Ethical Challenges Confronted When Providing Nusinersen Treatment for Spinal Muscular Atrophy

Burgart, Alyssa M.; Magnus, David; Tabor, Holly K.; Paquette, Erin Daksha Talati; Frader, Joel; Glover, Jacqueline J.; Jackson, Brian M.; Harrison, Charlotte H.; Urion, David K.; Graham, Robert J.; Brandsema, John F.; Feudtner, Chris

doi:10.1001/jamapediatrics.2017.4409

Cited by 54 publications

(44 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, clinicians and ethicists have been engaging in the medical and bioethics literature about the ethical challenges associated with providing nusinersen in the USA. Notwithstanding variations between the American and Canadian health‐care systems, ethical challenges highlighted by Burgart and colleagues, associated with cost, limited evidence, informed consent, treatment allocation, fair geographic distribution of treatment centres, transparency and stakeholder engagement, are similarly relevant. Assistance in the Canadian context may come from values entrenched in relevant federal and provincial legislation and additional values‐grounded expressions of stakeholder deliberation and processes .…”

Section: Ethical Considerations Of Nusinersen Therapy For the Treatmementioning

confidence: 99%

Putting our best foot forward: Clinical, treatment‐based and ethical considerations of nusinersen therapy in Canada for spinal muscular atrophy

Vukovic

McAdam

Zlotnik-Shaul

et al. 2018

J Paediatrics Child Health

View full text Add to dashboard Cite

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is a spectral disorder and is categorised based on symptom onset and severity. The median life expectancy for infants with SMA presenting before 6 months of age is less than 2 years without respiratory support. To date, there is no cure for SMA. In June 2017, nusinersen was approved in Canada as the first disease-modifying drug for SMA because of its demonstrated benefits on motor function and survival in clinical trials. However, with a price tag of almost 1 million dollars for the first year of therapy, careful clinical, treatment-based and ethical consideration of the principles of (i) best interests; (ii) universality; (iii) portability; (iv) public administration; (v) accessibility; and (vi) comprehensiveness are important guideposts to ensure transparent and equitable allocation of health-care resources for nusinersen and all other future orphan drugs.Nusinersen is a modified antisense oligonucleotide that prevents nucleases from binding at a specific sequence on SMN2 premessenger RNA, thus promoting exon retention. More specifically, exon 7 of the SMN2 pre-messenger RNA is retained. As a result, full-length, functional SMN protein is produced. 5,6

show abstract

Section: Ethical Considerations Of Nusinersen Therapy For the Treatmementioning

confidence: 99%

Putting our best foot forward: Clinical, treatment‐based and ethical considerations of nusinersen therapy in Canada for spinal muscular atrophy

Vukovic

McAdam

Zlotnik-Shaul

et al. 2018

J Paediatrics Child Health

View full text Add to dashboard Cite

show abstract

“…Sometimes it may just be impossible to know. Moreover, the launch of Nusinersen for SMA raised several medical concerns[46]. First, the primary outcome of the ENDEAR trial, which led to the authorization of the drug, was changed while the study was ongoing[47,48].…”

Section: Case Discussion #3mentioning

confidence: 99%

“…Based on the result of the ENDEAR trial and on other uncontrolled trials, Nusinersen was granted marketing authority for all types of SMA. However, the achievements shown in ENDEAR were not as clearly proven for all types of the disease and at any age[46]. Secondly, whilst the proof of efficacy of the drug was obtained in subjects with SMA1 who were younger than 6 mo old at the time Nusinersen was first administered, the drug had been approved for all types of the disease.…”

Section: Case Discussion #3mentioning

confidence: 99%

Innovation for rare diseases and bioethical concerns: A thin thread between medical progress and suffering

Tommasini

Magnolato

Bruno

2018

WJCP

View full text Add to dashboard Cite

With the development of precision medicines based on small molecules, antibodies, RNAs and gene therapy, technological innovation is providing some exciting possibilities to treat the most severe genetic diseases. However, these treatments do not always lead to a cure for the disease, and there are several factors that may hinder their overall success. Patients living during a period of great medical change and innovation may benefit from these technological advances but may also just face failures, both in terms of frustrated hopes as well as suffering. In this article, we are telling the stories of three children with rare and severe disorders, who live in an age of significant medical changes, bearing the burden of difficult scientific and ethical choices. The first two cases that are suffering respectively from severe immunodeficiency and beta thalassemia have already been described in scientific journals, as well as in popular magazines. Although similar when considering the medical challenges, the two cases had opposite outcomes, which resulted in distinct ethical implications. The third case is a baby with spinal muscular atrophy, living at a time of continued innovation in the treatment of the disease. With these cases, we discuss the challenges of providing correct information and proper counseling to families and patients that are making the bumpy journey on the road of medical innovation.

show abstract

“…Because it is administered intrathecally, limited numbers of facilities and clinicians can safely administer the drug and provide follow up care. 14,15 The astronomical cost of $370 000 per year for life (after $750 000 in the first year) is insurmountable for many, especially since insurance coverage seems to vary by region, insurance company, and individual symptom profiles. 14,15 There are several other innovative SMA therapies in the drug development pipeline, 16 and consequently patients and clinicians are unclear about what advice to take or to give about the relative benefits and risks of as yet unproven alternatives that might be even more "precise."…”

Section: Precise Interventions Might Exacerbate Health Disparities Anmentioning

confidence: 99%

“…14,15 The astronomical cost of $370 000 per year for life (after $750 000 in the first year) is insurmountable for many, especially since insurance coverage seems to vary by region, insurance company, and individual symptom profiles. 14,15 There are several other innovative SMA therapies in the drug development pipeline, 16 and consequently patients and clinicians are unclear about what advice to take or to give about the relative benefits and risks of as yet unproven alternatives that might be even more "precise." Treatment with nusinersen for SMA is just one of several recent examples of innovative targeted and precise therapies based on genetic diagnosis that have had implications for patients beyond effectiveness.…”

Section: Precise Interventions Might Exacerbate Health Disparities Anmentioning

confidence: 99%

What Precision Medicine Can Learn from Rare Genetic Disease Research and Translation

Tabor

Goldenberg

2018

AMA Journal of Ethics

View full text Add to dashboard Cite

The goal of this article is to examine the intersections of precision health and rare diseases. Specifically, we propose 3 lessons from the last decade of applying genomics to rare diseases: (1) precision can end one odyssey and start another;(2) precise interventions can exacerbate health disparities and create other ethical dilemmas; and (3) democratization of data will transform research and translation. By studying experiences of patients with rare diseases, researchers, clinicians, and policymakers can anticipate similar challenges in precision medicine and hopefully mitigate potential harms or injustices. Rare Diseases and Precision MedicineMore than 25 million Americans suffer from one of over 7000 rare conditions, 1 each one of which has an incidence of 1 in 200 000 or less. The rarity of these conditions creates challenges, such as convincing agencies and companies to fund development of effective and affordable treatments, provide programmatic support, and facilitate patient interaction and support opportunities. content/uploads/2018/03/ALK-Positive_Outreach-Update_20180315.pdf. Published March 15, 2018. Accessed March 26, 2018. 23. Arbour KC, Riely GJ. Diagnosis and treatment of anaplastic lymphoma kinasepositive non-small cell lung cancer.

show abstract

Ethical Challenges Confronted When Providing Nusinersen Treatment for Spinal Muscular Atrophy

Cited by 54 publications

References 39 publications

Putting our best foot forward: Clinical, treatment‐based and ethical considerations of nusinersen therapy in Canada for spinal muscular atrophy

Putting our best foot forward: Clinical, treatment‐based and ethical considerations of nusinersen therapy in Canada for spinal muscular atrophy

Innovation for rare diseases and bioethical concerns: A thin thread between medical progress and suffering

What Precision Medicine Can Learn from Rare Genetic Disease Research and Translation

Contact Info

Product

Resources

About