- Email: [email protected]
provider safety: A surgical conundrum
Seminars in Pediatric Surgery 24 (2015) 323–326
Contents lists available at ScienceDirect
Seminars in Pediatric Surgery journal homepage: www.elsevier.com/locate/sempedsurg
Surgical innovation-enhanced quality and the processes that assure patient/provider safety: A surgical conundrum Jennifer Bruny, MDn, Moritz Ziegler, MD Department of Surgery, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 E 16th Ave, Aurora, Colorado 80045
a r t i c l e in fo
Keywords: Innovation Ethics Quality improvement
a b s t r a c t Innovation is a crucial part of surgical history that has led to enhancements in the quality of surgical care. This comprises both changes which are incremental and those which are frankly disruptive in nature. There are situations where innovation is absolutely required in order to achieve quality improvement or process improvement. Alternatively, there are innovations that do not necessarily arise from some need, but simply are a new idea that might be better. All change must assure a significant commitment to patient safety and beneficence. Innovation would ideally enhance patient care quality and disease outcomes, as well stimulate and facilitate further innovation. The tensions between innovative advancement and patient safety, risk and reward, and demonstrated effectiveness versus speculative added value have created a contemporary “surgical conundrum” that must be resolved by a delicate balance assuring optimal patient/provider outcomes. This article will explore this delicate balance and the rules that govern it. Recommendations are made to facilitate surgical innovation through clinical research. In addition, we propose options that investigators and institutions may use to address competing priorities. & 2015 Elsevier Inc. All rights reserved.
Introduction—the birth of an innovation The story behind many impactful innovations in surgery starts with “I have an idea.” This is how Alberto Pena starts the story of his journey with posterior sagittal anorectoplasty for the treatment of anorectal malformations. The exact line is used in telling the story of HB Kim's idea for the serial transverse enteroplasty (STEP) procedure while a surgical resident at Boston. Dr. Pena says that in today's environment of regulation and institutional review board (IRB) oversight, he is not sure if he would have the courage to start his journey from the beginning again. Institutions need a mechanism of approach that will allow application of clinical innovations in a timely fashion. The goals should be to protect the patient, protect the surgeon, and continue to stimulate and not stifle further innovations. At the same time, this mechanism should assess quality improvements that resulted from the application of these innovative ideas.
Historical regulatory factors for innovation In 1750 BC, Hammurabi recommended when a surgical outcome was deficient; the surgeon would best be admonished by a n
Corresponding author. E-mail address: [email protected] (J. Bruny).
http://dx.doi.org/10.1053/j.sempedsurg.2015.08.013 1055-8586/& 2015 Elsevier Inc. All rights reserved.
ceremonious cutting off of his hands. Most physicians are aware of the more acceptable practice appealed for by Hippocrates in 400 BC when he described “Primum Non Noncere,” first do no harm! This pledge could be used to define the boundaries of innovation, clinical research, optimal outcomes, and patient safety, but it is limited by its sweeping nature. The contemporary guru of surgical patient safety was Ernst Codman, the Boston surgeon working in the early 1900s.1 He emphasized the surgeon's need and responsibility to measure operative outcomes on each and every patient. Codman held to this position despite being vilified by the Boston surgical community and being forced to continue his surgical practice elsewhere. He opened his own private hospital, which he called the “End Results Hospital.” It is noteworthy that Codman's disruptive innovation would eventually serve as the basis for the now very successful surgical outcomes program, the National Surgical Quality Improvement Program (NSQIP) as well as its pediatric arm, NSQIP-Pediatric. 2 An “Innovation is a new intervention, not yet accepted as meeting the standards of safety, reliability and familiarity with its effects, side effects, and complications.” World War II brought perhaps the low-point in the history of human experimentation when Nazi Germany used systematic experimentation on human war prisoners to test various therapies and their limits of safety. These crimes against humanity were addressed by the Nuremberg war trials in 1946.3 The 1964 Helsinki Doctrine codified the protection of patients declaring the human
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subject to have precedence in clinical research.4 However, the issue was raised yet again by Beecher5 when in 1968 he published an expose paper of unethical physician behaviors in clinical research entitled “Ethical problems created by the hopelessly unconscious patient.” In response to this article, the Belmont Commission was charged with defining the boundaries that distinguish clinical research from the practice of medicine, or surgery, in a manner that clearly states the limits of the need to assure patient safety and protection. Not surprisingly, the Belmont Commission Report of 19796 revealed the blurred nature of this interface concluding that research and care often occur together in the same patient such as occurs in the research evaluation of a therapy. The report further defined experimental as a departure from the standard of practice. The Belmont Commission Report also defined an analytic framework for clinical practice as an intervention solely defined to enhance the well-being of an individual patient, a practice that should have a reasonable expectation of success, a practice that includes a purpose to provide a diagnosis, or a preventative treatment or therapy for a specific individual. In contrast, the analytic framework for research was defined as an activity designed to test a hypothesis, permit a conclusion(s) to be drawn, to contribute to the general knowledge, and finally, be directed by a formal protocol with an objective as well as a set of procedures designed to reach that objective.6 A “disruptive technology” is defined as a “technological innovation, product or service that uses a disruptive strategy rather than a revolutionary or sustaining strategy to overturn existing dominant technologies or status quo.” An innovation was defined as a departure from the standard of care or accepted practice that in and of itself does not constitute research. Furthermore, experimental, defined as new, untested or different, does not in and of itself equate to research. The Belmont report clearly emphasized the need and desire for new procedures at an early stage to be the object of formal research, specifically focusing on the need to assure patient safety and treatment effectiveness. Furthermore, research and practice may be simultaneous when research is done to evaluate therapeutic safety and efficacy.6 Any element of research in an activity obligates the need for human subject protection. Based upon these regulatory guidelines research was defined as a “systematic investigation designed to develop or contribute to the generalizable knowledge.” Clinical investigation of an FDA regulated product was also defined as “any experiment in which a drug (biologic) or significant risk device is administered or dispensed or used for one or more human subjects.” In the end, innovative procedures did not fall under the regulatory process of the FDA. While it is recommended to incorporate innovations into a research protocol at an early stage, this is not mandated by regulation leaving the onus on the local institution. A recent publication has attempted a more rigorous algorithmic distinction between quality improvement efforts and human subject's research, but even here the interfaces remain somewhat blurred.7 To take an example from industry, Forbes magazine declared the “driverless automobile” as one of the most disruptive innovations featured at the Consumer Electronic Show in 2014. The technology will quickly be available to make automated vehicles a reality; however, the legality of the issue will likely constrain its introduction into society. Governments currently do not have an answer as to how to test and introduce these new vehicles. It is widely held that this technology will improve quality, safety, and value in reducing collisions and congestion, and increasing energy efficiency. Yet without a framework to introduce this disruptive technology, the risk of stifling the advance is real. The same challenge existed for Gauderer et al.8 in his 1980 introduction of the Percutaneous Endoscopic Gastrostomy (PEG) a minimally invasive approach to gastric feeding access or
decompression that was unprecedented as a minimally invasive concept and it proved to be a disruptive innovation. Kim et al.9 introduced his conceptualized “simpler” technique for intestinal lengthening, the Serial Transverse Enteroplasty (STEP) procedure, 20 years later in 2000. With this innovation a surgeon could enhance intestinal length while reducing intestinal luminal diameter. Putatively, this could promote a more effective prograde peristalsis in bowel of increased length; however, this would be done at the expense of a reduction of the functional mucosal absorptive area, secondary to the technique used for the enteroplasty, in a patient whose functional bowel is already foreshortened. In principle, it was demonstrated to be done with less technical difficulty when contrasted with other intestinal lengthening procedures then available. With the readiness of such disruptive innovations for application, what next steps were the investigators to take? Were they dealing with an incremental minimal clinical care modification or instead were these procedures identifying innovative research and experimentation as well that historically would fall under the purview of an Institutional Review Board (IRB).
Need for human subject protection: Is operative innovation better managed by a differing paradigm With these guidelines now defined, a broader focus could be used to define ethical principles that were also applicable to the clinical care/research interface. Basic ethical principles included a respect for a person's autonomy (presumed ability of patients to choose options); an emphasis on beneficence (maximize the benefits and minimize or eliminate harm); and the application of justice (equitable distribution of the research burden and benefits). These principles were a natural extension of existing standards including the informed consent of a procedure-based therapy; the risk/benefit assessment of a pending therapy; and subject selection processes when applying a therapy or designing a research protocol. The surgical aphorism “if you promise not to learn anything from the work that you are doing you do not have to go through an Institutional Review Board” is both over simplified and naïve when it comes to defining the differences between research and clinical care. Furthermore, the challenges are more complex. First the surgical spectrum of care or research has wide variability and a plan might be to improve the patient condition by incremental change. Examples could be the trial of a differing suture material, incisional approach, location of a laparoscopic port site, or an anatomical versus non-anatomical incisional approach. An incremental change could also take the form of re-engineering the process of care, such as instituting an algorithm to assist with decision making in diagnosing appendicitis in order to reduce the use of CT scans and radiation exposure. Second, there is often an urgent operative challenge while caring for a life-threatening disease that may lack an effective treatment. For example, the application of the Kasai procedure and liver transplantation to the previously uniformly fatal condition of biliary atresia resulted in significant surgical advancement. Similarly, the Norwood procedure advanced the treatment of the hypo-plastic left heart syndrome, and fetal intervention appears to improve the outcomes of severe cases of congenital cystic adenomatoid malformation of the lung. During the developmental stages of these interventions, the morbidity and mortality tolls in these examples were extreme, challenging the requirement that therapies should enhance patient well-being with a high likelihood of success in a circumstance where no other effective treatment is known. Also in many circumstances, there has been the lack of development of a generalizable knowledge from such surgical experimentation,
J. Bruny, M. Ziegler / Seminars in Pediatric Surgery 24 (2015) 323–326
either because of a lack of communication in the form of critical peer reviewed publication or the lack of an evolution from incremental change to a level of contrasting and testable clinical approaches. These examples of innovation are currently held as great advances for the quality of care in these patient populations, yet at the time of their development, they may have stretched the Belmont report principles. Frader and Flanigan-Klygis10 summarized a series of obstacles that they found that often prevent comparative trials in surgery. In addition to the incrementalism of some procedural changes as discussed above, surgeons felt that it was ethically unjustifiable to apply a placebo or sham surgical arm to such a trial. It was also agreed that it was complicated by an inability to “blind” the investigating surgeon in many if not most comparative trials. It was further reported that the timing of an investigation as well as the status of the investigating surgeon on the learning curve of a procedure might have a critical influence on patient outcomes from the operation in question. Still another characteristic of the surgical challenge is a general reluctance of surgeons to apply regulatory standards to human subjects. In a striking report from Reitsma and Moreno, the authors reviewed 527 journal issues in which 59 publications were found that could be categorized as “surgical innovation.”11 Using a questionnaire, the author's reported that 14 of 21 respondents considered their work “research.” Only six of these authors sought IRB approval. Furthermore, 2/3 of respondents said that IRB governmental regulations were not appropriate for innovative surgery. Finally, it is perhaps the strength of the research department, the department of surgery, and/or the “field strength” of the surgical research team that has the most influence on the quality of the surgical care and research plan. The late Francis Moore, Surgical Chairman of the Brigham and Women's Hospital, Boston, has previously defined such important characteristics of surgical investigators and institutions contributing to the generalizable knowledge as well as critical surgical research. He points out the need for an influencing environment of solid science, institutional ethics, and a public/professional dialogue.12 When one considers what has not been resolved by careful and critical surgical research, the list of “black eyes” is long and the need is great. Details of some of the stories involve more emotion and less science than we would like to admit. The world's first laparoscopic appendectomy performed by Kurt Semm in 1980 brought sharp criticism. It is reported that his colleagues at the University of Keil voiced, “only a person with brain damage would perform laparoscopic surgery,” and he was ordered to undergo a brain scan.13 Yet only 10 years later, laparoscopic cholecystectomy was quickly adopted as a positive innovation, and the tipping point for laparoscopic surgery was reached without thorough investigation. In adults, amongst others, we still are unaware of a preferred outcome from comparative trials of radical versus modified mastectomy for cancer, heart transplantation, and living donor liver transplantation to name but a few. In children, the list includes congenital heart surgery including the arterial switch and the Norwood procedure, fetal surgery for diaphragmatic hernia, genitourinary obstruction as well as hydrocephalus; and there remains an ongoing debate as to the role of intestinal lengthening for short-bowel syndrome. Many additional examples can be detailed.
A balanced approach that assures innovative quality and concomitant patient/provider safety An idealized solution for the complexity of this problem would be protection of the patient without stifling of the innovation.
325
A logical application of mandatory IRB review and approval may, as noted above, forestall innovation for the reasons described in various polls of surgical scientists. The crux of the conundrum was well articulated by the American College of Surgeon's Drs. Sachdeva and Russell. “Introduction of a new procedure or an emerging technology should be timed carefully and strike a balance between waiting for sufficient data to support its use and the healthcare needs of the patients while data are being collected. Late introduction of a new modality may deprive the patients of adequate or state-of-the-art care.”14 We, as well as others, have utilized a series of processes to address this complex circumstance while ensuring both patient safety as well as surgical team protection. Strategy #1: “Minimizing the Risk” In the report of Strasberg and Ludbrook, a paradigm is described in which definitions of the significant innovation, patient protection process, oversight agencies, and funding mechanisms are made.15 The innovation is defined as being significant if there is a need to retrain the provider or complete a recredentialing process; if either the diagnosis or its treatment involves a process where none previously existed; and finally, if there is risk developed to a healthy non-benefited person during the total care process. Strasberg recommends that patient protection be assured by supporting patient autonomy. He supports the use of research registries to facilitate the early detection of negative patient outcomes. It was the use of such a registry by the Kim team that defined early procedural problems, procedural outcomes and their timing, and the time of predictable adaptation to independent bowel function, all findings that led to a more appropriate application of the novel STEP operation.16 Strategy #2: “Surgical Oversight” In another proposed action plan, McKneally transfers a good deal of responsibility to the Chief of the Surgical Service.17 They describe his/her responsibility to the public to include credentialing and privileging the surgical staff, publishing the operating room schedule, and providing oversight to the operating room as a moral community. The chief or chairperson also provides oversight to the Morbidity and Mortality Conference as well as supervision of surgical audit and quality improvement activity, which is regularly reported to the public. In this paradigm the surgeons have a moral obligation to improve the quality and outcomes of their interventions. Perhaps most importantly the study of quality and outcomes is not identical with formalized “research.” We have experience in applying this paradigm in conjunction with #3 that follows.
Strategy #3: The innovation and research combination By applying a third strategy, innovation and research are combined as one (Figure). While still posing a research question the oversight falls to the institution rather than the IRB. The challenge then becomes the appropriate identification of the stakeholders. Furthermore, are there other committees that might address these same issues? Would it be wise to set boundaries or combine approaches? This strategy also begs an open discussion about ethical concerns, regulatory requirements, informed consent, resource allocation and project oversight. Criteria for cases that require oversight need to be established. This would include the following: when a procedure carries a significant increase in risk when compared to alternative
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without migration to formalized research protocols with IRB review and approval.
Conclusions
Fig. In the current and previous paradigm, research and innovation each acts separately to influence disease outcomes. In the recommended new paradigm, research and innovation are combined as they determine clinical care and its outcomes. In this scenario, there is also a critical need for an enhanced peer review and informed consent process.
There is a long history in the world of medicine of innovation evolving through an informal, unregulated research process. Some of this has resulted in the darkest of unethical treatment of human subjects. 18 Alternatively, this has been the path for significant and lasting advances such as anesthesia, laparoscopy, antibiotics, and many of our pediatric surgical innovations. There is a moral imperative to continue innovation to advance the quality of care of patients, while at the same time, instituting safeguards to ensure the efficacy and safety of new techniques. While federal and IRB regulations may appear to be too constricting for surgical innovation, local oversight with collective judgment, open reporting of outcomes, and inclusion of research with the introduction of new techniques and technology will be imperative to the future of the field of surgery. References
approaches, the procedure is so novel that the risks and benefits are unknown, or the procedure raises resource allocation concerns. This paradigm is designed to promote accountability, increase patient protection, promote innovation that leads to research; and finally, to promote a culture of collaboration among scientific and regulatory communities, emphasizing their shared responsibilities as well as shared decision making. When implementing this third strategy, a first step is the presentation of the case summary of the proposed procedure and its rationale in a written document prepared by the surgeon care provider. It is then suggested that a minimum of two surgeons who have no conflicts of interest but with like surgical experiences review and provide a written summary/judgment as to the rationale for the procedure, either to proceed as described or instead, modify the proposal or prohibit it from being applied at all. It is wise at this step to also consider applying an enhanced written consent process, seeking input from the provider as well as the institution's medical-legal team. In this paradigm the IRB will serve as a record keeper and it will periodically review the case(s) and their progress. It also is critical in this paradigm that this review process be restricted to proceed with only one or two patients for the operative or experimental procedures followed by a review of the outcome quality and a decision to proceed with a formal IRB protocol or rather to continue the plan on a case-by-case basis. This latter paradigm was implemented in Boston at the start of HB Kim's STEP procedure innovation. It was viewed as successful in creating protection for patients as well as assuring the stimulation of continued institutional and individual provider innovation. The process may well require a change in culture. In early phases compliance with this may need to be mandated while over time it would shift to be voluntary. There is also some room for interpretation as to when this specific process is applicable. Again in our experience the peer review process involved has been well received by both investigator and patient and the enhanced written consent process has likewise proven useful. The problematic issues that we have encountered have included investigators who have continued to use this process for the same procedures
1. Codman EA. A Study in Hospital Efficiency. Reprinted by the Joint Commission on Accreditation of Healthcare Organizations Press, 1 Renaissance Blvd, Oakbrook Terrace, Illinois 60181, 199. 2. Dillon P, Hammermeister K, Morrato E, et al. Developing a NSQIP module to measure outcomes in children's surgical care: opportunity and challenge. Semin Pediatr Surg. 2008;17(2):131–140. 3. Grodin M. Historical origins of the Nuremberg code. In: Annas GJ, Grodin MA, editors. The Nazi Doctors and the Nuremberg Code: Human Rights in Human Experimentation. New York: Oxford University Press; 1992. p. 121–144. 4. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. J Am Med Assoc. 1964;284(23): 3043–3046. 5. Beecher HK. Ethical problems created by the hopelessly unconscious patient. N Engl J Med. 1968;278(26):1425–1430. 6. The Belmont Report: Department of Health, Education, and Welfare, Office of Human Subjects Research, Washington, DC. http://ohsr.od.nih.gov/guidelines/ belmont.html; 1979. 7. Raval M, Sakran JV, Medberry RL, et al. Distinguishing QI projects from human subjects research: ethical and practical considerations. Bull Am Coll Surg. 2014;99:121–127. 8. Gauderer MW, Ponsky JL, Izant RJ Jr. Gastrostomy without laparotomy, a percutaneous endoscopic technique. J Pediatr Surg. 1980;15(6):872–875. 9. Kim HB, Fauza D, Garza J, Oh JT, Nurko S, Jaksic T. Serial transverse enteroplasty (STEP); a novel bowel lengthening procedure. J Pediatr Surg. 2003;38(3):4. 10. Frader JE, Flanagan-Klygis E. Innovation and research in pediatric surgery. Semin Pediatr Surg. 2001;10(4):198–203. 11. Reitsma AM, Moreno JD. Ethical regulations for innovative surgery: the last frontier? J Am Coll Surg. 2002;194(6):792–801. 12. Moore FD. Three ethical revolutions: ancient assumptions remodeled under pressure of transplantation. Transplant Proc. 1988;20(suppl 1):1061–1062. 13. Bhattacharya K. Kurt Semm: a laparoscopic crusader. J Minim Access Surg. 2007;3:35–36. 14. Sachedeva AK, Russell TR. Safe introduction of new procedures and emerging technologies in surgery: education, credentialing, and privileging. Surg Clin North Am. 2007;87:853–866. 15. Strasberg SM, Ludbrook PA. Who oversees innovative practice? Is there a structure that meets the monitoring needs of new techniques? J Am Coll Surg. 2003;196(6):938–948. 16. Jones BA, Hull MA, Potanos KM, et al. Report of 111 consecutive patients enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: a retrospective observational study. J Am Coll Surg. 2013;216(3): 438–446. 17. McKneally MF, Daar AS. Introducing new technologies: protecting subjects of surgical innovation and research. World J Surg. 2003;27(8):930–934:[discussion 934–935]. Epub 2003 Jun 26. 18. Kohn A. False Prophets: Fraud and Error in Science and Medicine. New York: Basil Blackwell Inc; 1986.
Contents lists available at ScienceDirect
Seminars in Pediatric Surgery journal homepage: www.elsevier.com/locate/sempedsurg
Surgical innovation-enhanced quality and the processes that assure patient/provider safety: A surgical conundrum Jennifer Bruny, MDn, Moritz Ziegler, MD Department of Surgery, Children's Hospital Colorado, University of Colorado School of Medicine, 13123 E 16th Ave, Aurora, Colorado 80045
a r t i c l e in fo
Keywords: Innovation Ethics Quality improvement
a b s t r a c t Innovation is a crucial part of surgical history that has led to enhancements in the quality of surgical care. This comprises both changes which are incremental and those which are frankly disruptive in nature. There are situations where innovation is absolutely required in order to achieve quality improvement or process improvement. Alternatively, there are innovations that do not necessarily arise from some need, but simply are a new idea that might be better. All change must assure a significant commitment to patient safety and beneficence. Innovation would ideally enhance patient care quality and disease outcomes, as well stimulate and facilitate further innovation. The tensions between innovative advancement and patient safety, risk and reward, and demonstrated effectiveness versus speculative added value have created a contemporary “surgical conundrum” that must be resolved by a delicate balance assuring optimal patient/provider outcomes. This article will explore this delicate balance and the rules that govern it. Recommendations are made to facilitate surgical innovation through clinical research. In addition, we propose options that investigators and institutions may use to address competing priorities. & 2015 Elsevier Inc. All rights reserved.
Introduction—the birth of an innovation The story behind many impactful innovations in surgery starts with “I have an idea.” This is how Alberto Pena starts the story of his journey with posterior sagittal anorectoplasty for the treatment of anorectal malformations. The exact line is used in telling the story of HB Kim's idea for the serial transverse enteroplasty (STEP) procedure while a surgical resident at Boston. Dr. Pena says that in today's environment of regulation and institutional review board (IRB) oversight, he is not sure if he would have the courage to start his journey from the beginning again. Institutions need a mechanism of approach that will allow application of clinical innovations in a timely fashion. The goals should be to protect the patient, protect the surgeon, and continue to stimulate and not stifle further innovations. At the same time, this mechanism should assess quality improvements that resulted from the application of these innovative ideas.
Historical regulatory factors for innovation In 1750 BC, Hammurabi recommended when a surgical outcome was deficient; the surgeon would best be admonished by a n
Corresponding author. E-mail address: [email protected] (J. Bruny).
http://dx.doi.org/10.1053/j.sempedsurg.2015.08.013 1055-8586/& 2015 Elsevier Inc. All rights reserved.
ceremonious cutting off of his hands. Most physicians are aware of the more acceptable practice appealed for by Hippocrates in 400 BC when he described “Primum Non Noncere,” first do no harm! This pledge could be used to define the boundaries of innovation, clinical research, optimal outcomes, and patient safety, but it is limited by its sweeping nature. The contemporary guru of surgical patient safety was Ernst Codman, the Boston surgeon working in the early 1900s.1 He emphasized the surgeon's need and responsibility to measure operative outcomes on each and every patient. Codman held to this position despite being vilified by the Boston surgical community and being forced to continue his surgical practice elsewhere. He opened his own private hospital, which he called the “End Results Hospital.” It is noteworthy that Codman's disruptive innovation would eventually serve as the basis for the now very successful surgical outcomes program, the National Surgical Quality Improvement Program (NSQIP) as well as its pediatric arm, NSQIP-Pediatric. 2 An “Innovation is a new intervention, not yet accepted as meeting the standards of safety, reliability and familiarity with its effects, side effects, and complications.” World War II brought perhaps the low-point in the history of human experimentation when Nazi Germany used systematic experimentation on human war prisoners to test various therapies and their limits of safety. These crimes against humanity were addressed by the Nuremberg war trials in 1946.3 The 1964 Helsinki Doctrine codified the protection of patients declaring the human
324
J. Bruny, M. Ziegler / Seminars in Pediatric Surgery 24 (2015) 323–326
subject to have precedence in clinical research.4 However, the issue was raised yet again by Beecher5 when in 1968 he published an expose paper of unethical physician behaviors in clinical research entitled “Ethical problems created by the hopelessly unconscious patient.” In response to this article, the Belmont Commission was charged with defining the boundaries that distinguish clinical research from the practice of medicine, or surgery, in a manner that clearly states the limits of the need to assure patient safety and protection. Not surprisingly, the Belmont Commission Report of 19796 revealed the blurred nature of this interface concluding that research and care often occur together in the same patient such as occurs in the research evaluation of a therapy. The report further defined experimental as a departure from the standard of practice. The Belmont Commission Report also defined an analytic framework for clinical practice as an intervention solely defined to enhance the well-being of an individual patient, a practice that should have a reasonable expectation of success, a practice that includes a purpose to provide a diagnosis, or a preventative treatment or therapy for a specific individual. In contrast, the analytic framework for research was defined as an activity designed to test a hypothesis, permit a conclusion(s) to be drawn, to contribute to the general knowledge, and finally, be directed by a formal protocol with an objective as well as a set of procedures designed to reach that objective.6 A “disruptive technology” is defined as a “technological innovation, product or service that uses a disruptive strategy rather than a revolutionary or sustaining strategy to overturn existing dominant technologies or status quo.” An innovation was defined as a departure from the standard of care or accepted practice that in and of itself does not constitute research. Furthermore, experimental, defined as new, untested or different, does not in and of itself equate to research. The Belmont report clearly emphasized the need and desire for new procedures at an early stage to be the object of formal research, specifically focusing on the need to assure patient safety and treatment effectiveness. Furthermore, research and practice may be simultaneous when research is done to evaluate therapeutic safety and efficacy.6 Any element of research in an activity obligates the need for human subject protection. Based upon these regulatory guidelines research was defined as a “systematic investigation designed to develop or contribute to the generalizable knowledge.” Clinical investigation of an FDA regulated product was also defined as “any experiment in which a drug (biologic) or significant risk device is administered or dispensed or used for one or more human subjects.” In the end, innovative procedures did not fall under the regulatory process of the FDA. While it is recommended to incorporate innovations into a research protocol at an early stage, this is not mandated by regulation leaving the onus on the local institution. A recent publication has attempted a more rigorous algorithmic distinction between quality improvement efforts and human subject's research, but even here the interfaces remain somewhat blurred.7 To take an example from industry, Forbes magazine declared the “driverless automobile” as one of the most disruptive innovations featured at the Consumer Electronic Show in 2014. The technology will quickly be available to make automated vehicles a reality; however, the legality of the issue will likely constrain its introduction into society. Governments currently do not have an answer as to how to test and introduce these new vehicles. It is widely held that this technology will improve quality, safety, and value in reducing collisions and congestion, and increasing energy efficiency. Yet without a framework to introduce this disruptive technology, the risk of stifling the advance is real. The same challenge existed for Gauderer et al.8 in his 1980 introduction of the Percutaneous Endoscopic Gastrostomy (PEG) a minimally invasive approach to gastric feeding access or
decompression that was unprecedented as a minimally invasive concept and it proved to be a disruptive innovation. Kim et al.9 introduced his conceptualized “simpler” technique for intestinal lengthening, the Serial Transverse Enteroplasty (STEP) procedure, 20 years later in 2000. With this innovation a surgeon could enhance intestinal length while reducing intestinal luminal diameter. Putatively, this could promote a more effective prograde peristalsis in bowel of increased length; however, this would be done at the expense of a reduction of the functional mucosal absorptive area, secondary to the technique used for the enteroplasty, in a patient whose functional bowel is already foreshortened. In principle, it was demonstrated to be done with less technical difficulty when contrasted with other intestinal lengthening procedures then available. With the readiness of such disruptive innovations for application, what next steps were the investigators to take? Were they dealing with an incremental minimal clinical care modification or instead were these procedures identifying innovative research and experimentation as well that historically would fall under the purview of an Institutional Review Board (IRB).
Need for human subject protection: Is operative innovation better managed by a differing paradigm With these guidelines now defined, a broader focus could be used to define ethical principles that were also applicable to the clinical care/research interface. Basic ethical principles included a respect for a person's autonomy (presumed ability of patients to choose options); an emphasis on beneficence (maximize the benefits and minimize or eliminate harm); and the application of justice (equitable distribution of the research burden and benefits). These principles were a natural extension of existing standards including the informed consent of a procedure-based therapy; the risk/benefit assessment of a pending therapy; and subject selection processes when applying a therapy or designing a research protocol. The surgical aphorism “if you promise not to learn anything from the work that you are doing you do not have to go through an Institutional Review Board” is both over simplified and naïve when it comes to defining the differences between research and clinical care. Furthermore, the challenges are more complex. First the surgical spectrum of care or research has wide variability and a plan might be to improve the patient condition by incremental change. Examples could be the trial of a differing suture material, incisional approach, location of a laparoscopic port site, or an anatomical versus non-anatomical incisional approach. An incremental change could also take the form of re-engineering the process of care, such as instituting an algorithm to assist with decision making in diagnosing appendicitis in order to reduce the use of CT scans and radiation exposure. Second, there is often an urgent operative challenge while caring for a life-threatening disease that may lack an effective treatment. For example, the application of the Kasai procedure and liver transplantation to the previously uniformly fatal condition of biliary atresia resulted in significant surgical advancement. Similarly, the Norwood procedure advanced the treatment of the hypo-plastic left heart syndrome, and fetal intervention appears to improve the outcomes of severe cases of congenital cystic adenomatoid malformation of the lung. During the developmental stages of these interventions, the morbidity and mortality tolls in these examples were extreme, challenging the requirement that therapies should enhance patient well-being with a high likelihood of success in a circumstance where no other effective treatment is known. Also in many circumstances, there has been the lack of development of a generalizable knowledge from such surgical experimentation,
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either because of a lack of communication in the form of critical peer reviewed publication or the lack of an evolution from incremental change to a level of contrasting and testable clinical approaches. These examples of innovation are currently held as great advances for the quality of care in these patient populations, yet at the time of their development, they may have stretched the Belmont report principles. Frader and Flanigan-Klygis10 summarized a series of obstacles that they found that often prevent comparative trials in surgery. In addition to the incrementalism of some procedural changes as discussed above, surgeons felt that it was ethically unjustifiable to apply a placebo or sham surgical arm to such a trial. It was also agreed that it was complicated by an inability to “blind” the investigating surgeon in many if not most comparative trials. It was further reported that the timing of an investigation as well as the status of the investigating surgeon on the learning curve of a procedure might have a critical influence on patient outcomes from the operation in question. Still another characteristic of the surgical challenge is a general reluctance of surgeons to apply regulatory standards to human subjects. In a striking report from Reitsma and Moreno, the authors reviewed 527 journal issues in which 59 publications were found that could be categorized as “surgical innovation.”11 Using a questionnaire, the author's reported that 14 of 21 respondents considered their work “research.” Only six of these authors sought IRB approval. Furthermore, 2/3 of respondents said that IRB governmental regulations were not appropriate for innovative surgery. Finally, it is perhaps the strength of the research department, the department of surgery, and/or the “field strength” of the surgical research team that has the most influence on the quality of the surgical care and research plan. The late Francis Moore, Surgical Chairman of the Brigham and Women's Hospital, Boston, has previously defined such important characteristics of surgical investigators and institutions contributing to the generalizable knowledge as well as critical surgical research. He points out the need for an influencing environment of solid science, institutional ethics, and a public/professional dialogue.12 When one considers what has not been resolved by careful and critical surgical research, the list of “black eyes” is long and the need is great. Details of some of the stories involve more emotion and less science than we would like to admit. The world's first laparoscopic appendectomy performed by Kurt Semm in 1980 brought sharp criticism. It is reported that his colleagues at the University of Keil voiced, “only a person with brain damage would perform laparoscopic surgery,” and he was ordered to undergo a brain scan.13 Yet only 10 years later, laparoscopic cholecystectomy was quickly adopted as a positive innovation, and the tipping point for laparoscopic surgery was reached without thorough investigation. In adults, amongst others, we still are unaware of a preferred outcome from comparative trials of radical versus modified mastectomy for cancer, heart transplantation, and living donor liver transplantation to name but a few. In children, the list includes congenital heart surgery including the arterial switch and the Norwood procedure, fetal surgery for diaphragmatic hernia, genitourinary obstruction as well as hydrocephalus; and there remains an ongoing debate as to the role of intestinal lengthening for short-bowel syndrome. Many additional examples can be detailed.
A balanced approach that assures innovative quality and concomitant patient/provider safety An idealized solution for the complexity of this problem would be protection of the patient without stifling of the innovation.
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A logical application of mandatory IRB review and approval may, as noted above, forestall innovation for the reasons described in various polls of surgical scientists. The crux of the conundrum was well articulated by the American College of Surgeon's Drs. Sachdeva and Russell. “Introduction of a new procedure or an emerging technology should be timed carefully and strike a balance between waiting for sufficient data to support its use and the healthcare needs of the patients while data are being collected. Late introduction of a new modality may deprive the patients of adequate or state-of-the-art care.”14 We, as well as others, have utilized a series of processes to address this complex circumstance while ensuring both patient safety as well as surgical team protection. Strategy #1: “Minimizing the Risk” In the report of Strasberg and Ludbrook, a paradigm is described in which definitions of the significant innovation, patient protection process, oversight agencies, and funding mechanisms are made.15 The innovation is defined as being significant if there is a need to retrain the provider or complete a recredentialing process; if either the diagnosis or its treatment involves a process where none previously existed; and finally, if there is risk developed to a healthy non-benefited person during the total care process. Strasberg recommends that patient protection be assured by supporting patient autonomy. He supports the use of research registries to facilitate the early detection of negative patient outcomes. It was the use of such a registry by the Kim team that defined early procedural problems, procedural outcomes and their timing, and the time of predictable adaptation to independent bowel function, all findings that led to a more appropriate application of the novel STEP operation.16 Strategy #2: “Surgical Oversight” In another proposed action plan, McKneally transfers a good deal of responsibility to the Chief of the Surgical Service.17 They describe his/her responsibility to the public to include credentialing and privileging the surgical staff, publishing the operating room schedule, and providing oversight to the operating room as a moral community. The chief or chairperson also provides oversight to the Morbidity and Mortality Conference as well as supervision of surgical audit and quality improvement activity, which is regularly reported to the public. In this paradigm the surgeons have a moral obligation to improve the quality and outcomes of their interventions. Perhaps most importantly the study of quality and outcomes is not identical with formalized “research.” We have experience in applying this paradigm in conjunction with #3 that follows.
Strategy #3: The innovation and research combination By applying a third strategy, innovation and research are combined as one (Figure). While still posing a research question the oversight falls to the institution rather than the IRB. The challenge then becomes the appropriate identification of the stakeholders. Furthermore, are there other committees that might address these same issues? Would it be wise to set boundaries or combine approaches? This strategy also begs an open discussion about ethical concerns, regulatory requirements, informed consent, resource allocation and project oversight. Criteria for cases that require oversight need to be established. This would include the following: when a procedure carries a significant increase in risk when compared to alternative
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without migration to formalized research protocols with IRB review and approval.
Conclusions
Fig. In the current and previous paradigm, research and innovation each acts separately to influence disease outcomes. In the recommended new paradigm, research and innovation are combined as they determine clinical care and its outcomes. In this scenario, there is also a critical need for an enhanced peer review and informed consent process.
There is a long history in the world of medicine of innovation evolving through an informal, unregulated research process. Some of this has resulted in the darkest of unethical treatment of human subjects. 18 Alternatively, this has been the path for significant and lasting advances such as anesthesia, laparoscopy, antibiotics, and many of our pediatric surgical innovations. There is a moral imperative to continue innovation to advance the quality of care of patients, while at the same time, instituting safeguards to ensure the efficacy and safety of new techniques. While federal and IRB regulations may appear to be too constricting for surgical innovation, local oversight with collective judgment, open reporting of outcomes, and inclusion of research with the introduction of new techniques and technology will be imperative to the future of the field of surgery. References
approaches, the procedure is so novel that the risks and benefits are unknown, or the procedure raises resource allocation concerns. This paradigm is designed to promote accountability, increase patient protection, promote innovation that leads to research; and finally, to promote a culture of collaboration among scientific and regulatory communities, emphasizing their shared responsibilities as well as shared decision making. When implementing this third strategy, a first step is the presentation of the case summary of the proposed procedure and its rationale in a written document prepared by the surgeon care provider. It is then suggested that a minimum of two surgeons who have no conflicts of interest but with like surgical experiences review and provide a written summary/judgment as to the rationale for the procedure, either to proceed as described or instead, modify the proposal or prohibit it from being applied at all. It is wise at this step to also consider applying an enhanced written consent process, seeking input from the provider as well as the institution's medical-legal team. In this paradigm the IRB will serve as a record keeper and it will periodically review the case(s) and their progress. It also is critical in this paradigm that this review process be restricted to proceed with only one or two patients for the operative or experimental procedures followed by a review of the outcome quality and a decision to proceed with a formal IRB protocol or rather to continue the plan on a case-by-case basis. This latter paradigm was implemented in Boston at the start of HB Kim's STEP procedure innovation. It was viewed as successful in creating protection for patients as well as assuring the stimulation of continued institutional and individual provider innovation. The process may well require a change in culture. In early phases compliance with this may need to be mandated while over time it would shift to be voluntary. There is also some room for interpretation as to when this specific process is applicable. Again in our experience the peer review process involved has been well received by both investigator and patient and the enhanced written consent process has likewise proven useful. The problematic issues that we have encountered have included investigators who have continued to use this process for the same procedures
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