Health Economics @NIHR GSU

Health Economics is the study of how individuals, healthcare providers and governments make health and healthcare decisions in the presence of limited resources. Thus, it applies the general principles of economics to the allocation of scarce resources in health and healthcare. In limited resource settings, appropriate information on the relative clinical effectiveness and cost-effectiveness of health care interventions are vital to support decisions on resource allocation.

In collaboration with the NIHR Global Surgery Unit (GSU) Policy & Implementation Committee, health economic information will be used to guide and support decision making in low- and middle- income (LMIC) settings. To this end, the planned health economic evidence generation includes the undertaking of a range of different approaches such as systematic reviews, economic modelling, cost studies and economic evaluations alongside trials.

Health Economics Activities with Clinical Trials at Global Surgery Unit

Surgical patients are at high risk of exposure to respiratory infections transmissions including coronavirus disease 2019 (COVID-19) and other complications. Despite this, some surgeries especially non-elective ones have to be performed even during the pandemic period which will likely increase post-operative pneumonia cases, hospital resource use and mortality rates.

The PROTECT Surg Trial has been planned to estimate the impact of interventions hypothesised to avert postoperative pulmonary complications during the COVID-19 pandemic. It is an international multicentre adaptive trial which will establish as quick as possible beneficial interventions, drop interventions with no evidence of effectiveness and introduce new interventions with potential of reducing pulmonary complications during the COVID-19 pandemic. In the initial design, the trial will assess the effectiveness of three interventions compared to normal practice (no trial drug): (1) lopinavir-Ritonavir (2) hydroxychloroquine and (3) a combination of Lopinavir-Ritonavir and hydroxychloroquine.

The health economics team will collaborate with the clinical team on the PROTECT Surg Trial to evaluate whether the initial three treatment drugs or other drugs that might be introduced in the trial will reflect value for money in the trial settings. The cost-effectiveness analysis which will be conducted for each participating country will be important in determining whether the benefits of the intervention drugs are reflects value for money in the trial countries.  The analysis will be conducted after completion of follow-up of the first 250 patients per arm and thereafter for every 200 patients. Because of little evidence on the cost and benefits of the interventions there is a possibility of another intervention having higher once more patients are assessed. Therefore cost-effectiveness decision will have uncertainties which can be reduced by conducting further research. So during every analysis we will calculate the expected cost of uncertainty and the next 200 patients should be recruited if expected cost of uncertainty is higher than the cost of the next recruitment.

The FALCON trial looks into the prevention of surgical site infections (SSI) in low- and middle- income countries.

The health economics sub-study within FALCON is named KIWI (Key Resource Use In Wound Infection).

Surgical site infection (SSI) is a worldwide problem which has morbidity, mortality and financial consequences [1-3].Previous studies in LMICs on the costs of SSI have been limited by small sample size single-centre hospitals which did not capture costs occurring after hospital discharge. The lack of follow up is a problem as SSI can occur after discharge [4] and costs associated with SSI have been shown to persist beyond 30 days [5]. The main FALCON trial is assessing different treatment combinations to reduce Surgical Site Infection (SSI). The FALCON KIWI sub study is assessing the resource use and costs for patients with and without SSI across several hub countries.

KIWI includes resource use collection (via additional CRFs) up to the 30 day follow-up assessment for patients and extended follow-up for any patients with an ongoing wound infection up to 60 days post-surgery.

References

1. Allegranzi B, Bagheri Nejad S, Combescure C, Graafmans W, Attar H, Donaldson L, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet (London, England). 2011;377(9761):228-41. Epub 2010/12/15. doi: 10.1016/s0140-6736(10)61458-4. PubMed PMID: 21146207.
2. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. American journal of infection control. 1999;27(2):97-132; quiz 3-4; discussion 96. Epub 1999/04/10. PubMed PMID: 10196487.
3. Gheorghe A, Moran G, Duffy H, Roberts T, Pinkney T, Calvert M. Health Utility Values Associated with Surgical Site Infection: A Systematic Review. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research. 2015;18(8):1126-37. Epub 2015/12/22. doi: 10.1016/j.jval.2015.08.004. PubMed PMID: 26686800.
4. Lankiewicz JD, Yokoe DS, Olsen MA, Onufrak F, Fraser VJ, Stevenson K, et al. Beyond 30 days: does limiting the duration of surgical site infection follow-up limit detection? Infect Control Hosp Epidemiol. 2012;33(2):202-4. Epub 2012/01/10. doi: 10.1086/663715. PubMed PMID: 22227993; PubMed Central PMCID: PMCPMC3608264.
5. Petrosyan Y, Thavorn K, Maclure M, Smith G, McIsaac DI, Schramm D, et al. Long-term Health Outcomes and Health System Costs Associated With Surgical Site Infections: A Retrospective Cohort Study. Ann Surg. 2019. Epub 2019/03/26. doi: 10.1097/sla.0000000000003285. PubMed PMID: 30907758.

The PENGUIN trial is a 2 x 2 factorial, international pragmatic randomised trial. The trial aims to assess whether preoperative chlorhexidine mouthwash when compared to no-mouthwash-surgery can reduce incidence of post-operative pneumonia (POP) and whether perioperative liberal oxygen versus restrictive oxygen can reduce incidence surgical site infections (SSI) at 30-days among abdominal surgery patients.

Two preliminary economic evaluations will be conducted prior to the clinical trial:

(1) The PENGUIN mouthwash preliminary economic evaluation. POP is associated with high healthcare costs, post-operative adverse events and mortality. The post-operative mortality rates associated with POP are more frequent in low and middle-income countries (LMICs) compared to high income countries (HICs). There is some evidence from studies conducted among cardiac surgery subjects in HICs suggesting that preoperative chlorhexidine mouthwash can reduce the incidence of POP however there is no evidence of it being effective in other income settings and other surgeries. Furthermore, due to the emerging of the corona virus 2019 disease (COVID-19) it is expected that POP rates will be higher during the COVID-19 pandemic period compared to the pre-COVID-19 period.

The preliminary economic evaluation will assess the potential cost-effectiveness of preoperative chlorhexidine mouthwash surgery in reducing POP among abdominal surgery patients when compared to no-mouthwash surgery. A decision model taking the South African health care perspective will be built for the analysis. Model input parameters: costs, probabilities and outcomes will be estimated from literature. The analysis will compare the cost-effectiveness of the intervention in the absence and presence of COVID-19 to identify the impact of COVID-19 on mouthwash cost-effectiveness.

Alongside the trial, the health economics team will also conduct a trial-based economic evaluation to assess the cost-effectiveness of the mouthwash in reducing POP using primary data.

Systematic review: costs of pneumonia following abdominal surgery

The objective of the systematic review is to estimate the costs of post-operative pneumonia among abdominal surgery patients. This information will be important in prioritising healthcare resources by informing healthcare providers and policy makers about the costs that can be saved by reducing post-operative pneumonia incidence. Feeding into the PENGUIN mouthwash preliminary cost-effectiveness analysis, the cost estimates from the review will be used as input parameters in the preliminary model.

(2) The PENGUIN oxygen preliminary economic evaluation. Surgical site infections (SSI) are one of the most common medical care advents events. The world Health Organisation (WHO) recommended perioperative high dose fraction of inspired oxygen as an intervention for reducing SSIs. However, there is mixed evidence on the effectiveness and safety of the intervention compared to using perioperative low dose oxygen concentration. One of the objectives of the PENGUIN trial is to provide evidence whether perioperative high dose oxygen concentration is effective and safe in reducing the incidence of SSIs.

The Global Surgery Collaborative health economics team will conduct a preliminary economic evaluation to evaluate the potential cost-effectiveness of high dose fraction of inspired oxygen in reducing SSIs when compared to low dose fraction of inspired oxygen. The evaluation will estimate the costs associated with delivering high dose compared to low dose fraction of inspired oxygen, SSI rates of the two oxygen concentrations and the identify data gaps as well as uncertainties associated with the input parameters to strengthen health economics data collection during the trial.

Furthermore, a trial based cost-effectiveness analysis will be conducted at the end of the using the decision tree from the preliminary model and primary data collected from the PENGUIN trial.

Training Global Surgery collaborators on health economics

Health economics knowledge is important to program managers, physicians and all healthcare workers in the implementation of programs and projects to ensure that interventions represent efficient use of healthcare resources. The NIHR Global Health Research Unit on Global Surgery organised a Prioritisation Workshop in Accra, Ghana in November, 2019 for countries involved in the Global Surgery Collaboration Initiative.

As part of the workshop the health economics team from Birmingham oriented the participants on fundamentals of health economics. The short training course equipped the participants with knowledge to help them prioritise surgical interventions to fund based on health economics. The training focused on fundamentals of health economics such as scarcity, opportunity cost, economic evaluations alongside clinical trials including costing resource use, using health outcomes especially disability adjusted life years (DALYs) and quality adjusted life years (QALYs), and how to use the costs and outcomes in cost-effectiveness analysis.

Immediately after the Accra workshop a similar workshop was held in Tamale, Ghana, which was attended by anaesthetists, medical doctors, surgeons and Nurses from the Ghana healthcare system.

The main CHEETAH trial is assessing whether the practice of using separate, sterile gloves and instruments to close wounds at the end of surgery can reduce surgical site infection at 30-days post-surgery for patients undergoing clean-contaminated, contaminated or dirty abdominal surgery, compared to current routine hospital practice.

Using information from FALCON KIWI and primary data collection in CHEETAH, the cost-effectiveness of the changing gloves/instruments prior to wound closure compared to current routine hospital practice will be assessed.

Cost of illness of Surgical Site Infection in Appendectomy patients across income settings
A cost of illness study aims to identify and quantify all the costs of a particular disease or complication. Such information can help guide research and funding priorities by highlighting areas where waste may exist and savings be made. Surgical site infection (SSI) is a potential adverse event associated with surgery and imposes additional costs from additional healthcare consumed. We conducted a literature review[6], which has provided evidence to show that the additional costs associated with SSI across studies from different income settings. However, comparing the SSI cost estimates is difficult given the heterogeneity in cost items, comparators, procedures, time period and patient mix. Studies were almost entirely based in a single centre which has implications of the representativeness of the findings beyond those settings. Estimating the global burden of SSI requires harmonised datasets to begin making a comparison across settings.
The objective of this study is to calculate the additional cost burden of SSI across income settings. Using appendectomy ( a common surgery worldwide) as an example case study a model based analysis will be undertaken to estimate the additional cost burden of SSI in this surgical area. Information from the GlobalSurg 1 & 2 datasets will be used to populate the model.

References

6. Monahan M, Jowett S, Pinkney T, Brocklehurst P, Morton DG, Abdali Z, et al. Surgical Site Infection and Costs In Low and Middle Income Countries: A Systematic Review Of The Economic Burden. PLOS ONE. 2020;In press.

CRANE is a feasibility study of a nutritional intervention to improve outcomes after cancer surgery in low-income countries. It aims to identify and validate a nutritional screening tool; identify a low cost sustainable nutritional intervention; and investigate recruitment and retention, data collection methods and the acceptability of a nutritional intervention to improve outcomes after cancer surgery in low- and middle-income countries.

The health economics component looks at the feasibility of collecting economic data and the design of resource use forms for a full trial. The health economics is particularly important essential given the importance of cost effectiveness in developing a long term sustainable solution.

Health Economics Activities with Pump Priming Studies at the Global Surgery Unit

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.

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.

The project, led by Professor Stephen Tabiri from the NIHR Global Surgery Unit hub in Ghana, will be coordinated from Tamale Teaching Hospital. A further 11 district hospitals in Ghana will act as a ‘test bed’ to investigate whether 3 month outcome data can be reliably tested in rural surgical settings, whether post-operative pain assessment tools are transferable to Low and Middle income settings and if cost analysis data can be captured in rural hospitals.

Results of this first pilot trial will inform the design of a much larger trial aiming to increase safe and affordable inguinal hernia repair across 5 Sub-Saharan African countries including Ethiopia, Benin, Sierra Leone, Rwanda and Zambia