Ethical regulations for innovative surgery: the last frontier?

ETHICS

Ethical Regulations for Innovative Surgery:The Last Frontier?Angelique M Reitsma, MD, Jonathan D Moreno, PhD

BACKGROUND: There are no clear federal regulations governing innovative surgery, even though general guide-lines regulating research with human subjects do exist. We hypothesized that US surgeons areunaware of Department of Health and Human Services regulations, rarely seek IRB review,generally oppose outside regulation of innovative surgery, and are uncertain what constitutesinnovation and research. These circumstances, if true, would pose a significant ethical problemand present potential harm to patients as unwitting subjects of research.

STUDY DESIGN: In a pilot study we reviewed 527 issues of US surgical and medical journals, selecting 59 articlespublished between 1992 and 2000, that described innovative surgery. Corresponding authorsfrom university hospitals (71%) and other facilities (29%) were sent an anonymousquestionnaire.

RESULTS: The survey was conducted between November 2000 and May 2001. Twenty-one question-naires were returned, completed with responses, constituting a 35% overall response rate.Fourteen authors confirmed their work was research, yet only six had sought prior IRB review.The majority of authors (15 of 21) did not submit their protocol to IRB. Only seven authorshad mentioned the innovative nature of the procedure in the informed consent form. Sevenauthors claimed familiarity with Office for Human Research Protections definitions of researchand human subject. Two-thirds of the respondents stated that government regulations for theprotection of human subjects of innovative surgery would not be appropriate.

CONCLUSIONS: The current system of definitions, ethical theories, and voluntary professional guidelines may beinadequate to meet the challenge of surgical innovation. Further research is proposed to exam-ine the adequacy of the existing guidelines. ( J Am Coll Surg 2002;194:792–801. © 2002 by theAmerican College of Surgeons)

Although precedents for current law on informed con-sent in clinical practice emerged largely from the surgicalcontext, this has not led to formal scrutiny of innovativesurgery.1-3 There are regulations and guidelines for par-ticipation of human subjects in biomedical and behav-ioral research,4-9 and there are federal laws pertaining tohuman testing of drugs and devices,10 but there are cur-rently no clear federal regulations pertaining to innova-tive surgical procedures.

The somewhat exceptional position of innovative sur-

gery within the realm of research has long been recog-nized. In 1961 Beecher11 wrote: “One may question themoral or ethical right to continue with casual or un-planned new surgical procedures—procedures whichmay encompass no more than a placebo effect—whenthese procedures are costly of time and money, and dan-gerous to health or life.” Others from the surgical com-munity wrote in 1991: “When large numbers of inno-vative treatments are being continuously introducedinto clinical practice, rigorous testing is mandatory forthe protection of individual patients and the just use oflimited resources. This holds true with even greater forcein light of the evidence that many innovations show noadvantage over existing treatments when they are sub-jected to properly controlled study.”12

The American College of Surgeons13 has adopted self-imposed guidelines for emerging surgical technologiesand their application to the care of patients in 1994 and1995, as formulated by the Committee on Emerging

No competing interests declared.

The authors are grateful to the Donchian Foundation for providing supportthat helped to make this research possible.

Received August 30, 2001; Revised January 16, 2002; Accepted January 22,2002.From the Center for Biomedical Ethics, University of Virginia, Charlottes-ville, VA.Correspondence address: Jonathan D Moreno, PhD, Center for BiomedicalEthics, PO Box 800758, University of Virginia, Charlottesville VA22908-0758.

792© 2002 by the American College of Surgeons ISSN 1072-7515/02/$21.00Published by Elsevier Science Inc. PII S1072-7515(02)01153-5

Surgical Technologies and Education (CESTE).14,15 Theintroduction of new technology to surgeons and thepublic must be done ethically in accordance with theStatement on Principles of the American College of Sur-geons. These Principles require earlier and continuedIRB (or equivalent) review of the protocol, full descrip-tion of the procedure, and informed consent of the pa-tient. But current guidelines remain open to individualinterpretation and are not restrictive in character.

There appears to be a tradition in surgery that signif-icant changes in technique, and often even those involv-ing medical devices, are regarded as mere modificationsand not as research. If not properly recognized as re-search, surgical innovations fall beyond the scope ofmedical research guidelines that were designed to pro-tect human subjects. The combination of desperate pa-tients willing to try anything and compassionate sur-geons wanting to help frequently leads to the practice ofsurgical treatment that is not tried and true, let alonecost effective. McKneally16 writes: “Non-validated sur-gical procedures are being ‘smuggled’ past RCTs andIRBs, our societal checkpoints for innovations, in thesame way that minor variations in surgical practice havealways been introduced, without institution review.”Part of the difficulty with this issue may be semanticbecause the terms innovative, experimental, and researchhave overlapping meanings and application. As has longbeen recognized, all medical and surgical practice is, in asense, “experimental” insofar as every patient presentsunique circumstances; the very term practice embodiesthis point.

Yet there is growing concern about the performanceof surgical treatments of unproven worth.1,17 As Lantos18

states: “Consent for innovative procedures may be ob-tained in a manner governed only by the risk of malprac-tice litigation, and adverse events may not necessarily benoticed or analyzed.” This holds true even more outsideacademia, in private practice, where there is even lessoversight and peer review.19,20

There is reason to believe that there is a knowledgedeficit in the surgical community about federal require-ments and the role of IRBs in conducting clinical re-search.21 In this pilot study, our hypotheses were thatboth academic and private surgeons are largely unawareof current regulations, do not seek prior IRB review, andgenerally oppose regulation of innovative surgery. Surgi-cal innovation was defined here as a novel procedure, asignificant modification of a standard technique, a new

application of or new indication for an established tech-nique, or an alternative combination of an establishedtechnique with another therapeutic modality that wasdeveloped and tested for the first time. We believe thatthere are uncertainties and disagreements among sur-geons as to what is an acceptable variation on a surgicaltechnique versus what is a new or innovative techniquethat warrants prior IRB review and the patient’s in-formed consent. These circumstances pose a significantethical problem and present the possibility that patientsserve as unwitting subjects of research.

METHODSFirst, an online review was conducted of recent issues ofpreselected journals that are currently influential in theirparticular surgical and medical communities. Also, anextensive online literature search was done using thefollowing key words: new, novel, innovative, different,and alternative, combined with: surgery, surgical, opera-tive, approach, technique, procedure, and model.

Last, consultation was sought from local surgical spe-cialists, who kindly provided information on currentsurgical cutting-edge technology and assisted with edit-ing the questionnaire. Journals searched and the numberof articles selected are shown in Table 1.

Selected literature was carefully screened for new sur-gical procedures, techniques, and therapies. Articleswere selected that introduced novel procedures, signifi-cant modifications of a standard technique, new appli-cations of or new indications for an established tech-nique, or an alternative combination of an establishedtechnique with another therapeutic modality reportedfor the first time. Publications were selected regardless ofreferences to earlier publications in foreign medicalliterature.

The innovation as described was reviewed carefullyfor methods used and patients presented, with attentionto the mention of any research protocol. A summary ofselected articles is given in Appendix 1. Correspondingauthors of the selected articles were then sent an anony-mous survey (Appendix 2). Space was left for anecdotesand personal comments of the author-surgeons. Thisstudy was approved by the Human Investigation Com-mittee of the University of Virginia.

RESULTSFifty-nine articles were selected from a total of 527 issuesfrom 18 different journals. Selected articles had been

793Vol. 194, No. 6, June 2002 Reitsma and Moreno Ethics of Innovative Surgery

published between February 1992 and November 2000;71% of the articles originated from academic institu-tions and 29% from other institutions. Questionnaireswere sent to the 59 corresponding authors between No-vember 2000 and May 2001. Fifty-two authors weresent the full two-page questionnaire. Seven authors whomentioned that IRB review had been sought before im-plementing the research were sent an abbreviated ques-tionnaire because adequate and appropriate subjects’ in-formed consent was presumed in those cases.

Between November 2000 and July 2001, 25 ques-tionnaires were returned. Four questionnaires were un-deliverable; 21 questionnaires were completed with re-

sponses, constituting a 35% overall response rate. Of the21 respondents, 72% were academicians and 28% werefrom nonuniversity hospitals. Nineteen of the respon-dents completed the full questionnaire; two returned theshorter questionnaire. Mainly, authors of more recentpublications responded to our questionnaire (Table 2).Sixteen questionnaires were returned after the first mail-ing (12 completed, 4 undeliverable). Nonresponderswere sent an email reminder (n�11) or another ques-tionnaire in the mail (n�27), resulting in an additionalnine completed questionnaires.

Per definition, all articles were headed under the cap-tion “research,” because scientific publications essen-

Table 1. Journals Searched and Articles SelectedJournals Issues n Year

Preselected journalsJournal of the American Medical Association 2000–1998 (144 issues) 1 1999Archives of Surgery 2000–1996 (60 issues) 7 1997–2000Plastic and Reconstructive Surgery 2000–1998 (36 issues) 14 1998–2000Journal of Bone and Joint Surgery 2000–1994 (72 issues) 9 1995–1999Journal of Thoracic and Cardiovascular Surgery 2000–1996 (60 issues) 8 1996–2000New England Journal of Medicine 2000–1999 (96 issues) 1 1999Journal of the American College of Surgeons 2000–1997 (48 issues) 4 1997–2000

Online keyword searchAnnals of Thoracic Surgery 3 1996, 1997Catheterization and Cardiovascular Diagnosis 1 1998Clinical Orthopedics 1 1999Journal of Cardiac Surgery 1 1997Journal of Heart Valve Diseases 1 1994Journal of Laparoendoscopic Surgery 2 1992, 1999Journal of Neurosurgery 1 1999Journal of Surgical Oncology 1 1999Journal of Urology 1 1998Laryngoscope 1 1996Surgical Endoscopy 2 1995, 2000

Number of journal issues searched 527Number of selected articles 59

Table 2. Journals in Which Responding Authors Published

Journal nYears

published

Annals of Thoracic Surgery 1 1997Plastic and Reconstructive Surgery 5 1998–2000Archives of Surgery 2 1997, 2000Journal of Bone and Joint Surgery 6 1995–1999Journal of Thoracic and Cardiovascular Surgery 3 1996–2000Journal of the American College of Surgeons 2 1997, 2000Journal of Urology 1 1998Journal of Surgical Oncology 1 1999

794 Reitsma and Moreno Ethics of Innovative Surgery J Am Coll Surg

tially are designed to contribute to generalizable knowl-edge. Reporting results requires systematic investigationand review of facts before such a report can be submittedfor publication.

Accordingly, most authors (14 of 21) responded pos-itively to the question whether their publication in factdescribed research. Of those, six authors sought previousIRB review to perform their studies. Of this group, threeof six publications clearly described surgical innovations;we were unable to determine the innovative character ofthe other three procedures. The two authors who com-pleted the abbreviated questionnaire described their ex-perience with the IRB as favorable.

The majority of the self-described researchers (n�8)did not seek IRB review. In this group, four of eightpublications were truly innovative, one was not, andthree could not be determined. Authors incorrectly be-lieved that retrospective studies did not warrant IRBreview. These responses clearly represent inaccurate be-liefs about when IRB approval is required. Some (n�3)believed that the nature of the procedure did not justifyIRB review or specific consent to research because theprocedure “wasn’t particularly innovative.” Interestinglyenough, such publications were found in the “Ideas andInnovations” section of a journal.

Conversely, 7 of 21 authors did not believe that thereported work constituted research. Surprisingly, themajority of this group (five of seven publications) in-volved actual surgical innovations; two publications didnot, in retrospect.

Seven of the 21 authors claimed to be familiar withcurrent federal regulations defining research and humansubject. Of the 14 who did not know of these regulations,3 authors stated that knowing now, they would answerdifferently. One author used a personal definition ofresearch: “It is experience and knowledge of the anatomyand its assimilation.”

Most respondents to the full questionnaire (75%)claimed that their patients had been aware of the factthat they underwent an innovative procedure, but inonly one-third of the cases (7 of 21) had this been spe-cifically mentioned in the informed consent form. Thisresult raises some concerns about the adequacy of con-sent forms used in these procedures.

Only one out of the 21 respondents replied that he orshe had some formal background or training in biomed-ical ethics, in the form of a course.

Last, one question asked if government regulations

for the protection of human subjects of innovative sur-gery would be appropriate. Sixty-one percent (13) of theauthors answered “No,” and the remaining eight said“Yes” to federal rules for surgical innovation. One authorbelieved that explicit guidelines would be helpful forprotection of both patient and provider.

Of those opposed to government regulations, one au-thor did not specify any reasons; the rest could roughlybe grouped into four categories: A, B, C, and D.

Category A (n�4) involved those who found thatcurrent regulations are effective and adequate. A reac-tion in this group reiterates the difficulties for regula-tions specific to surgery: “There is no way to regulateeverything. Also the definition between innovative andincrementally innovative procedures is difficult to de-fine.”

Group B authors (n�2) sought other ways of ensur-ing the safety of those patients involved in surgical inno-vation: “No, it should follow locally accepted standardsfor practice and honest discussion between patient andinvestigator.” In groups A and B, 50% of authors soughtIRB review for their innovative work.

In contrast, in these last two groups, C and D, none ofthe authors had sought IRB review before implementingtheir new procedure. Clearly in favor of a continuedfederal hands-off approach were authors in category C(n�4): “I think government should take care of politics,not of medicine and science.” Another author claimed,“No, it would stifle progress.” One author wrote, “Pro-tection intimates that the surgeons are not providingmedical care in the best interest of the patient.” Finally,one author wrote, “The government has no knowledgeof surgery, its principles, and the application of soundtechnique.”

The two authors within the last category with miscel-laneous responses, D, reacted somewhat vehemently toour survey. One author wrote: “All surgery is innovative,the government should take the opposite argument andask if MDs who are not always questioning existingdogma should be the ones regulated.” This is a goodpoint; although the “publish or perish” mantra rules inacademia, private practitioners enjoy relative freedomfrom the pressures to improve and innovate. Last, oneauthor was offended by our survey, writing, “Your ques-tion and questionnaire are quite typical andmanipulative—oversimplistic and is obviously self-serving. Shame on you!”


DISCUSSIONAlthough 21 responses constitute a relatively smallgroup of surgeons, we believe these answers may verywell be representative of the larger surgical community.A 65% nonresponse rate might not merely be a sign oflack of time, but it may also suggest inattentiveness tothe subject or resistance to the prospect of guidelinesimposed by others, especially those who are not from thesurgical community.

Comments some authors made were often quite rea-sonable. For example, the worry that additional reviewor regulations would stifle progress is a frequently ut-tered concern.22 Yet following formal rules for develop-ing a study protocol and going through IRB review be-fore implementing a new technique does not have totake up much additional time, and it could help to en-sure sound scientific method, which, in turn, promotestrue progress. Objecting to government involvement inmedicine seems somewhat naive. Of course, the federalgovernment already “takes care” of medicine and thedevelopment of medical therapies and devices throughthe Department of Health and Human Services, theFood and Drug Administration, the Centers for DiseaseControl, the National Institutes of Health, and licensingagencies. Claiming that the government has no knowl-edge of surgery is also contestable. Indeed, random in-dividual members of the federal government, whetherelected or appointed, probably know little about surgery.But American physicians do trust the knowledge of theSurgeon General, and the Department of Health andHuman Services and its subdivisions, accepting theirleadership and guidance within medicine in general.Some authors believed their good intentions towardtheir patients were being questioned. Within research,tension almost always exists between the individual pa-tient’s best interest and the interest of future patients.The interests of the first patients to undergo an innova-tive technique may or may not directly be served; futurepatients might benefit once the new procedure has beentried and found beneficial. That the well being of thosefrontline patient-subjects does require protection hasbeen demonstrated more than adequately in the historyof clinical research.23

From our literature review and responses to our pilotsurvey several conclusions may be drawn. First, the sur-geons addressed appear to be largely unaware of currentregulatory definitions of research with human subjects.

Second, in spite of familiarity with the federal regu-lations, it remains difficult for the respondents (as, infairness, for the present authors) to determine whenefforts to benefit their patients actually constitute re-search. Third, even if the investigational nature of thework is recognized, it remains difficult to decide whenIRB review is appropriate and whether additionalconsent procedures are warranted. In theory, in-creased education of surgical residents and establishedsurgeons alike should overcome such lack of informa-tion. Fourth, it is a challenge to recognize truly inno-vative procedures, techniques, and surgical therapies,and to acknowledge the specific ethical issues thatsuch innovations bring about.

This last point illustrates again that a large “gray zone”exists between sound research and incrementally intro-duced novelties, although both ultimately produce in-novations. Apparently, distinguishing between gradualimplementation of minor surgical modifications andmore permanent or extensive alterations of a techniqueis a challenge. This is especially true when modificationsare made on an as-needed basis for the benefit of theindividual patient. Such distinctive modifications havebeen and will always be necessary for the best possiblepatient outcomes, and surgeons know best when tomake them. But a surgeon may begin to change hisstandard operating room technique more permanentlybased on experiences with individual cases. If he thendecides to publish results of the new technique, the lineis clearly crossed and even originally spontaneous, andpatient-centered modifications become research in ret-rospect, justifying IRB review and sometimes informedconsent of the patients, who have now become researchsubjects.

Several surgeons have brought these issues to the atten-tion of the medical community and attempted to producesolutions. In 1999, McKneally16 suggested a review boardspecifically for nonvalidated treatments (unproved surgicalinnovations). This board would be a regionally coordinatedsystem and would include surgeons, patients, payers, andadministrators. Apart from such boards, McKneally alsocalled for more rules, enforced by professional organiza-tions, granting agencies, and governments. One author’ssuggestion to improve ethical innovation (“Better with peerreview”) had been mentioned before in the literature as apotential solution to regulate surgical innovation fairly andreasonably. In 2000, Francis Moore24 restated his earlierethical guidelines: laboratory background, field strength,


and institutional stability. The latter would lead to devel-opment of consensus within a trusting environment, peerreview, and consultation before implementation of the newprocedure. More recently, Bunch and Dvonch25 advocateda “case method of ethical analysis” to assist orthopaedicsurgeons in their decision-making process concerning in-novative surgery. They conclude by stating that, “as sur-geons, we cannot wish for the days of unfettered activity,but must be responsive to the present ethical norms.”

A similar statement regarding the ethics of surgicalinnovation was recently made by Cronin and associ-ates.17 In their compelling 2001 article, they examinethe ethical aspects of liver transplantation in adultswith the use of grafts from living donors, an innova-tive application of a technique originally developedfor the pediatric population. This is a paradigm ex-ample of an innovation spreading like wildfirethroughout the surgical community without any ear-lier studies that demonstrate its actual benefit. Theauthors state that surgical specialty societies couldhave taken an earlier active role in self-regulating,although they rightfully question the impact of suchmeasures. They conclude that internal, professionalcontrol should be supplemented by an external mech-anism for prospective regulation, which may includegovernment intervention. Taking it one step beyond,they conclude that unless professional self-regulationfor other innovative procedures improves, govern-ment regulation may be necessary. The ethics of in-novative surgery is also becoming increasingly inter-esting to the general public. The New York Timesrecently published an article on maternal-fetal surgeryfor meningomyelocele, a new and unproved proce-dure that presents risks to mother and unborn child.26

The current system of formal definitions, ethical the-ories, and voluntary professional guidelines to protectpatients from unwittingly becoming subjects of researchappears to be inadequate to meet the challenge of surgi-cal innovation. Further research is indicated to deter-mine whether additional government regulations arenecessary or if amendments to the current federal regu-lations and societal guidelines are required. These ques-tions cannot be answered in advance. We must subjectthis domain of human research ethics to closer examina-tion. Questions to be addressed include: When doessurgical innovation become research involving humansubjects? How can we distinguish between variations onan existing technique and true innovations? How could

we better regulate and monitor these innovations? Isthere a role for IRB review of innovation? How can weimprove the consent process, to better inform and pro-tect patients? Should we educate surgeons to introducesurgical innovations in a more ethically and scientificallysound manner, and if so, how should this education beaccomplished?

The rules that should govern innovative surgery andsurgical research have long subsisted in an unchartedfrontier of medical ethics. The time has come to advanceto that last frontier.

Acknowledgment: We are indebted to John S Minasi, MD,and Charles W Miller, MD, for their helpful comments on thedevelopment of the questionnaire and for their valuable sug-gestions on surgical and orthopaedic innovations. We aregrateful to Paul A Lombardo, JD, PhD, and David F Kalmess,MD, for reviewing the draft of our manuscript, and to twoanonymous reviewers who made excellent suggestions. Fi-nally, we thank Kathryn E Kraaij for providing administrativesupport.

Appendix 1. Summary of selected articlesMinimally invasive coronary artery bypass grafting; caseseries, n�3; coronary artery bypass grafting by thora-coscopy is used to obtain internal mammary artery forgraft, avoiding usual median sternotomy and cardiopul-monary bypass.

Total mesenteric excision in surgical treatment of rec-tal cancer; cohort, n�65; total mesenteric excision in-volves removal of entire rectal mesentery as intact unit;study to determine efficacy of minimizing locoregionalrecurrence rates.

Lengthening of Achilles tendon in diabetic patients;case series, n�10; percutaneous lengthening of theAchilles tendon in diabetic patients in attempt to reduceulceration.

Bioabsorbable weave technique for repair of pectusexcavatum; retrospective case series, n�12; new bioab-sorbable weave used as posterior support for correctionof pectus excavatum.

Fetal surgery for myelomeningocele; case-controlstudy, n�29:23; in utero closure of fetal myelomenin-gocele in fetuses with spina bifida, between 24 and 30weeks gestational age.

Articular cartilage transplantation; cohort study, n�55; resurfacing of the knee by transplantation of viable,fresh osteochondral shell allograft.


End-to-end pancreaticoduodenostomy: alternativereconstruction for partial resection of head of pancreas;case study, n�1; alternative to pancreaticoduodenos-tomy; technique spares pancreatic tissue.

Hand-assisted laparoscopic vertical banded gastro-plasty; case series, n�26; hand-assisted laparoscopicvertical banded gastroplasty offers similar weight lossand morbidity to open techniques.

Simplified transblepharoplasty subperiosteal cheeklift; cohort study, n�62; by resecting less eyelid skin,this simplified approach provides correction of midfacialaging without the need for canthoplexy or canthoplasty.

Reduction mammaplasty; case series, n�38; com-bining vertical skin resection with central mound reduc-tion increases the amount of breast tissue that can beremoved.

Transcatheter closure of anomalous venous connec-tion; case study, n�1; an alternative to surgical repair,minimally invasive transcatheter venous closure.

Transmyocardial laser revascularization; case series,n�20; transmyocardial laser revascularization providesdirect perfusion of ischemic myocardium.

Endoscopic transpedicular thoracic discectomy; caseseries, n�25; technique uses 70° endoscope for directvisualization of spinal cord, thereby minimizinginvasiveness.

Laparoscopic cryoablation of hepatic metastases; ret-rospective case series, n�9; laparoscopic cryoablation ofhepatic metastases is a minimally invasive alternative toopen cryosurgical hepatic procedures.

In situ splitting of a rib graft for reconstruction; caseseries, n�9; in situ split rib graft harvest for orbital floorreconstruction reduces complications from complete riband split cranial bone harvests.

Modified Norwood procedure with high-flow cardio-pulmonary bypass; cohort study, n�59; modificationof the Norwood procedure uses only autologous tissuerather than homograft material to reconstruct aorticarch for patients with hypoplastic left heart syndrome.

Laparoscopic repair of paraesophageal hernia; case se-ries, n�10; paraesophogeal hernia can be repaired usingstandard surgical technique with new laparoscopicaccess.

Transfer of pectoralis major tendon to treat paralysisof serratus anterior muscle; case series, n�16; transfer ofpectoralis major tendon with addition of fascial graft inpatients with paralysis of serratus anterior muscle.

Another indication for liposuction: small facial lipo-

mas; case report, n�5; liposuction is used to treat smallfacial lipomas.

Mini laparoscope; cohort control, n�100:100; thenew 2-mm laparoscopic equipment minimizes invasive-ness in laparoscopic cholecystectomy.

Esophagectomy with gastric reconstruction for acha-lasia; case series, n�32; esophagectomy with gastricrather than colon reconstruction.

Endoscopic staple-assisted esophagodiverticulostomyfor Zenker’s diverticulum; case series, n�6; endoscopicstaple-assisted esophagodiverticulostomy divides thecommon wall between the esophagus and diverticulum,sealing the mucosal and muscular edges with staples.

Clinical outcomes in patients undergoing coronaryartery bypass grafting with preferred use of radial artery;case-control study, n�138:228; this procedure uses theradial artery for coronary artery bypass grafting(CABG).

Technique of pancreaticojejunostomy that optimizesblood supply to pancreas; case series, n�40; pancreati-cojejunostomy that includes optimization of blood sup-ply to the pancreas.

‘Domino’ liver transplantation combined with multi-visceral transplantation; case report, n�3; this “domi-no” procedure involves a multivisceral graft; the ex-planted liver is transplanted into a second patient.

Transnasal endoscopic excision of midline nasal der-moid from anterior cranial base; case report, n�2; trans-nasal endoscopic access was used to remove the intracra-nial origin of the dermoid tract without the need forcraniotomy.

Capsulorraphy through an anterior approach; case se-ries, n�10; capsular reconstruction procedure throughan anterior, rather than posterior, approach is used forglenohumeral instability with multidirectional laxity ofthe shoulder.

Arthrodesis of the knee with a vascularize fibular ro-tatory graft; retrospective review, n�13; the use of avascularized fibular graft and an intramedullary rod is analternative method of arthrodesis of the knee.

Alternative approach to multivessel coronary diseasewith integrated coronary revascularization; cohort, n�31; integrated coronary revascularization combinesminimally invasive coronary artery bypass grafting withleft internal thoracic artery–left anterior descending ar-tery grafting and percutaneous coronary intervention.

Endoscopic intracorporal abdominoplasty; case-control, n�85:25; an alternative to the open procedure,


endoscopic intracorporal abdominoplasty combines tra-ditional abdominal wall liposuction with endoscopic in-tracorporal plication of the rectus fascia.

Laparoscopic paraesophageal hernia repair; case re-port, n�2; laparoscopic paraesophageal hernia repair asan alternative to the open technique.

Reduction of lower palpebral bulge by plicating atten-uated orbital septa: a technical modification; retrospec-tive cohort study, n�138; cosmetic blepharoplastywithout removal of the periorbital fat pad.

Reconstruction of irradiated postpneumonectomyempyema cavity; case report; first description of a com-plete hemithoracic reconstruction of an irradiated post-pneumonectomy recurrent empyema cavity, with chain-link of two coupled free flaps.

Mandibular matrix implant system to restore thelower face; case series, n�3; new method of skeletalsupport restoration for entire mandible.

Enterostomy and its closure in newborns; retrospec-tive cohort study, n�109; morbidity and mortality as-sociated with newborn enterostomy and its closurestudied.

Laparoscopic Nissen fundoplication: a new techniquefor true fundoplication; technique description; newtechnique developed, article describes steps to performnew maneuver.

Early clinical and hemodynamic evaluation of theaortic intact porcine bioprosthesis; cohort, n�89; newaortic valve prosthesis compared with established stan-dard valve.

Comparison of minimally invasive esophagectomywith thoracic and transhiatal esophagectomy; retrospec-tive comparison of 3 techniques, n�18, 16, and 20;laparoscopic technique compared with the conventionalapproaches.

Endovascular stent-graft placement for the treatmentof acute aortic dissection; cohort, n�19; new treatmentfor selected patients, further evaluation suggested.

Less invasive arterial CABG on a beating heart; co-hort study, n�156; minimally invasive direct coronaryartery bypass grafting, with regional cardiac wall immo-bilization of coronary artery target sites.

Minimally invasive radioguided parathyroidectomy;case series, n�39; minimally invasive radioguided par-athyroidectomy is compared with standard neck explo-ration for correcting hyperthyroidism.

Transconjunctival orbital fat repositioning: transposi-tion of orbital fat pedicles into a subperiosteal pocket;

case series, n�24; fat is repositioned, rather than ex-cised, to rejuvenate lower eyelid complex.

Transmyocardial laser revascularization combinedwith coronary artery bypass grafting; randomized con-trolled clinical trial, n�132:131; transmyocardial revas-cularization with coronary artery bypass grafting is usedin patients who are not amenable to complete revascu-larization by coronary bypass alone.

Local excision of rectal carcinoma; case series, n�20;local excision, either transanal or transacral, combinedwith selective chemoradiation therapy for patients withlarger (�3cm) tumors where this was previously onlydone for patients with tumors �3cm.

Complex reconstruction for treatment of dorsolateralperitalar subluxation of the foot; retrospective case se-ries, n�36 (41feet); lengthening of the lateral column,osteotomy of the medial cuneiform, and advancementof the posterior tibial tendon traditionally designed tocorrect flatfoot in children, are used to correct acquiredflatfoot in adults.

Femoral lengthening over an intramedullary nail; casecontrol, n�29:31; femoral lengthening over an in-tramedullary nail, with the nail and the external fixatorapplied concomitantly, allows removal of the externalfixator at the end of the distraction phase, comparedwith standard Ilizarov femoral lengthening.

Scalp autografts and hair transfer to the face in theburned child; retrospective review, n�109; this studyexamines the incidence of hair transfer in scalp au-tografts to the face for burned children.

The use of micrografts and minigrafts for the treat-ment of burn alopecia; case report, n�2; micrograftsand minigrafts are a possible alternative treatment forburn alopecia, rather than scalp flaps, free scalp flaps, ortissue expansion.

Oblique osteotomy for the correction of tibia mal-union; case series, n�15; this study examines the effi-cacy of oblique tibial osteotomy, with the use of one cutin the bone for the treatment of multiplanar malunionof the tibial shaft, when the desired lengthening is lessthan 2.5 centimeters.

Laparoscopic total esophagectomy; case series, n�9;this review is an examination of the efficacy of laparo-scopic total esophagectomy as treatment for cancer ofthe esophagus.

Total hip arthroplasty with insertion of the acetabular


component; case series, n�21 (24 hips); assessing theintermediate results associated with use of a porousingrowth acetabular component for treatment of pa-tients with congenital dysplasia or total dislocation ofthe hip.

Treatment of supracondular nonunions of the femurwith plate fixation and bone graft; retrospective review,n�18; compares single- and double-plate fixation andbone grafting from the iliac crest for treatment of supra-condular nonunions of the femur.

Conversion of modified Fontan procedure to lateralatrial tunnel cavopulmonary anastomosis; retrospectivereview, n�8; conversion to a lateral tunnel Fontan pro-cedure for patients with giant right atria or pulmonaryvein compression.

No-cut thoracoscopic lung plication; case series, n�32;no-cut thoracoscopic lung plication, which avoids cuttingthe visceral pleura, is a less invasive technique than tradi-tional lung volume reduction surgery (LVRS).

Transverse orbicularis oculi myocutaneous flap usedas nasal lining; case report, n�2; for nasal reconstruc-tion: transverse orbicularis oculi myocutaneous skin isused for nasal lining and the donor site offers improvedaesthetics and large tissue area.

Excision of the submandibular gland by an intraoral ap-proach; case report, n�2; this new, intraoral approach tosubmandibular gland excision avoids scarring and risk tothe marginal mandibular branch of the facial nerve.

Extraanatomic aortic bypass via sternotomy for com-plex aortic arch stenosis in children; case series, n�19;extraanatomic aortic bypass as an alternative techniquefor complex aortic reconstruction.

The T pouch: an orthotopic ileal neobladder incor-porating a serosal lined ileal antireflux technique; co-hort, n�40; the T pouch is a new orthotopic ileal neo-bladder that incorporates an effective antirefluxmechanism created by a serosal lined ileal tunnel.

Laparoscopic Roux-en-Y gastric bypass for morbidobesity; cohort, n�400; a less invasive technique oflaparoscopic Roux-en-Y gastric bypass.

Appendix 2. Full questionnaireYou were chosen to participate in this survey because yourecently published an innovative surgical procedure(added: citation).

This questionnaire will take you about 10 minutes tocomplete. Anonymity is guaranteed and your participa-tion is greatly appreciated.

1.You recently published about an innovative surgical procedure.Would you say that the development of your procedure is in factresearch?

Y: N:

If not, why not?

2.Federal regulations define “research” as “any systematicinvestigation designed to develop and contribute togeneralizable knowledge.” Are you familiar with this regulation?(http://ohsr.od.nih.gov/guidelines, http://ohrp.osophs.dhhs.gov/humansubjects/guidance/decisioncharts.htm)

Y: N:

3. In light of this regulation, would your answer to question 1 beany different?

Y: N:

4.Prior to developing your procedure, was your protocol reviewedby an investigational review committee (IRB) or another medicalethical board in your institution?

Y: N:

If not, why not? If you answered yes, please skip questions 5 and 6and proceed to question 7.

5.Were your patients aware of the fact that they underwent aninnovative procedure?

Y: N:

6.Was the innovative nature of the procedure specificallymentioned in the Informed Consent form they signed?

Y: N:

If not, why not?

7.Do you have any formal background or training in biomedicalethics?

Y: N:

If yes, please elaborate:

8.For the protection of human subjects of innovative surgery, doyou agree that government regulations would be appropriate?

Y: N:

If not, please explain:

Thank you very much for completing this question-naire. We appreciate your input greatly. If you have anysuggestions how to improve this survey, please [email protected].

REFERENCES

1. Frader JE, Caniano DA. Research and innovation in surgery. In:McCullough LB, Jones JW, Brody BA, eds. Surgical ethics. Ox-ford University Press; 1998:217–241.


2. Siegler M. Ethical issues in innovative surgery. Should we at-tempt a cadaveric hand transplantation in a human subject?Transplant Proc 1998;30:2779–2782.

3. Pernick MS. The patient’s role in medical decisionmaking: Asocial history of informed consent in medical therapy. In: Mak-ing health care decisions, the ethical and legal implications ofinformed consent in the patient-practitioner relationship. Vol. 3:Appendices studies on the foundations of informed consent. ThePresident’s Commission for the Study of Ethical Problems in Med-icine and Biomedical and Behavioral Research. October 1982.

4. Pendergast MK, Deputy Commissioner and Senior Advisor tothe Commissioner of the Food and Drug Administration. Tes-timony on human subjects in biomedical research. Washington,DC: US Department of Health and Human Services; 1997.

5. World Medical Association. Declaration on the rights of thepatient. Amended September 1995. Available at: http://www.wma.net/e/policy.html.

6. World Medical Association. Recommendations guiding physi-cians in biomedical research involving human subjects (doc.17.1) Helsinki, June 1964. Available at: http://www.wma.net/e/policy.html.

7. US National Commission for the Protection of Human Subjectsof Biomedical and Behavioral Research. The Belmont report:Ethical principles and guidelines for the protection of humansubjects of research. September 30, 1978.

8. Office for Human Research Protections. Available at: http://ohrp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm.

9. Office for Human Subject Research homepage. Available at:http://ohsr.od.nih.gov/guidelines.

10. Code of Federal Regulations Title 21, Parts 50 and 56, addi-tional FDA regulations: parts 312 (Investigational New DrugApplication), 812 (Investigational Device Exemptions), and860 (Medical Device Class Procedures).

11. Beecher HK. Surgery as placebo, a quantitative study of bias.JAMA 1961:176:1102–1107.

12. Troidl H, Spitzer WO, McPeek B, et al (eds). Principles andpractice of research: Strategies for surgical investigation. Chap-ter 12. New York: Springer-Verlag; 1991.

13. American College of Surgeons website. Available at: http://www.facs.org.

14. American College of Surgeons. Statement on emerging surgicaltechnologies. Bull Am Coll Surg 1994;79:40–41.

15. American College of Surgeons. Statement on issues to be con-sidered before new surgical technology is applied to the care ofpatients. Bull Am Coll Surg 1995;80:46–47.

16. McKneally MF. Ethical problems in surgery: Innovationleading to unforeseen complications. World J Surg1999;23:786–788.

17. Cronin DC II, Millis JM, Siegler M. Transplantation of livergrafts from living donors into adults—too much, too soon.N Engl J Med 2001;344:1633–1637.

18. Lantos JD. The ‘inclusion benefit’ in clinical trials. J Pediatr1999;134:130–131.

19. Ivy EJ, Lorenc PZ, Aston SJ. Is there a difference? A prospectivestudy comparing lateral and standard SMAS face lifts with ex-tended SMAS and composite rhydectomies. Plastic and Recon-str Surg 1996;98:1135–1143.

20. Fost N. Ethical dilemmas in medical innovation and research:Distinguishing experimentation from practice. Semin Perinatol1998;22:223–232.

21. Rutan RL, Deitch EA, Waymack PJ. Academic surgeons’ knowl-edge of Food and Drug Administration regulations for clinicaltrials. Arch Surg 1997;132:94–98.

22. Moreno JD. Protectionism in research involving human sub-jects. National Bioethics Advisory Commission, Ethical andPolicy Issues in Research Involving Human Participants, Vol-ume II (Commissioned Papers), Washington, DC; 2001.

23. Faden RR, Beauchamp TL. A history and theory of informedconsent. New York: Oxford University Press; 1986.

24. Moore FD. Ethical problems special to surgery: Surgical teach-ing, surgical innovation and the surgeon in managed care. ArchSurg 2000;135:14–16.

25. Bunch WH, Dvonch VM. Moral decisions regarding innova-tion. Clin Orthop 2000;378:44–49.

26. Jones M. A miracle, and yet. New York Times, July 15, 2001.


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Ethical regulations for innovative surgery: the last frontier?