SMArtCAREFollow-up observation and therapy evaluation in spinal muscular atrophy

The medical data held in the SMArtCARE registry are used for the following purposes:
1) Regulatory requirements by authorities
such as the EMA (European Medicines Agency), the FDA (Food and Drug Administration) or the G-BA (Gemeinsamer Bundesausschuss der Krankenversicherungen und der Leistungserbringer):

• Health Technology Assessment - HTA (evaluation of medical procedures and technologies):

An HTA is intended to examine criteria such as efficacy, safety and costs of a therapy, taking into account social, legal and ethical aspects. The aim of the HTA report is to enable health authorities and health insurers to make conclusive medical decisions in order to clarify health policy issues.

• Application-accompanying data collection (AbDE) according to §35a paragraph 3b SGB V:

With the help of an AbDE commissioned by the G-BA, additional data from health care practice are to be collected in order to better evaluate the benefit or harm of a therapy after (conditional) authorization compared to an existing comparator therapy.

• Post-authorization efficacy study (PAES):

A PAES examines questions about the efficacy of a drug after approval.

• Approval extension

The health benefits, i.e. the efficacy, safety and pharmaceutical quality, of an industrially manufactured drug are tested in an approval procedure. Only drugs approved by the drug authorities may be marketed.
If, after market launch, the pharmaceutical company plans to have the drug administered in a manner other than that described in the expert information, it requires an extension of the approval by the authorities.
2) Reporting side effects to the appropriate manufacturing companies.
Side effects (also called adverse events) are unwanted and harmful reactions to a drug. To monitor drug safety, side effects must be reported to the appropriate authorities or the pharmaceutical manufacturer.
Side effects that occur during or after administration with SMA-specific medications are documented by the treatment center in the SMArtCARE database.
Side effect are reported by your treating physician as follows:

• Gene Therapy (Onasemnogen-Abeparvovec): Paul Ehrlich Institute (PEI)
• Nusinersen and Risdiplam: Federal Institute for Drugs and Medical Devices (BfArM)

Adverse drug reactions are reported by SMArtCARE in pseudonymized form as follows:

• Risdiplam: Roche Pharma AG

As a patient or family member, you also have the right to report side effects that occur in connection with SMA-specific drugs via the corresponding websites of the PEI or the BfArM.

Biogen International GmbH, Neuhofstr. 30, 6340 Baar, Switzerland

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SMA Therapy: Spinraza (active ingredient: nusinersen)

• Health Technology Assessment (HTA):

The purpose of the data analysis in 2020 and 2021 was to obtain additional information on the disease course of SMA type 3 and type 4 neurological patients on Spinraza therapy from the SMArtCARE data collection and other European SMA registries. The overall goal was to better understand the clinical evolution of patients with SMA and to identify factors for successful patient care. To this end, the SMArtCARE data managers provided one-time pseudonymised patient data to the University of Genova, Italy.
The research project has been completed.

Novartis Gene Therapies, Inc, 2275 Half Day Road, Suite 200, Bannockburn, IL 60015, USA

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SMA Therapy: Zolgensma/AVXS-101 (active ingredient: onasemnogene bebeparvovec)

• Application accompanying data collection (AbDE) according to § 35a para. 3b SGB V for the drug Zolgensma from 01/02/2022:

In 2021, Novartis Gene Therapies was commissioned by the G-BA to conduct an AbDE, in which routine data from the SMArtCARE data collection will be used over a period of 5 years to assess the added benefit of Zolgensma compared to the comparator therapy Spinraza (nusinersen). In this context, the independent company IGES will receive pseudonymised data from the SMArtCARE registry in order to perform the data analysis using the G-BA-approved protocol and the Statistical Analysis Plan (SAP). As part of the monitoring process, CSG performs source data verification at the centres. Novartis Gene Therapies will only have insight into the aggregated data of the evaluated question.
Centres wishing to treat their infants and toddlers with 5q associated SMA with Zolgensma were required by the G-BA in 2022 to document the required routine data in the SMArtCARE .
The analyses will be published following the AbDE and will be freely available to all interested parties. 

• Health Technology Assessment (HTA):

In February 2023, SMArtCARE provided one-time anonymized and aggregated patient data of children with SMA type 2 treated with Zolgensma and patients* with symptom onset after 6 months to Novartis Gene Therapies Switzerland GmbH (Suurstoffi 14,6343 Rotkreuz, Switzerland) as part of an HTA evaluation in Italy. Patient data from SMA children without therapy or SMA children with pre-treatment (Risdiplam/Spinraza) were used as comparative data. Novartis Gene Therapies is submitting the analyses to the National Centre for health technology assessment in Italy to expand reimbursement for the drug Zolgensma in Italy. It is expected that data analysis will be completed year 2023.

Roche Pharma AG, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany

Roche Austria GmbH, Engelhorngasse 3, 1211 Vienna, Austria

F. Hoffmann - La Roche Ltd, Grenzacherstrasse 124, 4058 Basel, Switzerland

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SMA Therapy: Evrysdi (active ingredient: risdiplam)

• Application Accompanying Data Collection (AbDE) according to § 35a paragraph 3b SGB V - Risdiplam (spinal muscular atrophy):

The G-BA initiated a procedure in 2021 to require an AbDE for the drug Risdiplam. Roche Pharma AG is thus required to collect and evaluate data for patients with 5q-associated SMA in patients aged 2 months or older, with clinically diagnosed type 1, type 2, or type 3 SMA, or with one to four copies of the SMN2 gene. Data required to perform this analysis is provided by the SMArtCARE registry. AbDE will start in the summer 2024.

• Post-authorization efficacy study (PAES):

The objective of this observational study, commissioned by the EMA and started in May 2023, is to compare the disease course of patients with genetically confirmed 5q-SMA treated with risdiplam versus patients not receiving therapy for SMA. Over an 8-year period, progression of care data from worldwide SMA registries will be collected and analysed. Analysis of the SMArtCARE data will be performed by the independent company Evidera Ltd, based in England, and the data subprocessor PPD Skandinavia, based in Sweden.

OpenApp Consulting Limited, Avoca House, 189 Parnell Street, Dublin 1, Ireland, D01 H578

OpenApp is responsible for the installation, maintenance, monitoring of the SMArtCARE platform and provision of the monitoring tool. Further information about our service provider can be found in our data protection concept.

 

Flying Study Team, Michael Nagel GbR, Freiburg, Germany

If newly initiated centres need support in entering the first SMA patient data into the SMArtCARE database, the ZKS establishes contact between the company Flying Study Team and the centre.

 

CSG- Clinical Studies GmbH (Monitoring), Friedrichstraße 180, 10117 Berlin, Germany

Subsidiary of IGES

Authorized employees of CSG who are bound to secrecy and who have been commissioned by Novartis and the head of data collection in the context of the AbDE according to § 35a para. 3b SGB V for the drug Zolgensma will inspect existing personal data at the participating centres for the purpose of quality assurance and monitoring, as far as this is necessary for the verification of the proper implementation of the AbDE.

 

The following collaborating partners statistically analyse SMA data from the SMArtCARE data collection:

For various requests for statistical data analysis of SMA data using a Statistical Analysis Plan (SAP) accepted by the Head of Data Collection and the Steering Committee, SMArtCARE will forward pseudonymised data to the following third parties:

Academic Research Network within the SMArtCARE Data Collection. 

Each participating centre has the right, if the research idea has been accepted by the governing body and the head of the data collection, to receive data suitable to its research question in anonymized or pseudonymised form for statistical analysis and publication (Publication Requests). Participating centres are required to consult with their lead ethics committee to determine whether an independent vote is required for their research project.

 

Institute for Medical Biometry and Statistics (IMBI), University Medical Centre Freiburg, Stefan-Meier-Strasse 26, 79104 Freiburg, Germany

In addition to the biometrics of the ZKS, the IMBI is responsible for the analyses commissioned by SMArtCARE on scientific questions concerning the follow-up data of SMA patients. These data are published.

 

IGES (Infrastructure and Health) Institute GmbH, Friedrichstraße 180, 10117 Berlin, Germany

On behalf of Novartis Gene Therapies and SMArtCARE, IGES evaluates the pseudonymised data requested in the AbDE for the drug Zolgensma commissioned by the G-BA.

 

Evidera Ltd. (Geschäftsbereich von Pharmaceutical Product Development, LLC (PPD)), The Ark, 201 Talgarth Rd, Hammersmith, London, United Kingdom

PPD Scandinavia (Geschäftsbereich von Pharmaceutical Product Development, LLC), Löfströms alleè 5, 3^rd Floor, Stockholm, Sweden

On behalf of F. Hoffmann - La Roche Ltd. (Roche), the company Evidera and the data sub-processor PPD Skandinavia evaluate patient data requested in the PAE-study for the drug Risiplam commissioned by the EMA. For this purpose, the data are transmitted in pseudonymized form from SMArtCARE data management to the server of PPD Skandinavia, in Sweden. The storage as well as the analysis of the data will take place exclusively in Sweden. Evidera Ltd. will analyze and evaluate the data and prepare and deliver reports with aggregated and anonymized data to the EMA. Roche will only have access to the aggregated data.

 

University of Genova, Italy, Department of Health Research, Via Balbi N. 5, Partita V.A.T./Fiscal Code 00754150100

On behalf of Biogen International GmbH, the University of Genova evaluated one-time pseudonymised SMA data on adult patient populations (SMA type 3 and type 4) from the SMArtCARE data collection and other European SMA registries requested by the G-BA Health Technology Assessment (HTA) evaluation in 2020 and 2021.

Data will be deleted 10 years after study completion. The project has been completed.