Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting

Amy Riddell¹, Aislinn Cook¹, Nathalie Khavessian², Sally Ellis², Davide Bilardi³, Erika Correia², Tomislav Kostyanev⁴, Alessandra Nardone³, Neal Russell¹, Tuba Vilken⁴, Wolfgang Stohr⁵, Bethou Adhisivam⁶, Iana Rosa Alves de Moraes⁷, Nawshad Uddin Ahmed⁸, Adrie Bekker⁹, Eitan Naaman Berezin⁷, Suppawat Boonkasidecha¹⁰, Cristina G Carvalheiro¹¹, Prachi Chauhan¹², Sara Chiurchiù¹³, Elisavet Chorafa¹⁴, Angela Dramowski⁹, Madhusudhan Ds¹⁵, Jinxing Feng¹⁶, Shengnan Jia¹⁷, Yuan Kong¹⁸, Mary Kyohere¹⁹, Angeliki Kontou²⁰, Sorasak Lochindarat¹⁰, Maia De Luca¹³, Aripfani Mphaphuli²¹, Marisa M Mussi-Pinhata¹¹, Sheila Murunga²², Firdose Lambey Nakwa²³, Sushma Nangia¹², Erinah Nassolo¹⁹, Ngoc Thi Bin Hoang²⁴, Christina W Obiero^{22

25}, Linus Olson²⁶, Wang Ping^{27

28}, Nishad Plakkal⁶, Priyanka Prasad¹⁵, Kanchana Preedisripipat²⁹, Sheikh Wasik Rahman⁸, Tiffany Seef²¹, Pra-Ornsuda Sukrakanchana³⁰, Reenu Thomas²³, Zhang Yu^{27

28}, Qiaoru Zhang¹⁷, A Sarah Walker⁵, Julia Bielicki¹, Paul T Heath¹, Michael Sharland¹, Tatiana Munera-Huertas¹

Affiliations

¹ Centre for Neonatal and Paediatric Infection, St. George's University of London, London SW17 0RE, UK.
² GARDP, 1202 Geneva, Switzerland.
³ Fondazione Penta ETS, 35127 Padova, Italy.
⁴ Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, 2610 Antwerpen, Belgium.
⁵ MRC Clinical Trials Unit, University College London, London WC1V 6LJ, UK.
⁶ Department of Neonatology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
⁷ Santa Casa de São Paulo, Sao Paulo 01221-010, Brazil.
⁸ Child Health Research Foundation, Dhaka 1207, Bangladesh.
⁹ Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa.
¹⁰ Queen Sirikit National Institute of Child Health, Bangkok 10400, Thailand.
¹¹ Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil.
¹² Department of Neonatology, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi 110001, India.
¹³ Academic Department of Pediatrics (DPUO), Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
¹⁴ Infectious Diseases Unit, 3rd Dept Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University and Hippokration General Hospital, 546 43 Thessaloniki, Greece.
¹⁵ Seth G. S. Medical College & KEM Hospital, Mumbai 400012, India.
¹⁶ Department of Neonatology, Shenzhen Children's Hospital, Shenzhen 518048, China.
¹⁷ Department of Neonatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100051, China.
¹⁸ Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen 518048, China.
¹⁹ MUJHU Research Collaboration, Kampala P.O. Box 23491, Uganda.
²⁰ 1st Neonatology Department and Neonatal Intensive Care Unit, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital, 546 42 Thessaloniki, Greece.
²¹ School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa AND Department of Paediatrics and Child Health, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg 2193, South Africa.
²² Clinical Research Department, KEMRI-Wellcome Trust Research Programme, Kilifi P.O. Box 230, Kenya.
²³ Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 1864, South Africa.
²⁴ Department of Microbiology, Vietnam National Children's Hospital, Hanoi 100000, Vietnam.
²⁵ Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Global Health, 1081 Amsterdam, The Netherlands.
²⁶ Department of Women's and Children's Health, Karolinska institutet, Stockholm, Sweden and Department of Global Public Health, Karolinska Institutet, 171 77 Stockholm, Sweden.
²⁷ Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.
²⁸ Beijing Maternal and Child Health Care Hospital, Beijing 100026, China.
²⁹ Chiangrai Prachanukroh Hospital, Chiang Rai 57000, Thailand.
³⁰ AMS-PHPT Research Collaboration, Chiang Mai University, Chiang Mai 50200, Thailand.

PMID: 37237826
PMCID: PMC10215156
DOI: 10.3390/antibiotics12050923

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting

Amy Riddell et al. Antibiotics (Basel). 2023.

. 2023 May 17;12(5):923.

doi: 10.3390/antibiotics12050923.

Authors

Affiliations

¹ Centre for Neonatal and Paediatric Infection, St. George's University of London, London SW17 0RE, UK.
² GARDP, 1202 Geneva, Switzerland.
³ Fondazione Penta ETS, 35127 Padova, Italy.
⁴ Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, 2610 Antwerpen, Belgium.
⁵ MRC Clinical Trials Unit, University College London, London WC1V 6LJ, UK.
⁶ Department of Neonatology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry 605006, India.
⁷ Santa Casa de São Paulo, Sao Paulo 01221-010, Brazil.
⁸ Child Health Research Foundation, Dhaka 1207, Bangladesh.
⁹ Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa.
¹⁰ Queen Sirikit National Institute of Child Health, Bangkok 10400, Thailand.
¹¹ Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil.
¹² Department of Neonatology, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi 110001, India.
¹³ Academic Department of Pediatrics (DPUO), Infectious Disease Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
¹⁴ Infectious Diseases Unit, 3rd Dept Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University and Hippokration General Hospital, 546 43 Thessaloniki, Greece.
¹⁵ Seth G. S. Medical College & KEM Hospital, Mumbai 400012, India.
¹⁶ Department of Neonatology, Shenzhen Children's Hospital, Shenzhen 518048, China.
¹⁷ Department of Neonatology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100051, China.
¹⁸ Clinical Laboratory, Shenzhen Children's Hospital, Shenzhen 518048, China.
¹⁹ MUJHU Research Collaboration, Kampala P.O. Box 23491, Uganda.
²⁰ 1st Neonatology Department and Neonatal Intensive Care Unit, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Hippokration General Hospital, 546 42 Thessaloniki, Greece.
²¹ School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa AND Department of Paediatrics and Child Health, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg 2193, South Africa.
²² Clinical Research Department, KEMRI-Wellcome Trust Research Programme, Kilifi P.O. Box 230, Kenya.
²³ Department of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 1864, South Africa.
²⁴ Department of Microbiology, Vietnam National Children's Hospital, Hanoi 100000, Vietnam.
²⁵ Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Global Health, 1081 Amsterdam, The Netherlands.
²⁶ Department of Women's and Children's Health, Karolinska institutet, Stockholm, Sweden and Department of Global Public Health, Karolinska Institutet, 171 77 Stockholm, Sweden.
²⁷ Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.
²⁸ Beijing Maternal and Child Health Care Hospital, Beijing 100026, China.
²⁹ Chiangrai Prachanukroh Hospital, Chiang Rai 57000, Thailand.
³⁰ AMS-PHPT Research Collaboration, Chiang Mai University, Chiang Mai 50200, Thailand.

PMID: 37237826
PMCID: PMC10215156
DOI: 10.3390/antibiotics12050923

Abstract

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network.

Keywords: LMIC; antibiotic treatment; antimicrobial resistance; clinical trials; empiric antibiotics; global collaboration; neonatal sepsis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. GARDP as funder and sponsor of the study was involved in the design of the study and study monitoring.

Figures

**Figure 1**
Site-specific recruitment chart for the primary enrolment cohort (clinical sepsis cohort) illustrating 15 high-volume sites meeting the 200-baby target and 4 lower-volume sites recruiting between 35 and 80 babies.

**Figure 2**
The study timelines for the NeoOBS study include study setup, recruitment, analysis, and the NeoSep1 trial design and setup. The NeoSep1 study setup will continue through 2023.

See this image and copyright information in PMC

References

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Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting

Affiliations

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources