1| TREAT-NMD

Current landscape of TREAT-NMD SMA registries

TREAT-NMD Alliance

Biogen SMA Registry Development Meeting Amsterdam

8th -9th May 2017

Professor Hugh DawkinsData Steward, Australian Neuromuscular Diseases Registry (ANMDR) Chair, ANMDR Advisory GroupPast Chair, TREAT-NMD Global Data Oversight CommitteeMember, TREAT-NMD Alliance Executive Committee

2| TREAT-NMD

Take home message• TREAT-NMD funded under FP6 to accelerate clinical trials

into NMD through trial ready patient registries • A global network of national registries that has successfully

helped Pharma and Biotech companies trial design and recruitment

• Embodies a culture of trust that works transparently with patients, industry, clinicians, academics using privacy preserving approaches for NMD familes to access best care

• Has the infrastructure and proven track record to be able to help Pharma and Biotech meet regulatory requirements of post marketing jurisdictionally and internationally.

3| TREAT-NMD

BioBank

Patient Registries

Care & Trial Site Registry

Outcome Measures

Standards ofDiagnosis &

CareTACT

Website & Communications

Joint Research

Standard Operating

Procedures

Threeyearworkplan

www.treat-nmd.eu

ActionPlan

3yearplan

Milestone-drivenapproach

Maintainsnetworkmomentum&establishnew

goals

Website&Communication

Extensivewebsite

250,000annualpagehits

70,000visitorsannually

Monthlynewslettersentto3,500recipients

Provencommunicationplatform

Secretariat- KateBushbyVolkerStraub

Funding– EC(operatinggrant)

TACT

TREAT-NMDAdvisoryCommitteeforTherapeutics,

Expertmultidisciplinarybody

Independentandobjectiveguidanceonadvancingnewtherapiesforneuromuscular

diseases

Chair– DominicWells

Funding- US(Dept ofDefense)

Jointresearch

Regularmeetingstoconsolidateeffortsandjointlytacklecommon

problems

Topicsbasedonnecessity,hostingtoberotated

betweenpartners

Leads- EricHoffmanAnnemieke Aartsma-Rus

FilippoBuccella

Funding- COST

SOPs

Unifiedexperimentalprotocolsimprovethe

comparabilityofstudies

Drawnupbyagroupofindependentresearchers(listedineachprotocol)

Approx 40sopsupdatedregularly

EuroBioBank

Uniquenetworkof18members

Stores&distributes440,000qualityDNA,cellandtissue

samples

Leads- MarinaMoraLuciaMonacoMarcoCrimi

Funding- FondazioneTelethon

PatientRegistries

Standardizedgenetic&clinicalcoredatafortrial

recruitment

Interfacecanvarybetweencountrieswhilststillableto

sharecoredata

Ethical&governancebestpractice

>10,000DMDpatientsacross30countries

Chair - NathalieGoemansViceChair- CraigCampbellPastChair-HughDawkins

Funding- AFM&EC(operatinggrant)

Care&TrialSiteRegistry

Informationabouteachregisteredtrialsitekeptinonelocationforeaseof

comparison

Addressesorganisationaldifficultiesofidentifyingappropriatesiteswhen

settingupatrial

CoordinatedbyUniversityMedicalCenter Freiburg

Outcomemeasures

Teststodecidewhethertreatmentbeingtestedina

trialishavinganyeffect

Vitaltousethecorrectoutcomemeasuretoproveif

atreatmentworks

Workingtoharmonisetheuseofmostappropriateoutcomemeasuresfor

differentdiseases

Lead- EugenioMercuri

Funding- Telethon&ParentOrganizations

StandardsofDiagnosis&Care

Internationalconsensuspublicationrecommended

standardsofcare

DMD-SMA-CMD-LGMD

Familyguidesin25differentlanguages

translationsverified

Printedbookletsordownloadfromwebsite

Leads- ThomasSejersenKathyNorth

2007-2011EUfundedNetwork

2012onwardsAlliancefunded

throughmultiplestreamswithglobal

partners&membership

GovernanceChair– KevinFlanigan

PastChair– AnnemiekeAartsma-Rus

ExecutiveCommitteeSupportedbyacademicadvisory

board(“taskforce”)ofNMDleaders

HowdoestheGlobalRegistrywork?

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

ClinicianEntered PatientEntered

Oracombination

NationalSMA/DMDregistry

GlobalRegistry

HighlyEncourageditems

GlobalRegistrySteroid

status

Cardiacmedication

use

Gastric/nasalfeeding

PersonalDataSex,Name,contact,

DOB

Involvementinclinicaltrials

GeneticTestResultsMutationname

followingHGVSrules

Clinicaldiagnosis

WheelchairUse

AmbulationStatus/

Bestmotorfunction

ScoliosisSurgery

PersonalDataSex,Name,contact,DOB

Involvementinclinicaltrials

GeneticTestResultsMutationname

followingHGVSrules

Clinicaldiagnosis

WheelchairUse

AmbulationStatus/

Bestmotorfunction

ScoliosisSurgery

FamilyHistory

PulmonaryFunction

VentilationStatus

SMAClassification

SMN2Copies

Otherregistry

CardiacVentilationStatus/

Pulmonary

FamilyHistory

Sittingwithoutsupport

MuscleBiopsy

Otherregistry

DMDMandatory SMAMandatory

GlobalSMARegistry

SMA

AllNMD DevelopingallNMD

DevelopingSMA

48nationalSMAregistries

EuropeanSMARegistry

SMA

AllNMD DevelopingallNMD

DevelopingSMA

Globalregistryenquiries

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

NationalSMA/DMDregistry

GlobalRegistry

TREAT-NMDrequestsData

NationalregistryreturnsData

Enquiryreceivedfromindustryoracademia

TGDOCVote

9| TREAT-NMD

An example from the global SMA registry – Feasibility Enquiry

10| TREAT-NMD

Registries audit: 2016/2017TREAT-NMD Alliance

11| TREAT-NMD

Mandatory Data items54 registries completed the audit

12| TREAT-NMD

Highly encouraged data items

SMA

13| TREAT-NMD

49%

17%

14%

10%

6%4%

Excel / Access Custom Other RDRF REDCAP Alta voice

Which IT System is used?-across all registries

14| TREAT-NMD

• 30 registries• 3 were from All Neuromuscular

SMA respondents

SMA-Countrieswhoresponded

BelgiumNetherlandsSwitzerlandDenmarkUKFinlandGermanyAustria

BulgariaCzechRepublicMacedoniaRussiaUkraine

PolandCroatiaSerbiaSloveniaHungary

ArgentinaColumbiaBrazil

Mexico

Canada

China

Egypt

India

AustraliaNew Zealand

TurkeyAlgeria

16| TREAT-NMD

What type of organisation runs the National SMA registry?

Medical 8

Academic 7

Patient Organisation (PO) 5

Academic & Medical 3

Academic, Medical & PO 3

Institute of public Health 1

Medical, PO & genetic lab 1

Genetic Lab 1

Did not specify 1Total 30

0

1

2

3

4

5

6

7

8

9

Medical Academic Patient Organisation

(PO)

Academic & Medical

Academic, Medical & PO

Institute of public Health

Medical, PO & genetic lab

Genetic Lab Did not specify

17| TREAT-NMD

Who enters the data? SMA

Patients only 2Patients and professionals 2Professionals only 24No response 2

Total 30

6%

7%

80%

7%

Who enters the data?

Patients only Patients and professionals Professionals only No response

18| TREAT-NMD

17 SMA registries collect additional data…

Age, type and complication of steroids, scoliosis (yes/no), loss of gait, densitometría osea, fractures, Bifosfonatos, additional diagnosis, carrier study of the mother

Activlim scale, for all neuromuscular diseases

Ambulation status, wheelchair use, steroid intake

Living status (living independently, with a parent etc.); age at onset; first symptoms; diagnosis (nerve biopsy, muscle biopsy, EMG, clinical, genetic test), upper extremity function, tissue samples provided (type and lab location), airway interventions (cough assist, breath stacking, chest physiotherapy, oral suctioning and frequency of use), sociodemographic, community servicesCreatine kinase, etc

Quality of life questionnaire

SMA: QOL DMD: QOL DM: Epworth, SF MPQ (pain), pain localizer, SF36, I-PSS urinary symptoms, depression scale FSHD: Epworth, SF MPQ (pain), pain localizer, SF36, depression scale

Yes did not specify

Yes did not specify

A unique patient identifier called NHI

Demographic data

Patients asked to fill out questionnaire regarding their: underwent therapies, different diagnostic procedures

Cognitive status in DMD and SMA

Gastroenterological items, endocrinological items, bone densityDMD: age at diagnosis, age at first signs, familiy history, first CK, age at sitting/walking, diagnostic circumstances, age at scoliosis and surgery, treatment (pharmacologic and physical therapy), weight, genetic. SMA: approximatively the sameFor research base quality of life

Surgery, scoliosis, age of milestones of functions, exon deletions in 7, 8, 5, taking part in CTs

19| TREAT-NMD

Other info (SMA) • All but 2 (India and Algeria) ask for patient consent• All but 2 update the data at least annually• 19 use Microsoft software (Excel 16) (Access 3)• The only other common systems are is REDcap (3) and

RDRF (2)