- Email: [email protected]
The need to revise the Helsinki Declaration
Correspondence
programme, the new executive order allows the government the option of excluding all refugees from certain countries to be identified later. This new pernicious travel and refugee ban represents a repudiation of the long-standing US commitment to refugee resettlement. During the past 30 years, 3 million refugees have been welcomed to and successfully resettled in the USA. Last year, the leading source country for refugees was the Democratic Republic of the Congo,3 a country where brutal violence against the civilian population, including the use of rape as a weapon of war, has led to massive displacement, illness, and psychological trauma. Burmese people fleeing government repression and widespread human rights abuses that result in increased child and maternal mortality and malnutrition constituted another large group of resettled refugees.3 The need to resettle a small fraction of the 5 million Syrians who have fled ISIS and the Syrian Government, whose military strategies include bombardment of and torture and murder of civilians,4 is compelling. In issuing the order, the Trump administration purports to cite evidence of the security threat that refugees pose.2 But apart from nonspecific claims of counterterrorism investigations involving refugees, its sole evidence is a man convicted of attempting to plant a bomb in the USA who was not a recently admitted refugee.2 The individual came to the USA at 2 years of age, became a US citizen long before he attempted this act, and there is a cloud over his conviction whether he was induced by the FBI to commit the act.5 The new order suspending and then shrinking the refugee resettlement programme does not bring any security gains and imposes tremendous mental and physical harm on people who have suffered more than most of us can even imagine. Let them in. We declare no competing interests.
*Leonard Rubenstein, Paul Spiegel [email protected] 1190
Center for Humanitarian Health, Johns Hopkins University, Baltimore, MD 21205, USA (PS, LR); and Center for Public Health and Human Rights, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA (LR) 1 2
3
4
5
Spiegel PB, Rubenstein LS. The academic case for repealing Trump’s refugee and travel ban. Lancet 2017; 389: 679–80. The White House Office of the Press Secretary. Executive order protecting the nation from foreign terrorist entry into the United States. March 6, 2017. https://www.whitehouse.gov/ the-press-office/2017/03/06/executive-orderprotecting-nation-foreign-terrorist-entryunited-states (accessed March 7, 2017). Krogstad JM, Radford J. Key Facts about refugees to the U.S. Pew Research Center. Jan 30, 2017. http://www.pewresearch.org/ fact-tank/2017/01/30/key-facts-aboutrefugees-to-the-u-s/ (accessed March 8, 2017). UN Human Rights Council. Report of the Independent International Commission of Inquiry on the Syrian Arab Republic. A/HRC/34/64. March 1, 2017. https://documents-dds-ny.un.org/doc/ UNDOC/GEN/G17/026/63/P (accessed March 8, 2017). Ansari T. Here’s how the White House is justifying the new refugee and immigration ban. BuzzFeed News; March 6, 2017. https://www.buzzfeed.com/talalansari/hereshow-the-white-house-is-justifying-the-newrefugee-and?utm_term=.rawY0kG3q#. td12X9zbo (accessed March 7, 2017).
The need to revise the Helsinki Declaration In 2011, The Lancet published an Article (Dec 10, p 1997)1 on the first case of a transplant using a synthetic trachea seeded with the patient’s own stem cells. The senior author was Paolo Macchiarini, a thoracic surgeon working at the Karolinska University Hospital, Stockholm. Macchiarini performed another three transplantations with the same technique at the Karolinska. Since research misconduct was suspected and several of the authors of the 2011 article retracted their authorships, The Lancet added an expression of concern to the article in April, 2016.2 The transplantations at the Karolinska were also severely criticised from an ethical point of view. Macchiarini and the hospital have consistently advocated that the transplantations were entirely motivated by a dedication to help patients with severe disease, in whom
conventional therapeutic options were exhausted (as described in a Correspondence letter by Macchiarini3 in The Lancet). They have referred to the final (37th) paragraph in the World Medical Association’s Helsinki Declaration: “In the treatment of an individual patient, where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorised representative, may use an unproven intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering.”4 There are examples of much stricter recommendations by professional organisations. The most elaborate are the guidelines for stem-cell research and clinical translation by the International Society for Stem Cell Research (ISSCR).5 They require a written plan, approved through a peer-review process, for the procedure, including a scientific rationale and justification explaining why it has a reasonable chance of success and preclinical evidence of proof of principle for efficacy and safety. Other key requirements are voluntary informed consent, an action plan for adverse events, and reporting of outcomes (including negative outcomes and adverse effects), enabling critical review of the intervention by the scientific community. The intervention should be provided to ”at most a very small number of patients outside the context of a formal clinical trial”.5 The Macchiarini case illustrates how the 37th paragraph of the Helsinki Declaration can be misinterpreted, especially if read in isolation from the other articles. It emphasises the need to revise this part of the declaration to better safeguard against experimentation at the physician’s own discretion. The ISSCR guidelines provide a reasonably strict alternative framework for applying innovative www.thelancet.com Vol 389 March 25, 2017
Correspondence
KA performed an independent investigation of Paolo Macchiarini’s tracheal transplantations, commissioned by the Karolinska University Hospital and its owner. GH was a member of the working party drafting the first ISSCR guidelines for stem cell research and clinical translation (2008). We declare no other competing interests.
*Kjell Asplund, Göran Hermerén [email protected] Department of Public Health and Clinical Medicine, Umeå University, 901 87 Umeå, Sweden (KA); and Department of Medical Ethics, Lund University, Lund, Sweden (GH) 1
2
3 4
5
Jungebluth P, Alici E, Baiguera S, et al. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 2011; 378: 1997–2004. The Lancet. Expression of concern— Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 2016; 387: 1359. Macchiarini P. Tracheobronchial transplantation. Lancet 2016; 387: 339. World Medical Association. Declaration of Helsinki. Ethical principles for nedical research involving human subjects. http://www.wma. net/en/30publications/10policies/b3/ (accessed Jan 31, 2017). International Society for Stem Cell Research. Guidelines for stem cell research and clinical translation. 2016. http://www.isscr.org/docs/ default-source/guidelines/isscr-guidelines-forstem-cell-research-and-clinical-translation. pdf?sfvrsn=2 (accessed Jan 31, 2017).
Tracheal implants revisited An Article in The Lancet by Philipp Jungebluth and colleagues published in 2011 (Dec 10, p 1997),1 can now be found online with four of the original authors having since withdrawn their authorship. That alone is certainly a rare development. The authors described how a seriously ill 36-year-old male patient, with recurrent primary cancer of the distal trachea and main bronchi after complete tumour resection, received a tracheal implant made of polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU). 1 This material is recognised as an alternative to medical grade poly(carbonateurea)urethane (PCU) because of www.thelancet.com Vol 389 March 25, 2017
its excellent biocompatibility, in-vivo biostability, and superior mechanical properties. However, important facts are disregarded in the Article, especially regarding the long-term effect of an unsterile environment, such as the trachea, on implant material. In 2009, our interdisciplinary research group published a study2 on the effect that the tracheal environment had on various tracheostomy tube materials after months of exposure. Medical grade silicone, polyvinyl chloride (PVC), and PCU were evaluated, with material degradation evident in all tubes. Jungebluth and colleagues continued using their implants in younger patients with a benign indication for tracheostomy. From an ethical point of view, this is even more troublesome, since outpatients with chronic tracheostomy have unaffected life expectancy.3 However, the research group moved on towards disaster as their institutions and uncritical reviewers, appearing to sense a scientific breakthrough, cheered them on. The mechanisms at play are now being exposed, resulting in multiple administrative corrective actions. In addition to this, editors of prestigious journals also need to contemplate how to interact more carefully with deviating academic cultures. CF reports other financial activities from Claes Frostell Research and Consulting AB, Linde Healthcare, and Bactiguard, outside the submitted work. GB reports grants from Bactiguard AB, outside the submitted work. The other authors declare no competing interests.
*Claes Frostell, Gunilla Björling, Emma Strömberg, Sigbritt Karlsson, Ragnhild E Aune [email protected] Department of Clinical Sciences, Division of Anaesthesia and Intensive Care, Danderyd Hospital, Karolinska Institutet, SE-182 88 Stockholm, Sweden (CF, GB); The Swedish Red Cross University College, Huddinge, Sweden (GB); School of Chemical Science and Engineering, Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden (ES, SK); and Department of Materials Science and Engineering, Norwegian University of Science and Technology, Trondheim, Norway (REA)
1
2
3
Jungebluth P, Alici E, Baiguera S, et al. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 2011; 378: 1997–2004. Backman S, Björling G, Johansson U–B, et al. Material wear of polymeric tracheostomy tubes—a six-month study. Laryngoscope 2009; 119: 657–664. Björling G, Johansson U–B, Andersson G, et al. A retrospective survey of outpatients with long-term tracheostomy. Acta Anaesthesiol Scand 2006; 50: 399–406.
Feedback of results to trial participants: be upfront or risk affront We commend Erik Stenberg and colleagues for their well designed and delivered large randomised trial (April 2, p 1397),1 which investigated the utility of mesenteric defect closure in reducing the incidence of internal hernia after laparoscopic gastric bypass surgery. The study robustly answers the authors’ research question and a plenary audience at the European Obesity Summit in Gothenburg, Sweden, agreed almost unanimously that closure of mesenteric defects should now be standard practice. However, the identification of a substantial gap between the closure and non-closure groups in the incidence of this potentially life-threatening primary endpoint raises two important ethical questions. First, should participants who received what we now understand to be suboptimum care—ie, non-closure— be informed of the inferior nature of their treatment compared with that received by their counterparts? Second, should these individuals be routinely offered an additional procedure to close their defects? Regarding the first question, although no formal consensus or standard of practice regarding feedback of results to patients participating in trials exists at present, consistent evidence shows that most clinicians and patients support the idea of offering results to trial participants.2,3
iStock
methods outside a clinical research project.
1191
programme, the new executive order allows the government the option of excluding all refugees from certain countries to be identified later. This new pernicious travel and refugee ban represents a repudiation of the long-standing US commitment to refugee resettlement. During the past 30 years, 3 million refugees have been welcomed to and successfully resettled in the USA. Last year, the leading source country for refugees was the Democratic Republic of the Congo,3 a country where brutal violence against the civilian population, including the use of rape as a weapon of war, has led to massive displacement, illness, and psychological trauma. Burmese people fleeing government repression and widespread human rights abuses that result in increased child and maternal mortality and malnutrition constituted another large group of resettled refugees.3 The need to resettle a small fraction of the 5 million Syrians who have fled ISIS and the Syrian Government, whose military strategies include bombardment of and torture and murder of civilians,4 is compelling. In issuing the order, the Trump administration purports to cite evidence of the security threat that refugees pose.2 But apart from nonspecific claims of counterterrorism investigations involving refugees, its sole evidence is a man convicted of attempting to plant a bomb in the USA who was not a recently admitted refugee.2 The individual came to the USA at 2 years of age, became a US citizen long before he attempted this act, and there is a cloud over his conviction whether he was induced by the FBI to commit the act.5 The new order suspending and then shrinking the refugee resettlement programme does not bring any security gains and imposes tremendous mental and physical harm on people who have suffered more than most of us can even imagine. Let them in. We declare no competing interests.
*Leonard Rubenstein, Paul Spiegel [email protected] 1190
Center for Humanitarian Health, Johns Hopkins University, Baltimore, MD 21205, USA (PS, LR); and Center for Public Health and Human Rights, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA (LR) 1 2
3
4
5
Spiegel PB, Rubenstein LS. The academic case for repealing Trump’s refugee and travel ban. Lancet 2017; 389: 679–80. The White House Office of the Press Secretary. Executive order protecting the nation from foreign terrorist entry into the United States. March 6, 2017. https://www.whitehouse.gov/ the-press-office/2017/03/06/executive-orderprotecting-nation-foreign-terrorist-entryunited-states (accessed March 7, 2017). Krogstad JM, Radford J. Key Facts about refugees to the U.S. Pew Research Center. Jan 30, 2017. http://www.pewresearch.org/ fact-tank/2017/01/30/key-facts-aboutrefugees-to-the-u-s/ (accessed March 8, 2017). UN Human Rights Council. Report of the Independent International Commission of Inquiry on the Syrian Arab Republic. A/HRC/34/64. March 1, 2017. https://documents-dds-ny.un.org/doc/ UNDOC/GEN/G17/026/63/P (accessed March 8, 2017). Ansari T. Here’s how the White House is justifying the new refugee and immigration ban. BuzzFeed News; March 6, 2017. https://www.buzzfeed.com/talalansari/hereshow-the-white-house-is-justifying-the-newrefugee-and?utm_term=.rawY0kG3q#. td12X9zbo (accessed March 7, 2017).
The need to revise the Helsinki Declaration In 2011, The Lancet published an Article (Dec 10, p 1997)1 on the first case of a transplant using a synthetic trachea seeded with the patient’s own stem cells. The senior author was Paolo Macchiarini, a thoracic surgeon working at the Karolinska University Hospital, Stockholm. Macchiarini performed another three transplantations with the same technique at the Karolinska. Since research misconduct was suspected and several of the authors of the 2011 article retracted their authorships, The Lancet added an expression of concern to the article in April, 2016.2 The transplantations at the Karolinska were also severely criticised from an ethical point of view. Macchiarini and the hospital have consistently advocated that the transplantations were entirely motivated by a dedication to help patients with severe disease, in whom
conventional therapeutic options were exhausted (as described in a Correspondence letter by Macchiarini3 in The Lancet). They have referred to the final (37th) paragraph in the World Medical Association’s Helsinki Declaration: “In the treatment of an individual patient, where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorised representative, may use an unproven intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering.”4 There are examples of much stricter recommendations by professional organisations. The most elaborate are the guidelines for stem-cell research and clinical translation by the International Society for Stem Cell Research (ISSCR).5 They require a written plan, approved through a peer-review process, for the procedure, including a scientific rationale and justification explaining why it has a reasonable chance of success and preclinical evidence of proof of principle for efficacy and safety. Other key requirements are voluntary informed consent, an action plan for adverse events, and reporting of outcomes (including negative outcomes and adverse effects), enabling critical review of the intervention by the scientific community. The intervention should be provided to ”at most a very small number of patients outside the context of a formal clinical trial”.5 The Macchiarini case illustrates how the 37th paragraph of the Helsinki Declaration can be misinterpreted, especially if read in isolation from the other articles. It emphasises the need to revise this part of the declaration to better safeguard against experimentation at the physician’s own discretion. The ISSCR guidelines provide a reasonably strict alternative framework for applying innovative www.thelancet.com Vol 389 March 25, 2017
Correspondence
KA performed an independent investigation of Paolo Macchiarini’s tracheal transplantations, commissioned by the Karolinska University Hospital and its owner. GH was a member of the working party drafting the first ISSCR guidelines for stem cell research and clinical translation (2008). We declare no other competing interests.
*Kjell Asplund, Göran Hermerén [email protected] Department of Public Health and Clinical Medicine, Umeå University, 901 87 Umeå, Sweden (KA); and Department of Medical Ethics, Lund University, Lund, Sweden (GH) 1
2
3 4
5
Jungebluth P, Alici E, Baiguera S, et al. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 2011; 378: 1997–2004. The Lancet. Expression of concern— Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 2016; 387: 1359. Macchiarini P. Tracheobronchial transplantation. Lancet 2016; 387: 339. World Medical Association. Declaration of Helsinki. Ethical principles for nedical research involving human subjects. http://www.wma. net/en/30publications/10policies/b3/ (accessed Jan 31, 2017). International Society for Stem Cell Research. Guidelines for stem cell research and clinical translation. 2016. http://www.isscr.org/docs/ default-source/guidelines/isscr-guidelines-forstem-cell-research-and-clinical-translation. pdf?sfvrsn=2 (accessed Jan 31, 2017).
Tracheal implants revisited An Article in The Lancet by Philipp Jungebluth and colleagues published in 2011 (Dec 10, p 1997),1 can now be found online with four of the original authors having since withdrawn their authorship. That alone is certainly a rare development. The authors described how a seriously ill 36-year-old male patient, with recurrent primary cancer of the distal trachea and main bronchi after complete tumour resection, received a tracheal implant made of polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU). 1 This material is recognised as an alternative to medical grade poly(carbonateurea)urethane (PCU) because of www.thelancet.com Vol 389 March 25, 2017
its excellent biocompatibility, in-vivo biostability, and superior mechanical properties. However, important facts are disregarded in the Article, especially regarding the long-term effect of an unsterile environment, such as the trachea, on implant material. In 2009, our interdisciplinary research group published a study2 on the effect that the tracheal environment had on various tracheostomy tube materials after months of exposure. Medical grade silicone, polyvinyl chloride (PVC), and PCU were evaluated, with material degradation evident in all tubes. Jungebluth and colleagues continued using their implants in younger patients with a benign indication for tracheostomy. From an ethical point of view, this is even more troublesome, since outpatients with chronic tracheostomy have unaffected life expectancy.3 However, the research group moved on towards disaster as their institutions and uncritical reviewers, appearing to sense a scientific breakthrough, cheered them on. The mechanisms at play are now being exposed, resulting in multiple administrative corrective actions. In addition to this, editors of prestigious journals also need to contemplate how to interact more carefully with deviating academic cultures. CF reports other financial activities from Claes Frostell Research and Consulting AB, Linde Healthcare, and Bactiguard, outside the submitted work. GB reports grants from Bactiguard AB, outside the submitted work. The other authors declare no competing interests.
*Claes Frostell, Gunilla Björling, Emma Strömberg, Sigbritt Karlsson, Ragnhild E Aune [email protected] Department of Clinical Sciences, Division of Anaesthesia and Intensive Care, Danderyd Hospital, Karolinska Institutet, SE-182 88 Stockholm, Sweden (CF, GB); The Swedish Red Cross University College, Huddinge, Sweden (GB); School of Chemical Science and Engineering, Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden (ES, SK); and Department of Materials Science and Engineering, Norwegian University of Science and Technology, Trondheim, Norway (REA)
1
2
3
Jungebluth P, Alici E, Baiguera S, et al. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 2011; 378: 1997–2004. Backman S, Björling G, Johansson U–B, et al. Material wear of polymeric tracheostomy tubes—a six-month study. Laryngoscope 2009; 119: 657–664. Björling G, Johansson U–B, Andersson G, et al. A retrospective survey of outpatients with long-term tracheostomy. Acta Anaesthesiol Scand 2006; 50: 399–406.
Feedback of results to trial participants: be upfront or risk affront We commend Erik Stenberg and colleagues for their well designed and delivered large randomised trial (April 2, p 1397),1 which investigated the utility of mesenteric defect closure in reducing the incidence of internal hernia after laparoscopic gastric bypass surgery. The study robustly answers the authors’ research question and a plenary audience at the European Obesity Summit in Gothenburg, Sweden, agreed almost unanimously that closure of mesenteric defects should now be standard practice. However, the identification of a substantial gap between the closure and non-closure groups in the incidence of this potentially life-threatening primary endpoint raises two important ethical questions. First, should participants who received what we now understand to be suboptimum care—ie, non-closure— be informed of the inferior nature of their treatment compared with that received by their counterparts? Second, should these individuals be routinely offered an additional procedure to close their defects? Regarding the first question, although no formal consensus or standard of practice regarding feedback of results to patients participating in trials exists at present, consistent evidence shows that most clinicians and patients support the idea of offering results to trial participants.2,3
iStock
methods outside a clinical research project.
1191