherapy boost, external radiation therapy, and car-
mustine. Neurosurgery 51:343–357, 2002
45. Shaw E: Looking through the retrospectoscope in the era of evi-
dence-based medicine. J Clin Oncol 15:1289–1290, 1997
46. Slater EE: IRB reform. N Engl J Med 346:1402–1404, 2002
47. Steiger HJ: How to control the risk of novel surgical procedures.
Acta Neurochir Suppl 78:179–184, 2001
48. Taylor MD, Bernstein M: Awake craniotomy with brain mapping
as the routine surgical approach to treating patients with supraten-
torial intraaxial tumors: a prospective trial of 200 cases. J Neuro-
surg 90:35–41, 1999
49. Taylor WA, Thomas NW, Wellings JA, et al: Timing of postoper-
ative intracranial hematoma development and implications for the
best use of neurosurgical intensive care. J Neurosurg 82:48–50,
1995
50. Wall LL: Innovation in surgery: caveat emptor. Int Urogynecol J
Pelvic Floor Dysfunct 12:353–354, 2001
51. Weijer C: Placebo trials and tribulations. Can Med Assoc J 166:
603–604, 2002
52. Williams RW: Microlumbar discectomy: a conservative surgical
approach to the virgin herniated lumbar disc. Spine 3:175–182,
1978
53. Winter RB: Innovation in surgical technique. The story of spine
surgery. Clin Orthop 378:9–14, 2000
54. World Medical Association Declaration of Helsinki: Ethical Prin-
ciples for Medical Research Involving Human Subjects. Edin-
burgh: World Medical Association, 2000
Manuscript received January 31, 2003.
Accepted in final form September 4, 2003.
Address reprint requests to: Mark Bernstein, M.D., Division
of Neurosurgery, Toronto Western Hospital, 399 Bathurst Street,
4W451, Toronto, Ontario M5T 2S8, Canada. email: mark.bernstein
@uhn.on.ca.
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