26 Innovation in medical care: examples from surgery
C, a newborn infant, develops persistent vomiting on the second day of life. X-rays show midgut volvulus, a condition in which the intestines have twisted around their blood supply. Surgical exploration reveals necrosis of all but 15 cm of his small bowel. The necrotic bowel is removed and total parenteral nutrition (TPN) is initiated. At one year of age, he is taking half of his nutritional needs through his intestinal tract; the other half is given intravenously. Blood chemistry tests show that he is starting to develop significant liver damage from the TPN. C’s remaining small bowel has become dilated and dysfunctional. You have recently read about a new operation called the serial tapering enteroplasty (STEP), an innovative technique, which may be able to lengthen the remaining intestine and permit it to function more effectively. A surgical stapler in common use is deployed to segment the dilated bowel into a tapered, lengthened tube more closely resembling the shape of the small intestine (Kim et al., 2003). This operation, first developed in dogs, has been undertaken in a small number of infants with short bowel syndrome. It is considered a non-validated innovation by most pediatric surgeons and is not yet accepted as part of standard surgical practice. You would like to offer the procedure to your patient, but you do not think that there is time to go through the full Research Ethics Board approval process at your hospital. Your intention is to try to help, and perhaps other patients like him. You do not have a formal research protocol, but will develop your approach to treatment of this problem as you gain experience with this new procedure.
You struggle to manage your patient, a young soldier with severe respiratory failure caused by a blast injury. Conventional ventilation, at the high levels of positive pressure now required to maintain adequate gas exchange, is further damaging the lungs. An innovative lung assist device (ILA) has been proven in the laboratory and in preliminary human trials to remove carbon dioxide directly from the bloodstream, permitting ventilation at lower pressure and reducing treatment-related injury, but it is not yet approved for use in the institution. You contact the manufacturer, who agrees to supply the device on a compassionate basis at no charge. The company will provide a professional support team to instruct and assist you and your team in introducing and managing the ILA.
What is innovation?
Innovation is a notional concept: there are many notions of its meaning and no widely accepted definition. For the purpose of this chapter, we will define innovation as “a new evolving intervention whose effects, side effects, safety, reliability, and potential complications are not yet generally known in the community of practitioners” (McKneally and Daar, 2003). As a practical matter, we also include cost, convenience, and impact on institutional resources and personnel among the important aspects of innovation that should be taken into consideration when an innovation is introduced.
We will exclude from this discussion incremental improvements in established procedures and evolutionary variations, such as stapled instead of sutured anastamoses. Such variations and refinements are generally accepted as implicit components of improving standard practice. They fit well within professional and institutional practice and policies for quality improvement. An informal process of collegial oversight of practice and its innovative variations is already in effect, as operating rooms, hospitals, and clinics form moral communities of caregivers who share a commitment to safeguard their patients, colleagues, and institutions from unnecessary risks. Accreditation, “credentialing” (validating qualifications), peer review, and quality improvement practices strengthen this protection. When an innovation introduces unknown risks, potential side effects, complications, resource requirements, or costs, the protection of the patients, innovators, institutions, and device manufacturers can be enhanced by collegial review (McKneally and Kornetsky, 2003; Morreim et al., 2006).
Innovation is not formal research as defined by the Belmont Report (National Commission for the Protection of Human Subjects of Biological and Behavioral Research, 1979), which designates research as “an activity designed to test an hypothesis, permit conclusions to be drawn and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships). Research is usually described in a formal protocol that sets forth an objective and a set of procedures designed to reach that objective.” Under the current regulatory ethics paradigm, “innovative treatments are regarded as questionable until they are framed in a research protocol with formal mechanisms of informed consent” and innovators participate in the exploratory phase that precedes formal research, working “in the borderland outside the regulatory ethics paradigm” (Agich, 2001). Hypotheses and protocols can only be developed after exploration by innovators to stabilize techniques and identify appropriate patients for study.
Why is innovation important?
Most of the important advances in medical practice, from anesthesia and appendectomy to heart surgery and transplantation, were introduced through an informal process we will call the innovation pathway. This pathway has become the major driver of increasing medical costs, as expensive innovative technologies for diagnosis and treatment are added to healthcare budgets. Generally motivated by strong financial incentives, biotechnology and medical device companies are constantly pushing out the boundaries of medical treatment. Since the passage of the Bayh-Dole Act (1980), clinicians, hospitals, and universities in the USA have had similar incentives to pursue patents and equity shares in industry. The biotechnology industry’s growth has been further accelerated by venture capitalists seeking investment opportunities in this volatile, high-stake market (Leaf, 2005). In this setting of dynamic growth in medical innovation, traditional safeguards may be overwhelmed. Research ethics boards (REB) and institutional review boards (IRB) utilize mechanisms to review protocols that are designed to systematically generate generalizable data rather than strategies uniquely tailored to individual patients. There is a clear need for a nimble, informed, flexible mechanism of collegial oversight to protect the interests of patients, innovators, and institutions.
Ethics
According to Wilton et al. (2000, p. 49), “Continued innovation is necessary if there are to be future gains in our ability to serve patients.” Improvements in clinical care are dependent upon the development and integration of safe and effective innovations. The clinician’s ethical responsibility to act in the best interests of patients, and continue to improve his or her knowledge and skills, is consistent with the pursuit of innovation (Canadian Medical Association, 2004; American Medical Association, 2005). Establishing a pathway that minimizes risk to patients while facilitating the pursuit of innovation is consistent with these values as well as the principles of beneficence and non-maleficence.
In most ethical formulations of the issues that arise in health research involving human subjects, research is defined by its ends: that is, what is to be learned (Lantos, 1994). Research is generally considered an activity designed to test a hypothesis systematically, permit conclusions to be drawn, and thereby develop or contribute to generalizable knowledge. By contrast, “[i]nnovation is focused solely on the benefit of the individual being cared for. If at any point it appears that any aspect of what is being done is not in that person’s best interest, the physician must change course” (Morreim, 2005, p. 42). These formulations have some overlap but they help to distinguish which frameworks should apply to a given intervention. In some cases, new practices should be introduced through the protective framework of research ethics and in others it is appropriate to have new or innovative practices governed by traditional medicolegal standards combined with professional and institutional policies.
The threshold at which innovation becomes accepted standard practice is not sharply defined. Many widely accepted procedures remain unvalidated, despite their acceptance (Levine, 1988). A commitment to accountability grounds the clinician’s ethical responsibility to evaluate innovative healthcare interventions. Conducting good research not only protects patients from unevaluated, potentially harmful interventions, it also fosters and maintains the integrity of clinical knowledge (Frader and Flanagan-Klygis, 2000).
Law
The fact that there may be unexpected harms resulting from innovative procedures does not in and of itself qualify them for the same type of review and oversight as research, but it does justify an increase in the level of safeguards to protect patients. The challenge is to delineate methods that offer protection to patients without stifling innovation (Strasberg and Ludbrook, 2003).
Canadian case law, for example, provides an articulation of standards clinicians will be expected to meet when providing innovative treatment. A clinician’s standard of care is often described as “the degree of care and skill which could reasonably be expected of a normal, prudent practitioner of the same experience and standing in the similar circumstances” (Lyne v. McClarty, 2001). When treating a patient, whether the treatment is innovative or standard practice, the clinician “… owes a duty to the patient to use diligence, care knowledge, skill and caution in administering the treatment …” (Lyne v. McClarty, 2001). In terms of reasonable precautions, it would be expected that a clinician using an innovative treatment would be able to show that others in the same field would have considered the precautions taken to be sufficient, that the clinician “… could not have learnt how to avoid the accidents by example of another, that most probably no other practical precautions could have been taken” (Lyne v. McClarty, 2001).
While many forms of oversight for the introduction of innovative procedures have been proposed in the literature (Reitsma and Moreno, 2005), the best options are those mechanisms that are consistent with standards that have been generated through the law in the relevant jurisdiction and that operationalize the values of fiduciary responsibility and accountability.
The legal standard of informed consent requires that patients and substitute decision makers not only understand and appreciate the potential risks and benefits of a procedure but also the innovative nature of the procedure (Coughlin v. Kuntz, 1987). The law of informed consent requires that the consent be voluntary; that the patient be capable of understanding and appreciating the potential risks, benefits and impact of the intervention in his or her own life situation; and that the patient be informed – must be told and comprehend all that a reasonable person would want to know about the risks, benefits, and impact of the proposed treatment. In the consent discussion, clinicians need to discuss the kind of information that a “reasonable patient” might consider material information for making an informed decision about whether or not to consent to the innovative procedure (Coughlin v. Kuntz, 1987).
Professional standards are developed within professional bodies and healthcare institutions and are relevant to innovative practices. Maintenance of professional standards through continuing education and examinations are intended to help to ensure that clinicians have the skill level and knowledge to meet the challenges of rapidly changing technology and scientific information.
Policy
Surgeons are constantly exposed to new procedures and devices through medical journals, conversations with colleagues at meetings, and through advertising and promotion by representatives from the companies making new products. Most hospitals do not have a specific policy in place for surgeons to follow when introducing innovative procedures, other than the REB, which is infrequently used for this purpose (Reitsma and Moreno, 2002). A policy for the introduction of innovative procedures and devices should have a number of attributes if it is going to be used by surgeons. These include ease of use and a short timeline between application and approval or rejection. The policy should provide transparent accountability, patient protection, and legal protection for the surgeon and the hospital.
We have developed a policy at The Hospital for Sick Children, Toronto, for the introduction of innovative procedures and devices that attempts to address as many of the relevant issues as possible, and have implemented and carried out a preliminary evaluation of the policy. At the time of this writing, the policy addresses only procedures or devices that have been introduced previously at other institutions but are new to this hospital. An on-line form contains 10 points about the proposed innovation (Table 26.1) that the surgeon must address and then submit to the surgeon-in-chief, who has three options: approve of the proposal, request for expert advice, or recommend submission to the REB/IRB. The process is evaluated using structured interviews and a compliance review as part of the hospital’s quality assurance program.
Over a one-year period, 14 applications to perform innovative procedures were submitted through this policy. All were approved, two after expert consultation, and 23 procedures were performed. Case review revealed perceived benefit to the patient in 78% of the cases, and lower cost in 56% of the cases compared with the standard approach. Surgical innovators strongly supported the process. Compliance review indicated incomplete written documentation of the innovative nature of the procedure/device in 10% of the cases. Experience with this policy suggests that innovative procedures and devices can be introduced through a user-friendly process that promotes accountability and responsible resource utilization, intending to protect patients, surgeons, and hospitals, but that the evolving consent process needs further improvement.
Empirical studies
Reitsma and Moreno (2002) identified 59 published papers that described surgical innovations, then surveyed the corresponding authors: 15 of 21 authors did not submit their protocol to an REB/IRB; seven mentioned the innovative nature of the procedure on the consent form. Although 14 authors described their work as research, only six sought prior REB/IRB review.
In a subsequent study, Reitsma and Moreno (2005) surveyed surgeons for their definitions of innovative surgery and research, and for their attitudes toward regulation, the need for specific informed consent, and IRB review of surgical innovations. The surgeons’ responses differentiated routine surgical variation from research requiring IRB review by two criteria: a formal protocol and prior consent regarding the experimental nature of the procedure. Suggestions regarding oversight for significant innovations that are not formal research include clearance with the chief of surgery or a hospital committee, registries, tracker trials, and review by experts in a particular field.
Strasberg and Ludbrook (2003) analyzed experience with the introduction of laparoscopic cholecystectomy, live donor liver hemitransplantation, radiofrequency tumor ablation, and coronary artery angioplasty. They emphasized the value of registries of early experience for detecting new or unexpected problems that were not discovered in randomized trials of the same procedures. Hazelrigg et al. (1993) reported a registry of early experience with 1820 video-assisted thoracic surgical procedures. The early publication of this collective experience helped to identify the problems encountered during the learning phase, and to establish safe limits to the application of this innovative technology.
At the time of writing, the Children’s Hospital in Boston (Kornetsky, 2001) and the Massachusetts General Hospital had similar effective policies that emphasized expert collegial review, and consultation with the REB/IRB when appropriate. The Hospital for Sick Children and the University Health Network in Toronto have both adopted a somewhat similar model, as described in the policy section of this chapter.
How should I approach innovation in practice?
Innovation should be encouraged and facilitated in a supportive setting that includes collegial oversight, full patient consent that is explicit about the fact that the consent is for an innovative procedure, attention to effects on institutional personnel and resources, and responsible reporting of outcomes. Innovators should participate in registries of early experience to teach and learn from colleagues about the effects, side effects, useful modifications, and complications of the new procedures or devices. Where doubt exists as to whether an innovation should be the subject of an REB/IRB review, consultation should be pursued.
Innovations should improve healthcare because of greater convenience, less disability or pain, reduced cost, improved accuracy and safety, or better treatment outcomes. Claims to these advantages should be validated before the innovations are widely accepted. Expensive innovations should be held to a high standard of validation before they alter the allocation of institutional resources, and healthcare budgets should include an allocation for innovations to protect standard services from destabilization. While collaboration with industry can accelerate progress toward technological solutions, clinicians should give highest priority to their fiduciary obligation to their patients.
The cases
C’s parents should be informed of the novelty of the STEP procedure, the rationale and experience at other centers, and the fact that C will be the first patient in your hospital to be treated using this innovative technique. Collegial review and support should be sought from a well-informed pediatric surgeon and the surgeon-in-chief, who should ensure that responsible members of the healthcare team who will be involved in C’s care have the appropriate skills and endorse the treatment plan. A specific pre-agreed number of the serial tapering enteroplasties should then be evaluated, including their cost, outcome, and impact on the institution. Information on the experience with C should be shared with the registry (T. Jaksic, personal communication, 2006). A formal research protocol to establish the scientific validity of the procedure should then be developed in collaboration with the REB/IRB and other clinical scientists. This might include a formal protocol to measure the absorptive capacity of the newly formed intestine and the quality of life of the patient before and after the innovative procedure.
Emergency approval to use the innovative lung assist device (ILA) should be sought from the authorities responsible for evaluating medical devices in human patients. The surgeon-in-chief should be provided with a summary of the evidence supporting the use of the ILA in this young soldier, a summary of the potential risks and benefits, and the endorsement of the planned procedure signed by an informed colleague. All relevant team members should have the necessary skill or training to perform the procedure. The consent process should clearly disclose the innovative nature of the procedure. The experience gained should be carefully evaluated and reported in a registry of ILA applications. This experience and the advice of the innovating team should be shared with the manufacturer to help to improve the effectiveness and safety of the innovative device to enable their research. When the technical and procedural details of the treatment and the most appropriate patients have been identified, a formal research study should be developed working with the REB/IRB to validate the innovation.