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FOLLOW-UP OF OFF-LABEL TOCILIZUMAB PRESCRIPTIONS IN COVID-19 IN A FRENCH UNIVERSITY HOSPITAL

European Statement

Education and Research

Author(s)

Caroline TRAN VAN HO, Marie-Anne ESTEVE, Pierre BERTAULT-PERES, Marjorie ROUDOT

Why was it done?

SARS-CoV-2 infection leads to pro-inflammatory molecules production (in particular IL-6). If the immune system is overwhelmed and cytokine production spikes, a hyper-inflammatory phenomenon occurs: the cytokinic storm, which can bring lead to the admission in an intensive care unit. Due to the absence of authorized treatment, several clinical trials (CTs) and off-label use of drugs have been set up.

What was done?

The aim of this study is to analyse the off-label use of tocilizumab in a French university hospital in comparison with different CTs.

How was it done?

A retrospective study of tocilizumab prescriptions in Covid-19 was conducted between 01/03/2020 and 30/04/2021 by extracting data from Computerised Physician Order Entry and Pharmacy Management software (Pharma®). History of patients was recovered by electronic medical records (Axigate®).
Results were compared to (1) RECOVERY Collaborative Group. Lancet. 2021, (2) Hermine O. JAMA. 2021, (3) Rosas IO. N Engl J Med. 2021, (4) Salama C. N Engl J Med. 2021.

What has been achieved?

Between 01/03/2020 and 30/04/2021, 68 patients received tocilizumab.
Seventy-seven percent of patients were in the intensive care unit and 42.6% died, whereas 31.0%, 19.7%, 11.1% and 10.4% died according to (1), (3), (2) and (4), respectively. Mechanical or invasive ventilation at the time of tocilizumab prescription was widely used (84%) compared to CTs (54.0%, 27.9%, 24.0%, 12.2% for (1), (3), (2), (4)). According to (1), there is a synergistic action between tocilizumab and dexamethasone. Eighty-four percent of patients received at least one dose of corticosteroids in agreement with (1) and (4).

What next?

The increase in off-label use of tocilizumab is related to the results of CTs. Because of the low number of patients, the differences in COVID-19 stages at tocilizumab initiation, and the absence of a control group, it is difficult to explain our data. Given the weak iatrogenic effects revealed in CTs and in-label use, the benefit/risk seems in favor of tocilizumab use against COVID-19. Further studies are needed to confirm the first hopes. Since Casirivimab / imdevimab, and amlanivimab / etesevimab have been granted early access in France, the therapeutic strategy will be updated.

Managing Shortages

European Statement

Selection, Procurement and Distribution

Author(s)

Alison Anastasi, Karl Farrugia

Why was it done?

The amount of shortages was considerable leading to interruption of treatment, hoarding, wastage, hospital admissions incurring more expenses. Malta is one of the small EU Member states and its geographical position does not facilitate sourcing. Thereby on analysing the matter further, walking directly into the chaos creating order, inventing, creating, connecting and making things happen was the mainstay since then. The industry accepted the partnership invitation and sourcing increased both from the local and international scenario. Best in class operational efficiency, quality & functional excellence was achieved. According to the National Audit office in 2012, Malta had a recurring issue with shortages of medicines and now in 2016 we have had nil shortages for 30 weeks.

What was done?

1. Establishment of a dedicated team – Emergency Response Unit (ERU)
2. Enterprise Resource Planning inventory management
3. Customer demand forecast modelling
4. Partnership with the industry
5. Innovative procurement strategies e.g. negotiations, therapeutic time-based agreements, e-auctioning, framework agreements, managed entry access
6. Registration: Allowing bidders to register after they were awarded the tender; parallel importation

How was it done?

The challenges faced included influencing and providing leadership to partners in the delivery of on demand innovative solutions, strategic sourcing involving language translations, registering medicines by the department, demand supplier relationships, payment within 60 days, ageing population, procurement services revenue and profit growth. The winning strategy foundation was the interaction and integration of people (internal and external stakeholders) to business information and business intelligence.

What has been achieved?

The department has achieved good results measured by the number of shortages, better quality of life, by reduction of hospital admissions thereby reduction in costs. The average medicine shortages in 2013 was 56; in 2014 (40); in 2015 (5) and in 2016 (1) till October. The budget allocated per year has increased due to longevity however more patients are being treated and the cost savings lead to innovative technology access.

What next?

Having mitigation measures in place such as pre-planned need analysis; choosing the right process; reducing unnecessary care and focusing on sustainability is good practice. Locally this is being implemented for the procurement of non-medicines and in fact cost savings running into millions have resulted.

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