The ethics of innovation: Columbus and others try something new IA L McKneally Editorials D IT O R The ethics of innovation: Columbus and others try something new E Martin F. McKneally, MD, PhD When is it ethically acceptable to embark on an innovation that involves the life and health of human subjects? Our au- thors regularly submit new operations, devices, and man- agement techniques for publication in the Journal. Because professional journals and organizations are held accountable for their implicit endorsement of off-label and novel practices that prove to be dangerous or harmful, Editor Larry Cohn asked me to comment on the ethics of in- novation. I’ll begin and end with a case, describe an ethics framework for innovation, and recommend a practical approach that has served us well. THE CASE Christopher Columbus hypothesized that he could de- velop a shorter trade route to India by sailing straight west across the Atlantic. He was an experienced captain who had exceptional knowledge of ocean currents and celestial navigation. He had sailed as far west as the Canary Islands, 100 km off the west coast of Africa. During these innovative excursions, he did not fall off the edge of the world or en- counter the dragons depicted on maps of that era. The cur- rents off the Canaries, where he was alleged to have kept a mistress, ran westward toward an uncharted new world. Should Columbus have told the sailors he recruited that he was not planning to follow the navigational convention of sailing down the coast of Africa and around the Cape of Good Hope in constant sight of land? His seasoned col- league Pinchon, the captain of the Ni~na, advised recruiting seamen with the usual inducements—a good ship, good captain, rum, and the prospect of shared treasure—without mentioning the innovation of sailing an uncharted course. If Columbus insisted on full disclosure, Pinchon recommen- ded recruiting convicted prisoners with the promise of a royal pardon if they survived. Columbus retired to a mon- astery to seek consultation with the monks, pray for guid- ance, and make a decision. What should Columbus do? ETHICS FRAMEWORK Ethics is a plural noun. An ethic is a set of values, princi- ples, beliefs, and standards of conduct that guide the behav- ior of a specified group, such as journalists, lawyers, or From the Department of Surgery and Joint Centre for Bioethics, University of Toronto, Toronto, Ontario, Canada. Received for publication Dec 14, 2010; revisions received Dec 14, 2010; accepted for publication Jan 3, 2011. Address for reprints: Martin F. McKneally, MD, PhD, University of Toronto, 77 For- est Grove Dr, Toronto, ON M2K1Z4, Canada (E-mail: martin.mckneally@ utoronto.ca). J Thorac Cardiovasc Surg 2011;141:863-6 0022-5223/$36.00 Copyright � 2011 by The American Association for Thoracic Surgery doi:10.1016/j.jtcvs.2011.01.003 The Journal of Thoracic and Ca doctors. The ethic of surgery, with its foundational values of competence and commitment, is a singularly intense ver- sion of the ethic of medicine. The magnitude of the viola- tions of physical integrity and dignitary rights of surgical patients 1 and the immediacy of the surgeon’s personal en- gagement and responsibility contribute to this singularity. Surgeons take pains to explain in detail the goals, conse- quences, and expected outcomes of the surgical interven- tions they plan to perform. The variability of the terrain in which we practice leads to inevitable unplanned innovation: ‘‘We couldn’t remove the tumor, but we were able to bypass it,’’ or ‘‘We had only one donor lung, so we did a contralat- eral volume reduction on the recipient to maximize func- tion.’’ 2 Such innovations are morally justified in the court of professional opinion by their reasonableness, the lack of better alternatives, and their congruence with the values and principles of the surgical community. Planned innovations, like Columbus’ voyage, require definition and forethought. Innovation is a notional concept. There are many notions of its meaning, and no widely ac- cepted definition. To distinguish innovation from the minor incremental changes that surgeons introduce in the course of everyday practice, we have defined surgical innovation as ‘‘a new evolving intervention whose effects, side- effects, safety, reliability and complications are not widely known.’’ 3 This definition is intended to encompass transfor- mative rather than incremental changes. Although the boundary between minor incremental improvements and major transformative innovations is difficult to define, it is easy to recognize. McBurney’s decision to remove the ap- pendix through a small, muscle-splitting incision trans- formed the treatment of appendicitis. Prestigious advocates of traditional management, including William Osler, were adamantly opposed to his approach. McBurney thought that the conventional treatment—hot packs to the abdomen, morphine analgesia, turpentine enemas, rectal in- sufflation of tobacco smoke, and eventual drainage of the periappendicial abscess—was inadequate. Against the pre- vailing beliefs of medical and surgical colleagues, he devel- oped a bold new transformative treatment. The guidance documents on the ethics of innovation are reasonable but insufficient. For example, the Declaration of Helsinki 4 is the Journal’s reference standard; it autho- rizes us to try unproven treatments when nothing else works, to save life, re-establish health, or alleviate suffer- ing. ‘‘In the treatment of a patient, where proven interven- tions do not exist or have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorized representative, may use an unproven intervention if in the physician’s judgment it rdiovascular Surgery c Volume 141, Number 4 863 mailto:martin.mckneally@utoronto.ca mailto:martin.mckneally@utoronto.ca http://dx.doi.org/10.1016/j.jtcvs.2011.01.003 Editorials McKneally E D IT O R IA L offers hope of saving life, re-establishing health or alleviat- ing suffering. Where possible, this intervention should be made the object of research designed to evaluate its safety and efficacy. In all cases, new information should be re- corded and, where appropriate, made publicly available.’’4 The problem with this principle is that it allows innovation only where proven interventions do not exist or are ineffec- tive. Innovations in areas that might make the treatment cheaper, quicker, less debilitating, or easier to teach are ig- nored. We innovate to improve interventions that are al- ready in existence and effective but may be too expensive, slow, uncomfortable, or inconvenient. A thoughtful book, Ethical Guidelines for Innovative Surgery, 5 summarizing 5 years of study and 2 conferences on surgical innovation, addresses some of these issues. It will reward careful reading and provides a basis for further research. ETHICAL ISSUES SPECIFIC TO INNOVATIVE SURGERY An issue is an important social question to which there is often more than one reasonable answer. The important issues confronting innovators and those accountable for innovations are consent, validity, competence, conflict of interest, cost, and oversight. Consent The issue of consent is particularly sensitive and easily mismanaged. In a progressive society, procedures that are described as new are often presumed to be improvements relative to those that are older. Patients subjected to un- proven interventions should be explicitly informed about the innovation’s novelty and lack of a proven record of ef- fectiveness. Consent for the first patient to undergo heart surgery with cross-circulation is well described in G. Wayne Miller’s excellent book King of Hearts: The True Story of the Maverick Who Pioneered Open Heart Surgery. 6 ‘‘The Gliddens remembered their daughter LaDonnah, who had been born with the same [ventricular septal] defect.. They were willing to try almost anything to spare their baby Gregory their daughter’s fate.’’6 In obtaining their con- sent for a landmark innovative operation, ‘‘[Walt] Lillehei told the Gliddens that his ‘‘artificial heart’’ was actually an- other person—in fact, one of them. [He] drew a diagram of cross-circulation and talked of his experimental success with dogs.’’ 6 In contrast, many innovators are tempted to take the easy and less transparent approach, saying simply, ‘‘We have a new [and, by implication, better] way to do your operation.’’ Participants undergoing innovative interven- tions should be informed of the novelty of the undertaking. Validity The issue of validity is less settled with innovation than with accepted standard procedures, although many of the 864 The Journal of Thoracic and Cardiovascular Surg latter remain unvalidated. Valid interventions are effective, well-founded, and able to produce the desired result. The word valid derives from the Latin validus, meaning strong. An innovation may be presumed to be valid if it is founded on reasonable evidence of feasibility and effectiveness. This evidence may come from unplanned successful experience in an emergency, studies in animals, or demonstrations in the anatomy or pathology laboratory. Further support may come from the experience and endorsement of peers work- ing with similar frontier technologies and techniques. Intro- duction of an innovation is ethically justified on the grounds of probable validity, as judged by competent professionals. This remains a claim until validating evidence has been de- veloped with the help of well-informed, willing patients. Successful application in their care provides the basis for eventual recognition of the innovation as a validated com- ponent of the surgical armamentarium. Competence A foundational element of the surgical ethic is compe- tence to perform the appropriate surgical intervention with a high probability of success and a low risk of compli- cations. Many innovations challenge the competence of the surgical team. The learning curve—the progression in knowledge and skill in performance of innovative procedures—should be managed collaboratively with col- leagues under professional oversight. 7 There is an addi- tional issue of the impact on training. As teachers work on mastering new techniques, such as robotic cardiac sur- gery or video-assisted thoracic surgery, the operative expe- rience of their residents and fellows is inhibited. In some instances, gaining sufficient confidence to teach new proce- dures can take a year or longer. Conflicts of Interest Conflicts of interest arise in ‘‘situation(s) in which an in- terest (financial, personal, political) can interfere with a duty.’’ 8 The financial, personal, or reputational interests of innovative surgeons can compete with their fiduciary duty to put patients’ interests first. The temptation to in- crease market share, academic credit, or personal notoriety may lead to overuse or less attention to the cost of new tech- nology. Professional oversight can help to manage this risk. Cost The issue of cost arises because innovations in health care have been linked to the rapid rise in the cost of health care, potentially disadvantaging such other priorities as educa- tion and highway safety. Technologic innovation is believed to be responsible for the rise of the cost of health care at 2 to 3 times the rate of inflation. At hospitals emphasizing fron- tier technologies, the rate may be substantially higher. This conflict is an issue in societal justice, not simply a hospital management problem. ery c April 2011 McKneally Editorials E D IT O R IA L Oversight The issue of oversight requires special consideration. Re- sponsibility for ensuring that consent, validity, conflicts of in- terest, and cost are managed correctly is a professional issue. The chief of service and the institutional trustees are held publicly accountable when innovations go awry. Although some institutions delegate responsibility for oversight to in- stitutional [ethics] review boards or research ethics boards, innovation is not research. There is a family resemblance between them, arising from their experimental nature. Research is designed to produce generalizable knowl- edge, with carefully controlled methods for patient selec- tion and treatment assignment and with specified uniform techniques and outcome measures. The conduct of research is specified in predetermined, agreed, approved protocols to minimize the effects of chance variables. In contrast, the methods, patient selection, technical steps, and manage- ment are constantly evolving during the development of an innovative surgical procedure (Table 1). The innovators’ question is, ‘‘How can we make this work?’’ With time, pa- tient selection, management approaches, instrument modifi- cations, and techniques evolve. When all these have been settled, formal research can be undertaken to test hypothe- ses about the innovation, to answer the question, ‘‘Is this better than the standard approach?’’. Almost every major advance in medicine and surgery has been introduced through the pathway of innovation. Anes- thesia, antibiotics, arthroscopy, aneurysmectomy, and aortic valve replacement exemplify only a few of the a’s. Innova- tions can be hypothesis generating, but formal research to compare the outcomes with conventional treatment follows relatively rarely. THE CASE REVISITED Columbus did disclose his novel plan to the men he re- cruited. Unlike Pinchon, he reasoned that they should not all be thought of as identical members of a single category, with identical attitudes toward risk. This wise decision gave more risk-averse candidates, or those with pregnant wives or aging parents, the opportunity to opt out of a heroic ad- venture with unknown risks. Rejection of Pinchon’s prisoner proposal may have saved Columbus’s life. When the voyage stretched longer and lon- TABLE 1. Innovation versus research Innovation Research Techniques Evolving Defined Outcome measures Evolving Defined Patient selection Evolving Defined Conclusions Tentative, particular Generalizable Oversight Professional Societal (institutional review board, research ethics board) The Journal of Thoracic and Ca ger and the crew became restless, some turned against the captain, considering mutiny. If he had chosen criminals, with their ingrained distrust of authority and advanced edu- cation in violence, he might not have lived to celebrate his discovery of Hispaniola and the new world. HOW WE INTRODUCE SURGICAL INTERVENTIONS At several of the teaching hospitals at the University of Toronto, a helpful ‘‘Enabling Innovation’’ protocol has been in place for several years. 9 1. The surgeon initiates an ‘‘Enabling Innovation Let- ter’’ to the Surgeon-In-Chief (SIC), describing the in- novative procedure or device, the rationale for the request (including expected benefits, risks, and costs), and the names of 2 informed colleagues who endorse the validity of the proposal. These may be internal or external advisors whom the SIC can consult if needed. 2. The surgeon pledges to add the ‘‘Columbus Clause’’ to the standard consent form: ‘‘Iunderstandthatthistreat- ment is new to this hospital. I will be one of the first [x] patients to receive it here. I have been offered the stan- dard treatment. My doctors and nurses are working to find the best way to perform the new treatment and learn which patients will benefit most from it.’’ 3. If needed, the SIC consults members of an unconv- ened innovation task force of nursing, anesthesia, en- gineering, ethics, and legal personnel who are familiar with the Enabling Innovation pathway. 4. The SIC shows the letter and consent form to the chair of the research ethics board, who accepts or advises full review. This step proved useful in the early adop- tion phase of the policy. The research ethics boards no longer consider this necessary unless the SIC decides it is appropriate. 5. The innovator reports the outcomes of the first patients treatedtotheSIC,withhelpfromhospitaldatamanagers and cost estimates from the operating room manager. 6. Formal research is initiated if and when appropriate. Like Columbus’ sailors, patients are not identical mem- bers of a single category with identical attitudes toward risk. Some are intensely risk averse, some are foolishly ad- venturous, and some are heroes who are well suited to partic- ipate in advancing the frontier of medical science. Because the risks and outcomes of innovative surgical procedures are not always predictable, it seems fair and responsible to use more thorough procedures for disclosing the uncer- tainties associated with innovative surgical interventions. In summary, surgical innovations should be able to meet ethical standards of appropriate consent (including disclo- sure of their novelty), validity, competence, management of the conflicts of interest that might encourage their over- use, assessment of the impact of their cost on institutional or rdiovascular Surgery c Volume 141, Number 4 865 Editorials McKneally E D IT O R IA L societal resources, and oversight to ensure that the consent, validity, conflict of interest, and cost criteria are managed correctly. Bryce Taylor, Jacob Langer, John Wedge, and Randi Zlotnik- Shaul contributed to the development of the Enabling Innovation policy. Deborah McKneally made helpful revisions to the manuscript. References 1. McKneally MF. Managing expectations and fear: invited commentary on ‘‘Inde- cency in cardiac surgery: a memoir of my education at a super-esteemed medical place (SEMP),’’ by Dr. Edmund Erde. J Card Surg. 2007;22:49-50. 2. Todd TR, Perron J, Winton TL, Keshavjee SH. Simultaneous single-lung trans- plantation and lung volume reduction. Ann Thorac Surg. 1997;63:1468-70. 866 The Journal of Thoracic and Cardiovascular Surg 3. McKneally MF, Daar A. Introducing new technologies: protecting subjects of sur- gical innovation and research. World J Surg. 2003;27:930-5. 4. World Medical Association. WMA declaration of Helsinki ethical principles for medical research involving human subjects [Internet]. Ferney-Voltaire, France; 2008. Available at: http://www.wma.net/en/30publications/10policies/b3/index. html. Accessed January 30, 2011. 5. Reitsma AM, Moreno JD. Ethical guidelines for innovative surgery. Hagerstown, MD: University Publishing Group; 2006. 6. Miller GW. King of Hearts: the true story of the maverick who pioneered open heart surgery. New York, NY: Random House; 2000:4-6, 107. 7. McKneally MF. Video-assisted thoracic surgery: standards and guidelines. Chest Surg Clin North Am. 1993;3:345-51. 8. Khushf G, Gifford R. Understanding, assessing, and managing conflicts of interest. In: McCullough LB, Jones JW, Brody BA, eds. Surgical ethics. New York, NY: Oxford University Press; 1998:342-66. 9. McKneally MF. Editor’s column: enabling innovation. Univ Toronto Surg Spotlight [Internet]. Winter 2005-2006:15. Available at: http://www.surgicalspotlight.ca/ Shared/PDF/Winter06.pdf. Accessed January 30, 2011. ery c April 2011 http://www.wma.net/en/30publications/10policies/b3/index.html http://www.wma.net/en/30publications/10policies/b3/index.html http://www.surgicalspotlight.ca/Shared/PDF/Winter06.pdf http://www.surgicalspotlight.ca/Shared/PDF/Winter06.pdf Outline placeholder The case Ethics framework Ethical issues specific to innovative surgery Consent Validity Competence Conflicts of Interest Cost Oversight The case revisited How we introduce surgical interventions References