- Email: [email protected]
Addressing Scientific Integrity Through Education in the Responsible Conduct of Research
1538
ETHICS IN CARDIOTHORACIC SURGERY BANDO ET AL SCIENTIFIC INTEGRITY IN CLINICAL RESEARCH
research, and between research publication and financial rewards: publication bonuses, future research funding, paid advisory boards, and so forth. In other words, so long as publication leads to funding and so long as unethical research practices advance publication without a significant downside, the observed increases in retracted papers and problems of reproducibility, as well as more blatant misconduct, are likely to continue. At a minimum, in order to sever the link between FFP and publication, retracted papers that are the result of willful intent to deceive or negligent supervision should not be republished after retraction; the underlying study (or relevant portion) should have to be redone by different researchers to be republishable. I am speaking here not of retracted papers that are timely corrections of unwilling errors; these could, in principle, be republished with appropriate notes by a willing journal [2, 3]. A second aspect of an ecological understanding is the degrading effect of failures of integrity on institutional and professional values. Research is a mentored profession, one in which the close relationships between mentors and mentees can also be corrupting and, for less powerful members, inescapable. This is one reason organizations, such as the military and many large corporations, regularly dismantle teams and reassign them to prevent undesirable behaviors from going undetected and from becoming endemic. Career paths that do not depend on a single relationship or laboratory should be encouraged and rewarded in science as well. Finally, failures of research integrity are costly, both to the research enterprise and to the patients and families who participate in research or are consumers of the products of research [4, 5]. It is time to hold individual researchers accountable for their failures of research integrity, including being accountable in the literal sense for the negative externalities such as additional peer reviews, investigations, promising lines of research aborted, dubious research resourced, research subjects
Ann Thorac Surg 2015;100:1534–40
and patients harmed, and so forth. Investigators who are found to have fabricated or falsified data must refund any personal compensation over and above basic salary associated with the study in question—bonus, award, indirect payments, etc. (Because plagiarism has different ethical consequences I exclude it here). An institution should use such refunded amounts first, to publicize the retraction and second, to repeat or correct the study with another research team. The recommendations above are steps toward making scientific misconduct less likely by considering the larger ecological context and reward system in which FFP thrives. Robin N. Fiore, PhD University of Miami Miller School of Medicine Bioethics Program 1400 NW 10th Ave, Ste 912 PO Box 016960 (M825) Miami, FL 33136 e-mail: rfi[email protected] http://dx.doi.org/10.1016/j.athoracsur.2015.08.040
References 1. Bando K, Schaff HV, Sato T, Hashimoto K, Cameron DE. A multidisciplinary approach to ensure scientific integrity in clinical research. Ann Thorac Surg 2015;100:1534–40. 2. Van Noorden R. The trouble with retractions. Nature 2011;478: 26–8. 3. Fang FC, Casadevall A. Retracted science and the retraction index. Infect Immun 2011;79:3855–9. 4. Haberman C. A discredited vaccine study’s continuing impact on public health. N Y Times, Feb 1, 2015. Available at http:// www.nytimes.com/2015/02/02/us/a-discredited-vaccine-studyscontinuing-impact-on-public-health.html?_r¼0. Accessed August 12, 2015. 5. Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation systematic review and meta-analysis. JAMA 2013;309:678–88.
ADDRESSING SCIENTIFIC INTEGRITY THROUGH EDUCATION IN THE RESPONSIBLE CONDUCT OF RESEARCH Bando and colleges [1] highlight the fact that the incidence of academic misconduct in published clinical research has been increasing during the past decade. The reasons for this misconduct are multifactorial, and as such, there is no single solution to addressing this important issue. Bando and colleges suggest four sound proposals, for which we wish to discuss the third—the establishment of a solid research training system. Before the institution of any systemic measures to address scientific integrity, one must first begin with establishing a clear understanding of the problem itself, and we therefore agree that further work needs to be done in education and training. However, many medical schools have already introduced courses in Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
evidence-based medicine at a time when there is increasing pressure to master a growing body of medical knowledge [2, 3]. In addition, there may be significant lag time between graduate or postgraduate training and the time when a student will become the primary investigator in a study. We therefore feel that the most effective solution to providing education in scientific misconduct would be to design a research training system administered through the major medical journals or societies using a Web-based curriculum. This curriculum will have at its core the already developed and successful “responsible conduct of research training program” [4]. Successful completion of the curriculum would be a condition for publication. 0003-4975/$36.00
Ann Thorac Surg 2015;100:1534–40
To be successful, such a program would need to be concise and pragmatic. The course must have safeguards to prevent sharing of answers and mechanisms to ensure that the researcher has indeed completed the module. Also, the information conveyed should be implicitly usable to the researcher and ideally appropriate for a wide variety of journals, researchers, and data. The successful completion of this module would be made available in a format that could be verified and transferred to all major medical journals and conferences. Some may argue that implementation of such a training module will impose additional time constraints on busy investigators; however, we stress the importance of maintaining the course as concise, practical, and applicable to wide array of journals. Maintaining scientific integrity in our journals is of critical importance, and ultimately, such efforts will benefit our medical community and the populations we serve through the dissemination of reliable and actionable new information. Although a multifactorial approach to scientific misconduct is necessary, establishing educational awareness is a sound first step in the process.
ETHICS IN CARDIOTHORACIC SURGERY BANDO ET AL SCIENTIFIC INTEGRITY IN CLINICAL RESEARCH
1539
Alexander Iribarne, MD, MS Jock N. McCullough, MD Section of Cardiac Surgery Department of Surgery Dartmouth-Hitchcock Medical Center 1 Medical Center Dr Lebanon, NH 03766 e-mail: [email protected] http://dx.doi.org/10.1016/j.athoracsur.2015.08.039
References 1. Bando K, Schaff HV, Sato T, Hashimoto K, Cameron DE. A multidisciplinary approach to ensure scientific integrity in clinical research. Ann Thorac Surg 2015;100:1534–40. 2. Blanco MA, Capello CF, Dorsch JL, Perry G, Zanetti ML. A survey study of evidence-based medicine training in US and Canadian medical schools. J Med Libr Assoc 2014;102:160–8. 3. Oude Rengerink K, Thangaratinam S, Barnfield G, et al. How can we teach EBM in clinical practice? An analysis of barriers to implementation of on-the-job EBM teaching and learning. Med Teach 2011;33:e125–30. 4. Stenbeck NH. ORI: introduction to the responsible conduct of research. Washington, DC: Department of Health and Human Services. Available at http://www.ori.dhhs.gov/sites/default/ files/rcrintro.pdf. Accessed August 7, 2015.
OPEN DATA: CAN IT PREVENT RESEARCH FRAUD, PROMOTE REPRODUCIBILITY, AND ENABLE BIG DATA ANALYTICS IN CLINICAL RESEARCH? The reliability and reproducibility of biomedical research is under increasing scrutiny as the number and scope of high-profile manuscript retractions for research fraud has increased [1]. Bando and colleagues [2] provide an important contribution with strategies to prevent scientific misconduct. Their suggestion to mandate preservation of raw research data and making anonymized patient data available on reasonable request merits further discussion. The Office of Science and Technology Policy asserted in 2013 that federally funded research data should be made publicly available for access, search, and analysis. The Public Library of Sciences was the first mainstream journal to introduce an open-data mandate for all submissions in 2014. The Gates Foundation announced in 2014 that it would demand open data of the researchers it funds [3]. Finally, the Institutes of Medicine issued an extensive report on sharing clinical trial data earlier this year [4]. These different initiatives have stimulated discussion on open data policies, although they remain quite marginal to this date [3]. The reasoning for open-data mandates is that providing the raw data underlying a clinical trial should allow reproduction and validation of the analysis, to detect errors and deter fraud, in an era plagued by irreproducible results [5]. It should also allow other investigators to answer secondary research questions or aggregation into large-scale meta-analyses. Data sharing should maximize the benefits from the vast amount of research data collected and the contribution of each study subject, while respecting the privacy of the study subjects. This Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
should also provide a fair opportunity for researchers to publish results before secondary investigators gain access to the data and protect the commercial interests of sponsors in gaining regulatory approval [4]. Beyond prevention of research fraud, open data mandates offer an exciting opportunity to confront the “small sample size” issue in clinical research. Other industries, such as finance and energy, have embraced data analytics [6], and researchers at Google have shown that an order of magnitude growth in the size of data sets leads to significant improvements in performance of analyses and can overshadow improvements in modeling techniques [7]. Big data have only been reported in a select few epidemiologic studies, such as those linking myocardial infarction and rosiglitazone [8] or rofecoxib [9]. Two significant issues need to be resolved to enable open data mandates: guaranteeing the privacy of study subjects [10] and creating a safe, fair, and open infrastructure for data sharing [4]. The National Institutes of Health lists 65 open data repositories (http://www.nlm.nih.gov/ NIHbmic/nih_data_sharing_repositories.html) that it supports. Unfortunately, though, the lack of an adequate data-sharing platform is often listed by authors in justifying noncompliance with open data mandates [3]. In conclusion, data sharing should become normal, to allow verification of data and statistical analyses or allow big data mining across multiple study populations. The Society of Thoracic Surgeons should take a leading role in implementing open data in the field of cardiothoracic surgery. We owe it to our specialty and to our study
0003-4975/$36.00
ETHICS IN CARDIOTHORACIC SURGERY BANDO ET AL SCIENTIFIC INTEGRITY IN CLINICAL RESEARCH
research, and between research publication and financial rewards: publication bonuses, future research funding, paid advisory boards, and so forth. In other words, so long as publication leads to funding and so long as unethical research practices advance publication without a significant downside, the observed increases in retracted papers and problems of reproducibility, as well as more blatant misconduct, are likely to continue. At a minimum, in order to sever the link between FFP and publication, retracted papers that are the result of willful intent to deceive or negligent supervision should not be republished after retraction; the underlying study (or relevant portion) should have to be redone by different researchers to be republishable. I am speaking here not of retracted papers that are timely corrections of unwilling errors; these could, in principle, be republished with appropriate notes by a willing journal [2, 3]. A second aspect of an ecological understanding is the degrading effect of failures of integrity on institutional and professional values. Research is a mentored profession, one in which the close relationships between mentors and mentees can also be corrupting and, for less powerful members, inescapable. This is one reason organizations, such as the military and many large corporations, regularly dismantle teams and reassign them to prevent undesirable behaviors from going undetected and from becoming endemic. Career paths that do not depend on a single relationship or laboratory should be encouraged and rewarded in science as well. Finally, failures of research integrity are costly, both to the research enterprise and to the patients and families who participate in research or are consumers of the products of research [4, 5]. It is time to hold individual researchers accountable for their failures of research integrity, including being accountable in the literal sense for the negative externalities such as additional peer reviews, investigations, promising lines of research aborted, dubious research resourced, research subjects
Ann Thorac Surg 2015;100:1534–40
and patients harmed, and so forth. Investigators who are found to have fabricated or falsified data must refund any personal compensation over and above basic salary associated with the study in question—bonus, award, indirect payments, etc. (Because plagiarism has different ethical consequences I exclude it here). An institution should use such refunded amounts first, to publicize the retraction and second, to repeat or correct the study with another research team. The recommendations above are steps toward making scientific misconduct less likely by considering the larger ecological context and reward system in which FFP thrives. Robin N. Fiore, PhD University of Miami Miller School of Medicine Bioethics Program 1400 NW 10th Ave, Ste 912 PO Box 016960 (M825) Miami, FL 33136 e-mail: rfi[email protected] http://dx.doi.org/10.1016/j.athoracsur.2015.08.040
References 1. Bando K, Schaff HV, Sato T, Hashimoto K, Cameron DE. A multidisciplinary approach to ensure scientific integrity in clinical research. Ann Thorac Surg 2015;100:1534–40. 2. Van Noorden R. The trouble with retractions. Nature 2011;478: 26–8. 3. Fang FC, Casadevall A. Retracted science and the retraction index. Infect Immun 2011;79:3855–9. 4. Haberman C. A discredited vaccine study’s continuing impact on public health. N Y Times, Feb 1, 2015. Available at http:// www.nytimes.com/2015/02/02/us/a-discredited-vaccine-studyscontinuing-impact-on-public-health.html?_r¼0. Accessed August 12, 2015. 5. Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation systematic review and meta-analysis. JAMA 2013;309:678–88.
ADDRESSING SCIENTIFIC INTEGRITY THROUGH EDUCATION IN THE RESPONSIBLE CONDUCT OF RESEARCH Bando and colleges [1] highlight the fact that the incidence of academic misconduct in published clinical research has been increasing during the past decade. The reasons for this misconduct are multifactorial, and as such, there is no single solution to addressing this important issue. Bando and colleges suggest four sound proposals, for which we wish to discuss the third—the establishment of a solid research training system. Before the institution of any systemic measures to address scientific integrity, one must first begin with establishing a clear understanding of the problem itself, and we therefore agree that further work needs to be done in education and training. However, many medical schools have already introduced courses in Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
evidence-based medicine at a time when there is increasing pressure to master a growing body of medical knowledge [2, 3]. In addition, there may be significant lag time between graduate or postgraduate training and the time when a student will become the primary investigator in a study. We therefore feel that the most effective solution to providing education in scientific misconduct would be to design a research training system administered through the major medical journals or societies using a Web-based curriculum. This curriculum will have at its core the already developed and successful “responsible conduct of research training program” [4]. Successful completion of the curriculum would be a condition for publication. 0003-4975/$36.00
Ann Thorac Surg 2015;100:1534–40
To be successful, such a program would need to be concise and pragmatic. The course must have safeguards to prevent sharing of answers and mechanisms to ensure that the researcher has indeed completed the module. Also, the information conveyed should be implicitly usable to the researcher and ideally appropriate for a wide variety of journals, researchers, and data. The successful completion of this module would be made available in a format that could be verified and transferred to all major medical journals and conferences. Some may argue that implementation of such a training module will impose additional time constraints on busy investigators; however, we stress the importance of maintaining the course as concise, practical, and applicable to wide array of journals. Maintaining scientific integrity in our journals is of critical importance, and ultimately, such efforts will benefit our medical community and the populations we serve through the dissemination of reliable and actionable new information. Although a multifactorial approach to scientific misconduct is necessary, establishing educational awareness is a sound first step in the process.
ETHICS IN CARDIOTHORACIC SURGERY BANDO ET AL SCIENTIFIC INTEGRITY IN CLINICAL RESEARCH
1539
Alexander Iribarne, MD, MS Jock N. McCullough, MD Section of Cardiac Surgery Department of Surgery Dartmouth-Hitchcock Medical Center 1 Medical Center Dr Lebanon, NH 03766 e-mail: [email protected] http://dx.doi.org/10.1016/j.athoracsur.2015.08.039
References 1. Bando K, Schaff HV, Sato T, Hashimoto K, Cameron DE. A multidisciplinary approach to ensure scientific integrity in clinical research. Ann Thorac Surg 2015;100:1534–40. 2. Blanco MA, Capello CF, Dorsch JL, Perry G, Zanetti ML. A survey study of evidence-based medicine training in US and Canadian medical schools. J Med Libr Assoc 2014;102:160–8. 3. Oude Rengerink K, Thangaratinam S, Barnfield G, et al. How can we teach EBM in clinical practice? An analysis of barriers to implementation of on-the-job EBM teaching and learning. Med Teach 2011;33:e125–30. 4. Stenbeck NH. ORI: introduction to the responsible conduct of research. Washington, DC: Department of Health and Human Services. Available at http://www.ori.dhhs.gov/sites/default/ files/rcrintro.pdf. Accessed August 7, 2015.
OPEN DATA: CAN IT PREVENT RESEARCH FRAUD, PROMOTE REPRODUCIBILITY, AND ENABLE BIG DATA ANALYTICS IN CLINICAL RESEARCH? The reliability and reproducibility of biomedical research is under increasing scrutiny as the number and scope of high-profile manuscript retractions for research fraud has increased [1]. Bando and colleagues [2] provide an important contribution with strategies to prevent scientific misconduct. Their suggestion to mandate preservation of raw research data and making anonymized patient data available on reasonable request merits further discussion. The Office of Science and Technology Policy asserted in 2013 that federally funded research data should be made publicly available for access, search, and analysis. The Public Library of Sciences was the first mainstream journal to introduce an open-data mandate for all submissions in 2014. The Gates Foundation announced in 2014 that it would demand open data of the researchers it funds [3]. Finally, the Institutes of Medicine issued an extensive report on sharing clinical trial data earlier this year [4]. These different initiatives have stimulated discussion on open data policies, although they remain quite marginal to this date [3]. The reasoning for open-data mandates is that providing the raw data underlying a clinical trial should allow reproduction and validation of the analysis, to detect errors and deter fraud, in an era plagued by irreproducible results [5]. It should also allow other investigators to answer secondary research questions or aggregation into large-scale meta-analyses. Data sharing should maximize the benefits from the vast amount of research data collected and the contribution of each study subject, while respecting the privacy of the study subjects. This Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
should also provide a fair opportunity for researchers to publish results before secondary investigators gain access to the data and protect the commercial interests of sponsors in gaining regulatory approval [4]. Beyond prevention of research fraud, open data mandates offer an exciting opportunity to confront the “small sample size” issue in clinical research. Other industries, such as finance and energy, have embraced data analytics [6], and researchers at Google have shown that an order of magnitude growth in the size of data sets leads to significant improvements in performance of analyses and can overshadow improvements in modeling techniques [7]. Big data have only been reported in a select few epidemiologic studies, such as those linking myocardial infarction and rosiglitazone [8] or rofecoxib [9]. Two significant issues need to be resolved to enable open data mandates: guaranteeing the privacy of study subjects [10] and creating a safe, fair, and open infrastructure for data sharing [4]. The National Institutes of Health lists 65 open data repositories (http://www.nlm.nih.gov/ NIHbmic/nih_data_sharing_repositories.html) that it supports. Unfortunately, though, the lack of an adequate data-sharing platform is often listed by authors in justifying noncompliance with open data mandates [3]. In conclusion, data sharing should become normal, to allow verification of data and statistical analyses or allow big data mining across multiple study populations. The Society of Thoracic Surgeons should take a leading role in implementing open data in the field of cardiothoracic surgery. We owe it to our specialty and to our study
0003-4975/$36.00