Gathering the patient’s experience of their disease, treatments and medical devices is of fundamental importance. On the one hand, it is because «understanding and trying to satisfy patients’ subjective needs is the highest meaning of our profession», as the president of Aiom medical oncologists Francesco Perrone on the occasion of World Cancer Day on 4 February, on the other hand because the involvement of patients is convenient for the entire health system.
What are Pros
For some time, thanks to structured questionnaires, it has been possible to collect the so-called patient-reported outcomes directly from the patient and without the filter of any operator, doctor or otherwise (patient-reported outcomes PROs), concerning the symptoms, their frequency and intensity, any side effects and, indeed, the quality of life. Measuring it, and including it among the endpoints of the studies, is the first step towards being able to include Pros in evaluating the value of a treatment, as regulatory agencies suggest, and therefore also make them a tool for comparing therapiesan aspect not addressed by the registration studies.
The appeal to the institutions
How to structure the involvement of patients in every phase of the health process was discussed in the Senate, during the presentation of the work carried out by the Working Group “PRO4All, patients protagonists for everyone’s health”, composed of various associations and scientific societies in the oncology and neuroscience area, such as the Italian myasthenia association Aim, Aiom, the Italian multiple sclerosis association Aism, the Italian Federation of Voluntary Associations in Oncology Favo, the Federation of Italian cooperative oncology groups Ficog , Italian neurology society Sin, Italian rare disease federation Uniamo, and by a team of researchers from SDA Bocconi University, experts in pharmacoeconomic measurements. The initiative, carried out with the support of Roche Italia, led to the drafting of a manifesto which intends to implement also in Italy the use of data collected directly from patients in decisions regarding clinical research and drug regulatory pathways.
European good practices
«The potential range of the patient’s contribution is very broad, from the generation of evidence to the determination of endpoints, to the evaluation of the risk/benefit ratio of each decision” he said Guido Rasi, executive director of EMA, listing the current presence of patient representatives in the agency, absent only in the CHMP Committee for Medicinal Products for Human Use. The involvement is certainly not recent, but dates back to 2006, with the establishment of Patients’ and Consumers’ Working Party. Rasi then recalled how in the history of patient participation in the regulatory world, we have now gone beyond the two well-known obstacles “of their being bearers of their own emotional request and not representatives of a community and of being bearers of commercial interests».
Advantages of Pros
One reason the Pros matter is that a lot often what is reported directly by the patient through self-compiled questionnaires correlates poorly with the actual clinical effects of the studies. In other cases, they are essential for the objective evaluation of the effects of the intervention, as in the case of anxiety for which there is no objective measurement, or in the case of “rare diseases for which there is no specific treatment and therefore the clinical part we can’t improve much, but we try to intervene on the quality of life” he explained Annalisa Scopinaro, president of Uniamo. In the case of disease-specific Pros, it is possible to reach where the rating scales do not reach: “Think of a progressive neuromuscular disease” explained neurology Adele D’Amico, coordinator of the Bambin Gesù neuromuscular team, PRO4All member and on the Aim board «where we cannot improve muscle function but it is possible to manage secretions, with a big difference for the quality of life».
The Pros become indicators of the value of a drug
Quality of life is a parameter recognized as important in the evaluation of a treatment, both by regulatory authorities and by the Magnitude of Clinical Benefit Scale of the ESMO, the rating scale for new cancer drugs. Furthermore, it is one of the three pillars of Mission on Cancer europea. «It must therefore be part of the evaluation of the value of a drug or device” he said Francesco De Lorenzo, president of Favo concluding that for this reason “a structured presence of patients at every stage is essential, as we asked Aifa”, which could also simply draw inspiration from consolidated best practices at European level. If quality of life became a decisive indicator for the evaluation of new drugs, even in negotiations on its reimbursement, this is the reasoning, then pharmaceutical companies would be much more encouraged to take it into account.
The Pros in clinical trials: a more accurate description of reality
«When doctor-researchers fill out patient records in clinical trials, an under-reporting of symptoms and subjective adverse events in cancer patients emerges» Massimo Di Maio, president-elect of Aiom and director of the University Medical Oncology of Molinette in Turin. «This changes when in data collection systems in which patients themselves record the symptoms and toxicities they have suffered. This is why we urge a formal incorporation of patient-reported outcomes (PROs) in the description of symptoms and toxicities» in clinical studies because, as di Maio himself observed (the study appeared in BMJ Oncology), quality of life is a parameter that is still not sufficiently considered in clinical trials despite the percentage of those that include it among the endpoints having increased from 52.9% in the five-year period 2007-2012 to 67.8% in the following five-year period. The problem is that even when the data is collected, it is not published and, therefore, shared with the clinical community. “Nevertheless, it is a crucial aspect in the communication I have with my patient when choosing the most suitable therapeutic option for the individual».
The patient co-pilots the healthcare machine
What is sometimes ahead of those who design profit studies are patient associations such as Aism, which has long been fighting for a new vision of the patient’s role and for their participation in every phase of the research, not only in the collection of data of real world or in the evaluation of a treatment but right from establishing the general strategies and research priorities: «It is now widely proven that to improve the National Health Service it is necessary to put patients’ needs and rights at the center of health policy decisions. Let’s no longer talk about “patient at the center”, the patient is a co-pilotcapable of exercising scientific citizenship in every phase and context” said Mario Alberto Battaglia, general director of Aism “In addition to competence, there is a second requirement: the patient represents a more or less large community and is not the bearer of a personal request.”
What’s left to do
If there is now no doubt about the usefulness of the Pros, there is still work to be done in terms of their “validation, harmonization and standardization of the questionnaires for collecting and evaluating the indicators” he explained Giulio Pompilio, scientific director of the Irccs Cardiologico Monzino in Milan, in the name of the IRCCS network where «non-profit clinical research is carried out at the highest level, which can respond to many functions such as supporting profits in post-marketing but also conducting Real World studies», which are those studies that more than anyone, they answer a clinical question and therefore inform daily practice, that which is conducted on real patients and not on highly selected populations of pharmacological clinical trials. Finally, Di Maio hopes for “the drafting of guidelines on the collection, analysis and interpretation of PROs in the treatment evaluation phase”.
«Many tools for collecting the patient’s voice are already in use in the centers of the European neuromuscular network, where the Pros have a key role in the clinic, but they must be made mandatory thanks to the intervention of the institutions» he explained Valeria Sansone, PRO4All Member and AIM Delegate, clinical-scientific director of the Nemo Clinical Center in Milan who recalled the inevitable slowness of cultural changes and the urgent need to include Pros also in university teaching.
A story repeating itself?
Don’t think that the issue is secondary, concluded Carmine Pinto, PRO4All Member and former FICOG President, recalling the story of law 38/2010 on palliative care and pain therapy which «forced everyone to think about it and change daily clinical practice». Here too, a law is needed, the stakes are high: guaranteeing the best standards of care for all citizens with an eye to the sustainability of our national healthcare system.
Here is the PRO4All manifesto signed by all members of the Working Group (also available Who):
PRO4All Manifesto signed by all members of the PRO4All Working Group
Photo by Mikael Kristenson on Unsplash