Project Crocodile
CatastROphic expenditure among COlorectal cancer patients in InDIa and barriers for treatment compLiancE (CROCODILE)
Research topic and its relevance:
Little is known about colorectal cancer treatment delivery in India and the associated costs. The aim of this study is to identify financial and non-financial barriers for colorectal cancer treatment compliance in India.
Financial protection is one of the global health priorities defined by the WHO (Sustainable Development Goal 3.8) and mitigating against catastrophic expenditure has also been prioritised by the Lancet Commission on Global Surgery.
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Study Design:
CROCODILE is a mixed-methods study including:
1. A quantitative workstream: prospective cohort feasibility study to assess catastrophic expenditure and treatment compliance rates among colorectal cancer patients in four hospitals in India.
2. a qualitative workstream: to explore patients and professionals perspectives on barriers and facilitators for treatment compliance.
Methodological details:
Quantitative workstream: Catastrophic expenditure will be defined as treatment cost being higher than 40% of non-subsistence household income. Treatment costs will include medical, non-medical and indirect expenses. Income assessment will be compared between three methods: patient-reported income, through the International Wealth Index and through the Gapminder tool.
Qualitative workstream: individual semi-structured interviews will be performed with colorectal cancer patients and cancer care professionals. A framework analysis will be performed from the raised categories.
The results will be triangulated with the quantitative workstream for mutual knowledge enrichment.
CROCODILE within the NIHR Global Health Research Unit on Global Surgery:
The feasibility of catastrophic expenditure data collection will be tested in this study, to inform future larger scale studies on the topic. It will also generate pilot work in the India setting, to be used in policy informing studies through modelling or other methodologies.
Project Feather
Retention is a major challenge in international trials, and has been recognised as a global research priority through a James Lind Alliance Priority Setting Partnership. The Standard Protocol Items: Recommendations for Interventional Trials’ (SPIRIT) guidelines define non-retention as ‘instances where participants are prematurely “off-study” (i.e., consent withdrawn or lost to follow-up) so outcome data cannot be obtained from them.
Trial retention may be particularly challenging in low resource settings where patients may have to travel long distances to return to hospital or take further time out of work where they are already financially vulnerable following their index operation. Minimising burden on trial participants during trial follow-up and identifying culturally-attuned methods for encouraging ongoing participation may reduce risk of both risk of attrition bias and the cost randomised studies. However, there is insufficient evidence to make recommendations for global surgery studies.
FEATHER is an investigation using qualitative methods embedded within several international multi-centre randomised trials (a study within a trial or SWAT).
Key Documents
You can view the FEATHER protocol here.
FEATHER Topic Guide – Patients can be accessed here.
FEATHER Topic Guide – Site Investigator can be accessed here.
FEATHER Patient Identification Log A can be accessed here.
FEATHER Patient Identification Log B can be accessed here.
FEATHER PIS – Adult can be accessed here.
FEATHER PIS – Stakeholder can be accessed here.
Project Starfish
CEI STARFISH Case Study
SToma cARe For Improvement reSearcH (STARFISH): Epidemiologic study of stoma cases in Lower- and Middle-Income Countries and qualitative research on the challenges of stoma care
The reasoning behind the STARFISH study
The STARFISH study was proposed in 2019 by Dr Carmela (Mela) Lapitan, who heads our NIHR GSU Centre in The Philippines.
Mela says even though there has been immense research done into stoma care in high income countries with patients now being well supported and top notch appliances being provided, there is little research into practical problems, as well as feasible and affordable solutions in low resource settings. Her NIHR-funded STARFISH study therefore sets out to assess the burden and experience of stoma surgery and the challenges of stoma care in LIMCs with the aim to capture patients’ biggest challenges, particularly on access to and availability of stoma appliances, and to generate information and develop methods to encourage further research.
Patients Doing Research vs. Patients Being Researched
As outlined in the ‘Background’ video, the study is heavily patient-centered with a major aspect of it being focus groups and one-to-one interviews with stoma patients, informal caregivers, health care providers and staff involved in stoma care services to gather information on experiences, priorities, challenges and coping strategies relating to stoma care. Mela therefore felt it was crucial to involve patients in the design of the study to help highlight barriers to participation and inform the smooth running of focus groups and interviews. Patients being part of the research team: A new concept in The Philippines that turned out to have its challenges and obstacles.
In the next video, Mela outlines the why, how and what of patient involvement with STARFISH.
Mela experienced the ‘challenge of engaging a patient as part of the research team because of very poor awareness on research and their potential contribution to such beyond being a participant.’ – Something that the Global Surgery Unit encounters in other LMICs, as well. Is this highlighting the need for more health education?
Take Home Messages
Mela’s Top Tipps
If possible, learn from other’s experience and utilise their expertise,
E.g. for STARFISH: Early engagement of a social scientist with links into communities in the conceptualisation and design of the study
Make sure that involved patients or community members represent people relevant to your study, preferably with lived experience
If possible, engage with patient groups. This will not only help inform and shape the study, but also help with recruitment of participants later on
" Bringing together surgeons, researchers and policy makers to set the local research agenda according to patient need in LMIC and ensuring all patients have the opportunity to take part in our research. "
John Smith, Head of Research
NIHR Global Health Research Unit on Global Surgery
Project Lion
LION (LaparoscopIc Versus Open Appendectomy): Cost comparison in a lower- middle income setting
This study aims to compare the outcome and cost of conventional open and laparoscopic appendectomy for clinically confirmed, uncomplicated, acute appendicitis in a low resource setting. Although the cost effectiveness of laparoscopic surgery has been investigated previously in high human development index (HDI) countries, similar studies are lacking in low and middle HDI countries.
Led by Dr Adewale Adisa at the NIHR hub in Nigeria, this study will compare outcomes following open and laparoscopic appendectomy in approximately 150 patients at 3 hospitals in Nigeria.
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Project Kiwi
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Project Giraffe
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You can view the initial concept slide for the GIRAFFE study here.
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Project Talon
Feasibility and diagnostic accuracy of Telephone Administration of an adapted patient-reported Wound HeaLth QuestiONnaire for assessment of surgical site infection following abdominal surgery in low and middle-income countries (TALON)
TALON is a substudy embedded in the FALCON and ChEETAh trials, run as part of an NIHR Doctoral Research Fellowship in Global Surgery. The aim of the substudies is to improve the quality and efficiency of surgical trial methodology across low- and middle-income countries.
We are very interested in hearing from anyone interested in trial methodology or outcome research in Low and Middle-income Countries.
Please contact us to open the discussion!
TALON Overview
The current ‘gold standard’ for assessment of surgical site infection (SSI) during the 30-days after surgery is an in-person review according to Centre for Disease Control Criteria. However, in-person assessment is labour and time intensive, and requires patients to take additional time-off work and incur costs of travel. More efficient follow-up pathways are required, for example over the telephone, that are of equal quality to in-person wound assessment. This has become particularly relevant in light of the COVID-19 pandemic, where visits to hospital put patients at increased risk of cross-infection.
TALON is a multi-centre, international, non-randomised Study Within a Trial, divided into two sections (TALON-1 and TALON-2). The overall aim is to evaluate the feasibility and validity of telephone administration of patient-reported questionnaire for wound follow-up in low resource settings.
TALON-1: Objectives
- To assess patient acceptability, cross-cultural and cross-language equivalence, and content validity of the Wound Healing Questionnaire (WHQ) across LMICs.
- To assess the scaling and psychometric properties of the Wound Health Questionnaire when used across different patient populations and subgroup
- To adapt the WHQ to improve validity of the PROM across different LMICs
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TALON-2: Objectives
- To evaluate the diagnostic accuracy of telephone administration of the WHQ in evaluation of abdominal surgical site infection across LMICs
- To assess the feasibility of delivery of the telephone WHQ by a non-surgeon researcher within the CHEETAH trial
- To assess the feasibility of wound photography as a diagnostic adjunct for telephone-based wound follow-up
You can view the TALON Statistical Analysis Plan here: TALON – Statistical Analysis Plan (V1-0)
Project Tiger
TIGER Case Study
TIGER (Task shifting Inguinal hernia Repair between surgeons and technicians): development of a randomised trial in low and middle income countries
Can technicians perform mesh inguinal hernia repair safely and cost-effectively in rural surgical settings in low and middle income countries?
This pilot trial aims to investigate delivery of a standardised, measurable training programme for technicians to perform a mesh inguinal hernia repair.
More information about our work in rural Ghana will be published soon. Until then, please have a look at the poster we presented at our annual GSU prioritisation workshop in Accra, Ghana, in November 2019.
Bringing together surgeons, researchers and policy makers to set the local research agenda according to patient need in LMIC and ensuring all patients have the opportunity to take part in our research.
Project Penguin
PENGUIN: perioperative respiratory care and outcomes for patients undergoing high risk abdominal surgery.
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Background
PENGUIN is the third global surgical randomised clinical trial following on from the success of FALCON and CHEETAH.
PENGUIN aims to reduce Surgical Site Infections (SSI) and pneumonia following abdominal surgery in low and middle-income countries.
Pneumonia and SSI are the most common complications following surgery across the world. They are the commonest healthcare-associated infections in low and middle-income countries, placing significant financial costs on healthcare systems. The increased costs can be a major problem in countries with lower incomes where patients often pay for their own treatment.
PENGUIN is an investigator-initiated and investigator-led trial. PENGUIN is funded by the UK National Institute for Health Research (NIHR).
Aims & Objectives
Primary Objective
The primary objectives of the main RCT is to assess whether preoperative 0.2% chlorhexidine mouthwash reduces the rate of postoperative pneumonia at 30-days compared to no mouthwash, and to assess if 80-100% fraction inspired oxygen (FiO2) used during surgery reduces the rate of postoperative SSI at 30-days compared to 21-30% FiO2.
Secondary Objectives
- To assess the impact of the interventions on secondary clinical outcomes up to 30 days post-surgery including: mortality rates, repeat abdominal surgery to treat complications (oxygen only), repeat abdominal surgery, length of hospital stay, return to normal activities and admission to z critical care unit.
- To explore the impact of the intervention on resource usage and additional costs to the secondary health service provider.
The recruitment target is 12,942 participants across all centres
Collaborating Countries
PENGUIN is an international trial being conducted in multiple NIHR funded countries. Click on the map below to see participating countries.
Safe and affordable surgery and anaesthesia is a global health priority. There is strong evidence that poor perioperative care is a key factor limiting the net improvements in health which could be achieved through improved global access to surgery. One in six patients experience complications after surgery in LMICs, most commonly infections. Surgical complications reduce life expectancy, quality of life, prevent return to work and cause catastrophic expenditure. For patients undergoing major abdominal surgery, complication rates exceed 30%. Seventy million such procedures are performed worldwide each year (excluding caesarean section) making this the most important global cause of post-operative morbidity and mortality.
An important route of bacterial entry into the lower respiratory tract is aspiration of bacteria in oral and pharyngeal secretions during endotracheal intubation. This results in colonisation of the lower respiratory tract, which overwhelms the patient’s mechanical, humoral, and cellular defences to establish infection following surgery. One potential method to prevent pneumonia after surgery may be to ask patients to use an antiseptic mouthwash with 0.2% chlorhexidine prior to anaesthesia. This treatment is very simple and low in cost, making it ideal for widespread implementation in low and middle-income countries. An international consensus statement from 1,000 anaesthetists, intensive care specialists, surgeons, and epidemiologists identified chlorhexidine mouthwash as a potential inexpensive intervention that may reduce perioperative mortality. However, the statement highlighted the need for effectiveness trials testing chlorhexidine mouthwash before it can be adopted into clinical pathways like perioperative care.
World Health Organisation guidelines recommend the use of liberal inspired oxygen concentrations of 80% during surgery and up to four hours after extubation to help prevent SSI. However, many clinical experts question this recommendation and highlight flaws in the evidence on which it is based. SSIs are clearly important being the most frequent healthcare-associated infection in LMICs, affecting one in three patients undergoing contaminated or dirty surgery. The delivery of high inspired oxygen concentrations during anaesthesia is technically difficult and expensive in resource poor settings. There is also some concern that high inspired oxygen concentrations may even increase mortality amongst acutely ill patients. There is an urgent need for high quality evidence across different settings to evaluate the clinical benefits and harms of high inspired oxygen concentrations to prevent SSI.
The trial aims to assess whether either:
1. Preoperative 0.2% chlorhexidine mouthwash versus no mouthwash can reduce the incidence of post-operative pneumonia 30 days after surgery.
2. 80-100% FiO2 (‘liberal’) versus 21-30% FiO2 (‘restrictive’) during surgery can reduce the incidence of post-operative SSI 30 days after surgery.
PENGUIN is an international, multi-centre, pragmatic, outcome assessor-blinded, 2×2 factorial randomised controlled trial, with an internal pilot designed to assess the effect of the trial interventions in low and middle-income countries.
Patients (adult and children) undergoing an elective or emergency midline laparotomy surgical procedure with an anticipated abdominal incision of at least > 5cm in length will be eligible.
Eligible patients will be randomised at the level of the individual in a 1:1:1:1 ratio between:
1. Preoperative chlorhexidine mouthwash and 80-100% FiO2 during surgery
2. No preoperative chlorhexidine mouthwash and 80-100% FiO2 during surgery
3. Preoperative chlorhexidine mouthwash and 21-30% FiO2 during surgery
4. No preoperative chlorhexidine mouthwash and 21-30% FiO2 during surgery
The PENGUIN trial has a 6-month internal pilot in four countries (India, South Africa, Nigeria and Mexico) which aims to assess:
• If recruitment to the randomised interventions is feasible
• Compliance with treatment allocation
• Patient retention and follow-up
• Adults and children aged 10 years or over (where permitted)
• Elective or emergency abdominal surgery via midline laparotomy with an anticipated abdominal incision of at least 5cm in length
• Written informed consent of patient (signature or a fingerprint)
NB: Age criterion is country specific. Each country decides the lower age limit for the trial. This is dependent on country-specific regulatory approvals. Age eligibility varies by country.
• Patients undergoing caesarean section
• Patients with a documented or suspected allergy to chlorhexidine
• Patient unable to complete postoperative follow-up (not contactable after discharge)
• Previous enrolment in PENGUIN within the past 30 days
• American Society of Anesthesiologists (ASA) grade V patients (expected to die with or without surgery)
Sponsor
The University of Birmingham is the Sponsor of the PENGUIN Trial in all collaborating countries.
International Coordinating Centre
The PENGUIN International Coordinating Centre trial office is at the University of Birmingham Clinical Trials Unit.
Each country will appoint a National Coordinating Investigator (NCI) and National Coordinating Centre (NCC) – the Hub – who will take national responsibility for the study. The Hubs will be responsible for coordinating recruitment from a range of representative local hospitals – Spokes.
Central and National Trial Management Groups
The Central and National Trial Management Groups (CTMG) include those individuals responsible for the day-to-day running management of the trial. This will include the Chief Investigator, lead methodologist, patient representatives and PENGUIN central management staff.
Trial Steering Committee
The Trial Steering Committee provides supervision of the trial and ensures the trial is being conducted in accordance with the principles of Good Clinical Practice and other relevant regulations.
Data Monitoring Committee
The Data Monitoring Committee will give advice on whether the accumulated data from the trial, together with the results from the other relevant research justifies the continuing recruitment of further participants.
Central Trial Management Group (University of Birmingham)
PENGUIN Trial Team
Birmingham Clinical Trials Unit, Public Health Building
University of Birmingham, Edgbaston, B15 2TT
Email: penguin@trials.bham.ac.uk
Tel: from UK 0121 414 4762, International +44 121 414 4762
Project Falcon
FALCON is the first global surgical trial testing measures to reduce Surgical Site Infection (SSI) following abdominal surgery in low and middle-income countries.
It was launched in December 2018 and on 07th September 2020, the final patients were randomised into the trial. In total, 5789 patients were randomised across three continents and seven countries – Mexico, Ghana, India, Nigeria, Rwanda, Benin and South Africa. With the recruitment phase having been projected to last approximately 3 years, FALCON was completed 15 months ahead of schedule – a great example of how collaboration can have truly inspiring results!
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Background
Surgical site infection is the most common complication after surgery across the world. It is the commonest healthcare-associated infection in low and middle-income countries.
Surgical site infection (SSI) causes pain, discomfort, disability and prolongs the period before the patient can taken to return to work. As such, the surgical site infection costs to healthcare systems increase significantly creating burden on a personal and a society level. The increased costs can be a major problem in countries with lower income where patients often may require paying for their own treatment.
FALCON is an investigator-initiated and investigator-led trial funded by the UK National Institute for Health Research (NIHR).
Aims & Objectives
Primary Objective
The primary objective of main RCT is to assess whether either (1) 2% alcoholic chlorhexidine versus 10% povidone-iodine for skin preparation, or (2) triclosan-coated suture versus non-coated suture for fascial closure, can reduce surgical site infection at 30-days post-surgery for each of (i) clean-contaminated and (ii) contaminated or dirty abdominal surgery.
Secondary Objectives
- To assess the impact of the interventions on secondary clinical outcomes up to 30 days post-surgery including: SSI at discharge, mortality, unplanned wound opening, re-operation, length of hospital stay, re-admission, and return to normal activities.
- To assess the impact of the interventions on the resistance of organisms isolated from wound swabs to prophylactic antibiotics administered.
- To explore the impact of the interventions on service delivery and additional costs to the secondary health service provider.
- The recruitment target is 5788 participants across all centres.
Collaborating Countries
FALCON is an international trial being conducted in multiple NIHR funded countries. Click on the map below to see participating countries.
Surgical site infection (SSI) represents a major burden for patients, doctors, and health systems across all settings. SSI is the commonest postoperative complication worldwide and the commonest healthcare-associated infection in low and middle income countries (LMICs). SSIs cause pain, discomfort, disability, and increase the time taken to return to work. SSIs increase health costs and this can have a major impact on patients, communities, and providers in LMICs where personal income is low and patients may be required to pay for their own treatment. SSI has also been associated with one-third of postoperative deaths and accounts for 8% of all deaths caused by a nosocomial infection.
The GlobalSurg-2 cohort study captured data on 12539 patients undergoing abdominal surgery across 343 hospitals in 66 countries, with a primary outcome measure of SSI. The overall SSI rate was 12.3% (1538/12539), which more than doubled across high, middle, and low human development index (HDI) countries (9.4%, 14.0%, 23.2%, respectively, p<0.001). The overall SSI rate in LMICs was 16.3% (847/5200). After risk adjustment for patient, disease, operative, and hospital factors, patients in low-income countries remained at greater risk of SSI than those in high-income countries (adjusted OR 1.60, 95% confidence interval 1.05-2.37, p=0.030). The overall SSI rates in children and adults were similar (12.1% vs. 12.3%).
Improving surgical outcomes is a global health priority, highlighted by the Lancet Commission on Global Surgery. Recent World Health Organisation (WHO) guidelines made 29 recommendations for intraoperative and postoperative measures to prevent SSI, including global perspectives relevant to LMICs. Despite inclusion of strongly graded recommendations, there was little high quality evidence in support of most interventions. In addition, none of the evidence used was derived from resource limited settings, leading to uncertainty about implementation of measures in these settings. A randomised trial with the potential to evaluate multiple interventions would establish a high quality evidence base that will inform guidance, and influence revisions to the WHO Surgical Safety Checklist. The specific interventions to be tested in the trial were selected by a Delphi process from a longlist of potential interventions based on the WHO guidelines.
The trial aims to assess whether either:
(1) 2% alcoholic chlorhexidine versus 10% povidone-iodine for skin preparation, or
(2) triclosan-coated suture versus non-coated suture for fascial closure, can reduce surgical site infection at 30-days post-surgery for each of:
(1) clean-contaminated or
(2) contaminated/dirty surgery.
FALCON is a pragmatic, patient and outcome assessor blinded, 2×2 factorial, stratified, multi-centre randomised controlled trial, with an internal pilot, to evaluate measures to reduce SSI rates in patients undergoing surgery with an abdominal incision. Strata are defined according to the anticipated category of wound contamination: (1) clean-contaminated and (2) contaminated/dirty.
Patients (adults and children) undergoing surgery with abdominal incision of at least ≥5cm, with an anticipated (1) clean-contaminated or (2) contaminated/dirty wound. Participants undergoing emergency or elective, and open or laparoscopic surgery are eligible.
Eligible patients will be randomised at the level of the individual in a 1:1:1:1 ratio between:
- 2% alcoholic chlorhexidine and non-coated suture
- 2% alcoholic chlorhexidine and triclosan-coated suture
- 10% aqueous povidone-iodine and non-coated suture
- 10% aqueous povidone-iodine and triclosan-coated suture
The FALCON trial has a 6-month internal pilot the aim of which is to assess:
- If recruitment to the randomised interventions is feasible
- Compliance with treatment allocation
- Patient retention and follow-up.
- Patients with at least one abdominal incision that is ≥5cm (open or laparoscopic extraction site), with an anticipated clean-contaminated, contaminated or dirty surgical wound. Definitions and examples of contamination are given in Table 1.
- Patients undergoing emergency (surgery on an unplanned admission) or elective (surgery on a planned admission) operations.
- Any operative indication, including trauma surgery.
- Patients able and willing to provide written informed consent (signature or a fingerprint).
- Adult and paediatric patients
NB: This criteria is country-specific. Each country decides the lower age limit for the trial. This is dependent on country-specific regulatory approvals. Age eligibility varies by country
- Patients with a documented or suspected allergy to iodine, shellfish, or chlorhexidine skin preparation solution.
- Patients unable to complete post-operative follow-up (i.e. will not be contactable after discharge).
Sponsor
The University of Birmingham is the Sponsor of the FALCON Trial in all collaborating countries.
International Coordinating Centre
The International Coordinating Centre FALCON trial office is at the University of Birmingham Clinical Trials Unit.
Each country will appoint a National Coordinating Investigator (NCI) and a National Coordinating Centre (NCC) – the Hub – who will take national responsibility for the study. The Hubs will be responsible for coordinating recruitment from a range of representative local hospitals – Spokes.
Central and National Trial Management Groups
The Central Trial Management Group (CTMG) includes those individuals responsible for the day-to-day management of the trial. This will include the trial CI, lead methodologists, patient representatives and FALCON central trial management staff.
Trial Steering Committee
The Trial Steering Committee provides overall supervision of the trial and ensures that the trial is being conducted in accordance with the principles of Good Clinical Practice and other relevant regulations.
Data Monitoring Committee
The Data Monitoring Committee will give advice on whether the accumulated data from the trial, together with the results from other relevant research, justifies the continuing recruitment of further participants.
Central Trial Management Group (University of Birmingham)
FALCON Trial Team
Birmingham Clinical Trials Unit, Public Health Building
University of Birmingham, Edgbaston, B15 2TT
Email: falcon@trials.bham.ac.uk
Tel: from UK 0121 414 4762, International +44121 414 4762