Summary of WHO symposium on meeting the global needs for oxygen and respiratory care: recent learning, current knowledge and future direction, 4 October 2023, Toronto, Canada

Problem Global access to oxygen and options to deliver respiratory support are limited, and patient needs in low- and middle-income countries (LMICs) are unmet. Opportunity Optimizing patient and health care facilities, and linking sites through research in respiratory care will transform patient outcomes. This document provides a high-level summary of wide-ranging presentations, discussion and feedback from participating experts. These were drawn from the O2CoV2 research investigators and representatives of global respiratory research networks (including ANZICS, BRICNet, CCAA, ICNARC, ISARIC, NIH, NIHR, REMAP-CAP). 102 participants took part, representing all WHO regions. Recent learning from the WHO O2CoV2 study The WHO O2CoV2 study demonstrated the need for oxygen and its intelligent and sustainable delivery. Findings • 23% mortality from acute respiratory infection requiring oxygen (with regional variations of 10–38%) • Oxygen and oxygen delivery devices are severely limited (non-invasive advanced respiratory support 1–3% patient beds and ventilators 2–25%, depending on region) Contextual issues noted by LMIC-based co-investigators • Continual communication and support from the central unit (WHO) was essential to research success • Including non-research staff gave local ownership • Research questions framed within the needs of high- income countries mean there are significant real-world evidence gaps in LMICs (e.g. the optimal use of non- rebreather masks for oxygen delivery) • Health facility designs and procedures determine clinical decisions, but there is a lot of flexibility • Understanding “how” interventions are applied in research is as important as the P value Summary: Uncertainty around the utility of non-invasive ventilation strategies and contextual considerations require pragmatic evaluation of existing options, including enhanced supportive care. Findings presented by Pryanka Relan and Yaseen Arabi. context from Masooma Aqeel (Pakistan), Zeina Bacha (Lebanon), Monica Cruz (Brazil), Mulinda Nyirenda (Malawi) Summary of WHO symposium on meeting the global needs for oxygen and respiratory care recent learning, current knowledge and future direction 4 October 2023, Toronto, Canada Clinical management unit, WHO Emergencies programme 2 Current knowledge Participants shared their experience of current clinical trials networks in supporting clinical research which benefits patients in LMICs. The main themes are summarized in the following figure. Opportunities and suggestions for WHO to improve equitable access to global research were identified: Regulation and oversight • Ensuring trust with regulators (overall framework and data policies for exchange and use). Harmonization and standardization of management of acute illness • Provision of a certification process for health care professionals involved in research which updates “Good Clinical Practice”, including addressing observational studies. • Framework for data (harmonization of data elements, e-medical record capability). • Disease/syndrome definitions (for example ARDS, COVID-19 severity), core outcome sets. Connection • Enabling links and supporting prioritization with policy-makers at country and regional level. • Convening “networks of trial networks”. • Interface with ministries of health through which academic/other institutions can partner. • Strengthening multi-layered partnerships within regions/countries to broaden beyond the typical high-income countries-LMICs linkages. Clinical management unit, WHO Emergencies programme 3 Thematic summary of the drivers of success of global respiratory research Equity and decolonization of evidence generation is extremely important Recognition including in authorship of those involved (and beyond “academics”) Representation of LMICs in decision-making bodies required from the design outset Distributed but interconnected oversight bodies can ensure sovereignty and improve efficiency Data ownership and security are sensitive, and in tension with maximal data use (novel anonymization and data federation techniques are potential solutions) Minimal case report form with close to real-time data cleaning has been proven during COVID-19 to allow research during surge conditions, and to improve clinical relevance Heterogeneity of outcomes, baseline levels of care, data facilities and others Context specificity requires implementation considerations within trials Crosstalk across specialty and geography reduces siloes and improves generalizability Innovation and equipoise may be specific to the local environment, and this may determine the potential inclusion of sites or countries in specific interventions Regulatory oversight is variable especially for equipment (compared with pharmaceuticals) Contractual arrangements are the source of the longest research delays Policy-maker engagement and prioritization from the start should include assessment of need, and that proposed solutions are feasible International themes Local themes Clinical management unit, WHO Emergencies programme 4 Future direction Participants were asked to translate their experience of observational studies to the future design of an intervention. The findings have been synthesized by the following themes. Scope of work Globally, and particularly in LMICs, care of critically ill patients is performed outside of intensive care units (ICUs), but current clinical trials of critically ill patients are almost universally ICU based. Broadening the focus to “acute care” or “critical care” is likely to be beneficial and relevant to more people. Inclusive populations, including obstetrics, paediatrics. Integration with routine care Research should serve clinical care, and health care professionals must be engaged for success. This can be enhanced by incorporation of quality improvement, local leadership/champions for clinical research and local data uptake (such as analytics and dashboards for feedback). Clinical expectations and standards of care Equipoise may vary depending on how interventions might perform within the wider environment. Heterogeneity of facilities, patient populations and overall levels of health will mean some questions are not universally relevant. WHO Basic Emergency Care and other initiatives can provide some fundamental standards on which a more even standard of care can be delivered or harmonized. Data Decentralized or federated data management and protocolized anonymization protocols can improve equity and reduce concerns related to local ownership. Sources of data, where possible electronic medical records, could enhance integration with care, but would currently exclude many LMIC facilities. Creating an enabling research environment Multiple enabling strategies were suggested, including research training, local data capabilities, paid research time, support for governance and infrastructure, import of therapeutics and other research-specific items, and logistics at country and site level. Inclusion Patient involvement at the country level through design and practical considerations is key. Prioritization of outcomes can be enacted at the higher/international level, in collaboration with priority-setting partnerships. Private providers may have significant importance on the supplier side or research delivery, depending on countries’ systems. Study designs Platform trials have practical and efficiency benefits, particularly within existing networks, but geographic areas of need must be expanded. System interventions should be strongly considered (including complex interventions which are context appropriate, e.g. protocolized care). Cluster trials have the potential to address these questions. Evaluation of how trial results can be interpreted (implementation science input) will be required to make sense of heterogeneity. Clinical management unit, WHO Emergencies programme 5 Conclusion The challenges extended by participants included: “Think big… …but do something tangible.” “Be inclusive and relevant.” The themes summarized in this document represent the most frequent, and the most consistent messages, from researchers and clinicians. Multiple requests were made for WHO support. Facilitating research which is patient-focused and globally useful will require broad discussion and inclusion of both existing and new partners. It should be as simple as possible to execute, driven by light data requirements, and incorporate relevant design and intervention choices to deliver affordable large-scale clinical trials. Next steps Resulting from these discussions, the WHO Health Emergencies clinical team will: • Develop and advertise an Expression of Interest to ensure engagement with an open and broad representation of a global network for acute respiratory research relevant to health emergencies. • Reconvene the group in May 2024. • Develop an upcoming trial (through 2024). Example research questions • High-flow nasal oxygen (HFNO) versus continuous positive airway pressure versus non-invasive ventilation for pneumonia and other respiratory failure. • How can protocolized therapy/ oxygen use decision-making enhance patient outcomes? • What is the typical oxygen consumption with HFNO? • How can clinical decision-making be safely driven by the most widely available measures (such as SpO2 rather than arterial blood gases in respiratory failure)? • What is the optimal use of therapeutics, e.g. corticosteroids, outside of SARS-CoV-2 infection? Clinical management unit, WHO Emergencies programme 6 Thanks With many thanks to all the partners who gave their time and consideration to this WHO symposium. List of participants Name Affiliation Country Adebiyi Adedamola National Center of Communicable Diseases Mongolia Olywabukola Adejumobi Olabisi Onabanjo University Teaching Hospital Nigeria Neill Adhikari University of Toronto Canada Shimaa Ahmed Hamed Suez Canal University Egypt Rabiul Alam Chittagong Medical College & Hospital Bangladesh Carlos Arthuro Alvarez Universidad Nacional de Colombia Colombia John Appiah WHO Ghana Masooma Aqeel Aga Khan University Pakistan Yaseen Arabi King Saud Bin Abdulaziz University for Health Sciences Saudi Arabia Diptesh Aryal Nepal Intensive Care Research Foundation Nepal Celine Baaklini Bellevue Medical Center Lebanon Shakira Babirya Infectious Diseases Institute Uganda Zeina Bacha Saint Joseph Universiy of Beirut Lebanon Barnabas Bakamutumaho Uganda Virus Research Institute Uganda Tim Baker Muhimbili University of Health and Allied Sciences Tanzania Debashis Basu Steve Biko Academic Hospital South Africa Abi Beane University of Edinburgh United Kingdom of Great Britain and Northern Ireland Ben Bepouka Cliniques Universitaires de Kinshasa Democratic Republic of Congo Anil Bilimale JSS Medical College India Frank Bloos Universitätsklinikum Jena Germany Fernando Bozza Fiocruz Institute Brazil Kathy Brickell King's College London United Kingdom of Great Britain and Northern Ireland Laurent Brochard University of Toronto Canada Luis Alberto Camputaro Hospital Nacional El Salvador El Salvador Itziar Carrasco Eurofins Megalab España Spain Gail Carson University of Oxford United Kingdom of Great Britain and Northern Ireland Gertrude Chapotera WHO Malawi Michael Chasse Universite de Montreal Canada DJ Christopher Christian Medical College India Clinical management unit, WHO Emergencies programme 7 Jeanine Condo University of Rwanda Rwanda Pauline Convocar Southern Philippines Medical Center Philippines Deborah Cook McMaster University Canada Monica Cruz Instituto Nacional de Infectologia Evandro Chagas/ Fiocruz Brazil Matthew Cummings Columbia University Uganda Brian Cuthbertson University of Toronto Canada Lennie Derde University Medical Center Utrecht Kingdom of the Netherlands Armand Dessap Hopital Henri-Mondor France Janet Diaz WHO WHO Headquarters Guillermo Dominguez Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico Kenneth Doya Nonesa Southern Philippines Medical Center Philippines Alejandro Duarte Ministerio de Salud de la Republica de El Salvador El Salvador Ryenchindorj Erkhembayar National Center of Communicable Diseases Mongolia Juliana Ferreira University of São Paulo Brazil Robert Fowler Sunnybrook Hospital Canada Faith Joan Gaerlan Southern Philippines Medical Center Philippines Aniruddha Ghose Chittagong Medical College & Hospital Bangladesh Ewan Goligher Toronto General Hospital Canada Anthony Gordon Imperial College London United Kingdom of Great Britain and Northern Ireland Priscilla Haguma Makerere University Uganda Rashan Haniffa University of Edinburgh United Kingdom of Great Britain and Northern Ireland Madiha Hashmi Ziauddin University, Karachi Pakistan Leanne Hays University College Dublin Ireland Lisa Higgins Monash University Australia Carol Hodgson Monash University Australia Shevin Jacob Liverpool School of Tropical Medicine Uganda Devdas Jaidev JSS Medical College India Nadia Jawad Jinnah Postgraduate Medical Centre Pakistan Halima Salisu Kabara Aminu Kano Teaching Hospital, Kano Nigeria Rashidatu Fouad Kamara WHO WHO Regional Office for Africa Leticia Kawano Dourado Research Institute, Hospital do Coração Brazil Karima Khalid Muhimbili University of Health and Allied Sciences Tanzania Khalid Kheirallah Medical School of Jordan University Jordan Michelle Kho McMaster University Canada Peter Kiiza Sunnybrook Research Institute Canada Francis Kiweewa Makerere University Uganda Mark Kizito Infectious Diseases Institute Uganda Clinical management unit, WHO Emergencies programme 8 Richard Kojan Alliance for International Medical Action Democratic Republic of Congo Ashok Kumar Ziauddin University Pakistan Barath Kumar Apollo Hospitals India Gary Kuniyoshi WHO WHO Regional Office for the Eastern Mediterranean Arthur Kwizera Makerere University College of Health Sciences Uganda John Laffey University of Galway Ireland Francois Lamontagne Universite de Sherbrooke Canada Aleks Leligdowicz Western University Canada Nombulelo Magula University of Kwazulu-Natal South Africa Undram Mandakh National Center of Communicable Diseases Mongolia John Marshall University of Toronto Canada David Maslove Queen's University Canada Steven McGloughlin WHO WHO Headquarters Maria Mendes Independent Guinea Bissau Martin Meremikwu University of Calabar Nigeria Laura Merson University of Oxford United Kingdom of Great Britain and Northern Ireland Deebya Mishra Koirala Institute of Health Sciences Nepal Samiha Mohsen University of Toronto Canada Bernard Moses University of Calabar Nigeria Paul Mouncey Intensive Care National Audit & Research Centre (ICNARC) United Kingdom of Great Britain and Northern Ireland Srinivas Murthy University of British Columbia Canada Lama Nazer King Hussein Cancer Center Jordan Alistair Nichol University College Dublin Ireland Sharon Nyesiga Walimu Uganda Mulinda Nyirenda University of Malawi College of Medicine Malawi Joshua Ofoli WHO Nigeria Alina Ogizbayeva Karaganda State Medical University Kazakhstan Darius Owachi Makerere University Uganda Parash Pandey Bheri Hospital Nepal Sasha Peiris WHO Pan American Health Organization Sanjeev Rai Father Muller Medical College Hospital India Adrienne Randolph Boston Children's Hospital United States of America Pryanka Relan WHO WHO Headquarters Felipe Reyes Universidad de La Sabana, Chía Colombia Elizabeth Riviello Beth Israel Deaconess Medical Center United States of America Bram Rochwerg McMaster University Canada Kathy Rowan Intensive Care National Audit & Research Centre (ICNARC) United Kingdom of Great Britain and Northern Ireland Clinical management unit, WHO Emergencies programme 9 Kristina Rudd University of Washington United States of America Jim Russel University of British Columbia Canada Jamie Rylance WHO WHO Headquarters Hiroki Saito Yokohama City Seibu Hospital, St. Marianna University School of Medicine Japan Amadou Seck Independent Senegal Israel Silva Maia Universidade de São Paulo Brazil Michael Sklar University of Toronto Canada Hassan Soleimanpour Tabriz University of Medical Sciences Iran (Islamic Republic of) Charlotte Summers University of Cambridge United Kingdom of Great Britain and Northern Ireland Louise Thwaites University of Oxford Viet Nam Aiman Touny Suez Canal University Egypt Jennifer Tsang McMaster University Canada Ubong Udoh University of Calabar Nigeria Sebastian Ugarte Universidad Andres Bello Chile Cesar Augusto Ugarte Universidad Peruana Cayetano Heredia Peru Valdilea Veloso Instituto Nacional de Infectologia Evandro Chagas/ Fiocruz Brazil Julie Viry WHO WHO Headquarters Nicole Yada University of Toronto Canada Summary of WHO symposium on meeting the global needs for oxygen and respiratory care: recent learning, current knowledge and future direction, Toronto, Canada, 4 October 2023 ISBN 978-92-4-009000-2 (electronic version) ISBN 978-92-4-009001-9 (print version) © World Health Organization 2024. 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