When will the EU take treatment optimisation seriously?

New, innovative treatments for disease are being brought to market with increasing speed and regularity. But without the organised, systematic international collection and analysis of their subsequent utilisation and their effect in different subsets of patients, how can we know that are they being put to their best use?  What can be done to ensure that they are used to maximum clinical effectiveness and at the same time provide best value to health services?  These are among the questions that the BioMed Alliance’s webinar on « How can current EU policy initiatives pave the way towards treatment optimisation as part of health systems? » held on 3 February 2021 tried to answer. The webinar was held on the same day as the launch of the European Cancer Plan, and participants were hopeful that this would contain some acknowledgement of the importance of treatment optimisation for patients and for society.

Dr Denis Lacombe, EORTC Director General, called for a re-engineering of the process of treatment development for drugs and therapies already on the market. To take the example of immunotherapy, the greatest innovation in cancer treatment in the last ten years, many questions about its best use remain unanswered, he said, even though the cost of treatment is around €150k per patient per year. The ultimate patient population is not defined, and the best duration of treatment remains unclear. Questions remain about the dose and schedule, and answering these could result in huge savings for health systems. The literature shows that the vast majority of cancer patients does not benefit from immunotherapy, yet this very expensive treatment is still given to those with tumour types where the evidence is that it will have little or no effect.

What is missing in the current practice is a checkpoint – where clinical research meets epidemiology and healthcare technology assessment – to ensure that we take into account not just the interests of patients, but also of society, he said. These two interests are totally compatible; by avoiding the unnecessary use of treatment and thus saving money, more patients can be treated.  But there is currently no framework for doing such trials at European level, and measures to facilitate this are not included in the new European Cancer Plan.

Professor Guy Brusselle, a respiratory disease specialist from Ghent University, also underlined the large gap between the pre-approval development of new treatments and their real-life use, which was often sub-optimal. This applied across all disease areas, he said. Although there are many EU initiatives aimed at improving health, treatment optimisation tended to be under-represented. « Our aim is that the EU should co-ordinate international treatment optimisation studies to evaluate the real-life effectiveness and safety of drugs and vaccines in the EU. » Clinical studies in real life are important to ensure that all groups of patients are included, and particularly in order to study comparative effectiveness, he said.

As an example, over the past year there have been hundreds of papers arguing that one or another drug was efficacious in treating Covid-19, he said. The studies on hydroxychloroquine were misleading because they were non-interventional, uncontrolled, observational, and mostly retrospective.  Such studies are subjected to bias; this is a systematic error that cannot be solved by increasing numbers and you can still end up with a false conclusion. Now large, interventional, controlled studies have clearly showed that hydroxychloroquine is ineffective in Covid-19.

Current EU policy initiatives that could help support treatment optimisation studies include the new mandate for the European Medicines Agency (EMA). This will move from simply monitoring and evaluating the safety of vaccines and medicines to include the co-ordination of studies to monitor their effectiveness, together with co-ordinating and advising on clinical trials. The Pharmaceutical Strategy for Europe will cover the full life cycle of a medicine, including drug repurposing.

These are encouraging moves, but there is still much to be done. Because health within the EU is still organised at national level, there is currently no EU-wide infrastructure to do the large-scale real-life effectiveness studies that are badly-needed to give speedy answers to important questions. « We need to be quicker, more ambitious and more flexible in therapy optimisation and its uses. There are too many hurdles in place at the moment, » said Jan Geissler, a member of the European Cancer Organisation’s Patient Advisory Committee, and co-founder of the CML Advocates Network. « Collaboration is so important. We can’t just drop new treatments on the market with no idea how they perform in real life. Treatment optimisation must be translated into all the important EU initiatives, and patients need to play a key role in getting this done.»

« We are spending millions on developing a new drug, but afterwards we don’t have the resources to run a proper registry or therapy optimisation study in clinical practice and feed that back into research to see whether what worked in Phase 3 studies actually works in real life. I hope we can discuss this at EU level because it is so important, » he said.

« There are already committees set up that focus on safety only, for example the pharmacovigilance committee of the EMA. But effectiveness is just as important as safety, and the EU should take it as seriously. There are a lot of problems within countries with different stakeholders – industry, clinicians etc. – claiming ownership of data, and it’s even more complicated at European level.  It’s at that level that it needs to be solved, but first of all it needs a structure, » said Guy Brusselle.

« We have been lobbying on this for some years, » said Denis Lacombe. « We see mentions of treatment optimisation from time to time, but I am not convinced that the EU has taken this seriously. It’s not at all clear the new structure that is needed is going to happen, what we are going to do, and how we are going to sequence the role of the different stakeholders. »

To return to the Cancer Plan, its omission of a strategy for treatment optimisation disappointed Denis Lacombe. « Maybe it is still open to change downstream. I sincerely hope so, » he says. « We are concerned that there is a missed opportunity for improvement here. And not just for cancer patients; treatment optimisation can benefit patients in all disease areas, and in all healthcare systems. We need to find a way of filling the gap between regulatory and real-world data; both are important, but neither on its own is enough to answer all the questions, and to assume, as some do, that real world data will solve all our problems is to do a disservice to patients and to society.»

« We have raised these ideas with the EMA, and we will continue to do so. It is clearly wrong that we are continuing to use expensive therapies on patients without data on optimal dosage and schedules. We have the tools to uncover this information, but we need help, encouragement, and co-ordination at European level. »