regulatory challenges and opportunities for the use of ... · compassionate use is a treatment...
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Regulatory challenges and opportunities for the use of
Real World Evidence for drug registration and labelling
Marianne Bork Samuelsen, Msc Pharm
Regulatory Affairs
Novo Nordisk A/S
Presentation title Date 1
Symposium
Drug Research Academy
14 March 2018
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• “Real-World data” (RWD) is a term used to describe healthcare related data that is collected outside of randomised clinical trials.
• “Real-World Evidence” (RWE) meaning evidence coming from registries, electronic health records (EHRs), and insurance data…..
What is Real-world evidence?
Presentation title Date 2
Real World
Evidence
Real World AnalyticsReal World Data
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Registries and databases
Social media
Electronic Health
Records
Case reports
Non-RCTs
Mobile technologies
Safety surveillance
Scientific communication
Pricing and reimbursement
Marketing claims
Label claims?
Use of RWE
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• Regulatory agencies are more cautious regarding evidence of benefit and would prefer randomised studies, but are beginning to define areas suitable for using RWD
• The decision makers in regulatory agencies, healthcare organisations and healthcare professionals will have increased confidence in using the evidence and insights developed from RWD if there is • confidence in the quality of the data• good understanding of the methodology• consensus on the relevance of the results
Regulatory challenges
Presentation title Date 4
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FDA draft guidance for medical devices
Presentation title Date 5
• FDA recommends use of the pre-submission process when considering the development of a study using RWD in a regulatory submission
• RWE to support a regulatory decision is based on the scientifically robust methods and approaches to determine whether submitted RWE is of sufficient quality to support a particular regulatory decision
• Protocols and analysis plan for RWD should address the same elements that a traditional clinical trial protocol and statistical analysis plan would cover
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• By end 2018: one or more public workshops to gather input into issues related to RWE use in regulatory decision-making
• By end 2019: initiate activities aimed at addressing key outstanding concerns and considerations in the use of RWE for regulatory decision making
• By end 2021: Publish draft guideline on how RWE can contribute to the assessment of safety and effectiveness in regulatory submissions
FDA Performance goals
Presentation title Date 6
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• Challenge move from a high degree of certainty to more of a degree of uncertainty and from structured data, represented by RCT data, to unstructured, unvalidated data of unknown provenance
• Need to address the prospect of cyber-attacks on data
• Senderovitz co-chair of the Heads of Medicines Agencies (HMA) and European Medicines Agency (EMA)’s joint task force on big data
• Assess whether label changes can be based entirely on real world data
Presentation title Date 7
Regulators need to move from ‘comfort zone’ and accept real world data
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• If you intend to use RWE: Engage early for scientific advice• Agree on protocol • Alternative/additional data sources• Data quality • Representativeness for Europe
• Regulatory acceptability of RWE in product development generally more acceptable for • If an RCT is not feasible (time, ethics, rarity) • Hard endpoints (to offset bias) • Conditions with known and predictable progression (note: prospective natural history) • Well thought proposals and trust in their reliability and feasibility
EMA recommendation
Presentation title Date 8
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• EU approval: 23-Feb-1996
• Indication: Treatment of bleeding episodes and prevention of excessive bleeding in connection with surgery in patients with inherited or acquired haemophilia with inhibitors to coagulation factors (FVIII or FIX).
• US approval: 25-Mar-1999
• Indication: Treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII or Factor IX
Example of use of RWE for NovoSeven
Presentation title Date 9
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• 4 patients in the clinical trial were also included in the International Registry as well as six out of 10 published case reports
• Commitment to establish a post-marketing registry of the treatment of patients with Glanzmann’s thrombasthenia.
• In registry: focus on the administered dosage regimens, efficacy and safety
EU – Glanzmann’s thrombasthenia
Presentation title Date 10
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• 4 patients in the clinical trial not enough
• 190 pts primarily from EU, but also from US and elsewhere from the Glanzmann’s Thrombasthenia Registry (GTR)
• 7 pts from Hemophilia & Thrombosis Research Society (HTRS) patient registry
• Published literature
US – Glanzmann’s thrombasthenia
Presentation title Date 11
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• 70 patients with Factor VII deficiency treated with NovoSeven• 32 were enrolled in emergency and compassionate use trials conducted by
Novo Nordisk
• 35 were reported in the published literature
• 3 were from a registry maintained by the Hemophilia and Thrombosis Research Society
Compassionate use is a treatment option that allows the use of an unauthorised medicine. Under strict conditions, products in development can be made available to groups of patients who have a disease with no satisfactory authorised therapies and who cannot enter clinical trials. Only for life-threatening, long-lasting or seriously debilitating illnesses.
EU & US - Congenital Factor VII Deficiency
Presentation title Date 12
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• Data collected from 4 studies in the compassionate use program conducted by Novo Nordisk and the Hemophila and Thrombosis Research Society (HTRS) registry.
• 70 patients with acquired hemophilia were treated with NovoSeven
• 61 patients were from the compassionate use program with 100 bleeding episodes
• 9 patients were from the HTRS registry with 13 bleeding episodes
EU & US - Acquired Hemophilia
Presentation title Date 13
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Update of Summary of Product Characteristics section 4.6 Fertility, pregnancy and lactation
• Meta-analysis of published data on the use in pregnancy
• Additional available clinical data published
• Post-marketing data
• Cumulative summary of exposure reports
since the launch of the product
Lantus - Pregnancy data
Presentation title Date 14
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• Regulatory applications of RWE for drugs could in the future be used for label updates for
• Safety
• Dosing
• Drug-drug interactions
• Sequence of therapies
• Subpopulations
• New indication
Use of RWE in the future
Presentation title Date 15
FutureNEXT EXIT
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• RWE is already used in post-marketing safety surveillance and for price and reimbursement
• RWE can be used to demonstrate efficacy and safety in post-marketing label expansions for products, more common for rare diseases
• Use of RWE for initial Marketing Authorisation applications is uncertain
Summary
Presentation title Date 16