Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza
A Phase III, Randomized, Double-Blind Placebo-Controlled, Multicenter Study To Evaluate the Efficacy and Safety of Baloxavir Marboxil in Combination With Standard-of-Care Neuraminidase Inhibitor in Hospitalized Participants With Severe Influenza
2 other identifiers
interventional
363
26 countries
151
Brief Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of baloxavir marboxil in combination with a standard-of-care (SOC) neuraminidase inhibitor (NAI) (i.e., oseltamivir, zanamivir, or peramivir) compared with a matching placebo in combination with a SOC NAI in hospitalized patients with influenza.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2019
Shorter than P25 for phase_3
151 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 24, 2018
CompletedFirst Posted
Study publicly available on registry
September 25, 2018
CompletedStudy Start
First participant enrolled
January 8, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 16, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 16, 2020
CompletedResults Posted
Study results publicly available
November 30, 2020
CompletedJanuary 6, 2021
December 1, 2020
1.2 years
September 24, 2018
September 9, 2020
December 14, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Time to Clinical Improvement
Time to Clinical Improvement (TTCI) is defined as Time to Hospital Discharge OR Time to NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
Up to Day 35
Secondary Outcomes (28)
Response Rates of the 6-Point Ordinal Scale at Day 7
Day 7
Time to Clinical Response
Up to Day 35
Percentage of Participants on Mechanical Ventilation
Up to Day 35
Duration of Mechanical Ventilation
Up to Day 35
Percentage of Participants Requiring ICU Stay
Up to Day 35
- +23 more secondary outcomes
Study Arms (2)
Baloxavir Marboxil
EXPERIMENTALParticipants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
Placebo
PLACEBO COMPARATORParticipants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
Interventions
Baloxavir marboxil will be administered as a weight-based dose on Days 1 and 4. A third dose will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5.
Eligibility Criteria
You may qualify if:
- Adult participants: Signed informed consent by any participant capable of giving consent, or, where the participant is not capable of giving consent, by his or her legal/authorized representative
- Adolescent participants not able to legally consent: written informed consent for study participation is obtained from participant's parents or legal guardian, with assent as appropriate by the participant, depending on the participant's level of understanding and capability to provide assent
- Participants who require hospitalization for severe influenza or acquire influenza during hospitalization, the severity of which requires an extension of hospitalization
- Diagnosis of influenza A and/or B by a positive Rapid Influenza Diagnostic Test (RIDT) or reverse transcriptase-polymerase chain reaction (RT-PCR)
- The time interval between the onset of symptoms and randomization is within 96 hours
- A score of ≥4 based on the National Early Warning Score 2 (NEWS2)
- Participants will require objective criteria of seriousness defined by at least one of the following criteria:
- Requires ventilation or supplemental oxygen to support respiration
- Has a complication related to influenza that requires hospitalization (e.g., pneumonia, central nervous system involvement, myositis, rhabdomyolysis, acute exacerbation of chronic kidney disease, asthma or chronic obstructive pulmonary disease (COPD), severe dehydration, myocarditis, pericarditis, exacerbation of ischemic heart disease)
- For women of childbearing potential: Agreement to remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 28 days after the last dose of study treatment. Hormonal contraceptive methods must be supplemented by a barrier method.
You may not qualify if:
- Participants who have received more than 48 hours of antiviral treatment for the current influenza infection prior to screening
- Participants who have received baloxavir marboxil for the current influenza infection
- Known contraindication to neuraminidase inhibitors
- Participants hospitalized for exclusively social reasons (e.g., lack of caregivers at home)
- Participants expected to die or be discharged within 48 hours, according to the investigator's judgement
- Participants weighing \< 40 kg
- Participants with known severe renal impairment (estimated glomerular filtration rate \< 30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis
- Participants with any of the following laboratory abnormalities detected within 24 hours prior to or during screening (according to local laboratory reference ranges:
- Alanine Transaminase (ALT) or Aspartate Transaminase (AST) level \> 5 times the upper limit of normal (ULN) OR
- ALT or AST \> 3 times the ULN and total bilirubin level \> 2 times the ULN
- Pregnant or breastfeeding, or positive pregnancy test in a predose examination, or intending to become pregnant during the study or within 28 days after the last dose of study treatment
- Exposure to an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization
- Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study
- Known hypersensitivity to baloxavir marboxil or the drug product excipients
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (170)
Torrance Memorial Medical Center
Torrance, California, 90505, United States
Denver Health Medical Center
Denver, Colorado, 80204, United States
Atlanta Institute For Medical Research, Inc; DeKalb Medical Pharmacy
Decatur, Georgia, 30030, United States
University of Chicago; Oncology Dept
Chicago, Illinois, 60637, United States
NorthShore University HealthSystem
Evanston, Illinois, 60201, United States
Barnum Medical Research, Inc.
Natchitoches, Louisiana, 71457, United States
Detroit Receiving Hospital
Detroit, Michigan, 48201, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercury Street Medical Group
Butte, Montana, 59701, United States
Creighton University Medical Center
Omaha, Nebraska, 68131, United States
New York-Presbyterian Brooklyn Methodist Hospital; Department of Emergency Medicine
Brooklyn, New York, 11215, United States
Temple University Hospital ; Lung Center
Philadelphia, Pennsylvania, 19140, United States
Salem Veterans Affairs Medical Center - NAVREF; Pharmacy
Salem, Virginia, 24153, United States
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Instituto Medico Platense
La Plata, 1900, Argentina
Royal Brisbane & Womens Hospital; Pharmacy Department
Herston, Queensland, 4029, Australia
Royal Children's Hospital Melbourne - PIN
Parkville, Victoria, 3052, Australia
Hopital Erasme; Chest Medicine, Cardiac & Thoracic Surgery
Brussels, 1070, Belgium
Cliniques Universitaires Saint-Luc; Hematology
Brussels, 1200, Belgium
UZ Leuven
Leuven, 3000, Belgium
Santa Casa de Misericordia; de Belo Horizonte
Belo Horizonte, Minas Gerais, 30150-221, Brazil
Hospital Sao Vicente de Paulo
Passo Fundo, Rio Grande do Sul, 99010-090, Brazil
Centro de Estudos Clinicos do Interior Paulista
Jaú, São Paulo, 17201-130, Brazil
Multiprofile Hospital For Active Treatment Sveta Ekaterina Dimitrovgrad EOOD; Internal Diseases
Dimitrovgrad, 6400, Bulgaria
Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases - Haskovo EOOD
Haskovo, 6305, Bulgaria
MHAT Stamen Iliev AD; Pharmacy
Montana, 3400, Bulgaria
University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD; Pharmacy
Plovdiv, 4002, Bulgaria
Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases Dr. D. Gramatikov - Ruse
Rousse, 7002, Bulgaria
Multiprofile Hospital for Active Treatment - Samokov EOOD
Samokov, 2000, Bulgaria
Multiprofile Hospital For Active Treatment Sliven То Military Hospital Sofia; Pharmacy
Sliven, 8800, Bulgaria
Multiprofile Hospital For Active Treatment - Dr. Bratan Shukerov AD; Pharmacy
Smolyan, 4700, Bulgaria
First Multiprofile Hospital for Active Treatment - Sofia EAD
Sofia, 1142, Bulgaria
Fifth Multiprofile Hospital for Active Treatment - Sofia EAD; Pharmacy
Sofia, 1233, Bulgaria
Military Medical Academy Multiprofile Hospital for Active Treatment - Sofia; Pharmacy
Sofia, 1606, Bulgaria
National Multiprofile Transport Hospital Tzar Boris Ill; Clinic of Internal Diseases
Sofia, 2233, Bulgaria
Multiprofile District Hospital for Active Treatment Dr. Stefan Cherkezov AD; Pharmacy
Veliko Tarnovo, 5000, Bulgaria
Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases-Vratsa; Pharmacy
Vratsa, 3000, Bulgaria
Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4, Canada
Foothills Medical Centre
Calgary, Alberta, T2N-2T9, Canada
Carlson Urology
Calgary, Alberta, T2V 1P9, Canada
South Health Campus
Calgary, Alberta, T3M 1M4, Canada
University of Alberta Hospital
Edmonton, Alberta, T6G 1Z1, Canada
Toronto East General Hospital; Main Pharmacy G Wing Basement
East York, Ontario, M4C 3E7, Canada
London Health Sciences Center; Pharmacy Dept.
London, Ontario, N6A 5W9, Canada
Institut Universitaire de Cardiologie et de Pneumologie
Québec, G1V 4G5, Canada
Beijing Ditan Hospital Capital Medical University
Beijing, 100015, China
Beijing Youan Hospital, Capital Medical University; Center for Infectious Diseases
Beijing, 100069, China
China-Japan Friendship Hospital
Beijing, 10029, China
West China Hospital, Sichuan University
Chengdu, 610041, China
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, 510120, China
The First Affiliated Hospital of College of Medicine, Zhejiang University
Hangzhou, 310003, China
The 1st Affiliated Hospital of Nanchang Unversity
Nanchang, 330006, China
Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)
Shanghai, 200025, China
Zhongshan Hospital Fudan University
Shanghai, 200032, China
Shanghai Public Health Clinical Center
Shanghai, 201508, China
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
Brno, 625 00, Czechia
Nemocnice Kyjov, prispevkova organizace
Kyjov, 697 33, Czechia
East Tallinn Central Hospital
Tallinn, 10138, Estonia
Kuopion Yliopistollinen Sairaala; Silmätaudit
Kuopio, 70210, Finland
Oulun Yliopistollinen Sairaala; Teho-osasto
Oulu, 90220, Finland
Turku University Hospital
Turku, 20521, Finland
Centre Hospitalier Victor Dupouy
Argenteuil, 95107, France
CHRU Dijon Complexe Du Bocage
Dijon, 21079, France
Centre Hospitalier Departemental de Vendee
La Roche-sur-Yon, 85925, France
Hôpital Universitaire Dupuytren
Limoges, 87042, France
CHRU Nantes
Nantes, 44093, France
CHU de Nîmes - Hôpital Carémeau
Nîmes, 30029, France
Hopital de La Source
Orléans, 45067, France
Groupe Hospitalier Pitie Salpetriere; Service De Pneumologie
Paris, 75651, France
Nouvel Hopital Civil - CHU Strasbourg
Strasbourg, 67091, France
CHRU Bretonneau
Tours, 37044, France
Uniklinik Koln; Klinik I fur Innere Medizin
Cologne, 50937, Germany
Krankenhaus Donaustauf der LVA Niederbayern Oberpfalz
Donaustauf, 93093, Germany
Universitätsklinikum Carl Gustav Carus an der TU Dresden
Dresden, 01307, Germany
St. Josefskrankenhaus - Freiburg; Klinik fur Pneumologieund Beatmungsmedizin
Freiburg im Breisgau, 79104, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I
Lübeck, 23538, Germany
Klinikum Mannheim GmbH Universitätsklinikum
Mannheim, 68167, Germany
Klinikum der Universität Regensburg
Regensburg, 93053, Germany
Universitatsklinikum Tubingen
Tübingen, 72076, Germany
Princess Margaret Hospital
Hong Kong, Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Prince of Wales Hospital
Shatin, New Territories, Hong Kong
Soroka University Medical Centre
Beersheba, 8410101, Israel
Edith Wolfson Medical Center
Holon, 58100, Israel
Galilee Medical Center
Nahariya, 22100, Israel
Chaim Sheba Medical Center; Allergy and Clinical Immunology Unit
Ramat Gan, 5266202, Israel
Rambam Health Corporation; Oncology Institute
Rambam, 3525408, Israel
ZIV Medical Center; Department Of Internal Medicine A
Safed, 13100, Israel
Tel Aviv Sourasky Medical Center; Pharmacy
Tel Aviv, 6423906, Israel
Baruch Padeh Poria Medical Center; Pharmacy
Tiberias, 15208, Israel
Fujita General Hospital
Dategun Kunimimachi, 969-1793, Japan
Shin Komonji Hospital
Fukuoka, 800-0057, Japan
Fukuoka Shin Mizumaki Hospital
Fukuoka, 807-0051, Japan
Fukuoka Wajiro Hospital
Fukuoka, 811-0213, Japan
Rinku General Medical Center
Izumisano, 598-0048, Japan
National Hospital Organization Minami Kyoto Hospital
Jōyō, 610-0113, Japan
National Hospital Organization Kanazawa Medical Center
Kanazawa, 920-8650, Japan
Japanese Red Cross Kumamoto Hospital
Kumamoto, 861-8520, Japan
Naha City Hospital
Naha, 902-8511, Japan
National Hospital Organization Ibarakihigashi National Hospital; Center for Clinical Research
Naka-gun, 319-1113, Japan
Japan Community Health care Organization Nihonmatsu hospital
Nihonmatsu, 964-8501, Japan
Social Corporation Keigakukai Minamiosaka Hosupital
Osaka, 559-0012, Japan
National Hospital Organaization Shibukawa Medical Center
Shibukawa, 377-0280, Japan
Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai
Shinagawa City, 140-8522, Japan
Saka General Hospital
Shiogama, 985-8506, Japan
Local incorporated administrative agency Shizuoka City Shizuoka Hospital
Shizuoka, 420-8630, Japan
Iwase General Hospital
Sukagawa, 962-8503, Japan
Center Hospital of the National Center for Global Health and Medicine
Tokyo, 162-0052, Japan
Nagata Hospital; Department of pulmonary medicine
Yanagawa-shi, 832-0059, Japan
Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran; Hamatologia y Oncologia
México, Mexico CITY (federal District), 14000, Mexico
Hospital Civil Fray Antonio Alcalde; Instituto de Patologia Infecciosa
Guadalajara, 44280, Mexico
Hospital Universitario Dr. Jose Eleuterio González; Enfermedades Pulmonares Crónicas
Monterrey, 64460, Mexico
Hospital General de Tijuana
Tijuana, 22320, Mexico
Leids Universitair Medisch Centrum; C5-P Stafcentrum Hartziekten
Leiden, 2333 ZA, Netherlands
Canisius Wilhelmina Ziekenhuis; Department Hematology
Nijmegen, 6532 SZ, Netherlands
Ikazia Ziekenhuis
Rotterdam, 3083 AN, Netherlands
Zuyderland Medisch Centrum - Sittard Geleen
Sittard-Geleen, 6162 BG, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
Wellington Hospital
Wellington, 6012, New Zealand
Hospital Alberto Sabogal Sologuren
Callao, Callao 02, Peru
Hospital Nacional Adolfo Guevara Velasco - ESSALUD; Servicio de Cardiología
Cusco, 08006, Peru
Prof. Dr. Matei Bals Institute of Infectious Diseases
Bucharest, 21105, Romania
Dr. Victor Babes Clinical Hospital For Tropical and Infectious Diseases
Bucharest, 30303, Romania
Spitalul Clinic de Boli Infectioase
Cluj-Napoca, 400000, Romania
Sf.Cuv. Parascheva Infectious Diseases Clinical Hospital
Galati, 800179, Romania
Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi
Iași, 700116, Romania
Sibiu Emergency Clinical County Hospital
Sibiu, 550245, Romania
Sf. Ioan cel Nou Emergency County Hospital
Suceava, 720224, Romania
Clinical Center of Serbia
Belgrade, 11000, Serbia
Clinical Hospital Center Zvezdara
Belgrade, 11000, Serbia
Institute of Lung Diseases Vojvodina
Kamenitz, 21204, Serbia
Clinical Center Kragujevac
Kragujevac, 34000, Serbia
Clinical Center Nis; Clinic for Pulmonary Diseases and Tuberculosis Knez Selo
Niš, 18204, Serbia
Clinical Centre of Vojvodina
Nova Sad, 21000, Serbia
General Hospital Dr Radivoj Simonovic Sombor
Sombor, 25000, Serbia
Tan Tock Seng Hospital
Singapore, 308433, Singapore
The Catholic University of Korea Incheon St. Mary's Hospital
Incheon, 21431, South Korea
Seoul National University Bundang Hospital
Seongnam-si, 13605, South Korea
Korea University Anam Hospital
Seoul, 02841, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Asan Medical Center
Seoul, 05505, South Korea
ChungAng University Hospital
Seoul, 06973, South Korea
Hallym University Kangnam Sacred Heart Hospital
Seoul, 07441, South Korea
Hospital Universitario Germans Trias i Pujol
Badalona, Barcelona, 08916, Spain
Hospital Sant Joan de Deu - PIN; Unitat de Recerca - Farmacia
Esplugues de Llobregat, Barcelona, 08950, Spain
Hospital Mutua de Terrassa
Terrassa, Barcelona, 08221, Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, 39008, Spain
Hospital Universitario de Torrejon
Torrejón de Ardoz, Madrid, 28850, Spain
Hospital General Universitario de Alicante
Alicante, 03010, Spain
Hospital del Mar
Barcelona, 08003, Spain
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 08035, Spain
Hospital Universitario Fundacion Jimenez Diaz.
Madrid, 28040, Spain
Hospital General Universitario Reina Sofia; Servicio de Nefrologia
Murcia, 30003, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Hospital de La Ribera
Valencia, 46600, Spain
Sahlgrenska Universitetssjukhuset
Gothenburg, 413 45, Sweden
Skånes Universitetssjukhus Malmö; Infektionskliniken
Malmo, SE-20502, Sweden
Hacettepe University Medical Faculty
Ankara, 06100, Turkey (Türkiye)
Akdeniz University Medical Faculty
Antalya, 07059, Turkey (Türkiye)
Selcuk University Medical Faculty; Internal Medicine
Konya, 42050, Turkey (Türkiye)
Karadeniz Technical University Faculty of Medicine
Trabzon, 61080, Turkey (Türkiye)
Regional Municipal Institution Chernivtsi Regional Clinical Hospital
Chernivtsi, Chernihiv Governorate, 58005, Ukraine
Kyiv Oleksandrivska Clinical Hospital; Infectious Box Department #2
Kyiv, Katerynoslav Governorate, 01601, Ukraine
Regional Municipal Institution Sumy Regional Infectious Clinical Hospital n.a. Z.Y. Krasovytskyi
Sumy, Katerynoslav Governorate, 40021, Ukraine
Ternopil City Municipal Emergency Hospital; Infectious Department
Ternopil, KIEV Governorate, 46008, Ukraine
Communal Non-Commercial Enterprise "Vinnytsia City Clinical Hospital №1"; Infectious Department
Vinnytsia, KIEV Governorate, 21029, Ukraine
MI Vinnytsia Regional Clinical Children's Infectious Hospital; Infectiuos Box department
Vinnytsia, KIEV Governorate, 21032, Ukraine
MI Dnipropetrovsk City Clinical Hospital #21 n.a. Prof. Popkova of DRC; The First Department
Dnipro, Podolia Governorate, 49006, Ukraine
Municipal Institution City Clinical Infectious Diseases Hospital
Odesa, 65023, Ukraine
Related Publications (3)
Stannard HL, Mifsud EJ, Wildum S, Brown SK, Koszalka P, Shishido T, Kojima S, Omoto S, Baba K, Kuhlbusch K, Hurt AC, Barr IG. Assessing the fitness of a dual-antiviral drug resistant human influenza virus in the ferret model. Commun Biol. 2022 Sep 28;5(1):1026. doi: 10.1038/s42003-022-04005-4.
PMID: 36171475DERIVEDKumar D, Ison MG, Mira JP, Welte T, Hwan Ha J, Hui DS, Zhong N, Saito T, Katugampola L, Collinson N, Williams S, Wildum S, Ackrill A, Clinch B, Lee N. Combining baloxavir marboxil with standard-of-care neuraminidase inhibitor in patients hospitalised with severe influenza (FLAGSTONE): a randomised, parallel-group, double-blind, placebo-controlled, superiority trial. Lancet Infect Dis. 2022 May;22(5):718-730. doi: 10.1016/S1473-3099(21)00469-2. Epub 2022 Jan 24.
PMID: 35085510DERIVEDYoung B, Tan TT, Leo YS. The place for remdesivir in COVID-19 treatment. Lancet Infect Dis. 2021 Jan;21(1):20-21. doi: 10.1016/S1473-3099(20)30911-7. Epub 2020 Nov 26. No abstract available.
PMID: 33248473DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 24, 2018
First Posted
September 25, 2018
Study Start
January 8, 2019
Primary Completion
March 16, 2020
Study Completion
March 16, 2020
Last Updated
January 6, 2021
Results First Posted
November 30, 2020
Record last verified: 2020-12
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).