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In addition to the independent IRB review described above, human subjects research must meet other certain minimal requirements in order to be ethical.9, 10 Emanuel and colleagues have proposed seven key ethical requirements for clinical research. Research involving human subjects must provide an aggregate benefit to society or future patients to warrant the risk (however small) to current research subjects. In addition, all research should be scientifically valid with robust methodology. Researchers must also ensure that all enrolled subjects are shown the highest respect, which is facilitated by the researcher being honest, careful, and trans- parent with relevant information. Finally, as noted, all human subjects must provide informed consent and be notified that withdrawal from the research study is not only permitted, but will also not affect any aspect of their future care.

Informed Consent

The process of informed consent remains a cornerstone of human subjects research. While not sufficient in itself, informed consent is a necessary prerequisite for virtually all research that involves human subjects. Paramount to the practice of surgery and the conduct of research is the ability to instill trust and facilitate communication. Over the past 50 years, patient autonomy as well as the right to individual self-determination has come to the forefront of medicine and medical research. Informed consent epitomizes the shift toward a patient-centered paradigm of care and clinical research and represents a formal mechanism both to recog- nize patient autonomy and to address human subjects as selfdetermined moral agents. Informed consent serves to identify and respect an individual’s best interests by giving each per- son the opportunity to decide autonomously what his or her best interests are in light of the research protocol.

Informed consent is particularly important in the realm of the surgeon-scientist. Research subjects need a significant amount of information to decide whether to enroll in a clinical trial, as many of the attendant risks and benefits are not

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inherently obvious. At times, researchers must approach patients who are facing significant illness and a bleak prognosis to ask them to participate in a clinical trial. Patients may have a wide range of emotions, from “profound distrust to unques- tioned faith” in the surgeon and the research process, thereby further complicating the process.11 For pragmatic purposes, there are three general steps to informed consent: disclosure/ information exchange, ensuring adequate understanding/ answering of questions, and subject decision-making/consent. Disclosure should convey the relevant and germane informa- tion about the study including the provision of information to subjects about the purpose of the research, its procedures, potential risks, benefits, and alternatives.10 The scope and nature of the information should be determined, in part, by an understanding of the subject’s situation and context. It is criti- cal that researchers bear in mind that disclosure of information may sometimes be mundane for research personnel, but the process is often novel and confusing for potential participants. As such,information should be presented as clearly as possible with honest admissions of variables that are not well known or understood. Informed consent may require the use of lay ter- minology, diagrams, or similar strategies to educate the

­potential study participant and evaluate that individual’s understanding. The language used by the surgeon-scientist in the information disclosure process should be as objective as possible. Surgeons with direct involvement in a clinical trial (either as primary investigator or as potential financial benefi- ciary) should involve other members of the research team to secure the informed consent process to avoid a potential con- flict of interest.Many patients will want their surgeon’s subjec- tive opinion of whether they should participate in a specific clinical trial. In general, it is best that the surgeon withhold an opinion until after the research team has met with the poten- tial study participant and discussed the details of the study. By separating the surgeon from the informed consent process for research, the clinical relationship and the surgeons’ fiduciary ­responsibility to the individual can be maintained.

Patients can come through the informed consent process without truly being “informed.” Having an individual simply

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sign a consent form to satisfy a legal requirement does not necessarily reflect that the person understands the risks and benefits of a research study.As such, while written consent is a routine and necessary part of the informed consent process, researchers should not overly focus on the paper while ignor- ing the process. Notwithstanding these comments, the study subject’s signature is almost always necessary to proceed with participation in clinical research, and therefore, some form of documentation must exist. The informed consent process is critical in respecting human subject autonomy and the right to self-determination as a moral agent.As such,the researcher must ensure that adequate time and priority are allocated for this process.

Surgical Innovation and Surgical Research

Surgeons are uniquely positioned to be innovators in medical therapy, specifically in surgical technique. As most surgeons are constantly tinkering to perfect their intraoperative skills and postoperative outcomes, there is a natural tendency and desire to improve surgical care incrementally. However, the boundaries between tinkering, innovation and research are not always clear cut. A great majority of surgical advance- ment is the result of surgical innovation, an unregulated pro- cess that can spread valuable and effective therapies rapidly but also has the potential to harm patients who are unaware of the innovation in progress. Furthermore, there are a large number of surgical innovations that ultimately proved to be hazardous to patients such as frontal lobotomy and internal mammary ligation for angina.

It is helpful to define the distinction between innovation and research in order to determine the level of oversight required as well as patient consent for participation. First, a minor modification (i.e., tinkering) is generally unplanned and involves a slight shift in technique. The evolution of the ileo-anal pull through with numerous pouch conformations is a good example of a minor modification. Surgical research is defined as the systematic investigation of a surgical problem

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that leads to generalized knowledge. A randomized trial of carotid endarterectomy versus carotid stenting is a good example of surgical research. Innovation is much more diffi- cult to define. The Society of University Surgeons took on this difficult challenge and defined innovation as any surgical procedure that has not been described in a North American surgical text. In addition to endorsing this definition of inno- vation, the Society of University Surgeons went on to recom- mend that all innovative procedures must be disclosed ahead of time if they are planned or discussed postoperatively with patients if the innovation is unplanned.12 Awareness of the distinction between innovation and minor surgical modifica- tion is important for the protection of our patients, as “sur- geons must remain alert to the possibility of acceptable clinical innovation, creeping inexorably toward reckless experimentation.”13

Ethics: Special Considerations Regarding

Research

David Resnik has argued that there are several aspects of the research environment that may make it particularly suscep- tible to moral strain.14 Researchers are pressured to publish papers, effectively utilize limited laboratory resources, and obtain funding. Unfortunately, occasionally a researcher may succumb to these pressures and begin to ignore ambiguous data and negative results or begin to “massage” the data.The laboratory environment – not unlike surgical training itself – can often be hierarchical in nature, making some students or residents feel pressured to do things to “satisfy” the expecta- tions of their supervisor. Power imbalances between the lead researcher and mentees may potentially affect how research is performed and how results are reported. Because positive results are often rewarded, while negative results are too fre- quently seen as failures, investigators may feel tempted to “fudge” the results. As most researchers can anticipate the “desired” or “correct” results, they may try to justify this

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behavior by telling themselves “I know this is how it really would have turned out if….”Dishonesty in scientific research, however, undermines the most fundamental ethical princi- ples: trust, honesty, and validity.

Dishonesty includes fabrication, falsification, and plagiari- sim.15 Whereas fabrication is the baseless creation of data in the absence of empirical experimental results, falsification is the manipulation or misrepresentation of data or results that were obtained from experiments. Misrepresentation may include both presentation of false material, but also the pur- poseful omission of certain unflattering facts. Falsification can also occur in data collection, such as the omission of cer- tain data points to “tighten up” the data (e.g., “I am going to leave these three data points out because they are clearly ‘outliers’”). Falsification can also occur in the analysis of the data (e.g., “torturing” the data with statistics to get a desired or anticipated result). Finally, the most overt form of dishon- esty is plagiarism, which is the wholesale appropriation of another researcher’s ideas, work, or written word as your own. Plagiarism can include the reproduction of another researcher’s ideas at a meeting or the reproduction of another researcher’s written word in publication. Plagiarism is a seri- ous infraction of research ethics and can have long-term negative implications for a researcher’s career. As such, investigators should take particular effort to give credit where it is due and fastidiously avoid reproducing the work of others. All forms of dishonesty seriously undermine and erode the integrity of scientific research and therefore should be avoided at all costs.

The hallmark of good, ethical laboratory research also needs to include both a commitment to an open research envi- ronment and a dedication to meticulous methodology. An open research environment can help cultivate the scientific process by allowing ambiguous or “wrong” results to be dis- cussed and examined. Errors can be quickly identified in a non-punitive manner, and corrective measures can be imple- mented expeditiously. Mentors and research leaders are therefore ethically obligated to help foster open communica- tion in the research setting. Mentors should interact with