An African, International Multi-centre Fourteen-day Evaluation of Patient Care and Clinical Outcomes for Paediatric Patients Undergoing Surgery (ASOS-Paeds)
Conditions: Paediatric Surgery, Perioperative/Postoperative Complications, Perioperative Outcomes, Hospital Mortality, Developing Countries, Outcome Assessment, Paediatrics, Prospective Studies, Surgery
Sponsor: University of KwaZulu

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Alexandra Torborg 12 July 2021 
 
ASOS-Paeds Protocol v1.0 
 
African Surgical Outcomes Study in Paediatric patients (ASOS-Paeds) 
 
An African, international multi-centre fourteen-day evaluation of patient care and 
clinical outcomes for paediatric patients undergoing surgery 
 
Protocol version 1.0 
12 July 2021 
 
 
 
 
 
 
   
 
Alexandra Torborg   
Chief Investigator 
 
 
 
Chief Investigator contact details 
Dr Alexandra Torborg 
Perioperative Research Group,  
Discipline of Anaesthesiology and Critical Care 
Nelson R. Mandela School of Medicine 
Private Bag 7, Congella, 4013 
KwaZulu-Natal, South Africa 
E-mail: alexandra@iafrica.com 
Telephone: +27 (0)833850217 
 
 

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ASOS-Paeds Protocol v1.0 
Steering committee 
1. Alexandra Torborg MBChB FCA(SA), Discipline of Anaesthesiology and 
Critical Care Medicine, Nelson R. Mandela School of Medicine, University of 
KwaZulu-Natal, Durban, South Africa  
2. Bruce Biccard MBChB FCA(SA) FFARC(I) MMedSci PhD, Professor and 
Second Chair, Department of Anaesthesia and Perioperative Medicine, 
Groote Schuur Hospital and University of Cape Town, South Africa 
3. Rupert Pearse MD(Res), Professor of Intensive Care Medicine, Queen Mary 
University of London, Royal London Hospital, London, E1 1BB, United 
Kingdom 
4. Priyanka Naidu MBChB, Department of Research, Education, and Innovation, 
Operation Smile, Virginia Beach, Virginia, USA, Centre for Global Surgery, 
Department of Global Health, Stellenbosch University, Tygerberg, South 
Africa. 
5. Hyla Kluyts DMed (Anaest), Department of Anaesthesiology, Sefako 
Makgatho Health Sciences University, South Africa 
6. Mary T. Nabukenya MMED, FCA(ECSA), Lecturer, Makerere University 
College of Health Sciences, Paediatric anaesthesiologist, Mulago National 
Referral Hospital, Kampala, Uganda 
7. Adesoji O Ademuyiwa, FACS, Professor of Surgery (Paediatric and Surgical 
Epidemiology), Department of Surgery, College of Medicine, University of 
Lagos and Lagos University Teaching Hospital, Lagos, Nigeria 
 
Patient advocate 
TBC 
 
 

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Funders 
None as yet 
 
 
 
 
 
 

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Table of Contents 
1. 
List of abbreviations ............................................................................................ 5 
2. 
Summary ............................................................................................................... 6 
3. 
Introduction .......................................................................................................... 7 
4. 
Study objectives ................................................................................................... 8 
4.1 Primary objective ........................................................................................................... 8 
4.2 Secondary objectives .................................................................................................... 8 
5. 
Methods ................................................................................................................. 8 
5.1 
Study design............................................................................................................. 8 
5.2 
Inclusion criteria ...................................................................................................... 8 
5.3 
Exclusion criteria ..................................................................................................... 9 
5.4 
Hospitals ................................................................................................................... 9 
5.5 
Research Ethics and Informed Consent ............................................................... 9 
5.6 
Recruitment and screening .................................................................................. 10 
5.7 
Data collection and collation ................................................................................ 10 
5.8 
Dataset .................................................................................................................... 11 
5.9 
Case record forms ................................................................................................. 12 
5.10 Sample size calculation ............................................................................................ 12 
5.11 Statistical analysis..................................................................................................... 12 
5.12  Primary outcome measures ................................................................................. 13 
5.13  Secondary outcome measures ............................................................................ 13 
6. 
Study organisation and management ............................................................. 13 
6.1 
Study steering committee ..................................................................................... 13 
6.2 
Patient advocate .................................................................................................... 14 
6.3 
Country co-ordinators ........................................................................................... 14 
6.4 
Local co-ordinators ............................................................................................... 14 
6.5 
Training of investigators ....................................................................................... 15 
7. 
Data management and ownership ................................................................... 15 
8. 
Publication plan ................................................................................................. 15 
9. 
References .......................................................................................................... 16 
10. 
Appendices ..................................................................................................... 17 
 
 
 

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1. List of abbreviations 
 
APRICOT  
           Anaesthesia PRactice in Children Observational Trial 
ASOS  
 
African Surgical Outcomes Study 
ASOS-2 
 
African Surgical OutcomeS-2 (ASOS-2) trial 
EuSOS 
 
European Surgical Outcomes Study 
SAPSOS 
 
South African Paediatric Surgical Outcomes Study 
 
 

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2. Summary 
 
Short title 
ASOS-Paeds 
Methodology 
A prospective international, multi-centre, African observational study 
Research sites 
Hospitals undertaking paediatric surgery in participating African 
countries. 
Objective 
To confirm the incidence of in-hospital postoperative complications in 
paediatric surgical patients aged < 18 years in Africa. 
Number of 
patients 
7000 patients 
Inclusion 
criteria 
All consecutive paediatric patients aged < 18 years admitted to 
participating hospitals undergoing elective and non-elective surgery 
Exclusion 
criteria 
Obstetric surgery 
Statistical 
analysis 
The primary outcome measure is in-hospital postoperative complications 
censored at 30 days postoperatively 
Proposed start 
date 
September 2021 
Proposed end 
date 
September 2022 
Trial duration  
Until hospital discharge, censored at 30 days 
 
 

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3. Introduction 
 
Surgery is a cost-effective public health intervention. There are significant disparities 
in access to and the safety of surgical and anaesthesia services in low and middle-
income countries (LMICs) compared to high-income countries (HICs).1 There is a 
large burden of surgical disease in the paediatric surgical population with a large 
unmet need.2 3 In Africa, children comprise a significant proportion of the population 
with approximately 50% of the population being ≤19 years old.4 
Postoperative complications are an important determinant of surgical morbidity and 
mortality. Limited data from Africa suggests the risk factors for, incidence and 
outcomes associated with paediatric surgical complications differ from HICs. In the 
prospective, observational South African Paediatric Surgical Outcomes Study 
(SAPSOS), the patients in this middle-income country (MIC),5 had double the 
incidence of complications6-8, and the types of complications differed from HICs, with 
a predominance of infective complications. Furthermore, the risk factors for 
complications (ASA physical status, urgency of surgery, severity of surgery and 
infective indication for surgery) were different from HICs, where risk factors include 
gestational age, ASA physical status >3, a history of cardiovascular disease, and 
cardiovascular, neurological, or orthopaedic surgical procedures.9 Postoperative 
mortality was ten times higher in South Africa than in a prospective study in HICs.10 
A prospective study of paediatric perioperative mortality in 24 Kenyan hospitals 
showed a 7 day postoperative mortality of 1.7%.11, which is 17 times higher than that 
reported in HICs. 
The African Surgical Outcomes Study (ASOS) has described surgical outcomes in 
adult patients in Africa.12  Patients had a lower risk profile and fewer complications 
compared to those in HICs. However, the postoperative mortality was twice that of 
the global average. 
There is a need to determine the burden of the complications in paediatric surgical 
patients in Africa, and the risk factors for and the type of complications experienced. 
If we do this, we will be able to target appropriate interventions to improve surgical 
outcomes for children in Africa. We have the capacity to do this important work, 
through the African Perioperative Research Group (APORG) group. 
 

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4. Study objectives 
 
4.1 Primary objective 
To determine the incidence of in-hospital postoperative complications up to 30 
days post-surgery in paediatric surgical patients <18 years in Africa 
 
4.2 Secondary objectives 
In paediatric surgical patients < 18 years in Africa: 
1. To determine the in-hospital postoperative mortality rate up to 30 days post-
surgery, 
2. To determine the incidence of intraoperative severe critical incidents, 
3. To determine the association between pre-operative, intra-operative and 
facility factors with postoperative complications and death.  
5. Methods 
5.1 Study design 
Fourteen-day, international African multi-centre prospective cohort study of 
paediatric patients (<18 years) undergoing surgery. This study will be 
registered on ClinicalTrials.gov. 
5.2  Inclusion criteria  
All consecutive patients < 18 years, admitted to participating hospitals during 
the study period who undergo elective and non-elective surgery. This will 
include day case surgery, operative procedures outside operating theatres 
where a general anaesthetic (GA) is performed. Recruitment will run for 
fourteen days, commencing on the date chosen by each participating hospital 
within the study cohort period of 01.09.2021 until 30.09.2022. Recruitment will 
start at 07h00 on day one and finish at 06h59 on the fourteenth day.  
 

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5.3  Exclusion criteria 
1. Patients undergoing radiological or other procedures not requiring general 
anaesthesia, or where general anaesthesia is performed but no procedure is 
performed e.g. general anaesthesia during magnetic resonance imaging 
(MRI).  
2. Patients having obstetric surgery. 
3. Prior participation in the ASOS-Paeds. 
 
5.4  Hospitals 
We aim to recruit as many African hospitals as possible. Each hospital will 
receive an individual report allowing comparison of their dataset to that of the 
overall national cohort.  
 
5.5  Research Ethics and Informed Consent  
Research ethics and regulatory approvals will be sought before starting the 
study at each site, in accordance with national research legislation/guidelines 
for that country.  
The national leaders will ensure the necessary ethics and regulatory 
approvals are obtained for the participating hospitals in their country. 
Hospitals will not be permitted to record data unless ethics approval or an 
equivalent waiver is in place. 
This study is in effect a large-scale clinical audit and thus does not pose a 
significant risk to the study population. We expect that in most, if not every 
country, there will be no requirement for individual patient consent as all data 
will be anonymised and is already recorded as part of routine clinical care.  
A precedent has already been set internationally. In the original EuSOS study, 
consent was waived in 27 of the 28 European countries participating13, in the 
ASOS study12  and in the ASOS-2 trial consent was waived in the majority of 
hospitals. In previous African paediatric perioperative studies, written consent 

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was waived by six out of the eight ethics committees in the SAPSOS study5 
and in a study in Kenya, written informed consent was waived in all 24 
participating hospitals.11  
‘Broadcasting’ signage documents will be used at participating sites to ensure 
that all patients and parents/guardians are aware that the hospital is 
participating in the study. These broadcasting documents will be placed in key 
areas around participating hospitals explaining the study dates and the nature 
of the study. (Appendix 1) 
 
5.6  Recruitment and screening 
We expect all consecutive paediatric patients aged <18 years undergoing 
elective and non-elective surgery to be included in the study.  
Broadcasting through appropriate hospital notices and signage will inform the 
patients, their parents/guardians and the public that the hospital is 
participating in the study. 
Each hospital will be required to record and submit a screening log of all 
eligible patients. 
 
5.7  Data collection and collation 
Each individual hospital will collect and record data on either an electronic or 
paper case record form (CRF) for every patient recruited. Paper CRFs will be 
stored within a locked office in each hospital as they will include identifiable 
patient data in order to allow follow-up of clinical outcomes. Data will then be 
pseudo-anonymised by generation of a unique numeric code and transcribed 
by local investigators onto a secure, password protected internet based 
electronic CRF in the REDCap platform. Each patient will only be identified on 
the electronic CRF by their numeric code; thus, the co-ordinating study team 
cannot trace data back to an individual patient without contact with the local 
team. A participant (patient) list will be used in each hospital to match 
identifier codes in the database to individual patients in order to record clinical 

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outcomes and supply any missing data points. Access to the data entry 
system will be protected by username and password delivered during the 
registration process for individual local investigators. All electronic data 
transfer between participating hospitals and the co-ordinating centre will be 
encrypted using a secure protocol (HTTPS/SSL 3.0 or better).  
Where individual hospitals are unable to access the internet-based case 
record form, pseudo-anonymised coded data may also be sent by facsimile 
(fax), by registered mail, e-mail or WhatsApp messaging to the coordinating 
centre if necessary. 
Each hospital will maintain a secure study file including a protocol, local 
investigator delegation log, ethics approval documentation, the participant list, 
and other additional documentation such as study definitions.  
A final summary printout of included patients with major variables should be 
produced for each hospital together with final data submission to double 
check for completeness and accuracy. 
 
5.8  Dataset 
A realistic data set will be fundamental to the success of the investigation, and 
this was confirmed in the EuSOS13, SASOS14 and SAPSOS5 studies where 
nearly complete data was available on patients. Based on the SAPSOS study 
of paediatric outcomes in 43 South African hospitals, we have adopted this 
dataset with minor changes to remove data which was found to be redundant, 
in order to develop a simple, lean and pragmatic data set. We believe that this 
simple data set will encourage hospitals to participate.  
Hospital-specific data for each hospital will be collected once (Appendix 2) 
including: hospital level of care (first, second, third), number of operating 
rooms, number of specialists, number and level of critical care beds, 
equipment appropriate to paediatric surgery and anaesthesia, availability of 
medication and blood, details about the reimbursement status of the hospital 
and public holidays or other local factors affecting patient throughput during 
the study period. 

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5.9  Case record forms 
An ASOS-Paeds CRF will be completed for every eligible patient who 
undergoes surgery during the cohort period (Appendix 3). Patients will be 
followed up until hospital discharge. This will be censored at thirty days i.e. 
patients will be followed up until discharge or for thirty days postoperatively if 
still in hospital, whichever is the shorter time period. The outcomes definition 
document is shown in Appendix 4. 
   5.10 Sample size calculation 
Our plan is to recruit as many hospitals as possible from each participating  
country and ask them to include all eligible patients in the study. We do not 
have a specific sample size and statistical models will be adapted to the event 
rate provided by the sample recruited, in order to prevent overfitting of any 
logistic regression models. 
   5.11 Statistical analysis 
The data to be collected are all collected as part of routine clinical care. 
Categorical variables will be described as proportions and will be compared 
using chi-square tests. Continuous variables will be described as mean and 
standard deviation if normally distributed or median and interquartile range if 
not normally distributed. Comparisons of continuous variables between 
groups will be performed using t-tests, one-way ANOVA or equivalent non-
parametric tests as appropriate. Univariate analysis will be performed to test 
factors associated with postoperative complications, critical care admission 
and in-hospital death. 
Single-level and hierarchical multi-level logistic regression models will be 
constructed to identify factors independently associated with these outcomes 
and to adjust for differences in confounding factors. Factors will be entered 
into the models based on their univariate relation to outcome (p<0.05), 
biological plausibility and low rate of missing data. 
 
Results of logistic regression will be reported as adjusted odds ratios (OR) 
with 95% confidence intervals. The models will be assessed through the use 

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of sensitivity analyses to explore possible interacting factors and examine any 
effect on the results. A statistical analysis plan will be written prior to analysis. 
 
 5.12  Primary outcome measures 
Incidence of in-hospital postoperative complications in paediatric surgical 
patients in Africa.  
5.13  Secondary outcome measures 
1 a. The day of surgery mortality rate for patients < 18 years undergoing 
surgery in Africa.  
b. The in-hospital mortality rate for patients < 18 years undergoing 
surgery in Africa censored at 30 days. 
2 Risk factors associated with in-hospital complications 
3 Time from first presentation to operation 
4 Incidence of severe intraoperative critical incidents 
5 Level of qualification of anesthesia and surgery providers and number of 
specialists per paediatric population. 
6 Rate of admission to critical care. 
 
6. Study organisation and management  
6.1 Study steering committee  
The Steering Committee will be chaired by AT. The study management team 
will be appointed by the Steering Committee and led by AT. The duties of this 
team will include administration of all project tasks, communication between 
project partners (including funders, Steering Committee members, national 
and local coordinators, etc.), data collation and management and preparation 
of reports for individual study sites. The Steering Committee is responsible for 
the scientific conduct and consistency of the project. The Steering Committee 
will ensure communication between the funder(s), study management team 
and co-ordinators as necessary. 

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6.2 Patient advocate 
Patient advocate(s) will be appointed who will advise the Steering Committee 
on possible protocol amendments if required, based on patient concerns 
regarding delivery of the study or communication of the study. 
  
6.3 Country co-ordinators 
Country co-ordinators will be appointed by the steering committee to lead the 
project within individual countries and:  
• Identify local co-ordinators in participating hospitals 
• Assist with translation of study paperwork as required 
• Ensure distribution of research manuals, and other research materials 
• Ensure necessary regulatory and ethics approvals are in place prior to 
recruitment 
• Ensure good communication with the participating sites in her/his 
country 
 
6.4 Local co-ordinators 
Local co-ordinators in individual institutions will have the following 
responsibilities: 
• Provide leadership for the study in their institution 
• Ensure all relevant regulatory and ethics approvals are in place for their 
institution 
• Ensure adequate training of all relevant staff prior to data collection 
• Supervise daily data collection and site recruitment and follow up 
management 
• Act as guarantor for the integrity and quality of data collected 
• Ensure timely completion of electronic CRFs 

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• Communicate with the relevant national co-ordinator 
 
6.5 Training of investigators 
Training will be done using instructional videos placed on the study website. 
Each study site will be required to complete an online questionnaire as part of 
the site initiation, prior to starting data collection. 
 
7. Data management and ownership 
On behalf of the Steering Committee, the Department of Anaesthesia and 
Perioperative Medicine, Groote Schuur Hospital and University of Cape Town 
will act as custodian of the data. The Steering committee will retain the right to 
use all pooled data for scientific and other purposes. Members of the ASOS-
Paeds study group will have the right to access the pooled data for research 
purposes provided the research proposal has been reviewed and deemed 
appropriate by the Steering Committee. The primary consideration for such 
decisions will be the quality and validity of any proposed analysis. Only 
summary data will be presented publicly, and all institutions will be 
anonymised except in the individualised report provided to each institution at 
the end of the study. Individual patient data provided by participating sites 
remain the property of the respective institutions. 
 
8. Publication plan 
Data will be presented and disseminated in a timely manner. The Steering 
Committee will appoint a writing committee to draft the scientific report(s) of 
this investigation. The group will be known as ‘The ASOS-Paeds 
Investigators’. It is anticipated that a number of secondary analyses will be 
performed. ASOS-Paeds investigators will be given priority to lead such 
analyses and are encouraged to do so. Participation and authorship 
opportunities will be based on contribution to the primary study. On request, 
hospitals will be provided with an individual report allowing comparison of their 

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individual hospital’s summary data to that of their national cohort. In line with 
the principles of data preservation and sharing, the Steering Committee will, 
after publication of the overall dataset, consider all reasonable requests to 
make the dataset available in whole or part for secondary analyses and 
scientific publication. The Steering Committee will consider the scientific 
validity and the possible effect on the anonymity of participating hospitals prior 
to granting any such requests. Where appropriate, a prior written agreement 
will set out the terms of such collaborations. The Steering Committee will 
consider proposals for secondary analyses on the basis of the scientific 
quality of the proposal. The Steering Committee must approve the final 
version of all manuscripts prior to submission, whether they relate to part or all 
of the ASOS-Paeds dataset.  
 
9.  References 
 
1. Bainbridge D, Martin J, Arango M, et al. Perioperative and anaesthetic-related 
mortality in developed and developing countries: a systematic review and 
meta-analysis. Lancet 2012;380(9847):1075-81. doi: 10.1016/s0140-
6736(12)60990-8 [published Online First: 2012/09/25] 
2. Bickler SW, Rode H. Surgical services for children in developing countries. Bull 
World Health Organ 2002;80(10):829-35. [published Online First: 2002/12/10] 
3. Butler EK, Tran TM, Nagarajan N, et al. Epidemiology of pediatric surgical needs 
in low-income countries. PLoS One 2017;12(3):e0170968. doi: 
10.1371/journal.pone.0170968 [published Online First: 2017/03/04] 
4. 2014 World Population Data Sheet, 2014. 
5. Torborg A, Cronje L, Thomas J, et al. South African Paediatric Surgical Outcomes 
Study: a 14-day prospective, observational cohort study of paediatric surgical 
patients. Br J Anaesth 2019;122(2):224-32. doi: 10.1016/j.bja.2018.11.015 
[published Online First: 2019/01/29] 
6. GlobalSurg C. Determinants of morbidity and mortality following emergency 
abdominal surgery in children in low-income and middle-income countries. 
BMJ Glob Health 2016;1(4):e000091. doi: 10.1136/bmjgh-2016-000091 
[published Online First: 2017/06/08] 
7. Weinberg AC, Huang L, Jiang H, et al. Perioperative risk factors for major 
complications in pediatric surgery: a study in surgical risk assessment for 
children. J Am Coll Surg 2011;212(5):768-78. doi: 
10.1016/j.jamcollsurg.2011.02.006 [published Online First: 2011/03/26] 
8. Saito JM, Chen LE, Hall BL, et al. Risk-adjusted hospital outcomes for children's 
surgery. Pediatrics 2013;132(3):e677-88. doi: 10.1542/peds.2013-0867 
[published Online First: 2013/08/07] 
9. Wood G, Barayan G, Sanchez DC, et al. Validation of the pediatric surgical risk 
assessment scoring system. J Pediatr Surg 2013;48(10):2017-21. doi: 
10.1016/j.jpedsurg.2013.04.017 [published Online First: 2013/10/08] 

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10. Habre W, Disma N, Virag K, et al. Incidence of severe critical events in paediatric 
anaesthesia (APRICOT): a prospective multicentre observational study in 261 
hospitals in Europe. Lancet Respir Med 2017;5(5):412-25. doi: 
10.1016/S2213-2600(17)30116-9 [published Online First: 2017/04/02] 
11. Newton MW, Hurt SE, McEvoy MD, et al. Pediatric Perioperative Mortality in 
Kenya: A Prospective Cohort Study from 24 Hospitals. Anesthesiology 2019 
doi: 10.1097/ALN.0000000000003070 [published Online First: 2019/12/07] 
12. Biccard BM, Madiba TE, Kluyts HL, et al. Perioperative patient outcomes in the 
African Surgical Outcomes Study: a 7-day prospective observational cohort 
study. Lancet 2018;391(10130):1589-98. doi: 10.1016/S0140-6736(18)30001-
1 [published Online First: 2018/01/08] 
13. Pearse RM, Rhodes A, Moreno R, et al. EuSOS: European surgical outcomes 
study. Eur J Anaesthesiol 2011;28(6):454-6. doi: 
10.1097/EJA.0b013e328344907b [published Online First: 2011/05/06] 
14. Biccard BM, Madiba TE. The South African Surgical Outcomes Study: A 7-day 
prospective observational cohort study. South African Medical Journal 
2015;105(6):465-75. doi: 10.7196/SAMJ.9435 
 
 
10.  Appendices 
 
Appendix 1 – Broadcasting document 
Appendix 2 – Hospital Information and site initiation record form 
Appendix 3 – Case record form (CRF) 
Appendix 4 – Outcomes definitions document