Impact case study database

(1) Impact on UK clinical practiceYork research directly informed the NICE Guideline on the Prevention and Management of NS (for all ages of patients) [NICE CG151]. This included preliminary and unpublished findings that were shared by Phillips as part of his membership of the guideline development group; specifically providing evidence for adoption of a risk stratified (low-risk) approach [1.5.1 and 1.5.2] [A], use of a single inflammatory biomarker [1.4.1.2] [F], and discontinuing the use of routine chest X-rays on admission [1.4.2.2] [E]. The guideline was first published in 2012, but remains current; in 2020 NICE decided that recommendations required no substantial changes [1]. Subsequent York research including [B] and updates to [A] and [E] provided further and specific evidence on managing NS in CYP. Thus, York’s underpinning research has supported clinical decision making since 2012 and throughout the current REF period.

“*Research from the University of York on neutropenic sepsis (NS) in children and young people (CYP) with cancer directly informed NICE CG151, the NICE Guidelines on the Prevention and Management of NS, in particular providing supporting evidence for adoption of a risk stratified approach, which subsequently results in both benefits for patients and resulting cost savings for the NHS in terms of earlier discharge lower intensity antibiotic therapies and discontinuing use of routine chest x-rays on admission.*” CEO, Children’s Cancer and Leukaemia Group (CCLG) [2]

Repeated 14-day snapshot audits of UK NS admissions by the national network of heath care professionals treating CYP with cancer (the CCLG) demonstrated increasing alignment with NICE guideline recommendations and with our research findings, which were specific to paediatric patients. Published audits showed that:

• Implementation of risk stratification programmes increased from 36% in 2012 to 75% in 2017, reducing (in-patient) stays from a median of 5 to 3.5 days.

• Broad spectrum intravenous antimicrobial use decreased; the proportion of patients who either transitioned from intravenous to oral antibiotics or stopping at 48 hours after admission increased from 43% to 76% in the same period.

• Centres no longer undertake routine chest X-rays.

• Despite increasing use of serum inflammatory biomarkers in other paediatric specialities, use in this patient group has been minimal. [2]

The CCLG CEO noted how this impacts on patients and families:

“The impact of this important work is multifactorial, from informing guidance to supporting its implementation and changing practice across the UK, to cost savings for the NHS, and informing international clinical practice. Ultimately of course, I would argue the benefits to young patients and families are the most important impact of this work. A childhood cancer diagnosis is a distressing, isolating and challenging time for any family, and any work that improves provision of supportive care will improve quality of life. We know from our work with patients and families that seemingly small things make a huge difference – a shorter hospital stay, not undertaking additional tests and procedures, or being able to go home with oral medication rather than a sustained admission for IV therapy – impacting in a number of domains on quality of life including mental wellbeing and stress, finances, and family life.” [2]

Implementation accelerated in 2020 with the emerging SARS-CoV2/COVID-19 pandemic. UK paediatric oncology services were prioritised to continue delivering therapy but urgently required a strategy to safely minimise hospitalisation and switch to lower-toxicity approaches, including full implementation of risk-stratified management of NS, and to shorten treatment duration even further. Within two weeks, the York team validated the PICNICC Australia ‘AUS’ risk prediction score for a UK population [C] and evaluated use of very short duration admission, leading to a new agreed national strategy through the CCLG. Acknowledging provider fears about risks of home-based care [D] with clear messaging and consistent information, and supporting the use of a ‘virtual ward’ with daily structured phone calls to parents was also part of the response.

Health care provider implementation tools and patient-information materials based on York research were developed, as was an evaluation package to assess breadth and quality of uptake. The importance of York input to the pandemic response was confirmed by both the Chair [3] and CEO [2] of the CCLG:

“…the York team validated the PICNICC Australia ‘AUS’ risk prediction score for a UK population and evaluated its use within two weeks. In turn this led a new agreed national strategy through the CCLG. This extremely short turn around period would not have been possible without the underpinning programme of research carried out by the York team who had validated the approach to risk stratification and empiric treatment of febrile neutropenia.“ [3]

“Full implementation of risk stratified management of NS, and a further reduction in treatment duration, was made possible by the rapid validation by the York team ……This enabled a newly agreed national strategy to be delivered through the CCLG.” [2]

Data from CCLG audits comparing length of stay and antibiotic use in 2017 and preliminary data from 2020, combined with NHS National Cost Collection data illustrates that implementation of risk stratified management has resulted in a substantial cost saving for the NHS. The proportion of NS episodes discharged within 24 hours increased from 0% to 27%, and average inpatient stay reduced from 3.5 days to 1.8 days for those who were hospitalised. Given costs of GBP997 per inpatient bed day and GBP538 for day case management, this generates savings of GBP2,010 per episode. A further small saving of GBP21 per episode accrues from low risk patients switching from IV to oral antibiotics. Using 2020 estimated annual incidence of 3,011 NS episodes, this equates to freeing up 5,703 bed days and reducing NHS costs by GBP6,115,563 per year [4][5].

(2) Impact on international clinical practice: York research has also directly informed and “ been instrumental to the development and completion” [5] of international guidelines, which have in turn changed practice and delivered international impact as the clinical lead/corresponding author of the International Society of Paediatric Oncology guidelines notes:

“… research on the management of fever and neutropenia in children and young people being treated for cancer undertaken by the team at the Centre for Reviews and Dissemination at the University of York was an important source of evidence for the international clinical guidelines that were produced by an international panel of pediatric oncology experts, including Dr Bob Phillips. The guidelines were subsequently adopted by The International Society of Paediatric Oncology (SIOP). During development, the York team’s published and not yet published research … was particularly important in informing recommendations about the initial management of FN. The guidelines … have since been adopted by the American Society of Pediatric Hematology/Oncology, the Pediatric Oncology Group of Ontario, the American Society of Clinical Oncology, C17 Council (an organisation including institutionally appointed heads of the 16 paediatric hematology, oncology and stem cell transplant programmes across Canada), the Multinational Association of Supportive Care in Cancer (MASCC) and Children’s Oncology Group (COG). [5]

Guideline recommendations are now included in every new anti-cancer study undertaken across the North American COG network and widely within Europe [5].

Studies carried out in children’s hospitals in the US have also reported benefits arising from guideline-congruent low risk management. In Oklahoma costs of NS management in low risk patients were halved: “ The mean total cost of an LRFN episode was $12,500 per patient pre implementation and $6168 post implementation, a decrease of $6332 (51%) per patient”. In Massachusetts “40% of [NS] episodes were defined as low risk and managed either entirely in the outpatient setting ...or with a step down strategy involving a very brief inpatient stay” and in Missouri over 60% of CYP presenting with NS were discharged early (“ 188/299 FN admissions”). The Missouri study noted that “ by reducing the overall length of stay in a subset of patients, early discharge can improve quality of life and reduce costs. This practice may also benefit patients in terms of safety by decreasing the risk of hospital-acquired infections and avoiding prolonged antibiotic exposure that leads to resistant bacterial and fungal infections” [6].

The Melbourne based PICNICC-Australia team demonstrated that adopting risk stratified management saved “290 in-hospital bed days in 18 months” and reported that with in-hospital management of paediatric low-risk NS costing AUD2,200 per day and home-based NS care approximately AUD830 per day , “the cost benefit …is likely to be substantial” and that the “program is currently being scaled nationally, thereby increasing the clinical, economic and quality of life impact of this model of care” [7].