EUnetHTA Joint Action 3 WP4 “Rolling Collaborative Review” of Covid-19 treatments INTERFERON (IFN) AND NOVAFERON (NOVA) FOR THE TREATMENT OF COVID -19 Project ID: RCR13 Monitoring Report Version 4.0, December 2020 Template version November 2020 This Rolling Collaborative Review Living Document is part of the project / joint action ‘724130 / EUnetHTA JA3’ which has received funding from the European Union’s Health Programme (2014-2020) Dec2015 ©EUnetHTA, 2015. Reproduction is authorised provided EUnetHTA is explicitly acknowledged 1 Rolling Collaborative Review - Living Report RCR13 - Interferon beta-1a (IFN β-1a) and Novaferon (Nova) for the treatment of COVID-19 DOCUMENT HISTORY AND CONTRIBUTORS Version Date Description of changes V 0.1 01/09/2020 Literature searches, Literature screening, Data extraction V 0.2 02/09/2020 Data extraction and analysis complete V 0.3 03/09/2020 Check of data extraction and analysis V 1.0 15/09/2020 First version V 1.1 28/09/2020 Literature searches, Literature screening, Data extraction V 1.2 01/10/2020 Data extraction and analysis complete V 1.3 12/10/2020 Check of data extraction and analysis V 2.0 15/10/2020 Second version V 3.0 15/11/2020 Third version V 4.0 15/12/2020 Fourth version Major changes from previous version Chapter, page no. Major changes from version 3.0 Effectiveness and Safety evidence from Additional studies included RCTs, p.11 Ongoing studies, p. 12 Additional trials included Disclaimer The content of this “Rolling Collaborative Review” (RCR) represents a consolidated view based on the consensus within the Authoring Team; it cannot be considered to reflect the views of the European Network for Health Technology Assessment (EUnetHTA), EUnetHTA’s participating institutions, the European Commission and/or the Consumers, Health, Agriculture and Food Executive Agency or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains. Rolling Collaborative Review team Author(s) Division for Health Services, Norwegian Institute of Public Health (NIPHNO), Norway Co-Author(s) Department of Epidemiology Lazio Regional Health Service (DEPLazio), Italy December 2020 EUnetHTA Joint Action 3 WP4 2 Rolling Collaborative Review - Living Report RCR13 - Interferon beta-1a (IFN β-1a) and Novaferon (Nova) for the treatment of COVID-19 Further contributors Project Management Zorginstituut Nederland (ZIN), Coordination between involved parties throughout the assessment Netherlands Austrian Institute for Health Coordination of RCR Technology Assessment (AIHTA), Austria Conflict of interest All authors and co-authors involved in the production of this living document have declared they have no conflicts of interest in relation to the technology and comparator(s) assessed according to the EUnetHTA declaration of interest (DOI) form. Conflict of Interest was evaluated following the EUnetHTA Procedure Guidance for handling DOI form (https://eunethta.eu/doi). Copyright EUnetHTA assessments are published under a “CC/BY/NC” Creative Commons Licence. How to cite this assessment Please cite this assessment as follows: EUnetHTA Rolling Collaborative Review (RCR13) Authoring Team. [Interferon (IFN) and Novaferon (Nova) for the treatment of COVID-19]. Diemen (The Netherlands): EUnetHTA; 2020. [date of citation]. 64 pages. Report No.: RCR13. Available from: https //www.eunethta.eu. Contact the EUnetHTA Secretariat [email protected] with inquiries about this assessment. December 2020 EUnetHTA Joint Action 3 WP4 3 Rolling Collaborative Review - Living Report RCR13 - Interferon beta-1a (IFN β-1a) and Novaferon (Nova) for the treatment of COVID-19 TABLE OF CONTENTS DOCUMENT HISTORY AND CONTRIBUTORS .....................................................................................2 TABLE OF CONTENTS ...........................................................................................................................4 LIST OF TABLES AND FIGURES...........................................................................................................4 1 OBJECTIVE .......................................................................................................................................6 2 METHODS ..........................................................................................................................................6 2.1 SCOPE ...........................................................................................................................................6 2.2 SOURCES OF INFORMATION .............................................................................................................8 3 ABOUT THE TREATMENT ............................................................................................................ 10 3.1 MODE OF ACTION ........................................................................................................................ 10 3.2 REGULATORY STATUS ................................................................................................................. 10 3.3 LEVEL OF EVIDENCE .................................................................................................................... 10 4 SUMMARY ...................................................................................................................................... 11 4.1 EFFECTIVENESS AND SAFETY EVIDENCE FROM RCTS .................................................................... 11 4.2 SAFETY EVIDENCE FROM OBSERVATIONAL STUDIES ....................................................................... 11 4.3 ONGOING STUDIES ....................................................................................................................... 12 4.4 SCIENTIFIC CONCLUSION ABOUT STATUS OF EVIDENCE GENERATION .............................................. 12 5 REFERENCES ................................................................................................................................ 55 6 APPENDIX ...................................................................................................................................... 57 6.1 SEARCH STRATEGY TO IDENTIFY RANDOMISED CONTROLLED TRIALS ............................................... 57 6.2 SEARCH STRATEGY TO IDENTIFY OBSERVATIONAL STUDIES ............................................................ 60 6.3 SEARCH STRATEGY TO IDENTIFY ONGOING STUDIES ....................................................................... 62 6.4 FLOW DIAGRAMS ......................................................................................................................... 63 LIST OF TABLES AND FIGURES Table 2-1 Scope of the RCR ....................................................................................................................6 Table 4-1 Summary of findings (SoF) table for published RCTs related to effectiveness and safety of IFN and Novaferon ...................................................................................................................... 13 Table 4-2 Study characteristics of included RCTs ................................................................................ 27 Table 4-3 Study characteristics of included RCTs (continued) ............................................................. 31 Table 4-4 Study characteristics of included RCTs (continued) ............................................................. 35 Table 4-5 Ongoing trials IFN-α, single and in combination ................................................................... 41 Table 4-6 Ongoing trials IFN-α, single and in combination (continued) ................................................ 42 Table 4-7 Ongoing trials Single agents IFN β-1a and Novaferon ......................................................... 43 Table 4-8 Ongoing trials Single agents IFN β-1a and Novaferon (continued) ...................................... 46 Table 4-9 Ongoing trials Combination therapies IFN β-1a and Novaferon ........................................... 48 Table 4-10 Ongoing trials Single agents IFN β-1a and Novaferon (continued) .................................... 50 Table 4-11 Ongoing trials IFN β-1b, single and in combination ............................................................ 51 Table 4-12 Ongoing trials IFN Lambda ................................................................................................. 53 Table 6-1 Search strategy to identify randomised controlled studies.................................................... 58 Table 6-2 Search strategy to identify observational studies .................................................................. 60 Table 6-3 Search strategy to identify ongoing studies .......................................................................... 62 Appendix Figure 6-1. Flow diagram depicting the selection process of RCTs ...................................... 63 Appendix Figure 6-2. Flow diagram depicting the selection process of observational studies ............. 64 December 2020 EUnetHTA Joint Action 3 WP4 4 Rolling Collaborative Review - Living Report RCR13 - Interferon beta-1a (IFN β-1a) and Novaferon (Nova) for the treatment of COVID-19 LIST OF ABBREVIATIONS AE Adverse Event ATC Anatomical Therapeutic Chemical [Classification System] ATMP Advanced therapy medicinal product CI Confidence Interval DOI Declaration of interest EUnetHTA European Network of Health Technology Assessment GRADE Grading of Recommendations, Assessment, Development