00:00:00
Voix Off: "Cent jours pour réussir" is the podcast from G_NIUS, the Guichet National de l'Innovation et des Usages en E-Santé. Around Lionel Reichardt, meet E-health innovators and key experts to help you succeed in your projects.

00:00:20
Lionel Reichardt: Hello everyone and welcome to 100 Days to Success, the podcast for innovators and entrepreneurs in digital healthcare, but also for anyone curious about the field. This podcast is produced by G_NIUS, the Guichet national de l'innovation et des usages en e-santé. In this episode, we'll be talking about access to reimbursement for his online digital tool. To do so, we welcome Ayala Bliah, CEO of SIVAN Innovation, a company that developed MoovCare, a web application dedicated to lung cancer and reimbursed in France since July 2020.

00:00:53
Lionel Reichardt: We also have Corinne Colignon, deputy head of the medical device evaluation department at the Haute Autorité de santé, the HAS. Ayala Bliah Hello and thank you for sharing your experience. Can you tell us about your training and background?

00:01:13
Ayala Bliah: Hello, thank you for the invitation. I'm general manager of SIVAM before the Sivan adventure, I had no experience in e-health. So, after studying at Sciences Po and HSA Paris, I had worked for several years in investment banking, notably in deal financing in high tech and in corporate management in New York and Israel. So I joined Sivan in 2017 and was immediately fascinated by the Moovcare project. I thought it was fantastic, the idea of transforming healthcare using digital on our modest scale.

00:01:45
Ayala Bliah: Sivan is a startup that designs and develops innovative digital healthcare solutions, supporting healthcare professionals in their daily practices and optimizing patient follow-up throughout the care pathway by improving survival, life expectancy and quality of life for patients. Moovcare, Sivan's flagship product, is the first digital therapy to improve survival and gain reimbursement in France.

00:02:18
Lionel Reichardt: So you run Sivan Innovation, a company founded in 2014. Could you introduce us?

00:02:25
Ayala Bliah: The Moovcare is a long story. Already because as you mention that, it started since 2012. It's basically the fruit of a meeting between a French private investor, Daniel Israël, and a French research oncologist, also Dr. Fabrice Denis, and the meeting of a shared vision, that of the feasibility and relevance of a digital therapy based on an intelligent algorithm that can detect complications and problems in real time by tracking the remote evolution of patients' symptoms.

00:03:00
Ayala Bliah: The meeting between Daniel Israël and Fabrice Denis took place in 2014. Daniel Israël bought the intellectual property of this algorithm and the SIVAN adventure began. It's a long adventure that began in 2012 with a feasibility study at the Jean-Bernard Hospital in France, assessing symptom dynamics in lung cancer patients. This initial feasibility trial was followed by a prospective, non-randomized phase 2 study in 2013. Then in 2014, the SIVAN company funded a large, multicenter, randomized, prospective phase 3 study.

00:03:43
Ayala Bliah: In 2016, we presented the interim results at Lascaux. At the time, the scientific community greeted the results with great excitement because it was the first time a digital therapy had shown survival improvement of more than seven months. We had a lot of media buzz at the time and a publication in *J.N. Sinai*. In 2016, after the results were presented at Lascaux, an independent ethical committee ruled that it was no longer ethical to continue the study by keeping patients on the control arm in view of the survival result.

00:04:21
Ayala Bliah: So we switched over patients from the control arm to the experimental arm and continued the study until June 2018. In the meantime, we received *class 1 CE marking* in July 2017. So June 20, 2018, we returned to Lascaux to present the final results, which confirmed the interim results with a significant 7.6-month improvement in survival thanks to Moovcare follow-up. On the strength of these very strong scientific results, we were able to go to *H&S* and we submitted a reimbursement file in April 2018.

00:04:59
Lionel Reichardt: Moovcare is a digital therapy for lung cancer. The idea for this therapy has its reimbursement in France in July 2020 and it's been almost 9 years. Can you tell us about this journey?

00:05:09
Ayala Bliah: Yes, absolutely. It's been far from a smooth ride. We file the refund in April 2018 and a few months later, we received a rejection. But we didn't give up. We asked to be received for a hearing before the HAS and this time at the end of the hearing, we received an agreement from the HAS with an overwhelming majority of eight, which in the end was understandable, incredible, but also understandable.

00:05:46
Ayala Bliah: It's important to understand that Moovcare and digital care tools in general is a fundamental paradigm shift. With the HAS, we had to make a real effort to educate, to explain what Moovcare is, its essence, its rationale, how it works, its clinical benefits. We were lucky enough to have doctors' testimonials, and in particular Dr Alain's [inaudible], which also helped to explain Moovcare's therapeutic benefits. We're now at A3, which is also the first time a medical device of this type has received an A3. This is an improvement in the service expected by the HCS.

00:06:31
Ayala Bliah: And then, once the HAS had given its approval, we were able to begin negotiations with the CEPS, which lasted from April 2019 until July 2020. Once again, negotiations with CEPS were not easy. Once again, we had to educate them. It wasn't easy to reach an agreement because, in the end, there were no benchmarks to which Moovcare could be compared. However, despite the difficulty, it's fair to say that the agreement was built on good understanding with the CEPS, with a strong desire on both sides to reach an agreement in order to move things forward and promote innovation in healthcare.

00:07:20
Ayala Bliah: And so, we reached an agreement that took into account Moovcare's positive clinical impact, the A3 granted by the HAS. And then, a set of medico-economic indicators that we had presented to the CEPS that demonstrated Moovcare's medico-economic relevance to the healthcare system. Together, we were able to reach an agreement that ensured the viability of the business model.

00:07:47
Lionel Reichardt: So you submitted your file to the Haute Autorité de santé to obtain reimbursement for your solution. Then, what happened?

00:07:54
Ayala Bliah: Already for us, from the outset, there was a desire to follow a rigorous scientific approach, to be validated by the health authorities and to be validated by a publication. We didn't want to create an application like all the other health applications out there. There are plenty of them out there, but they're not clinically proven. As far as we're concerned, the reimbursement model was also a natural fit for Moovcare, given the proven clinical benefits.

00:08:36
Lionel Reichardt: Science is at the heart of Moovcare's development. You've written ten scientific publications between 2012 and 2019. Was this clinical validation work present from the outset?

00:08:46
Ayala Bliah: No, not at all. We didn't have the expertise. We only had strong clinical evidence in hand. And I think that one of SIVAN's strengths is to have surrounded itself with experts in the field. So, we're going to call on a firm with expertise in market access in France, and I think this was one of the best decisions SIVAN ever made. It's important to understand that the data to be presented, the reimbursement file, follows an extremely precise model. So, during the reimbursement procedure, we were confronted with a multitude of questions and a specific format to fill in. And we wouldn't have been able to do it without the help of a firm specializing in access to reimbursement.

00:09:31
Lionel Reichardt: When you came to the conclusion that you had enough clinical validation to be able to claim reimbursement. How did you go about this? Do you have in-house market access expertise? Or did you outsource?

00:09:42
Ayala Bliah: I think we had beginner's luck, but we did it right because we had very strong clinical evidence, evidence of survival, something that didn't exist before. Without having programmed it, it's basically a vision, an ideal. The fact of being able to follow patients at a distance to improve their life expectancy, their quality of life, and that proved to be the right strategy to get reimbursement.

00:10:15
Lionel Reichardt: How did you organize yourself internally to manage dialogues with the HAS, La Haute Autorité de santé and the CEPS, the Comité économique des produits de santé of the Ministère dela Santé et de la Prévention? Have you set up a specific team?

00:10:28
Ayala Bliah: Yes, a startup. So we're a small group and not the finished means in-house. So I was the main contact at SIVAN with regard to the HAS and CEPS, accompanied by a consultant. We also have a regulatory officer who played an active role in the reimbursement process. A medical director also helped us with this process. So, this is also one of the things that explains, I think the success of SIVAN, the fact of having invested sufficiently in human resources with people with strong expertise, be it medical, technological or regulatory.

00:11:23
Lionel Reichardt: You paved the way for digital therapies and were the first to gain access to reimbursement in France. So there wasn't a reference start-up on which to base your administrative procedures. How did you deal with the various health authorities?

00:11:36
Ayala Bliah: You really said it, we learned by walking. We also learned thanks to the help of experts who accompanied us. We didn't hesitate along the way. I'd recommend not hesitating to contact the health authorities to clarify their expectations. Rather than trying to guess what you should do. One thing we've realized is that for the developer, for the entrepreneur, the tool developed is often simple to understand. I'd even say obvious. It's our tool, but we have to make sure we explain it clearly to the health authorities too.

00:12:15
Ayala Bliah: Then, along the way, we could also see that a specific person we could meet certain people who understood faster than the majority and were ready to come to your aid if needed. To make the project more intelligible.

00:12:33
Lionel Reichardt: What's next for Moovcare? Will you be seeking reimbursement in other European countries? In the United States?

00:12:40
Ayala Bliah: The next step for Moovcare is that after this reimbursement, which is a great victory, it's already time to roll out Moovcare to as many patients as possible. The next challenge for SIVAN is to ensure that as many patients as possible can benefit from Moovcare. This is a real challenge, and one that needs to be taken up, because once again, it's a paradigm shift for doctors too.

00:13:07
Ayala Bliah: A different way of working for doctors, a certain amount of time on the part of doctors to be valued. In particular, we're in discussions with the *CNAM* about creating a medical act, to remunerate the doctor and precisely to value the doctor's time spent using Moovcare. It's a big challenge. Reimbursement is not enough. Moovcare must become part of the doctor's standard practice, for the benefit and in the interest of the patient. Beyond France, our aim is to deploy mosquito nets in Europe. Our next step is Germany. We're in the process of submitting a reimbursement application in Germany, and then we'll be moving on to the United States.

00:13:56
Ayala Bliah: This is a geographical extension. Our medium-term goal is also to be able to extend Moovcare to other indications. Today, we've proven that Moovcare works for patients with lung cancer. We're convinced that it also works for patients with other cancers. It can improve their quality of life, their life expectancy, but always driven by our same rigorous scientific strategy of wanting to prove things. We are going to set up clinical studies to prove and to be able to extend Moovcare to other indications.

00:14:48
Lionel Reichardt: It's a long time strategy almost 9 years between the idea and the repayment of your solution. How do you maintain such a strategy when you're a startup with short-term needs?

00:14:58
Ayala Bliah: Effectively, it's been a long journey. I don't think you should embark on this journey if you don't have strong means. You have to arm yourself with patience and a strong will, a belief in your product. You have to believe in it. And you also need to have substantial financial resources. So, to tell you the truth, since the beginning of the project, Daniel l'Israël has spent over 10 million euros not only to finance the clinical studies, but also to fund, over the years, this team of top-level regulatory, medical and technological experts. To obtain our certification, to be able to make pilots available free of charge while awaiting reimbursement. So, you have to know that the road is a long one, and you have to have the means to travel it.

00:15:47
Lionel Reichardt: Ayala Bliah, what advice would you give to an entrepreneur who wants to get reimbursed or take on an innovative healthcare solution?

00:15:54
Ayala Bliah: The first piece of advice already, to get reimbursement, to follow the reimbursement route, you need to have strong clinical evidence. I think that without irrefutable, unshakable clinical evidence, reimbursement is not the relevant model. So it was a question of improving survival. And I can tell you that this improvement in survival claimed by SIVAN was scrutinized with a very rigorous evaluation of clinical evidence by the HAS and a very rigorous evaluation of the methodology used in the clinical studies.

00:16:31
Ayala Bliah: So you already have to make sure you have the evidence. I think it's also to make sure that this evidence is published in the relevant magazines, reputable scientific magazines, to present your results at the relevant congress as well. For our part, we published the Moovcare results in the [inaudible]. As you said, several publications and we have twice presented the results of a Moovcare at ASCO. This aspect is unique and extremely important.

00:17:07
Ayala Bliah: Another success factor also for SIVAN as I mentioned earlier, was to always surround ourselves with experts, experts in the field in order to do things right, not to hesitate to contact the health authorities. Once again, to find out what their expectations are, to meet their expectations. To explain things clearly and, finally, to be patient. To know that the road is long and that, to succeed, you have to be prepared to do things right.

00:17:44
Lionel Reichardt: Ayala Bliah, thank you for this feedback and your advice.

00:17:52
Lionel Reichardt: Do you have questions about how to access reimbursement or how to pay for your innovative healthcare solution? Elements of an answer with Corinne Corinne COLLIGNON, deputy head of the medical device evaluation department at Haute Autorité de santé, the HAS. Corinne, Corinne COLLIGNON, good morning. You work for the HAS, the French National Authority for Health. Could you remind us of its main missions?

00:18:11
Corinne COLLIGNON: I work at HAS in the medical device evaluation department. This department is responsible for preparing dossiers for the Commission nationale d'évaluation des dispositifs médicaux et des technologies de santé. Its acronym is NEDIMTS. This commission's activity is exclusively linked to the reimbursement of medical devices, which means that it will assess the dossiers submitted by manufacturers when they wish to apply for their device to be included on the list of reimbursable products and services.

00:18:48
Lionel Reichardt: Reimbursement is the Holy Grail for a project owner. How do you go about getting your innovative healthcare solution covered and reimbursed?

00:18:55
Corinne COLLIGNON: When a manufacturer wants to have his solution taken over, the simplest thing is to save time by knowing precisely what the possible reimbursement channel is going to be. To put it simply, in fact, technologies used exclusively by healthcare professionals are financed globally via professional acts. And so, to date, there is no specific evaluation of each solution. This means that companies do not need to take any steps to obtain reimbursement. It will simply be via professional acts.

00:19:28
Corinne COLLIGNON: On the other hand, some of these technologies, particularly those used by patients, will go through a specific assessment. And that's where we come in. And that's where the industrialist has the hand to apply for reimbursement of his technology. Once they've checked that they are eligible for reimbursement on an individual basis, they'll be able to put together a development plan. And then, he will have anticipated his clinical development plan. Then, he'll optimize his path to reimbursement.

00:20:01
Corinne COLLIGNON: Because ideally, when a product reaches the market, the manufacturer should have the clinical data to document its clinical benefit and added value compared to the existing arsenal. So if a company has anticipated all these phases and has all the data it needs to document its reimbursement application, it won't waste any time once it has met all the prerequisites for market access.

00:20:26
Lionel Reichardt: Two possible paths are presented on the HAS websites of G_NIUS. On the one hand, the innovation package. On the other, common law and the LPPR list of reimbursable products and services. What are the differences between these two routes? Which one to choose?

00:20:41
Corinne COLLIGNON: It's really a question of maturity and the degree of technological disruption. Conventional coverage involves registration on the list of reimbursable products and services. This is what we call common law. The manufacturer has anticipated its clinical development program with all the clinical data to document the interest of its medical device and its added value in relation to the existing arsenal.

00:21:09
Corinne COLLIGNON: And will be submitting a reimbursement application to be included on this list of reimbursable products and services. For technologies that represent a break with what already exists, when there is a certain degree of innovation, and we can find quite a few in the digital field at the moment, there is a derogatory possibility that is effectively called the innovation package. The main principle of the innovation package is to finance an innovative technology. So it's aimed at certain technologies.

00:21:46
Corinne COLLIGNON: In the time it takes to conduct the Pivot clinical study, which will be used for conventional reimbursement under ordinary law. So, in an innovation package, the manufacturer will not only submit a file arguing for the interest of his product on the basis of initial data that I'm going to describe as embryonic, but also a fully-fledged study protocol. The innovation package is a request to cover the cost of a study. So, during this innovation package, the technology and the care associated with this technology will be covered, and the manufacturer will be able to conduct the pivotal princess study on his technology to request conventional coverage.

00:22:27
Lionel Reichardt: When the reimbursement file is submitted, what are the processing steps within the HAS?

00:22:33
Corinne COLLIGNON: The dossier that we call common law for an LDPR registration, is going to be filed with the HAS and the Ministry in parallel. And the HAS section will be investigated by our department so that the specialized wealth commission I mentioned earlier, called the CEDIMTS line, can issue an opinion on these criteria which are regulatory, common to all technologies that are the expected service which is a criterion for access to reimbursements. And then, the criterion of improvement in expected service, which is a criterion that enables the technology to be valued in relation to the existing arsenal.

00:23:12
Corinne COLLIGNON: Industrialists have control over when they submit their applications, filing them via a filing platform called Sésame. The file is examined by the CEDIMTS department, which issues an opinion. This opinion is then submitted to the company that submitted the file for a hearing. Once this contradictory phase is over, the final opinion is sent to the company, of course, but also to the ministry where the tariff negotiation phase takes place.

00:23:42
Lionel Reichardt: How long does it take to review refund files?

00:23:45
Corinne COLLIGNON: There is a regulatory deadline of 180 days, which covers the period from submission of the file to official inclusion on the list of reimbursable products and services. Arbitrarily, the commission allows itself 90 days to examine a file.

00:24:01
Lionel Reichardt: You talked about the Sésame platform provided by the Haute Autorité de santé, which enables manufacturers to carry out several procedures. Could you tell us more about this HAS support, bearing in mind that your role is not to advise manufacturers on the steps they need to take?

00:24:16
Corinne COLLIGNON: Yes, absolutely. I think you're right. In fact, we don't have a consulting role. We're not in a position to support a manufacturer in his project. But we can accompany them at certain key stages of their project. So we have early meetings dedicated to a clinical trial project. The aim is to meet with industrialists who are planning to set up a clinical study, before they implement it, to discuss any questions they may have about the design of the clinical study.

00:24:52
Corinne COLLIGNON: So, we can go into all the points of the methodology of this study, from the inclusion criteria, to the judgment criteria, the calculation of the number of follow-ups, etc. Really, all aspects of the protocol can be addressed in these appointments. The early meetings are really dedicated to discussing its implementation in advance. A clinical study project. At the same time, we have other types of meetings that take place once the industrialist already has his data, but is in the process of putting together his dossier. These tend to be ready-to-go appointments, so they're more practical in terms of the different aspects of the dossier.

00:25:23
Corinne COLLIGNON: L'industriel se pose des questions et on partage avec lui notre expérience de l'évaluation, qu'il s'agit du choix du comparateur approprié ou de la sélection des études qu'il va verser à son dossier qui peut être abordé, des rendez-vous après dépôt. Once he has his clinical data. A company may also need to discuss its global strategy. Our president generally responds very favorably.

00:25:50
Corinne COLLIGNON: So the industrialist sends the youth his request for a meeting and we respond whenever we think the exchange will be constructive. Whenever we can bring something to an industrialist, we gladly respond. So, of course, these exchanges are free of charge. The idea is not for manufacturers to abuse them, but to make good use of them whenever necessary.

00:26:13
Lionel Reichardt: To conclude Corinne Colignon, can you give us some advice for start-ups and industrialists who want to get reimbursed or take charge of their innovative solutions?

00:26:21
Corinne COLLIGNON: We have developed practical and methodological guides which manufacturers can find on our website and which we have also posted as links via the G_NIUS platform. We hope they will be easily accessible. The aim of this guide is to give players the keys to understanding both the process and the requirements, and the way in which the commission operates. For example, there's a document called Assessment Principles, which explains how the commission uses data and adapts its requirements to the different types of technologies submitted to it, because it assesses an extremely vast field of technologies.

00:27:04
Corinne COLLIGNON: I'd say the optimal approach consists of two steps. It's essential for a start-up or an industrial company with a project to know from the outset how this technology will be reimbursed and what clinical data are needed to establish its place in the healthcare arsenal. From there, he can build his plan, and in particular his development program. And then, having anticipated this, the more time he'll save when it comes time to bring the product to market. It's true that the only regulatory requirement is CE marking.

00:27:38
Corinne COLLIGNON: But we also know that access to reimbursement is going to be key to the spread of a technology. So, for me, these two questions are pivotal in the construction of an approach and will save a lot of time. On the HAS website, we have made a number of guides and documents available to manufacturers and project leaders, which are really key to their approach. Manufacturers will also be able to find these and other key documents on the G_NIUS platform. We've tried to include all the links that are useful for this approach.

00:28:13
Lionel Reichardt: Our episode is coming to an end. Thank you for listening. We'd like to thank our two guests for their availability, as well as you for listening. Feel free to subscribe to the podcast on the listening platforms. We look forward to seeing you soon for a new episode of "One hundred days to success".

00:28:32
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