104th Edition – September 2020

New IMI project SOPHIA hopes to change the conversation on obesity

The outdated way we treat obesity has to change, according to researchers from one of IMI’s newest projects, SOPHIA.

According to project coordinator Prof. Carel le Roux of University College Dublin, obesity treatment has traditionally involved creating a calorie deficit using diet and exercise, an approach that has not always proved effective. It can even makes things worse. Yet despite advances in pharmacological and surgical treatments in the last decade, many healthcare professionals still lack adequate training in new approaches. Moreover, obesity is not considered a disease in many countries, meaning that resources dedicated to treating it are minimal.

‘This means that we are treating the disease with basic and even outdated treatments that cause temporary weight loss, leading to long-term implications like untoward changes in body composition, weight regain, increased duration of patients living with obesity-related complications, stress and depression, and diminished quality of life,’ explains Prof. le Roux.

We currently don’t know which patients will develop complications secondary to their obesity, and who will respond to the new and expensive treatments. SOPHIA has set out to identify these predictors so that we can improve the quality of care. It will be the first project of this scale to address this important question, says Prof. le Roux.

Find out more

• Read the interview in full

Constant threat of 'hypos' takes heavy toll on people with diabetes

The Hypo-RESOLVE project wants to single out the risk factors for severe hypoglycaemic episodes, where diabetes patients’ blood sugar levels fall to dangerously low levels. Although there are certain widely recognised risk factors for hypoglycaemia like exercise, skipped meals or insulin dosing errors, hypoglycaemic episodes very often also occur quite unexpectedly. If a ‘hypo’ occurs, you have to act quickly to bring your glucose levels back to normal and make sure you’re not a threat to yourself.

Needless to say, this often interferes directly with daily activities. Episodes can even occur without causing any symptoms, and sometimes recovery is spontaneous. Not uncommonly, a partner or family member recognises it before the patient does. ‘In the long term,’ says Hypo-RESOLVE coordinator Bastiaan de Galan of the Radboud University Medical Centre in Nijmegen, ‘hypo events can cause fear and avoidant behaviour, which makes overall glucose control even more difficult. Severe episodes can increase the risk of cardiovascular disease, although we don’t know yet whether this relation is causal.’

The Hypo-RESOLVE project wants to find out more about the mechanisms of hypoglycaemic episodes beyond what is already known, including their effect on the psychosocial well-being of people who experience them. In an interview with the IMI Programme office, Bastiaan de Galan and Jill Carlton of the University of Sheffield describe how the project is working to tackle the challenge of hypoglycaemic episodes.

Find out more

• Read the interview in full

Interested in the regulatory aspects of digital health? Join the new #dHealth4Trials Slack channel

Digital technologies are playing an increasingly significant role in health research and healthcare, but debates about how best to get regulatory approval for these technologies are ongoing. Now, partners in IMI’s Mobilise-D project have set up a discussion channel on Slack called #dHealth4Trials to facilitate discussions on good practices in the use of in silico and digital technologies in clinical practice and in the regulatory evaluation of new drugs and medical devices.

The new channel is part of the wider In Silico World Community of Practice, and is open to anyone with a professional or educational interest in in silico medicine and digital health, including researchers from academia and industry as well as regulators, policy makers and patients’ representatives.

‘The #dHealth4Trials channel will provide to all practitioners an online community of practice where pre-competitive information can be exchanged freely,’ said Marco Viceconti, founder of In Silico World ‘We believe this is an essential step to accelerate the adoption of digital technologies in regulatory trials: this community of experts, in collaboration with experts from regulatory agencies worldwide, could develop good qualification practices for the qualification of digital health methodologies.’

The discussion is highly relevant to Mobilise-D, which is assessing the use of digital technologies to assess people’s mobility and has requested qualification advice from the European Medicines Agency (EMA) on this.

Find out more

• To join the discussion, fill in the form at www.insilico.world/digitaltechnologies/
• Visit the In Silico World website
• Visit the Mobilise-D website

IMI projects cited in new orphan drug development guidebook

Three IMI projects – c4c, EUPATI and PREFER – are cited in a new Orphan Drug Development Guidebook released by the International Rare Diseases Research Consortium (IRDiRC). Developing ‘orphan drugs’ (i.e. drugs for rare diseases) is highly challenging, and just 5 % of rare diseases have an approved treatment. The IRDiRC describes the new guidebook as ‘a patient focused guidebook that describes the available tools, incentives, resources and practices for developing traditional and innovative drugs/therapies for rare diseases and how to best use them.’ It lists a range of resources from organisations around the world, including IMI.

c4c aims to generate a sustainable infrastructure that optimises the delivery of clinical trials in children, and the guidebook suggests this could be useful for those developing medicines for rare paediatric diseases.

On EUPATI, the guidebook describes its patient education resources as ‘very relevant to rare disease medicines development and highly useful and appreciated by the rare disease patients that finished the academy and use the toolbox’.

On PREFER, the guide highlights how patient preference studies can be useful during regulatory benefit-risk assessment for certain drugs in several major ways.

The guidebook is presented in an article in Nature Reviews Drug Discovery. ‘By enhancing the use of available tools, delays in development timelines can be avoided, risks and costs reduced, and patient and regulatory acceptability improved,’ the authors conclude.

Find out more

• Read the paper in Nature Reviews Drug Discovery
• Read the guidebook entries on c4c, EUPATI, and PREFER
• Orphan Drug Development Guidebook Materials on the IRDiRC website

PREFER sets out 15 ways to listen to the patient voice

There is now broad recognition that patients can and should be involved in all stages of medical research and drug development, as understanding patients’ preferences can improve decision-making. However, putting ‘patient-centricity’ into practice is not always easy. IMI’s PREFER project has now identified 15 critical decision points in industry, regulatory and health technology assessment (HTA) decision-making where input on patient preferences can support the process.

Their findings are published in the journal Health Policy. ‘Currently, PP [patient preference] information is not considered as obligatory information to submit for any of the MPLC [medical product lifecycle] decision-points,’ the scientists write. ‘However, PP information is considered an important component by most stakeholders to inform future decision-making across the MPLC. The integration of PP information into 15 identified decision-points needs continued discussion and collaboration between stakeholders.’

First author Chiara Whichello of Erasmus University Rotterdam says: ‘We do see regulators and HTA having to take more steps to integrate patient preference information into their decision-making processes, compared to industry. Simply because they have to also take into account how much weight should be given to patients’ preferences compared to other required information, such as safety and cost-effectiveness.’

Find out more

• Read PREFER’s news item
• Read the paper in Health Policy

IMI safety project TransQST showcases activities at the R and I days

IMI’s safety project TransQST was one of the EU-funded projects featured at the virtual exhibition of the recent EU Research and Innovation Days. When developing a new medicine, scientists need to know if the compound will be harmful to vital organs such as the heart, liver, or kidneys. However, studying this is far from easy. TransQST is gathering data and developing computer-based tools to make it easier to assess the safety profile of potential medicines. This will both improve medicines safety and reduce the use of animals in research.

In a presentation at the event, project participant Elisa Passini of the University of Oxford explains that computer models can deliver more accurate results than animal experiments (89% for computer models compared to 75-85% for animal tests). In addition to models based on single heart cells, Dr Passini is also working on three-dimensional computer models of the heart that require a super computer to run.

In total, over 35 000 people attended the R&I days, which ran online from 22 to 24 September.

Find out more

• Visit the TransQST website
• Watch a video of Dr Passini’s presentation at the stand
• Visit the R&I days website