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Evaluating Benefit-risk Decision-making in Spinal Muscular Atrophy: A First-ever Study to Assess Risk Tolerance in the SMA Patient Community

Published on May 1, 2019in Clinical Therapeutics2.94
· DOI :10.1016/j.clinthera.2019.03.012
Rosangel Cruz4
Estimated H-index: 4
,
Lisa Belter + 2 AuthorsJill Jarecki7
Estimated H-index: 7
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Abstract
Abstract Purpose Patients’ perceptions of benefit–risk are essential to informing the regulatory process and the context in which potential therapies are evaluated. To bring this critical information to regulators, Cure SMA launched a first-ever Benefit-Risk Survey for spinal muscular atrophy (SMA) to characterize decision-making and benefit–risk trade-offs in SMA associated with a potential therapy. We hypothesized that risk tolerance would be correlated with SMA type/severity and disease progression. This article presents the results of a benefit–risk survey to enhance understanding of how patients with SMA and caregivers evaluate specific benefits and risks associated with potential therapies. Methods Affected adults, representing all SMA types (I–IV) within the Cure SMA database, and caregivers of affected individuals of all ages/types were invited via e-mail to participate. Best–worst scaling (BWS) was used to assess participants’ priorities on benefit–risk trade-offs, as it provides higher discrimination and importance scaling among tested attributes. Twelve potentially clinically meaningful treatment benefits and 11 potential risks (ranging in severity and immediacy) were tested. Multiple factors were correlated with individual responses, including: SMA type/disease severity, stage of disease, respondent type, sex, and quality of life/level of independence (current and expected). Survey respondents were also evaluated for "risk-taking attitudes." Findings A total of 298 responses were evaluated (28% affected adults and 72% caregivers, mostly parents). Most respondents were diagnosed >5 years ago (67.3%), with 22.1% SMA type I, 45.6% SMA type II, and 27.9% SMA type III. No strong correlation was found between risk tolerance and SMA type, stage of disease progression, respondent type, sex, quality of life assessment, or rated levels of independence. Irrespective of SMA type, respondents consistently rated the following risks, associated with a potential treatment, as "least tolerable": life-threatening allergic reactions; 1 in 1000 risk of life-threatening side effects leading to possible organ failure; or worsening quality of life. Furthermore, all SMA type respondents rated these risks as "most tolerable": invasive mode of treatment administration (including need for general anesthesia); side effect of dizziness; and other common side effects such as nausea, vomiting, loss of appetite, headaches, back pain, or fatigue. Implications With the approval of the first SMA treatment, these findings offer a unique opportunity to assess and characterize baseline risk-tolerance in SMA against which to evaluate future SMA treatment options. Although differences had been expected in risk tolerance among respondents based on disease baseline and certain patient attributes, this was not observed. Survey results should inform future SMA drug development and benefit–risk assessments.
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References51
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Published on May 29, 2018in Journal of neuromuscular diseases
Jacqueline J. Glascock10
Estimated H-index: 10
,
Jacinda B. Sampson16
Estimated H-index: 16
(Stanford University)
+ 12 AuthorsNancy L. Kuntz24
Estimated H-index: 24
(Children's Memorial Hospital)
Published on Feb 15, 2018in The New England Journal of Medicine70.67
Eugenio Mercuri67
Estimated H-index: 67
(UCSC: Catholic University of the Sacred Heart),
Basil T. Darras40
Estimated H-index: 40
(Harvard University)
+ 20 AuthorsKayoko Saito2
Estimated H-index: 2
Abstract Background Nusinersen is an antisense oligonucleotide drug that modulates pre–messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). Methods We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at...
Published on Dec 1, 2017in Orphanet Journal of Rare Diseases3.69
Cathy Lally11
Estimated H-index: 11
(Emory University),
Cynthia C. Jones3
Estimated H-index: 3
(Biogen Idec)
+ 3 AuthorsW. Dana Flanders3
Estimated H-index: 3
(Emory University)
Background Spinal muscular atrophy (SMA) is a progressive, devastating disease and a leading inherited cause of infant mortality. The limited population-based literature is confined to small regional studies. Estimates of prevalence are needed to characterize the burden of SMA and to understand trends in prevalence by disease type as new treatments become available. The reported estimates of SMA genotype prevalence at birth consistently range from 8.5–10.3 per 100,000 live births, with a mid-ran...
Published on Dec 1, 2017in Orphanet Journal of Rare Diseases3.69
Ingrid E.C. Verhaart10
Estimated H-index: 10
(Newcastle University),
Agata Robertson4
Estimated H-index: 4
(Newcastle University)
+ 5 AuthorsHanns Lochmüller68
Estimated H-index: 68
(Newcastle University)
Spinal muscular atrophy linked to chromosome 5q (SMA) is a recessive, progressive, neuromuscular disorder caused by bi-allelic mutations in the SMN1 gene, resulting in motor neuron degeneration and variable presentation in relation to onset and severity. A prevalence of approximately 1–2 per 100,000 persons and incidence around 1 in 10,000 live births have been estimated with SMA type I accounting for around 60% of all cases. Since SMA is a relatively rare condition, studies of its prevalence an...
Published on Dec 1, 2017in BMC Neurology2.23
Sarah McGraw2
Estimated H-index: 2
,
Ying Qian2
Estimated H-index: 2
+ 3 AuthorsWei-Shi Yeh1
Estimated H-index: 1
(Biogen Idec)
Abstract Background This qualitative study examined how individuals with Spinal Muscular Atrophy (SMA), their caregivers, and clinicians defined meaningful change, primarily in the Type II and non-ambulant type III patient populations, associated with treatment of this condition. In addition, we explored participants’ views about two measures of motor function routinely used in clinical trials for these SMA subtypes, namely the expanded version of the Hammersmith Functional Motor Scale (HFMSE) a...
Published on Dec 1, 2017in BMC Neurology2.23
Maria Carmela Pera10
Estimated H-index: 10
(CUA: The Catholic University of America),
Giorgia Coratti7
Estimated H-index: 7
(CUA: The Catholic University of America)
+ 26 AuthorsMaria Sframeli11
Estimated H-index: 11
(UNIME: University of Messina)
Abstract Background Reports on the clinical meaningfulness of outcome measures in spinal muscular atrophy (SMA) are rare. In this two-part study, our aim was to explore patients’ and caregivers’ views on the clinical relevance of the Hammersmith Functional Motor Scale Expanded- (HFMSE). Methods First, we used focus groups including SMA patients and caregivers to explore their views on the clinical relevance of the individual activities included in the HFMSE. Then we asked caregivers to comment o...
Published on Nov 2, 2017in The New England Journal of Medicine70.67
Richard S. Finkel35
Estimated H-index: 35
(Nemours Foundation),
Eugenio Mercuri67
Estimated H-index: 67
(UCSC: Catholic University of the Sacred Heart)
+ 395 AuthorsEduardo F. Tizzano20
Estimated H-index: 20
(Autonomous University of Barcelona)
BackgroundSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. MethodsWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primar...
Published on Nov 1, 2017in Neuromuscular Disorders2.61
Richard S. Finkel35
Estimated H-index: 35
(UCF: University of Central Florida),
Eugenio Mercuri67
Estimated H-index: 67
(UCSC: Catholic University of the Sacred Heart)
+ 19 AuthorsSimon Woods13
Estimated H-index: 13
(Newcastle University)
Abstract This is the second half of a two-part document updating the standard of care recommendations for spinal muscular atrophy published in 2007. This part includes updated recommendations on pulmonary management and acute care issues, and topics that have emerged in the last few years such as other organ involvement in the severe forms of spinal muscular atrophy and the role of medications. Ethical issues and the choice of palliative versus supportive care are also addressed. These recommend...
Published on Nov 1, 2017in Neuromuscular Disorders2.61
Eugenio Mercuri67
Estimated H-index: 67
(CUA: The Catholic University of America),
Richard S. Finkel35
Estimated H-index: 35
(UCF: University of Central Florida)
+ 60 AuthorsSusana Quijano-Roy33
Estimated H-index: 33
(French Institute of Health and Medical Research)
Abstract Spinal muscular atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 ( SMN1 ) gene. Its incidence is approximately 1 in 11,000 live births. In 2007, an International Conference on the Standard of Care for SMA published a consensus statement on SMA standard of care that has been widely used throughout the world. Here we report a two-part update of the topics covered in the previous recommendations. In part 1 we present the methods used to achiev...
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