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How Europe can get better at treating rare diseases

Experts from the IMI Scientific Committee weigh in on what needs to happen to speed up rare disease research

Girl with mask by Maidzhi Aleksandra via shutterstock
Some 75% of rare diseases affect children. Image by Maidzhi Aleksandra via Shutterstock.


In June 2020, the IMI Scientific Committee issued a set of recommendations that call for a new way to address problems in rare disease research. We asked two of the authors to explain their advice.

There are between 6,000 and 8,000 rare diseases, 80% of which have been identified as genetic in origin, and 75% of which affect children. Advances in genetic testing and gene therapy that have emerged in recent years have opened up possibilities for treatments that have been a source of hope for millions.

However, this hasn’t yet translated into many new drugs. The small numbers of people who have these conditions means there is a lack of incentive for drug makers to make so-called ‘orphan drugs’, though legislation has been trying to find a way around this problem. While nearly all genetic diseases are rare diseases, not all rare diseases are genetic diseases. Beyond policy incentives, however, there are other things that should happen, in particular relating to bringing patients into the decision-making fold, taking advantage of a flood of technological advances, and being more clear about the real costs of doing nothing.

Get better at going digital - the importance of patients

Patients are central to rare disease research. They are prime movers in raising awareness and advocating for policy support. Claas Röhl is a patient advocate and a member of the IMI Scientific Committee. He represents people living with neurofibromatosis, a rare genetic tumour risk syndrome. His young daughter is affected by this disease, which is what motivated him to start a patient organisation in his home country, Austria.

Advocacy groups like his are essential because patients, once they get a long-sought-after diagnosis, can end up feeling they have nowhere to turn. “Rare disease patients are often completely lost,” he says. “Once a diagnosis is made, they leave the doctor’s office and are completely on their own. The advocacy groups are complementary to the work of the clinics.”

Fellow Scientific Committee member, Prof. Olivier Blin of Aix-Marseille University, echoes this: “In France, the health system is generally very organised, but the patients don’t feel really involved. Once the diagnosis is made, they rarely get support in their daily life, whether it’s for physical therapy or psychological support or whatever else they need. And since the doctors they see are experts in hospitals, some patients only see them once a year, without any routine or personalised follow-up in between. We think this is something that we could really improve in the coming years.”

This disconnect not only cuts patients off from real support, it also makes it harder for researchers, regulators, health professionals, drug makers and legislators to know what’s really going on with these diseases. In the recommendations, Mr. Röhl, Prof. Blin and their colleagues propose that digital tools – like smartphones, apps, wearables, and online platforms – can go a long way towards bringing patient closer to the science and the decision-making process.

These tools could potentially allow patients access to lay interpretations of scientific research, find specialists or sign up to participate in clinical trials. They could also be used by researchers and other stakeholders to elicit patients’ opinions, through surveys, for example, which would give them access to an unfiltered look at the reality of their conditions. This helps set priorities and assess the impact of the different courses of action.

Sketching a natural history of diseases and predicting risk

While artificial intelligence (AI) algorithms and other technical advancements are getting better at using data to predict risk and disease trajectory in cancers and cardiovascular diseases, again, this has failed to happen in rare diseases so far. This needs to change. High-performance computational capabilities and the growing troves of biomedical data should be used to create new models of the natural history of rare diseases.

The data needed to create statistical rare disease models are thus far disparate and unmined. According to Prof. Blin, “One of the problems we have is that for some diseases there are only a few patients and they get lost in the database. For example, we have access to the French national health insurance database, but it’s not possible to localise the patients, or to make the link between the database and the natural history of the disease and the burden of disease. We have to bridge all the data together and work on whatever we think is valuable, whether it’s early diagnosis or identifying new treatment based on biological signature, not only on phenotype.”

He says that by studying the patient trajectory, we would be better able to predict which patients are likely to encounter a particular problem. “I was travelling on a plane when a young girl had her first epileptic seizure. When I got back to France, I called her primary care physician and told her about what had happened, and he said he was not surprised. He had never told her parents about the risk, because medical doctors tend not to focus on this.” This particular incident could have been predicted, and luckily did not end in tragedy. The medical community, he says, focuses primarily on diagnosis and treating symptoms. Having access to the right models could change this.

To know or not to know

Existing tools exist can carry out drug screening, DNA sequencing, newborn screening, and provide virtual cohorts that can be used to evaluate drug efficacy. Gene therapy technologies are also available, but more investment is needed. Mr. Röhl stresses the urgency of taking advantage of gene therapy technologies. “Because 80% of rare diseases are genetic in origin, the key to finding a cure is gene therapies, and for this we need to be able to identify patients as early as possible,” he says.

However, ‘as early as possible’ is not a sentiment that everyone shares. Genetic newborn screening practices across Europe are patchy. “The problem is that in some countries and for certain diseases, some patient groups are against newborn screening because they are afraid it will lead to selective abortion. This is the main concern. So the question is how to select the list of genes you can or should test and maintain the parents’ right to make decisions.”

Some diseases have treatments that are already on the market, and they need to be administered as soon as the baby is born, or even before. It is crucial to identify these children quickly. Mr. Röhl says: “It gets tricky with diseases for which there is no treatment. On the one hand, you would know what kind of symptoms you need to look out for, but would a family live a more happy life if they didn’t know?”

“Many people go years without a diagnosis, and when they finally do, it’s a relief. For example, my daughter was recently diagnosed with dyscalculia. Her teacher thought she was not trying hard enough or was perhaps not intelligent enough. But her IQ is above average. It turns out it’s a symptom of her disease. So even though the diagnosis is a shock, at some point you have to learn to live with it as part of your life. When it happens later in life, it’s even harder to adapt.”

“It prevents a family years of running from doctor to doctor,” adds Prof. Blin. “Of course it would also be a great help to medical research to better understand and measure it.”

But what’s it worth?

They also recommend a shakeup in the guidance on making value judgements about new technologies in rare diseases. According to Mr. Röhl, “When you look at the cost of a drug you cannot only look at the immediate cost of treating or not treating a patient. What is the cost of people who are getting sicker and sicker, of not being able to work? This often gets neglected - the accumulated cost over a lifetime.”

“Sometimes we don’t have the knowledge to be able to determine the real burden of a disease on the community and the health service,” says Prof. Blin. “So that’s why getting more familiar with the real-life trajectory is really key to determining the burden and the need, and for determining what might be ‘fair’ value of a new treatment or device. Giving the industry partner a better idea of the overall cost of the disease can motivate them to get involved in this domain.”

The importance of a neutral go-between

There is strong argument in favour of a PPP being the right vehicle to push rare disease research forward. IMI evolved, the authors argue, to facilitate interactions between stakeholders on a neutral basis, which helps iron out conflict of interest problems among competing partners. Rare disease research has its share of controversies, particularly as it relates to the justification of high prices for technologies to create orphan drugs and fundamental moral and economic questions. A neutral interlocutor is key to sorting out these thorny issues.

Read more

Find out more about the IMI Scientific Committee

Read the IMI Scientific Committee recommendations regarding rare diseases

Treating rare diseases: can new business models solve equity of access issues? - By Pierre Meulien, IMI Director

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