Development grant for a multicentre, randomised trial to reduce surgical site infection following emergency gastrointestinal surgery in LMICs

Lead Research Organisation: University of Birmingham
Department Name: Cancer Sciences

Abstract

THE PROBLEM: Infections in wounds after bowel surgery are common in all countries. They have adverse effects for patients, doctors and health systems. For patients, they are painful, smelly, reduce quality of life and reduce time taken to return to normal activities. They are hard to treat and require prescriptions of long courses of antibiotics and return trips to the operating theatre, increasing antibiotic resistance and reducing future available treatments. They are extremely costly and require long lengths of stay in hospital and lots of nursing time. In low and middle-income countries, they are at least twice as common as they are in high-income countries. Rates of antibiotic resistance are also higher, meaning they are even harder to treat. Wound infections affect both adults and children and since people of working age can't return quickly to work, their families and communities are also adversely affected.

FUTURE PROPOSED TRIAL: We aim to perform a large, multi-country randomised controlled trial looking at two simple interventions to reduce wound infections after emergency bowel surgery. Emergency surgery is the most common, demanding and burdensome type of bowel surgery in low and middle income countries (LMICs). Since the burden of wound infections is highest in these countries compared to other places in the world, this research proposal if timely and focussed toward a clinical need in LMICs. Wound infections are complex and testing two interventions at the same time may show even greater effect than just testing one, and it also improves value for money. The trial will be large and require around 2000 patients.

NEED FOR A DEVELOPMENT GRANT: Before we can submit a highly competitive, world-class grant proposal, we need to perform some development work to ensure that we are prepared. This work will develop a final, tangible plan for that application, and engage local doctors and research staff into the process. We aim to:

1. Hold on site meetings in participating countries, led by local surgeons, to engage a range of staff and shortlist interventions which could be tested in their units.
2. Deliver on-site research skills training that will increase local research capacity and leadership.
3. Perform small observational studies to ensure that sites have a strategy to follow-up patients during the main trial.
4. Hold our first face-to-face collaborator group meeting, to develop a finalised protocol based on the selected interventions, that can be used for a main trial application. This meeting will also allow us to foster the strongest possible relationships between our new collaborative and improve team working.
NEED FOR MORE SURGICAL RESEARCH: There is a lack of surgical research across the world, partly driven by a lack of doctors regularly performing surgical research. This initial proposal will allow is to form a collaborative that could last for many decades. We predict that this network will enable us to deliver more trials into the future, of larger sizes and complexity. In the UK, we have developed hub and spoke research networks to deliver similar trials. We aim to transfer these research skills from the NHS to LMICs to help disseminate best surgical research practice widely. This will also speed recruitment to trials and maximise generalizability. We aim that this development grant and subsequent main grant will produce a generation of surgical researchers focused on testing cost-effective interventions internationally.

Technical Summary

THE PROBLEM: Infections in wounds after gastrointestinal surgery are common in all countries. They have adverse effects for patients, doctors and health systems. They are hard to treat and require prescriptions of long courses of antibiotics and return trips to the operating theatre, increasing antibiotic resistance and reducing future available treatments. In low and middle-income countries, they are at least twice as common as they are in high-income countries.

FUTURE PROPOSED TRIAL: We aim to perform a large, multi-country randomised controlled trial looking at two simple interventions to reduce wound infections after emergency gastrointestinal surgery. Emergency surgery is the most common, demanding and burdensome type of bowel surgery in low and middle income countries (LMICs). Since the burden of wound infections is highest in these countries compared to other places in the world, this research proposal if timely and focussed toward a clinical need in LMICs.

NEED FOR A DEVELOPMENT GRANT: Before we can submit a highly competitive, world-class grant proposal, we need to perform some development work to ensure that we are prepared. This work will develop a final, tangible plan for that application, and engage local doctors and research staff into the process.

RESEARCH OBJECTIVES:
1. Hold on site stakeholder meetings in participating countries, led by local surgeons, to engage a range of staff and shortlist interventions.
2. Deliver on-site research skills training.
3. Perform small observational studies to ensure that sites have a strategy to follow-up patients during the main trial at 30-days after surgery.
4. Hold our first face-to-face collaborator group meeting.
5. Produce a finalised trial protocol based on selected interventions to either the Joint Global Health Trials Scheme or equivalent available programme.
6. To confirm our sample size calculation.

Planned Impact

-IMPACT OBJECTIVE 1: To create a world-first international network capable of delivering randomised controlled trials involving patients undergoing gastrointestinal surgery in low and middle income countries (LMICs).
-IMPACT OBJECTIVE 2: To deliver a first trial that will create a high quality evidence base to improve the health and well being of patients undergoing gastrointestinal surgery in LMICs.
-IMPACT OBJECTIVE 3: To develop trials that will test and prove cost-effective interventions relevant to surgical care in LMICs that can influence policy making.
-IMPACT OBJECTIVE 4: To develop a trial schema and supporting information that will attract major grant funding.
-IMPACT OBJECTIVE 5: To deliver research skills training to local investigators, allowing them to develop their own local research networks.

IMPACT OF THIS DEVELOPMENT GRANT (objectives 2, 4, 5): The programme of work from this development grant will immediately allow us to produce a high quality application for next year's trials grant call. This includes generating a final protocol, including a plan for implementation and quality control of the selected interventions, a strategy for follow-up and an accurate sample size calculation. In particular, local stakeholder engagement will generate unique information. For example, whilst some may have no concerns over changing gloves before wound closure, others may see it as a point for infection risk and would prefer to double glove and then remove the outer layer prior to wound closure. This type of modification is perfectly acceptable, but there is no current knowledge of these attitudes.

IMPACT OF THE FUTURE TRIAL (objective 1, 2, 3): Our future trial plans to test simple, cost effective interventions that aim to reduce surgical site infection. The interventions should be both cheap and easily implemented, but are not routinely performed at present due to a lack of evidence. If they are proved to reduce surgical site infection, they will lead to a wide scale change of practice both within network hospitals but also across all other LMIC centres too. We will build health economic assessment into the main trial application to reinforce this. We envisage that this will be publishable in a major general medical journal such as the Lancet.

IMPACT OF THE NETWORK (objective 1, 3): This collaborative represents a world first to deliver pragmatic randomised controlled trials in surgical interventions across a range of LMICs. This network will deliver research that is practice changing, and will disseminate evidence based clinical care to patients both within the research network but also to the many thousands of hospitals across all LMICs. We aim for the network to develop to deliver increasingly large and sophisticated trials in the future. By harmonising administration and setting up pathways now, we expect this to become increasingly efficient. Future example trials include:
1. Safe reduction of post-operative antibiotic use.
2. Reduction of post-operative pneumonia using simple interventions.
3. Improving pain control after surgery.
4. Early warning systems in hospital wards to reduce mortality.
IMPACT OF TEAM DEVELOPMENT (objective 5): We envisage that this programme of work will create a generation of surgical researchers with the ability to test cost-effective interventions across international networks. This includes development of the Chief Investigator, who will then be placed to apply for a career development grant and who is well supported by experienced Professorial teams. Overseas, we will support development of mirrored research leadership skills amongst collaborating surgical PIs, allowing them to develop their own hub and spoke networks, trials programmes and funding. This will be reinforced by on site research skills training, which will increase research capacity and local leadership for the future. In the future we aim to hold collaborator meetings in a participating LMIC.

Publications

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BendezĂș-Quispe G (2016) [GlobalSurg 1's participation from Peru and new challenges for GlobalSurg 2: epidemiology of surgical site infection]. in Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru

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GlobalSurg Collaborative (2016) Mortality of emergency abdominal surgery in high-, middle- and low-income countries. in The British journal of surgery

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Spence RT (2016) A multicentre evaluation of emergency abdominal surgery in South Africa: Results from the GlobalSurg-1 South Africa study. in South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde

 
Description GlobalSurg-2 SSI training module
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact As an entry requirement for GlobalSurg-2, we trained >1000 healthcare professionals from 100 countries in correct assessment of surgical site infection. This will enable healthcare professionals to better identify and treat SSI. Raising awareness will also help prevention.
 
Title Determining Universal Processes Related to Best Outcome in Emergency Gastrointestinal Surgery: an International Evaluation (GlobalSurg-1) 
Description database of 10 745 patients from 357 centres in 58 countries, undergoing emergency abdominal surgery. Outcome data provied. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact World first database. Will data share on application. 
URL https://clinicaltrials.gov/ct2/show/NCT02662231?term=globalsurg&rank=1
 
Title Determining the Worldwide Epidemiology of Surgical Site Infections After Gastrointestinal Surgery (GlobalSurg 2) 
Description GlobalSurg-2 project - 15,000 patients from 100 countries, undergoing abdominal surgery. Full outcome data available. Currently undergoing analysis prior to publication. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Currently undergoing analysis prior to publication. Will data share on application. Combining with GlboalSurg-1 dataset to create access to combined data 
 
Description GlobalSurg-RCT planning meeting 
Organisation Cairo University
Country Egypt 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation Lagos State University
Country Nigeria 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University for Development Studies
Country Ghana 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University of Benin
Country Nigeria 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University of Edinburgh
Department Centre for Cardiovascular Science
Country United Kingdom 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University of Lima
Country Peru 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University of Philippines Manila
Department National Center for Transportation Studies
Country Philippines 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University of Rwanda
Country Rwanda 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University of San Carlos of Guatemala
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University of Veracruz
Country Mexico 
Sector Academic/University 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016
 
Description GlobalSurg-RCT planning meeting 
Organisation University of the Witwatersrand
Department Department of Surgery
Country South Africa 
Sector Hospitals 
PI Contribution In November 2016, we invited 22 surgeons from 15 low and middle income countries to Birmingham to form a collaboration. This group planned their first randomised controlled trial to tackle surgical site infection. We are now finalising the protocol whilst applying for major trial funding.
Collaborator Contribution >needs assessment >trial feasability >study design >selection of interventions >follow-up pathways >committment in principle from supporting university >identification of research manager for contracts in host country
Impact >finalised protocol >subsequent funding application
Start Year 2016