Regulatory challenges and opportunities for the use of Real World Evidence for drug registration and labelling

Transcription

1 Presentation title Date 1 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 Symposium Drug Research Academy 14 March 2018

2 Presentation title Date 2 What is Real-world evidence? 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.. Real World Data Real World Analytics Real World Evidence

3 Use of RWE Registries and databases Social media Electronic Health Records Case reports Non-RCTs Safety surveillance Scientific communication Pricing and reimbursement Marketing claims Label claims? Mobile technologies

4 Presentation title Date 4 Regulatory challenges 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

5 Presentation title Date 5 FDA draft guidance for medical devices FDA recommends use of the pre-submission process when considering the development of a study using RWD in a regulatory submission RWE to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

6 Presentation title Date 6 FDA Performance goals 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

7 Presentation title Date 7 Regulators need to move from comfort zone and accept real world data 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

8 Presentation title Date 8 EMA recommendation 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

9 Presentation title Date 9 Example of use of RWE for NovoSeven 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

10 Presentation title Date 10 EU Glanzmann s thrombasthenia 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

11 Presentation title Date 11 US Glanzmann s thrombasthenia 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

12 Presentation title Date 12 EU & US - Congenital Factor VII Deficiency 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, longlasting or seriously debilitating illnesses.

13 Presentation title Date 13 EU & US - Acquired Hemophilia 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

14 Presentation title Date 14 Lantus - Pregnancy data 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

15 Presentation title Date 15 Use of RWE in the future 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 Future NEXT EXIT

16 Presentation title Date 16 Summary RWE is already used in post-marketing safety surveillance and for price and reimbursement RWE can be used to demonstrate efficacy and safety in postmarketing label expansions for products, more common for rare diseases Use of RWE for initial Marketing Authorisation applications is uncertain