Impact case study database

Hawkey’s work has impacted on the treatment of patients suffering from recurrent and refractory C. difficile infection (rCDI). Specifically, it has improved patient outcomes through provision of FMT for rCDI, reduced the costs of treatment, influenced healthcare guidelines and facilitated the introduction of FMT in new clinical indications.

Patient outcomes have improved through the provision of FMT for treatment of rCDI

Patient outcomes have improved as a direct result of the development and implementation of a new clinical intervention for FMT delivery for rCDI treatment (KF1-3). In 2017, Hawkey developed the first licenced FMT product (October 2017; S1) for patients with rCDI in England. Since then, the number of UK trusts using FMT has risen from 19 in 2018 to 54 in 2020 (S2). In addition, Hawkey contributed to the implementation of FMT within UK hospitals through establishment of UoB’s Microbiome Treatment Centre (September 2018; S1), which worked in partnership with NHS England, to ensure that FMT is the standard of care for all patients with rCDI. The FMT service was awarded the NHS England’s Innovation Tariff, which guaranteed free supply of FMT to all English trusts (2018–2020) thereby overcoming financial and procurement barriers to the introduction of FMT into clinical practice. Since its establishment in 2017, the Microbiome Treatment Centre has supplied/treated 215 patients across the UK.

FMT treatment is highly effective when compared to previous treatments. For example, an in-depth analysis of the first 124 treated patients showed that a clinical response was seen at day 7 in 84% of patients, and a clinical cure after 90 days in 78% (R6). This compares with studies using antibiotic therapy for the treatment of rCDI that report clinical cure rates of ≤40%.

For the 1,650 patients/year who suffer rCDI, and who do not respond to antibiotic therapy, there remains an unmet clinical need and approximately 15% (245) of infections will prove fatal. As a result of the high response rates, FMT treatment would be expected to cure up to 1,290 patients with rCDI per year (78% of 1,650) and reduce the number of deaths down to 55 (15% of the 22% of patients who do not respond) (R6). Adverse events were shown to be rare and unrelated to FMT. Of the first 124 patients treated, only 2 patients died within 7 days of receiving an FMT: 1 due to uncontrolled CDI and another from underlying bowel cancer (R6). Minor adverse events, including constipation, abdominal pain and bloating, were reported in ≤4 patients, demonstrating that the protocol developed by Hawkey is safe and minimises patient discomfort.

Improved patient outcomes were further evidenced by a reduction in bowel movements in FMT-treated patients. Recurrent CDI (rCDI) significantly impacts on daily life with patients being ill for 3–6 months and passing up to 20 bowel movements a day. Treatment with FMT through the UoB licenced service significantly improved symptoms. In recurrent CDI, clinical response to FMT was seen in 91% of patients (64/70) at day 7 with a reduction to <3 bowel movements per day, and a consequent improved quality of life (R6). A BBC interview with one of Hawkey’s patients who received FMT treatment through the service illustrates the beneficial effects that FMT treatment has on a patient’s daily life: “after 48 hours, it was like a miracle. At the time, I didn't like the idea at all, but I can only thank the person who donated for giving me back my life” (S3).

Healthcare guidelines have been developed for the use of FMT for recurrent CDI

UK guidelines on the use of FMT for recurrent/refractory CDI have been adopted by the joint British Society of Gastroenterology (BSG) and Healthcare and Infection Society (HIS) (S4i–ii). Hawkey acted as a key panel member in shaping these guidelines, contributing academic expertise and knowledge in key areas including: “preparation of FMT as a medicinal product” and “distributing to 3^rd party hospitals across the UK” (S5). Key to these guidelines was the incorporation of key findings (KF1–KF3) identified whilst the medicinal product was being developed.

The cost of treatment of patients with rCDI infection has been reduced

As the leading cause of hospital-acquired diarrhoeal disease worldwide, rCDI contributes a substantial economic burden with mean total costs for recurrent infection estimated to be £31,121 per patient/per episode (2014–2017) (S6). This includes hospital costs from prolonged stays, antibiotic therapy and chronic health incapacity. FMT treatment of rCDI represents a significantly cheaper treatment option and affords opportunities for costs savings (S7).

• Full cost of treatment for FMT using the nastrogastric route developed by Hawkey is £8,880/patient, which is substantially less than the standard treatment using the antibiotics fidaxomicin (£14,399) or vancomycin (£17,279).

• The cure rate in patients treated with FMTs (78%) versus antibiotic therapy (30–40%) indicates that FMT treatment leads to earlier hospital discharge and reduces the need for long-term treatment with antibiotics, thus minimising the risk of the development of antibiotic resistance.

The results of full economic evaluation illustrate that FMT is highly cost-effective. The methodology developed by Hawkey (administration via nasogastric tube, use of proton pump inhibitor and gastric propellant) meet the NICE cut-off of £20,000 per QALY (quality adjusted life year), the maximum allowed cost for a treatment to add 1 year of perfect health (S7).

In addition, Hawkey’s work on FMT is offering insights into the management of other diseases. As the UoB Microbiome Treatment Centre was the first clinical service aimed at restoration of the gut microbiome through FMT, it supported the use of this intervention in other diseases in which disruption of the microbial ecosystem of the human gut are a contributing factor. For example, a multicentre national trial supported by NIHR into the therapeutic benefits of FMT in ulcerative colitis (STOP COLITIS) led by Prof Tariq Iqbal (UoB) (S8).