Review | Published:

New treatments for serious conditions: ethical implications

Gene Therapy volume 24, pages 534538 (2017) | Download Citation

Subjects

Abstract

Approval of Spinraza (nusinersen) for treatment of spinal muscular atrophy prompts consideration of a number of ethical issues that arise whenever a new treatment is proposed for a serious condition, especially one that is rare and can devastatingly affect children. Patients, families, clinicians, researchers, institutions and policymakers all must take account of the ways that newly available treatments affect informed and shared decision-making about therapeutic and research options. The issues to consider include: addressing what is still uncertain and unknown; the possibility that potential benefits will be exaggerated and potential harms underemphasized in the media, by advocacy organizations, and in consent forms and processes; the high cost of many novel drugs and biologics; the effects of including conditions of variable phenotype in state-mandated newborn screening panels; and how new treatments can change the standard of care, altering what is and is not known about a disorder and posing challenges for decision-making at both individual and policy levels. The good news that Spinraza brings thus requires additional attention to its ethical and policy implications, to improve counseling and shared decision-making about treatment and research options for patients and all involved in their care.

Introduction

The approval of Spinraza (nusinersen) for treatment of spinal muscular atrophy (SMA) types 1–3 is undoubtedly an important achievement in a number of ways. It is a scientific advance, an example of productive collaboration between Biogen researchers and the patient advocacy organization CureSMA, and a cautionary tale about costs and charges for new biologics. But Spinraza also raises a host of ethical issues that are not new. Instead, they represent long-standing questions that appear once again in this particular context. In this essay, we address these familiar issues, all of which are still in need of further consideration in the context of SMA and Spinraza because they may have profound effects on the disease management decisions that are made by patients and families, and influenced by the practices and policies of clinicians, researchers, and institutions, both private and public. These issues include, but are not limited to:

  1. Uncertain and unknown effects of a newly approved treatment;

  2. Causes and consequences of overoptimism and hype;

  3. Implications of high treatment costs;

  4. Implications for newborn screening (NBS);

  5. Changing the standard of care.

SMA is the most common genetic cause of death in infants. It causes progressive proximal muscle weakness as a result of neuronal degeneration in the lower brain stem and spine. People with this condition are cognitively intact and have normal intellectual development, but experience increasing weakness and paralysis. The responsible genes have been identified; thus, the genetic diagnosis of SMA is definitive. However, there is a great range of phenotypic expression and potential clinical course, so that significant uncertainty often remains about the severity of the condition for each individual.

SMA is caused by mutations or absence of the survival motor neuron 1 (SMN 1) gene, which codes for the SMN protein, needed to maintain motor neuron integrity and function. The variability in phenotypic presentation results from the presence of the SMN2 gene on the same chromosome. The SMN2 gene is similar to the SMN 1 gene, but produces a truncated, inactive protein most of the time. Occasionally, however (about 10–50% of the time), the transcription process makes a mistake and creates the genetic blueprint for the translation of a functional SMN protein from the SMN2 gene.1 These ‘mistakes’ can alter the phenotypic presentation of SMA. Thus, an increased number of SMN2 genes has been reported to correlate with less severe symptoms and later onset of SMA, but the correlation is general and not algorithmic because there is considerable variation in transcription.

Currently, SMA is divided into five different types.2 SMA type 0 presents in the fetal and neonatal period with lack of fetal movement, contractures and severe hypotonia, and leads to very early death without aggressive supportive intervention. SMA type 1, Werdnig–Hoffman disease, presents in the neonatal and infant period prior to 6 months of age. Infants with typical development are expected to sit at ~6 months of age, and infants with SMA type 1, by definition, are never able to sit independently. They also have weakness of respiratory muscles and difficulty swallowing; this often leads to death by 2 years of age without aggressive intervention.3 These two types of SMA, the most severe and earliest onset forms, are characterized by the most certainty in prognosis and clinical course.

SMA types 2 through 4 have more variable presentation in timing and clinical course. SMA type 2 is characterized by onset of symptoms by 18 months of life and the inability to stand unassisted. Type 3 and 4 SMA are able to stand unassisted, but have variable symptoms, from progressive weakness resulting in the need for a wheelchair to mild proximal muscle weakness making it difficult to rise from a chair. Onset for type 3 is during childhood, but after at least 18 months of age, and onset for type 4 is during adulthood. The number of SMN2 gene copies can be helpful in predicting phenotype. While it is most helpful in types 0 and 1, which tend to have 1 and 2 copies of the SMN2 gene, respectively, SMN2 gene number is less helpful with types 2–4 because variability in number and expression is not clearly related to phenotype.4 This variability of phenotypic expression makes prognosis very difficult when an infant with a definitive diagnosis is asymptomatic or mildly symptomatic.

Introduction of Spinraza is a significant advance in the treatment of SMA. For the first time, there is an agent that can alter progression of the disease. Using the SMN2 copies that may already be altering the phenotype of the disease, the medication (an antisense oligonucleotide) enables transcription of the SMN2 gene in a way that will lead to production of the functional SMN protein by translation. Spinraza essentially forces the natural ‘mistake’ in transcription that may already be occurring. It is an elegant approach that uses what the body already possesses to alter symptom expression. Spinraza is thus creating excitement among scientists, health-care providers and affected families. And it is for this very reason that attention to the ethical implications of this important development is essential.

Uncertainty

Spinraza received Food and Drug Administration marketing approval on 23 December 2016 based on data from a small number of studies. Publications describing two studies can be found in PubMed. One is a Phase I single-dose-escalation trial enrolling 28 children aged 2–14 with SMA types 2 and 3;5 the other is a Phase 2 open-label dose escalation trial enrolling 20 infants with type 1.6 Information about five other studies is available through ClinicalTrials.gov and through press releases and other publicity in the media about Spinraza’s approval. CHERISH, a Phase III randomized trial enrolling children between 2 and 12 years of age with SMA type 2, was stopped early after interim findings of significant symptom modification in the treatment group. ENDEAR, a Phase III randomized study enrolling infants with SMA type 1, was also stopped early for this reason. EMBRACE, a Phase II randomized study enrolling patient-subjects who did not meet criteria for CHERISH or ENDEAR, enrolled 20 patients. NURTURE enrolls presymptomatic infants with known genetic diagnosis and, according to its listing, continues to recruit. An expanded access protocol, SHINE, is also current on ClinicalTrials.gov; it provides access to Spinraza for SMA type 1 patients of all ages, both those who were previously enrolled in CHERISH or ENDEAR and those who have never received Spinraza before.

Owing to the accelerated approval pathway and the rarity of the condition, the data on which Spinraza was approved thus comes from fewer than 200 patient-subjects.7, 8 Although these data appear quite promising, they are limited, and derive from only a few years’ experience with administration in humans. Thus, even the most optimistic view of Spinraza’s long-term success must be tempered with caution and acknowledgment of what is still unknown. Long-term follow-up is essential to determine whether the slowing of progression continues with continued treatment, whether there are significant effect differences for patients affected with different degrees of severity and whether any potential harms manifest over the long term.

Spinraza requires an initial series of six induction intrathecal injections (into the spinal canal) and additional intrathecal injections every 4 months for life. Because these injections are painful and patients must be immobilized during each procedure, patients older than infancy usually receive a local anesthetic or conscious sedation. This can require a certified sedation provider, appropriate monitoring and sedation recovery time. Patients often suffer transient post-lumbar puncture effects.9 Thrombocytopenia and nephrotoxicity, known side effects of antisense oligonucleotides, were minimal or unseen in the study populations to date, but may appear over time. Both disease progression and repeated lumbar punctures for intrathecal injections may compromise access to the intraspinal space over time; this could eventually make injection of the drug for ongoing therapy impossible for some patients.

In addition, now that Spinraza is approved, more patients are likely to receive it—some of whom may have characteristics and comorbidities that were not seen in clinical trials. Clinical trials generally enroll patients who will be the best research subjects; that is, the data on which Spinraza’s approval is based come from patients who were least likely to be disadvantaged by trial participation and most likely to provide good study data. Thus, although the studies provide some data about disease progression and side effects, little information is currently available to help predict how this newly approved treatment will affect the lives of the children receiving it and their families. The promising results that fast-tracked Spinraza to approval are real and exciting, but their long-term implications for SMA patients are as yet unknown.

As prominent physician-writer Atul Gawande has noted, uncertainty is the ground state of medicine and coping with uncertainty requires wisdom.10 A key ethical issue, then, is simply remembering that uncertainty cannot wholly be eliminated by even the most promising of novel biotechnologies. More information will be needed over time to improve knowledge of the harm–benefit balance of Spinraza for patients with all SMA types.

Hype

It is common and understandable but unfortunate that the increase in public access to information makes acknowledgment of uncertainty increasingly difficult. Public discussion of newly approved treatments like Spinraza often overestimates beneficial effects and underestimates potential harms. Excitement about the first drug therapy for SMA is entirely understandable, but when information about clinical trials and research progress is framed by compelling and emotional family stories told by advocacy groups to increase interest and garner support, exaggeration and misunderstanding can follow. This natural tendency to hype positive results often begins during clinical trials and increasingly appears even in descriptions of animal studies.

For example, giving clinical trials names based on clever and memorable acronyms may seem harmless, but the practice is also a marketing strategy designed to make research seem less like science and more like treatment. The Spinraza trials labeled ENDEAR, CHERISH, NURTURE, EMBRACE and SHINE exemplify this practice. If clinical trials were better understood, and clinical researchers were recognized as adhering to a duty to protect research subjects from harm while attempting to learn and find better treatments, it would not be necessary to disguise research as treatment in this way. Instead, patient-subjects and the public would know that caring for and about research subjects is already an essential part of every clinical trial.

In recent years, disease advocacy organizations have become key players in the promotion and funding of research on rare diseases. Advocacy organizations and the families who belong to them play significant roles in generating interest in treatment-finding research, which includes research funding, collaboration with researchers, providing patient-subjects, and promoting increased attention to diagnosis and treatment. They also have a role in publicly advocating for better financial support from governmental and private sources to meet the needs of affected children and their families. CureSMA is proud of its early financial support for Biogen’s SMA treatment-finding research, and proclaims a sense of ownership of Spinraza’s promise. Its social media presence and informational campaign undoubtedly influenced support for the research, and increased public knowledge about and positive reception for the drug. Yet, it is also well established that a close relationship between funders and researchers can run the risk of distorting information and even data. Thus, caution about CureSMA’s role in funding research is warranted. CureSMA is an invaluable support for families and patients facing the diagnosis of SMA, and their work has undoubtedly advanced treatment and awareness of the disease. Nonetheless, their role in supporting both families and drug discovery may unintentionally give rise to conflicts of interest and increase the likelihood of therapeutic misconception.11, 12, 13 CureSMA and Biogen seem to be aware of these risks, but continued vigilance is needed.

And finally, medical journalists love good stories with happy endings. They have less love for postscripts that remind readers of the uncertainties and occasional disasters that can go hand-in-hand with happy endings. Immunotherapy for treatment of malignant melanoma provides an instructive example. For more than a few years, news stories have been full of stories of near-miraculous cures, including former President Jimmy Carter’s apparently successful treatment. Yet, the New York Times recently tempered this happy ending with a cautionary tale alerting the public that cancer immunotherapy treatment can cause the immune system to run amok, with unexpected, unpredictable, unstoppable and tragic results.14

Hype is about both overestimating potential benefits and underestimating potential harms. Recognizing that the risks of harm arising from novel biotechnologies like Spinraza are and continue to be real and potentially significant is perfectly compatible with embracing its promise—and it is necessary to informed decision-making and vigilance. As important as it is to acknowledge and celebrate progress, it is equally essential that all stakeholders—scientists, physicians, journalists, families, advocacy groups and the public—keep trying to distinguish between justifiable hope and undue hype.

Price and cost

The extraordinarily high price tag that Biogen has placed on Spinraza has already been the subject of much discussion,15, 16, 17 which will no doubt continue. Two aspects of this discussion impress us as worth some additional mention. First, Biogen’s pricing justification includes not only the now-standard reference to the high costs of drug development and the need to recoup them, but also the argument that because SMA is a rare disorder, making a profit requires charging afflicted families more to make up for their lack of numbers. In addition, Biogen has emphasized that the price tag has little importance because few if any families are actually going to have to pay it. Private insurers will negotiate for lower charges, Medicaid and the Children's Health Insurance Program will pay, and Biogen, like other companies selling very expensive medications, offers advice to families about securing insurance coverage. It would be remiss of us to discuss cost issues without acknowledging the potential instability of the current systems of payment for medical care in the United States, and while it is outside the scope of this essay to speculate about the future of US health policy, significant changes in Medicaid and insurance systems (private and public) would certainly affect SMA patients and families.

Second, the price of Spinraza that has been widely quoted is, of course, for the drug itself. It does not include charges for the injection procedures, sedation, treatment of transient side effects, and so on. In other words, what families will actually be charged for regular intrathecal injections includes more than just the charges for the drug. Even more importantly, what families are charged does not fully represent what this treatment will cost them. Infants and children with SMA have extensive ongoing needs, including multiple medical appointments, and keeping up with their affected children’s needs is already challenging for many families. Adding a three-times-yearly visit to a site with the capacity to give these intrathecal injections could represent a considerable burden in time, travel and related costs for families already struggling to meet the needs of their children. Without considerable assistance, some families will no doubt be unable to take advantage of the full potential benefits of Spinraza for very mundane reasons, including ‘Who will take care of my other kids when I have to take 3 days off to travel across the state for my child’s next injection?’.

Newborn screening

One of the most interesting and difficult issues arising from the approval of Spinraza is how to address its implications for patients diagnosed with later-onset SMA. One important question arises immediately: should SMA be added to the NBS panel so that it can be diagnosed soon after birth? Infants with SMA1 often begin to exhibit symptoms within a few months, so, for those infants, the answer to this question depends on how treatment during the small presymptomatic window is regarded. Presymptomatic treatment is being studied in the NURTURE trial, and is likely to appear desirable. However, whether presymptomatic treatment is advisable for patients with later-onset/less severe SMA is a different question. Eliminating the diagnostic odyssey is arguably more important for later-onset SMA than for type 1. Yet, because it is difficult to know what is actually being prevented by presymptomatic treatment, it will no doubt be difficult to determine the effects of including screening for SMA in NBS and whether the benefit justifies the potential burden.

Moreover, many states already have difficulty making services available to families for more than a few of the conditions identified by NBS. Whether private insurance, Medicaid and the Children's Health Insurance Program will be able to pay for Spinraza, even after symptoms appear, is, as we have noted, open to question. Early diagnosis means early identification of a condition without complete information about whether and when symptoms might appear—unless and until confirmatory genetic testing and correlation of SMN2 number with phenotype and prognosis become much more precise. Even so, it may be especially difficult to obtain health insurance coverage for presymptomatic treatment. And finally, even though genetic discrimination in health insurance and employment is prohibited by the Genetic Information Nondiscrimination Act (GINA),18 thus ensuring that a presymptomatic diagnosis of SMA cannot be considered an excludable preexisting condition even if the Affordable Care Act is dismantled by Congress, GINA does not prohibit discrimination on the basis of genetic conditions outside the context of health insurance—such as in life insurance, disability insurance or long-term care insurance.19

Changing the standard of care

In the modern medical armamentarium, many (perhaps most) treatments are not cures. They are likely to be what Lewis Thomas called ‘halfway technologies’20—transforming serious diseases into chronic conditions by failing to return the patient to ‘normal’ functioning, or by instituting a permanent state of ongoing treatment and patienthood, or both. Treatment for HIV disease is a good example of turning a fatal infection into a chronic condition with ongoing treatment; another example is the treatment of organ failure with allotransplantation and a lifelong balancing act between graft failure and excessive immunosuppression.

Research on organ regeneration and gene editing are currently viewed as especially promising in large part because they appear to promise complete and genuine cures. However, Spinraza—like the gene transfer trial that is currently underway for SMA type 1—promises improvement, but not cure. What improvement means to patients and their families varies depending on how severely a given individual is affected and the functional implications of improvement in the life of the individual. Patients with SMA and their families consider not only study data, but also quality of life and treatment goals when making decisions. What counts as a good quality of life can vary greatly across patients and families. Without more attention to the needs, views and choices of all SMA patients and their families, the introduction of a new therapy can introduce as much confusion as hope. Only a few studies have examined treatment decision-making and the experience of living with SMA.21 Additional research exploring the broadest understandings of patient care in SMA is much needed as treatment options expand.

There is already variability in the meaning and significance of ‘improvement’ from Spinraza, and the availability of the drug seems likely to continue to change how SMA is regarded and treated. This phenomenon is not new; it is an inevitable consequence of medical progress and has some predictable effects. When the lifespan for patients with fatal or extremely disabling conditions lengthens, that changes patients’ lifelong needs for financial support, equipment and assistance in activities of daily living. It also has important existential and social implications, as those living longer with disabling conditions share the human desire to live independently, participate in the workforce and have their own families. These same changes have been historically evidenced in conditions like phenylketonuria (the very first focus of NBS) and cystic fibrosis, to give just two examples, and there are many others. Already, the availability of Spinraza may be increasing the likelihood that intubation and tracheostomy will be more commonly viewed as standard medical recommendations even for newborns with the earliest onset of SMA. And because different SMA types are primarily distinguished phenotypically, whether it will remain possible to predict symptom severity or classify SMA type by the current diagnostic framework is an open question. However, at least at present it is surely true that, even when children with SMA begin to live longer and have better lives, they will continue to face challenges and disease complications, including some that may not currently be anticipated.

The history of type 1 diabetes provides an especially vivid example for consideration.22 Before insulin was developed, diabetes was a life-shortening disease that was very difficult to manage. As more was learned about dietary management, affected children lived longer and much was learned about the disease’s effects on all organ systems. Patients began living into adulthood and facing increasing disability. When insulin became available, insulin replacement became a standard halfway technology, which is currently improving greatly with increasingly sophisticated delivery systems, but is still imperfect. Transplantation is also a halfway technology, for different reasons. However, development of the bioartificial pancreas is ongoing and could ultimately promise something that more closely resembles a cure.23 Treatment for SMA may already be on a similar path.

Two important implications arise from the changes in the standard of care that follow from advances in science. First, it is essential to avoid considering Spinraza a curative treatment. We recommend describing it as a palliative intervention, emphasizing that currently available data suggest that it can slow disease progression, but can neither halt it nor enable patients to regain lost function. We also consider it important to ensure that parents of severely affected children retain the ability to choose to avoid or abate aggressive life-sustaining treatment for their severely affected children, and instead to focus on palliative and supportive care choices, under appropriate circumstances. The availability of Spinraza, and enthusiasm for its use among health-care providers and advocacy groups, could make refusal or renunciation of aggressive treatment and preference for palliative care unpopular or disfavored, or even arouse suspicion. Nonetheless, parents must be able to learn about and talk about all options for their children, and those who have a different view must not be precluded from exploring, discussing and making different reasonable and reasoned choices.

Second, it is equally essential to continue not only to gather data about the long-term effects of Spinraza, but also to seek more effective treatments. The availability of Spinraza could affect current and future research simply because enrollment in a clinical trial should not disadvantage patient-subjects by denying them access to effective treatments. The very first gene transfer trial, in 1990, was a first-in-humans study of a gene transfer intervention for adenosine deaminase severe combined immune deficiency (ADA-SCID). The trial began not long after PEG-ADA was approved by the Food and Drug Administration as the first treatment for ADA-SCID. PEG-ADA is an infusion of the protein that is not produced by patients with ADA-SCID. In order not to disadvantage the first patient-subject, 4-year-old Ashanti da Silva, continued to receive PEG-ADA infusions after receiving the infusion of genetically altered hematopoetic stem cells in the trial. Thus, it was very difficult to distinguish the effects of the gene transfer intervention from those of PEG-ADA,24 and over the course of the trial it took some time to determine whether PEG-ADA could be stopped in any of the patient-subjects. If this problem arises now that Spinraza has been approved, the ethical challenges it poses must be addressed. Without careful consideration and discussion, the availability of Spinraza could, at best, make it increasingly difficult to enroll patient-subjects in ongoing or new trials.

Conclusions and recommendations

Spinraza is very good news, but newly approved biologics always raise ethical concerns along the way. It is important not to relax our vigilance about these concerns, because anticipation makes it possible to address them more effectively. Appreciation of the ethical implications helps physicians inform, support and counsel families in shared decision-making, both about treatment options and about research participation,25 and can also improve decision-making at the policy level. The emerging data about Spinraza and other treatments for SMA are exciting, but data addressing more than survival and symptoms are needed. Families need to know more about what it means to live with SMA and with the benefits and burdens of the available treatment. Parents of affected children—and later, more and more children themselves—face high-stake decisions about chronic treatment and potential aggressive life-prolonging therapies. Without considering the ethical, psychosocial, financial, and quality-of-life aspects of SMA and its treatment, physicians and families run the risk of treating patients without fully understanding how to care for them.

References

  1. 1.

    , , , , . Differential SMN2 expression associated with SMA severity. Nat Genet 1998; 20: 230–231.

  2. 2.

    . Spinal muscular atrophy: clinical classification and disease heterogeneity. J Child Neurol 2007; 22: 946–951.

  3. 3.

    , . The natural history of type 1 (severe) spinal muscular atrophy. Neuromuscul Disord 1994; 4: 497–502.

  4. 4.

    , . Spinal muscular atrophy. Neurol Clin 2015; 33: 831–846.

  5. 5.

    , , , , , et al. Results from a phase 1 study of nusinersen (ISIS-SMN Rx) in children with spinal muscular atrophy. Neurology 2016; 86: 890–897.

  6. 6.

    , , , , , et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet 2016; 388: 3017–3026.

  7. 7.

    Biogen Press Release, 2016. US. FDA approves Biogen’s Spinraza (nusinersen), the first treatment for spinal muscular atrophy. Available at: (accessed on 4 February 2017).

  8. 8.

    FDA News Release, 2016. FDA approves first drug for spinal muscular atrophy. Available at: (accessed on 4 February 2017).

  9. 9.

    , , , , , et al. Intrathecal injections in children with spinal muscular atrophy: nusinersen clinical trial experience. J Child Neurol 2016; 3: 899–906.

  10. 10.

    Gawande A. Complications: A Surgeon’s Notes on an Imperfect Science. Picador: New York, NY, USA, 2002..

  11. 11.

    , , , , , et al. Confronting the issues of therapeutic misconception, enrollment decisions, and personal motives in genetic medicine-based clinical research studies for fatal disorders. Hum Gene Ther 2005; 16: 1028–1036.

  12. 12.

    , , , , , . Conflicts of interest for patient-advocacy organizations. N Eng J Med 2017; 376: 880–885.

  13. 13.

    Tribble SJ. Drugmakers are turning patients with rare diseases into D.C. lobbyists, Kaiser Health News, 10 April 2017. Available at: (accessed on 15 April 2017).

  14. 14.

    Richtel M. Therapies that can attack cancer, and organs. New York Times 4 December 2016, pp A1..

  15. 15.

    Shobit S. Biogen, Ionis under fire for Spinraza. Investopedia, 4 January 2017. Available at: (accessed on 5 February 2017).

  16. 16.

    Thomas K. Hefty price set on a new drug that can stunt muscle disease. New York Times 31 December 2016, pp B1..

  17. 17.

    Biogen, SMA 360. Available at: (accessed on 5 February 2017).

  18. 18.

    Genetic Information and Nondiscrimination Act, 2008. Pub L No 110-233, 122 Stat 881..

  19. 19.

    US Department of Health and Human Services, 2009. 'GINA' the Genetic Information Nondiscrimination Act of 2008: information for researchers and health care professionals. Available at: (accessed on 5 February 2017).

  20. 20.

    Thomas L. The technology of medicine. In: Lives of a Cell: Notes of a Biology Watcher. Viking Press: New York, NY, USA, 1974, pp 31–36..

  21. 21.

    , , , , . A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy. Eur J Hum Genet 2015; 23: 575–580.

  22. 22.

    Feudtner C. The want of control: ideas and ideals in the management of diabetes. In: Bittersweet: Diabetes, Insulin, and the Transformation of Illness. UNC Press: Chapel Hill, NC, USA, 2003, pp 121–145..

  23. 23.

    , , . Ethical considerations in tissue engineering research: case studies in translation. Methods 2016; 99: 135–144.

  24. 24.

    , , , , . Genetic research as therapy: implications of 'gene therapy' for informed consent. J Law Med Ethics 1998; 26: 38–47.

  25. 25.

    . Enduring and emerging challenges of informed consent. N Engl J Med 2015; 372: 855–862.

Download references

Acknowledgements

This work was supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number U01TR001792.

Disclaimer

The content is solely the responsibility of the authors.

Author information

Affiliations

  1. Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Center for Bioethics Health, and Society and Graduate Program in Bioethics, Wake Forest University, Winston-Salem, NC, USA

    • N M P King
  2. Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC, USA

    • C E Bishop

Authors

  1. Search for N M P King in:

  2. Search for C E Bishop in:

Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to N M P King.

About this article

Publication history

Received

Revised

Accepted

Published

DOI

https://doi.org/10.1038/gt.2017.32

Further reading