Written by Gianluca Quaglio,
Introduction
The STOA workshop entitled ‘Innovative solution for research in healthcare’, chaired by Paul Rübig (EPP, AT), first STOA Vice-Chair, is an opportunity to discuss the implementation of an ‘innovation-centred’ system, exploring a truly ‘patient-centred’ paradigm with systematically coordinated applied clinical research carried out in conjunction with drug development. The workshop will be held on 10 January 2019, 9:30-12:30, at the European Parliament in Brussels (Altiero Spinelli building, room 5E2).
#HealthSTOA
In 2015, the Council of the EU, while accepting that there is no common definition of the term precision (personalised) medicine, noted at the same time that this is generally understood to refer to a medical model, which uses the characterisation of individuals’ phenotypes and genotypes for tailoring the right therapeutic strategy for the right person at the right time, and/or for determining the predisposition to disease, and/or for delivering a targeted prevention strategy.
As the number of authorised drugs that target specific proteins implicated in the disease phenotype increases on the market, and as next-generation sequencing and other technologies bring comprehensive genome-wide analyses to affordable levels, precision medicine begins to play a much wider role in routine practice.
However, once a drug enters the market following regulatory approval, each EU Member State determines its real-world use based on its own criteria: pricing, reimbursement and clinical indications. Such an innovation-centred clinical research landscape might neglect patient-relevant issues in a real-world setting. There is a demand for reform of the current system to create a truly ‘patient-centred’ paradigm, with systematically coordinated treatment optimisation in conjunction with the drug development process.
Two disconnected stages: from drug development to real-world application
In Europe, most of the clinical research dedicated to therapeutic innovations in drugs aims primarily at regulatory approval. In this first stage, scientific issues on the efficacy of a new drug are addressed in selected patient populations and lead up to European Medicine Agency (EMA) approval.
Once a drug enters the market, the second stage begins, where research addresses clinically relevant questions to tailor the therapeutic indications to ‘real-life’ clinical practice. Due to this discontinuity between the first and the second stage, research during the second stage results – for various reasons – in suboptimal uptake of findings into practice or clinical guidelines.
Administration of improper treatment may generate unnecessary toxicity for patients, but also affects national healthcare budgets and adds cost to already highly priced treatments. Therefore, following the drug development phase, independent investigations are needed on the optimal use of medicines (known as ‘treatment optimisation’).
Regulatory approval
The regulatory approval of new treatments does not address clinical issues relevant to patients in real-world settings, such as: (i) how to combine new treatments with the existing therapeutic options; most patients may need some form of combination therapy, which is determined individually, based on a number of clinical and biomarker predictors; (ii) how to evaluate the clinical outcomes when new treatments are administered in off-label indications; (iii) how to determine the optimal scheme/treatment duration and at which benefit/risk ratio; (iv) what the long-term issues related to the treatment are. When addressed, the above-mentioned issues are studied mostly following EMA’s approval and rely on the goodwill and agendas of independent research groups.
Reasons for a lack of real-world evidence
There are a number of reasons for such lack of real-world evidence, mentioned briefly here. First, regulatory approval of new treatments requires data on ‘quality, safety and efficacy’ and not on ‘comparability’. This approach is centred on the innovative treatment, as its value is assessed in absolute terms, not relatively to the pre-existing therapeutic armamentarium of medicines, equipment and techniques available. Second, in order to maximise the experimental treatment effect, patients included in clinical trials represent only 2-4% of the overall targeted population, leading to a poor external validity of clinical trials. Finally, there is a lack of evidence that would make it possible to rank the multiple therapeutic options available and define the conditions for optimal care.
Aim of the STOA workshop
This workshop will provide patients, clinicians, payers, Health Technology Assessment (HTA) agencies, regulators, pharmaceutical companies, researchers, policy-makers and the public at large with an opportunity to present their point of view and their innovative suggestions for future drug development in Europe.
The establishment of a new developmental framework through close collaboration between industry, patient representatives, and regulatory, governmental, academic and other stakeholders would hopefully facilitate comparisons of assay performance before regulatory approval, harmonising the approval process. Such a framework could mitigate the somewhat problematic current situation. The issue is ubiquitous in modern biomarker/drug development processes and is not related to particular targets or pathways.
