Member of the National Coordination for Medication and Health Products
Portuguese Ministry of Health
Dr. Helder Mota-Filipe has more than 15 years of senior executive expertise in the fields of pharmacology and regulatory affairs while also contributing to the development of key health policy in Portugal. As a Member of the National Coordination for Medication and Health Products at the Portuguese Ministry of Health, he is well placed to discuss reimbursement strategies and Health Technology Assessment procedures.
Section 1: PPI Studies
1.1. What is patient preference information and why are these studies becoming more important in medical product lifecycles (MPLCs)?
I was a payer in Portugal for 12 years as part of the management at INFARMED, which is the National Coordination for Medication and Health Products at the Portuguese Ministry of Health. INFARMED in Portugal is responsible for HTA pricing and reimbursement. During that time, I was also a member of the management for the EMA and certain groups of the European Commission.
Throughout my time, what I have felt overall is that there is a trend towards giving more and more importance to the information, interests and opinions coming from patients and through patient associations. There are some examples that can show the importance the regulators and payers are giving to this type of collaboration and information of patients.
It works in many ways; one is the involvement of patient associations and patient representatives in the committees at the EMA level. They are full members of the committees and their opinion is very valuable. At the level of payers, there is the same structure. For example, in Portugal, we had a new law for HTAs and during the development of the proposal for this new law, patients were involved. There were some working groups, including patient representatives and they were very involved in this discussion. Now there is a structure called the “Projeto Incluir”, which is a project that includes patients and is a consultative body of INFARMED to deal with problems of access and decisions on pricing and reimbursement. This is becoming more important as we move forwards.
The third level is the evaluation – the assessment of medicines in terms of HTAs, pharmacotherapeutic and pharmacoeconomic evaluations. The payers are giving more importance to the information generated by patients. This information is discussing the quality of life endpoint, which is now becoming more central in decision-making. The feedback of patients is now more important and not just at the clinical and biochemical endpoint. There are some examples that elements are changing and that the opinions and feedback of patients is becoming more significant and not just to say that we are involving patients to be politically correct.
The fourth level of importance is the real-world item and that is becoming vital not just at the first decision but in the reassessment process of the value of the product. Payers are asking more often for real-world data and some of this real-world data can be generated and obtained in collaboration with the patient. This has most definitely been a trend in Europe over the past decade.
1.2. What are the good practices required in conducting PPI studies?
The information on quality of life is very important because when we have these discussions, we can have different levels of analysis. Access and conditional factors are also crucial and with the economic crisis that is approaching it will be one of the elements that becomes significant. In terms of the market, I’m not talking about the clinical development and evaluation of a product for marketing authorization, but even in this case, it’s important that the quality of life information is available. I’m talking, for instance, about oncology products where we are giving more importance to the quality of life data and not just the quantitative aspect on the duration of the medical effect.
1.3. What are the major barriers to the acceptance of PPIs studies?
The major barrier is trust. The patient associations were seen as an extension of the interests of the industry and this was, in the past, very much like that. But now things are changing. There are still some factors to work on in terms of trust on the quality of opinions from patient associations, but I think that by bringing patients into this system, things can change. Trust now is stronger than it was before, and I think that we are moving in the right direction. However, I do believe that the main barrier is still the trust of the patient system and the independence of the patients’ opinions.
In terms of timelines for the standardization of PPI studies in HTAs, it will take several years. I think that we are now at the beginning of this process of involving patients and asking for their opinions. We tend, in some situations, to include information that originates from patient feedback and I think that, now, it is more reliant on feedback rather than the upfront opinion of patients. However, to change all the HTA guidelines and add another point about the specific or mandatory role of the patient’s opinion, will take several years; because as I said, we are now building that trust.
There is also another barrier – the quality of some patient associations. There is a heterogenicity in terms of the preparation of patient associations. In certain therapeutic areas, we have very well-prepared patient associations and we can involve them more thoroughly as we know that they have a level of opinion as required. In other areas, the patient associations, even at a European level are not strong in terms of preparation and this need time to be a standard.
The patient associations that in my opinion are more ahead of the curve are for rare diseases, Alzheimers, some areas of oncology as not all have the same preparation, and HIV. This is more from my experience at the EMA-level rather than as a payer. As payers, we are more involved at the national level. This translates more to the importance and preparation of the European associations.
Section 2: Potential Benefits and Future of PPI
2.1. What are the shifting attitudes towards PPI at regulatory agencies such as the EMA and FDA?
I think that the European system is much more prone to adopt PPI because of the social basis of the payers rather than the US system. In the US, they are not involving patients at the core of the process and although Europe is doing a process that is complex and not very fast, they are involving patients and patient feedback into the core. I think that in Europe, the process of patient involvement is more solid and deeper than in the US.
Within the European nations, it’s much more about the profile of the product than the individual methodologies that each country adopts. In Europe, in terms of HTAs, it’s not all the same as there are different marketing authorizations. In terms of HTAs, there is still a heterogenicity because it’s influenced by national characteristics, legislation and systems which change the practice of these PPI studies in different countries.
In countries where the HTA system is more robust such as the EU5, the importance given to these PPI studies depends on the characteristics of the product, because in the case of some products, the information that these studies can provide is not very important. In the case of other products this information can be valuable, and the company should be aware of this and once again, try to understand the anxiety and needs of the payers when they are discussing the value of the product.
It’s important to understand if a PPI study can be of value to the payer, because it’s not a given. It depends on the needs of information and the type of information because not all the feedback of patients can have the same importance for different products.
The big pharmaceutical companies are now the ones bringing these PPI studies to the table. I cannot identify a specific company, but the big ones are more on this ball than some of the smaller ones. In recent years, they are proposing PPI studies more often because of this emerging trend that involves information from the patient. As I said, this is a trend that is at the beginning in terms of good practice. Let’s say it’s not recognized yet, but my feeling is that the classic big pharma companies are more prone to adopt it.
2.2. What are the main advantages of utilising PPI in HTAs and reimbursement?
They are always important because what we are supposed to pay for is not efficacy but effectiveness in a real-world scenario. To have a good measure of the real world, in some respects, you cannot have this measurement without the involvement of patients. For that, you need to have patients really involved and prepared to be part of the process. I’ll give you an example that is very important, and in Portugal we are demanding that it is implemented. For rare diseases, at the beginning of the process we are paying based on clinical trials. Clinical trials for rare diseases are always with very limited information and you must pay based on often very imperfect and weak information.
In Portugal, we usually have contracts for two years. The reason is that when you renegotiate after two years, you can have much more clinical information and we give a very high value to the information that can be obtained during these two years in terms of the safety and effectiveness profile of the product in the real world. For that, it’s important to have the patients involved and prepared to give information on the quality of life.
2.3. How will PPI studies need to evolve in order to be greater implemented in MPLCs?
I wouldn’t change the methodology. I’m in pharmacology, so I have limited experience to discuss methodology, but I would advise that before you develop a PPI study, it’s important to discuss with the authorities and payers to have a study that can answer their problems and uncertainties. This communication is essential, and payers need that and give a lot of value to this information. Before you start one of these studies, try to have a clear vision from the payers and what they would like to know in order to make these studies more useful.
We had some examples that in some of these PPI studies, they were not addressing the main problems and main uncertainties of the payer when it came to give an opinion on reimbursement. It’s important to discuss with the payer before you start one of these studies what are the aspects that the payer would like to have addressed as well.
We have this issue in the cardiovascular area. You have new medicines that are very expensive, and they are supposed to have many characteristics that they probably don’t have. From my experience, we haven’t had very well-prepared patient associations and even the pharma companies are not very keen to do these kinds of studies at least, with an appropriate design. They are doing some studies that are more designed as marketing studies than studies that can answer these questions about the real utility and added value of products.
2.4. How can PPI be used in the post marketing phase of product launches?
PPI studies could in the future be used for the extension of indications of a therapeutic product but not right now. To include another indication, you must go through the marketing authorization regulation, and these always ask for a clinical trial. Where PPI studies can be important is to assure the authorities that when you use a product off-label because a company is not developing a product for any reason for this indication, the product may have to continue to be used in some patients in an off-label status. This can generate information to assure that this off-label use is safe enough and with enough efficacy in the absence of clinical data.
To include another indication and to have the basis of information coming from PPI studies, you must change the legislation to assess and give marketing authorization for another indication. You cannot today include another indication without clinical trials. In clinical trials, what you have, and what we are asking more of is to have an endpoint around the perception and feedback of the patient. This again is mainly focused around quality of life, but this becomes part of a clinical trial and not directly from a PPI study.
2.5 What will be the impact of COVID-19 on the perception of PPI studies?
I think that it will have an impact. I believe that because Portugal was one of the worst affected European countries in the last economic crisis, post-COVID, we will have another economic crash. With this new crisis we will again have a budget shortage. Therefore, the payers responsible for approvals will become more sensitive to this feedback of real-world patients when you don’t have a lot of money to approve new drugs. You must be surer of the impact of a new medicine and if what you are paying is giving the added value that you are looking for. You need to have information about effectiveness, about what the real benefit is for a patient, and not just in clinical trials. Clinical trials are just the beginning to make a first decision in terms of payment.
Patients will be more greatly involved because of this crisis that is approaching. The way payers will decide is to ensure that they are paying a fair value for what they are receiving.