Patient Input Template for CADTH CDR and pCODR Programs
Name of the Drug and Indication Spinraza (nusinersin) for Spinal Muscular Atrophy
Name of the Patient Group Canadian Organization for Rare Disorders and Cure SMA Canada
Author of the Submission Durhane Wong-Rieger and Susi Vander Wyk
Name of the Primary Contact for This Submission Durhane Wong-Rieger
Email durhane@sympatico.ca
Telephone Number 416-969-7435
1. About Your Patient Group
If you have not yet registered with CADTH, describe the purpose of your organization. Include a link to your website.
The Canadian Organization for Rare Disorders is registered charity that provides a strong common voice to advocate for health policy and a healthcare system that works for those with rare disorders. CORD provides education and resources to patient groups to enable them to better meet their members’ needs.
Cure SMA Canada is the national registered charity; supporting families and individuals affected by Spinal Muscular Atrophy from the point of diagnoses, through the life course and even after loss of life. Cure SMA Canada also funds critical Canadian research projects with the aim of affecting accessible treatments for SMA. Cure SMA Canada provides advocacy, information and resources to families, communities and health professionals.
2. Information Gathering
CADTH is interested in hearing from a wide range of patients and caregivers in this patient input submission. Describe how you gathered the perspectives: for example, by interviews, focus groups, or survey; personal experience; or a combination of these. Where possible, include when the data were gathered; if data were gathered in Canada or elsewhere; demographics of the respondents; and how many patients, caregivers, and individuals with experience with the drug in review contributed insights. We will use this background to better understand the context of the perspectives shared.
This submission summarizes the perspectives of individuals, family members, and other caregivers affected by spinal muscular atrophy (SMA) collected through a focus group, semi-structured interviews, and a survey created by the Canadian Organization for Rare Disorders (CORD) in collaboration Cure SMA Canada (CSC). The focus group and interview data provided rich in-depth understanding of the impact of all types of spinal muscular atrophy on the patient, the family, and extended family. The elicited patient experiences and perspectives were also used to develop the survey and, as importantly, provide a context for interpreting and validating the survey results and especially the quantitative analyses. The survey consisted of open-ended questions, rating scales, and forced-choice options. The individual participants were recruited through CSC as well as several localized patient networks. The links to the survey was distributed through the CSC database posted on the CSC website, CSC Facebook and Twitter, with request for secondary distribution to other patients and relatives. The survey was available only in English but responses in French to the open-ended questions were also submitted versions of the survey. They were active on Survey Monkey from 12 June to 7 July 2017.
This submission is based on responses obtained through one focus, four interviews, and 247 survey responses. The focus group included young adult patients and parents. The interviews were conducted with one patient and three parents of children with SMA Type I or II. Of the 247 survey responses, 178 were from patients or immediate family caregivers. (Other respondents were more distant relatives such as grandparents or friends and neighbors.)
While we recognize that SMA is increasingly regarded as a “spectrum” of severity and impact, most patients will have received a diagnosis that includes a “type” of SMA, sometimes with a qualifier as to severity. For the sake of consistency, the survey provided a very brief description of each “type” of SMA and they were asked to indicate which of the four types best described the person they were reporting about. Among the 247 respondents, 15% identified SMA Type I, 60% SMA Type II, 20% SMA Type III, and 1% SMA Type IV, with about 4% responding unsure or other. In terms of relation to SMA, only 12% self-identified as a patient. Most, 44%, were parents or guardians with another 24% identifying as another family member and 2% identified as a nonprofessional caregiver, 2% a professional care provider, 3% a patient advocate. The remaining 10% identified as “friends.” The gender of the person with SMA was almost evenly balanced, with 50% males and 48% females and the remainder choosing not to specify. In terms of age, the largest cohort (37%) were in the range of 5 to 10 years; the second and third cohorts were age range 1 to 5 years (26%) and 18 to 35 years (24%), with only 3% between 35 and 50 years, and 2% over the age of 50.
In terms of residence, 90% of respondents lived in Canada, 8% in the USA, and the remaining 2% in European countries. There was good representation across the provinces, with 23% from Ontario, 21% from BC, 17% each from Quebec and Alberta, 14% from Saskatchewan, another 6% from Manitoba, and 1% each from New Brunswick, Nova Scotia, and PEI.
The subsequent analyses were conducted on the responses from the 178 respondents who self-identified as patients or immediate family caregivers. These included those with Type I, Type II, and Type III. In this group, about 12% had been diagnosed for under 1 year, while 23% had been diagnosed for more than 20 years. The largest cohort (37%) had been diagnosed between 2 and 10 years, while 19% said they were diagnosed between 10 and 20 years ago, and 6% between 1 and 2 years ago. About 3% of the responses were for patients who were no longer living.
3. Disease Experience
CADTH involves clinical experts in every review to explain disease progression and treatment goals. Here we are interested in understanding the illness from a patient’s perspective. Describe how the disease impacts patients’ and caregivers’ day-to-day life and quality of life. Are there any aspects of the illness that are more important to control than others?
Respondents were asked to describe “how the disease impacts” their daily lives or those of their caregivers. Regardless of the type of SMA or the age of diagnosis, a diagnosis of SMA was experienced as “overwhelming”, “devastating”, “cataclysmic, or “just awful.” For parents with a child with SMA Type I, it was apparent almost from birth that there was “something very wrong” based on the limited physical capabilities. “She was never able to lift her head or sit up.” One parent talked about the challenges of getting an accurate diagnosis. “At two months, she was turning blue and had breathing issues. We were sent home from hospital with antibiotics.” Luckily, she was referred to a major hospital where they did a tracheotomy and got a diagnosis at five months. “By that time she had lost a lot of muscle function. She could only slightly wiggle or move her hands; she even lost the ability to smile or frown.” With Type I, swallowing is often difficult. “Due to her lack of strength she required a feeding tube and as she grew…required the use of a ventilator/bipap with oxygen to help her breathe.” Children with Type I may often die as infants or young children by the age of five.
For those with Type II SMA, there is an equally tremendous physical impact. “[She] cannot do anything independently. If she has an itch in the middle of the night, she can’t even scratch it.” “She had been losing function and was finally diagnosed at 18 months. She had lost the ability to sit up; she had never been able to crawl using her arms but was also not eating or napping; nothing could soothe her.”
For those with Type III, the loss of physical function will be later but is no less impactful. “Our daughter has SMA type 3. She is unable to get up by herself, go up or down the stairs or to the bathroom by herself. She can only walk with assistance and is unable to enjoy the playground like all other children. She has difficulty breathing at night and suffers from severe sleep apnea. Her tonsils and adenoids were removed to buy some more time but she will soon need a machine to help her breathe at night.” A parent of an 11-year-old boy with SMA type 3 said, “SMA is a devastating disease no matter the type or age of onset…. He lost the ability to walk and requires a manual wheelchair full time. It’s frustrating and heartbreaking to witness such a wonderful boy suffering from progressing paralysis and muscle atrophy.” The progressive loss of function, in some respects, can be even more challenging psychologically than not having these capabilities in early life. “Although my daughter is somewhat walking, she falls a lot and can’t get up and it is so painful to see your child so frustrated. The other day she fell and cried and with tears in her eye she said ‘mommy I’m broken’…..what do you say to that?”
“The pain/disease have caused my sister to be very depressed. She gets very sad, or angry, and will go days eating barely anything.”
The responses from young adults painted an equally devastating impact as physical capabilities declined. “I am confined to a wheelchair and have limited use of my arms…it is only bound to get worse. As a recent graduate of Mechanical engineering, I am losing my independence at the moment I should be flying from the nest. I will most likely never own a house, have children of my own, etc.”
Obviously, SMA is experienced as a tremendous toll on the whole (extended) family, in terms of time and physical support required, psychological and emotional impact, financial burden, and severe limitations on family and social functions. “The impact socially has been awful, it’s hard to get out of the house, hard to enjoy life.” “It’s has been incredibly hard for our family of 5… When the other kids are home or we are out and hear someone cough Owen is pretty much guaranteed to catch something.”
“We live and breathe SMA daily. I have had to go down in work to 2 days a week. We have a heightened level of anxiety because we fear going out in public in winter months, getting ill, what will happen if we get sick, school unknowns, if we will get the equipment she needs…”
“[Our family was in constant crisis mode awaiting the next time Hannah would need medical intervention. We had a wonderful family and support system yet we were isolated in so many ways. Financially we struggled to acquire deserved insurance coverage monthly, and to acquire the provincial help.”
“Our type 3 child has a manual wheelchair, a dynamic trainer, a scoliosis back brace, daytime orthotics and night time orthotics. He is also in need of a dynamic stander and a manual rigid wheelchair with power assist, an accessible bathroom, a shower wheelchair, a converted accessible van and a hoyer lift. He follows up with an Orthopedic Surgeon, Neurologist, Pulmonologist, Gastroenterologist, Occupational Therapy, Speech Therapist and Physical Therapist. It’s almost impossible to express how frustrating it is that all this intervention is NOT making him better and that we have been unable to treat the root cause of his SMA.”
“The cost financially has been tremendous, each year we have spent $18,000-$20000 out of pocket for expenses which are not covered.”
Respondents were asked to “rate” on a five-point the degree of difficulty experienced with each of five “common” symptoms of SMA (regardless of type). Overall, the action that posed the most difficulty was “walking”, rated by over 90% as “not at all able” to do. The second area of difficulty was “muscle strength” defined as lack of weakness, pain or fatigue; about 12% said they considered they were “not at all” able and another 68% said this was a major problem. About equally difficult were “fine motor skills” and “(deep) breathing, experienced as a “major problem” or “not at all able” by 42% and 41% of respondents, respectively. Finally, only 35% reported “swallowing or feeding” as a major problem or not do-able with 18% indicating it was “not at all” a problem. Clearly, most (if not all) of the patients represented experienced multiple physical challenges that severely limited mobility, required use of mechanical aides, and also required assistance from others to complete daily life activities.
4. Experiences With Currently Available Treatments
CADTH examines the clinical benefit and cost-effectiveness of new drugs compared with currently available treatments. We can use this information to evaluate how well the drug under review might address gaps if current therapies fall short for patients and caregivers.
Describe how well patients and caregivers are managing their illnesses with currently available treatments (please specify treatments). Consider benefits seen, and side effects experienced and their management. Also consider any difficulties accessing treatment (cost, travel to clinic, time off work) and receiving treatment (swallowing pills, infusion lines).
There are, of course, no previous treatments specific to SMA, with most supportive therapies consisting of mechanical aides, rehabilitation services, or supportive medications. When asked whether they had received treatment for SMA, only 34% responded affirmatively while 50% said “no” and 15% responded they were “not sure.” Consequently, only those who indicated they had received treatment went on to complete the questions as to the types of treatment and their effectiveness.
Among respondents, more than 88% used some mobility aides (braces, splints, walker, and/or wheelchair). More than 68% used some breathing support (mask, mouthpiece, ventilation, or tracheotomy), while 55% had spinal treatment (braces, rods, and/or surgery). About one-third had some form of feeding tube or other aide. More than 90% were currently or in the past had received some form of physiotherapy and 45% had received speech or language therapy. More than 45% had received medications such as valproic acid, phenylbutyrate, hydroxyurea, or albuterol.
When asked to rate the effectiveness of the mechanical aides or “treatments”, between 50 and 65% rated them as performing “well” or “very well” in managing the symptoms of SMA, while about 25% said they were not effective. About half said physiotherapy had been effective, while the other half, not so.
When asked to provide “open” comments about treatment effectiveness, most said there were really “no treatments” or they were only managing the symptoms and not really treating the cause of SMA. “There are no effective treatments for SMA. Treatments are limited to dealing with the results of SMA including respiratory support, physio, medication for pain, etc. I would love to see an effective treatment for SMA to help improve the strength and quality of life for people with SMA.”
“Although they have helped improve life it is like putting a bandaid and treating symptoms rather than being proactive and helping to eliminate the progression. Life has so much more to offer and I notice that her fatigue has impacted her quality of life and we are noticing more serious and severe problems arising as she is getting older.”
However some patients (parents) did credit the assistive devices in improving quality of life. “The motorized wheelchair and the kidwalk are pretty new to him but he’s is really enjoying it. We have fought a lot with him the first year to get him used to his Bipap, but now he knows that it is really helping him and his chest isn’t in a bell shape anymore. He is sleeping better. The feeding tube has helped him gain weight. Speech therapy is helping but he still has a lot of work to do with the pronunciation. Physiotherapy has helped him a lot with strength and posture.”
5. Improved Outcomes
CADTH is interested in patients’ views on what outcomes we should consider when evaluating new therapies. What improvements would patients and caregivers like to see in a new treatment that is not achieved in currently available treatments? How might daily life and quality of life for patients, caregivers, and families be different if the new treatment provided those desired improvements? What trade-offs do patients, families, and caregivers consider when choosing therapy?
Given that there have been no treatments for SMA, patients and parents express feelings of despair and near desperation. Parents of an infant with SMA Type I talk about the desire for any treatment that would improve their child’s breathing (fundamental to life), ability to feed, and ability to perform even small movements like rolling over. Parents, especially with Types II and III are looking for an intervention that would improve muscle functioning and slow the progression of the disease, so the child can perform activities independently as much and as long as possible, including self-care (such as feeding, operating a wheelchair, writing or typing). They also want to reduce the pain associated with SMA. For the patients with SMA, slowing progression and maintaining independence are primary goals, including continuing to attend school or to work.
6. Experience With Drug Under Review
CADTH will carefully review the relevant scientific literature and clinical studies. We would like to hear from patients about their individual experiences with the new drug. This can help reviewers better understand how the drug under review meets the needs and preferences of patients, caregivers, and families.
How did patients have access to the drug under review (for example, clinical trials, private insurance)? Compared to any previous therapies patients have used, what were the benefits experienced? What were the disadvantages? How did the benefits and disadvantages impact the lives of patients, caregivers, and families? Consider side effects and if they were tolerated or how they were managed. Was the drug easier to use than previous therapies? If so, how? Are there subgroups of patients within this disease state for whom this drug is particularly helpful? In what ways?
There is a lot of awareness about Spinraza (nusinersin), given that it is the only treatment available for SMA. Among respondents, about 24% responded that they knew about Spinraza and how it is used, with another 34% indicating they knew a lot about the drug. Only 25% said they knew little or nothing about the drug.
In an open-ended question, respondents said they expected (hoped) the therapy would improve overall quality of life, maintain or restore respiratory functions (breathing), retain or restore muscle strength/movement, slow or stop disease progression, and reduce or potentially reverse spinal damage. The hope is that it will prevent symptoms for those newly diagnosed.
Among respondents, 26 said they had received Spinraza through clinical trials, expanded access, compassionate access or other means. All represented patients with SMA Type I or Type II. For infants the responses are primarily parental observations; most speak with enthusiasm and optimism about the experience thus far. “It has made her stronger. Her breathing is also stronger. We think she is less frustrated to be able to reach and do things if she chooses. Difficult to ask a 9 month old.”
One parent provided a concise review of the impact since starting Spinraza. “Spinraza has helped my daughter to become stronger physically both externally and internally. She is able to do things she was unable to do before. She can reach, move her legs more, hold her head while sitting, push her head from side to side on her tummy, and sit with support. She is working on rolling over with assistance as well. Her breathing has gotten stronger and the shape of her chest has become less bell shaped. Her voice is louder and her coughs and sneezes are more effective. She is a much happier baby and is able to explore and play. We have not had increased medical needs for her since we began. It has given her so much more independence. It has also given our family hope for her and a chance at a life. We are so appreciative to have her receiving it.”
“Spinraza has been a miracle for him. He is now holding his head up, rolling from supine to prone, sitting by himself with back support and a couple of minutes without support, lifting his arms and legs up to his head and above, breathing deeply, coughing louder, walking with the kidwalk and using a little manual wheelchair.”
For those with a somewhat older child who have lived through crisis prior to Spinraza, the response is even more positive. “He has more movement while swimming. His voice has gotten stronger. He is eating more. We have recently been through a bad respiratory infection and stomach virus. Both times he got quite a bit weaker and afterwards his strength came back as well as a little bit more. This would be unheard of [when] he wasn’t on Spinraza! We feel better about the future and feel like he will continue to gain little bits of strength. We aren’t as worried when he gets sick.”
Similar observations were offered by other parents
“He is now able to stand assisted (and briefly unassisted) with AFO’s and we are working on getting him comfortable and strong enough to be able to use crutched or a walker. He is less sick and often heals quickly when ill. His overall stamina is better…”
“She is able to clap louder now. She is able to play on a grand piano compared to a keyboard before. She is able to turn a doorknob and open a door. She is gaining confidence. She has more energy in the day.”
When asked to comment on adverse (side) effects, most parents indicated there were very few, especially in response to the drug itself and some related to the administration (though surprisingly few given the invasive nature of the procedure). “Our son has had no side effects from Spinraza.” “We have not experienced any!” “After the first dose, she had a headache for 5 days, and vomiting for 1 day. This was because the nurse sat her up too soon and she had been fasting for too long as the dose was given in the late afternoon. For her last 5 injections, there have been no complications in terms of side effects.”
“We have experienced side effects associated with the lumbar puncture. We have not experienced side effects from the drug itself.” “Now she is receiving the drug at BC Children’s and they don’t give the anaesthetic gas [that she was getting at the London Clinic] so she has the poke when she is awake. She screamed her head off and didn’t want to do it. Now, with the sedation, it is okay.”
7. Companion Diagnostic Test
If the drug in review has a companion diagnostic, please comment. Companion diagnostics are laboratory tests that provide information essential for the safe and effective use of particular therapeutic drugs. They work by detecting specific biomarkers that predict more favourable responses to certain drugs. In practice, companion diagnostics can identify patients who are likely to benefit or experience harms from particular therapies, or monitor clinical responses to optimally guide treatment adjustments.
What are patient and caregiver experiences with the biomarker testing (companion diagnostic) associated with regarding the drug under review?
Consider:
• Access to testing: for example, proximity to testing facility, availability of appointment.
• Testing: for example, how was the test done? Did testing delay the treatment from beginning? Were there any adverse effects associated with testing?
• Cost of testing: Who paid for testing? If the cost was out of pocket, what was the impact of having to pay? Were there travel costs involved?
• How patients and caregivers feel about testing: for example, understanding why the test happened, coping with anxiety while waiting for the test result, uncertainty about making a decision given the test result.
We are not aware of any specific companion diagnostic tests to determine response to the therapy.
8. Biosimilar
If the drug in review is a biosimilar (also known as a subsequent entry biologic), please outline any expectations or concerns held by patients, caregivers, and families about the biosimilar. If the biosimilar was less expensive than the brand name drug, what would the impact be for patients, caregivers, and families?
9. Anything Else?
Is there anything else specifically related to this drug review that CADTH reviewers or the expert committee should know?
Most parents (and patients) are aware that Spinraza is approved for all types of SMA but has been clinically tested primarily in those with Types I and II. However, given that the disease is progressive and (eventually) has a severe debilitating impact on individuals with all types, there is a strong opinion that the drug should be available for all patients with SMA regardless of type. When asked, 100% of respondents said the drug was “very important” and should be available to all. “Spinraza is our only proven treatment that can not only save our kids’ lives, but *improve* them.”
Given the progressive nature of the disease, there is also a strong sense of urgency. “We need to get it to SMA patients ASAP before they get any weaker.” “We lost 2 babies in our city this last year. Every death hits our community so hard, especially knowing that there is a treatment that works so close to us, but not available to us.”
Appendix (A): Patient Group Conflict of Interest Declaration
To maintain the objectivity and credibility of the CADTH CDR and pCODR programs, all participants in the drug review processes must disclose any real, potential, or perceived conflicts of interest. This Patient Group Conflict of Interest Declaration is required for participation. Declarations made do not negate or preclude the use of the patient group input. CADTH may contact your group with further questions, as needed.
1. Did you receive help from outside your patient group to complete this submission? If yes, please detail the help and who provided it.
No outside help was provided. CORD and Cure SMA Canada collaborated to perform the background research, conduct the interviews, prepare the survey, analyze the data, and prepare the submission.
2. Did you receive help from outside your patient group to collect or analyze data used in this submission? If yes, please detail the help and who provided it.
See above.
3. List any companies or organizations that have provided your group with financial payment over the past two years AND who may have direct or indirect interest in the drug under review.
Company Check Appropriate Dollar Range
$0 to 5,000 $5,001 to 10,000 $10,001 to 50,000 In Excess of $50,000
Biogen X
I hereby certify that I have the authority to disclose all relevant information with respect to any matter involving this patient group with a company, organization, or entity that may place this patient group in a real, potential, or perceived conflict of interest situation.
Name: Durhane Wong-Rieger
Position: President & CEO
Patient Group: Canadian Organization for Rare Disorders
Date: 19 July 2017
Appendix (B): Patient Group Conflict of Interest Declaration
To maintain the objectivity and credibility of the CADTH CDR and pCODR programs, all participants in the drug review processes must disclose any real, potential, or perceived conflicts of interest. This Patient Group Conflict of Interest Declaration is required for participation. Declarations made do not negate or preclude the use of the patient group input. CADTH may contact your group with further questions, as needed.
4. Did you receive help from outside your patient group to complete this submission? If yes, please detail the help and who provided it.
No outside help was provided. CORD and Cure SMA Canada collaborated to perform the background research, conduct the interviews, prepare the survey, analyze the data, and prepare the submission.
5. Did you receive help from outside your patient group to collect or analyze data used in this submission? If yes, please detail the help and who provided it.
See above.
6. List any companies or organizations that have provided your group with financial payment over the past two years AND who may have direct or indirect interest in the drug under review.
Company Check Appropriate Dollar Range
$0 to 5,000 $5,001 to 10,000 $10,001 to 50,000 In Excess of $50,000
I hereby certify that I have the authority to disclose all relevant information with respect to any matter involving this patient group with a company, organization, or entity that may place this patient group in a real, potential, or perceived conflict of interest situation.
Name: Susi Vander Wyk
Position: Executive Director
Patient Group: Cure SMA Canada
Date: July 19, 2017