Objective delirium detection with an innovative EEG-based spot monitor

Project Information

Delirium Monitor

Grant agreement ID: 672974

DOI

10.3030/672974

Project closed

EC signature date 10 April 2015

Start date 1 May 2015

End date 31 October 2015

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 71 429,00

EU contribution

€ 50 000,00

Coordinated by

WILLEMS-TJOE NIJ ANNEMARIE
Netherlands

Periodic Reporting for period 1 - Delirium Monitor (Objective delirium detection with an innovative EEG-based spot monitor)

Reporting period: 2015-05-01 to 2015-10-31

Summary of the context and overall objectives of the project

Delirium –an acute decline in cognitive functioning– is common, serious, frightening, costly and sometimes fatal. Delirium is a great burden for patients because of horrifying hallucinations, impaired outcome and increased risk on dementia. It leads to prolonged length of hospital stay, and increased rate of discharge to a nursing home. Costs due to delirium total to €134 billion/year in Europe, equalling costs associated with diabetes.
Delirium particularly affects hospitalized elderly with reported incidences of 50-80% on the Intensive Care Unit, and 10-40% in surgical patients. As our society is ageing, the population at risk of delirium will double in the next decades.
Despite its frequency and impact, delirium remains underdiagnosed and therefor undertreated. It is not recognized in 50 - 70% of the cases, which hampers recovery. Early and objective detection of delirium is an unmet clinical need.
Research of UMC Utrecht (NL) showed that 1 minute recording of brain activity (EEG) with only 3 electrodes and automated processing can well identify patients with delirium. Our SME signed an exclusive license for the patent, to create and commercialize the world’s first biomarker based device to detect delirium. Yearly, millions of patients at risk of delirium need to be monitored daily.
This generates an annual market of €1.4 billion in the EU and USA, as for every measurement, a disposable electrode patch is necessary.
EU H2020 Phase 1 enabled us to work with international EEG experts which resulted in improved delirium recognition algorithms & artefact removal technology, and to manufacture a first batch of disposables patches with an Italian specialist SME.
We developed a market introduction strategy for major EU countries in which the benefits of the Delirium Monitor directly align with reimbursement regimes: NL, Germany and UK.
With expert/coaching input we developed a fast paced, but achievable, regulatory pathway for CE marking and FDA approval. We met with many potential clients, which resulted in a series of signed buying intentions from hospital departments.
Phase 1 results provide us with confidence in our technology, the market and our business model. The defined work packages are executed successfully and deliverables are met.
Phase 2 focuses on product engineering, clinical validation and regulatory approval, so that sales in EU can start in 2017, and in USA in 2018. Our SME is forecasted to grow to nearly €30 million in revenue, and raise European employability with 116 FTEs in 2021.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

From March 2015 – October 2015 our SME's team performed a feasibility study under the EU H2020 Phase 1 grant, for the action entitled:
“Objective delirium detection with an innovative EEG-based spot Monitor – Delirium Monitor”.

The work packages defined for Phase 1 were carried out:
1. Assess technology robustness and performance, in collaboration with international EEG expert ABV Sciences (Dr. P. Zeman, Canada) based on the analysis of existing and new patient clinical data.
2. Involve 10 European hospitals in the Early Access Program (EAP). Mount Medical & Team travel to potential lead customers and involve them in EAP.
3. Perform market analysis, customer development, financial planning, reimbursement strategies (with specialist Crefact Consultancy), development & production costs, to develop a detailed business plan.
4. Prepare final product engineering phase (Phase 2) by, among other things, finalize user requirements, start technical file (CE marking and FDA approval), and contracting necessary engineering partners.
5. Prepare H2020 Phase 2 SME Instrument proposal to enter end-product engineering.

The deliverables are summarised in our Feasibility report dd October 2015:
1. our technical feasibility report shows that it is technically feasible to develop a commercially successful Delirium Monitor; our team has (access to) all technical components to build an EEG-based monitoring device for routine use by nursing staff at the patient’s bedside in hospitals.
2. 6 signed buying intentions from hospital departments (EAP participation forms) and 2 support letters proof that a) delirium is a problem that needs to be addressed more seriously, b) clients embrace the Delirium Monitor as the right solution, and c) clients are willing to pay the proposed sales price. We are in advanced talks with 4 more hospital departments, that are most likely to sign up in the coming months. Gaining commitment for signing up will become easier when the device is at a more final stage than the current demonstrator.
3. a complete business plan for the Delirium Monitor has been written, and it is reviewed and approved by our Phase 1 coach Plock Consultancy. With this plan we attracted some local funds, a loan, enrolled 2 informal investors and attracted positive attention from several Dutch Health Investment Funds (IFs); 2 IFs are about to sign a termsheet for investment in our venture as we are writing this report. The businessplan confirms all of the most important components that demonstrate commercial feasibility, meaning that generating a profitable business from the Delirium Monitor is possible, and that it is worthwhile to invest in this venture.
4. Our venture is well positioned to realise the next technical and commercial steps. During phase 1 all preparations are made to proceed to the next step: the final product engineering. Partners for the final product engineering have been pre-selected and their quotations (containing realistic budgets and timelines) are submitted to us and they are in line with our business plan. With the currently secured funds we can continue for 6 months; after that we anticipate to speed up with the support of venture capital investments and a secured H2020 SME Instrument Phase 2 grant.
5. a H2020 Phase 2 SME instrument proposal will be submitted in November 2015.

After completion of Phase I we conclude that the overall objectives for the Delirium Monitor are feasible, validated and our team is prepared and equipped to reach them:
1. Clinical: to objectively detect brain function known to correlate with delirium severity
2. Technical: to transform the observed EEG biomarker into a practical, robust medical device (the Delirium Monitor) for use in routine clinical practice, with low production costs
3. Market: Our SME sells the Delirium Monitor in European in 2017, and in the USA in 2018. As the new parameter for delirium gains acceptance, other care departments and territories are conquered in 2018-2020. B2B deals with monitor integrators in 2018 expand the market further.

Therefore we will submit the EU H2020 SME Phase 2 application “Clinical Validation of biomarkers or diagnostic medical devices” for our biomarker based diagnostic medical device (aka the Delirium Monitor) in November 2015.
Further clinical studies, to demonstrate cost-effectiveness of using the Delirium Monitor, are required for general market uptake. Access to funds to conduct such studies will speed up the process as well as the European market uptake. The benefits for the European healthcare system, the healthcare workers, the patients and the job creation will then be reached at shortest notice.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our Delirium Monitor is a 360 degrees healthcare improvement: it benefits patients, caregivers ànd budgetholders.
Delirium is a serious acute medical condition; effectively a medical emergency. It can result in serious adverse outcomes for many patients – death and dementia. In any other condition it would have clinicians searching for information with the same commitment given to cancer or HIV. Delirium is a familiar term in and out of hospital describing a distressing experience of disorientation and agitation... We think we can all recognize the delirious patient, unable to reason, often a danger to themselves and staff. But in fact most delirium goes undiagnosed as it is a quiet confusion, a brain failing by shut down rather than firing up.”, quotes from www.icudelirium.co.uk.
Delirium is the most common neuropsychiatric condition in hospital. Delirium particularly affects hospitalized elderly with reported incidences of 50-80% on the Intensive Care Unit (ICU), and 10-40% in surgical patients. Yet it is (and always has been) a currently grossly underdiagnosed condition in hospital units. Especially in ICUs it can influence whether the patient lives or dies regardless of expensive drugs, vasopressin or low-volume ventilation. This situation will change, as in the near future a delirious state can be detected objectively in 2 minutes in an easy to apply, non-invasive test with our Delirium Monitor. Diagnosis is the key to treatment and recovery.
Large scale introduction of the Delirium Monitor will lead to better care and earlier treatment of all patients that need it, and to faster patient recovery. Furthermore better detection will reduce the risk of all delirium's downstream complications.

We apply to work programme 8 “Health, demographic change and wellbeing”. The European population is ageing rapidly, which implies that the sustainability and equality of Europe’s health and care system, on which Europe already spends nearly 10% of its gross domestic product (GDP), is jeopardized. In the EU population, the number of people aged 65 or over will rise from the current 17% to 30% in 2060 (Eurostat, 2011). In the US the population aged 65 and older is expected to more than double between 2012 and 2060, from 43 to 92 million. As advanced age is one of the major risk factors for delirium, increase of delirium is expected due to the ageing population.
The Delirium Monitor will be an effective device for detecting delirium and reducing healthcare costs. It contributes to the sustainability of the healthcare system by enabling improved clinical decision making, reducing the duration of hospital stay, improving patient wellbeing and patient outcome.

Through close cooperation with University Medical Center Utrecht, we have the key ingredients for a sensitive and specific diagnostic medical device for delirium diagnosis. This is the reason to apply for PCH 12 -2014-1 “Clinical research for the validation of biomarkers and/or diagnostic medical devices”.
Our reviewed and approved businessplan shows that a profitable business can be created around the Delirium Monitor, that is worthwhile to invest in it and that approx 130 jobs in Europe will be created in 5 years time.

Artist impression of Delirium Monitor

population delirious patients in hospitals