Table 2 Quotes of participants' perspectives on access schemes for fast-track delivery of orphan drugs

Early Temporary Authorization (ETA): compassionate use program/medical need program (CUP/MNP)

I1

15) “We checked how many percent of the compassionate use programs were approved orphan drugs, and that was one third of the compassionate use programs approved by the agency of orphan diseases.”

D1

16) “As of yet, there has also been a problem with the data collection associated with it.…I hear all sorts of things, I hear there are confidential issues involved. I also hear that the prescribers do not want to go to the trouble of collecting that data. Companies certainly do not want to go through all of that administration for data collection. There is a lot of ambiguity at the moment.”

C1

17) “It is necessary to decide who is responsible to collect data. So far, it is one that says, it is the companies, the other one says, it is the doctors and a third one says, it is the authorities but, in the end, insufficient data is collected. Until it is clear, maybe legally or another way, who is responsible for it, I am afraid nothing will happen…And also define who is the owner of the data…that owner also must be willing to share the data.”

18) “In day-to-day practice, I don't think everyone uses the same measurements necessarily, so it's very difficult to compare results between patients and draw a conclusion about that kind of data. It is also a kind of real-world data, hey, there must be some form of standardization to be able to interpret this data.”

D1

19) “Well, it's actually more complicated, I mean we tried to make it easier, the intention is that a parallel submission will be made to the FAMHP and the RIZIV/INAMI. At the same level, in collaboration with the FAMHP, the ethics committee would also intervene. However, that is something new, why do I mention it, because we also proposed it at European level and there was quite a bit of interest shown for it.”

I1

20) “Yes, it would be important to have an electronic system. Also, for the orphan drugs with a College because we support the collection of wearables.”

A2

21) “If that data then plays a major role, then we also have to be sure that it is correct, right? Yes, those systems must be validated, otherwise they are really not valuable.”

D1

22) “But if you link that to conditional reimbursement, then maybe it could be implemented, huh. Maybe not such a bad idea, that you ask the patient to fill in data 2–3 times a year for 5 or 10 min and that that is one of the conditions that he/she gets his/her medication. I don’t think these should be absolute conditions, but we should ask nicely anyway…a large framework has to be created to realize that, and if that is the case, I can imagine that the patient is invited to register data anonymously, of course. There needs to be a legal framework. Nowadays, it seems that there are mainly discussions since GDPR is unclear.”

E1

23) “I think with permission you never have problems, if the patient gives the informed consent. Suppose that something makes a real difference scientifically and as a society you invest disproportionate resources into it, then from an ethical point of view I think that is also a discussion that you should dare to have in order to say that we expect something in return. I also think that if you use solidarity in the context of very expensive resources… if it is really essential to demonstrate whether something provides sufficient efficacy and return to pay for it as a society, then I think you can discuss it every now and then.”

K1

24) “I think the philosophy is also not to centralize it all, but to ensure that the databases that are available can communicate with each other.”

C1

25) “But I think one of those solutions that are shared and discussed nowadays, is that we would actually register real-world data so that a real analysis could be done after a certain duration of treatment so that a better decision could be made in the end…The Orphan Drug Colleges would be a good opportunity for that …Well, in fact, it has to be decided upfront what data should be collected, for how long, by who…so that we have quality data in the end that can be interpreted.”

Early Temporary Authorization (ETA): Early Temporary Reimbursement (ETR)

I1

26) “…the idea of choosing the amount was to cover the logistics costs…and that amount is relatively low, but is to compensate for the administrative burden of the industry …We would like to improve the ETR and make it more appealing. But now it's relatively burdensome and doesn't bring much more than a CUP or MNP, so if the companies have to choose now, it's easy in fact, CUP or MNP…”

D1

27) “We have been very dynamic, in the beginning it was a compensation, a lump sum, which was initially seen as a kind of foreshadowing of the final reimbursement by the industry, it was then made clear that it was not the case and then it also disappeared…”

I2

28) “Yes, I can only speak for the industry, we are of course in favor of quick and temporary reimbursement until a final decision has been made about reimbursement. So, the principle (of ATU) is something that we as an industry are advocating for. Of course, the scope has to be aligned. Which medicines are now eligible for this? It goes without saying that you cannot reimburse all medicines the same way.”

D1

29) “in ideal circumstances that (unmet medical need) list would not only be fed by the industry, but also by the unmet need defined elsewhere, but yes, as long as the minister does not define what unmet need is…”

C1

30) “No, sorry to say, but I think yes, there should be suggestions but from the field, that is, from doctors, but also from the health insurance fund because they see what the medical need is in society.”

Off-label use

I2

31) “It is an increasing phenomenon…drugs that work via a certain pathway and if that pathway applies to a tumor in the lung or in the colon…doctors believe that if the pathway is the same for a tumor in a different location, I would like to try that (same medicine) with this patient, but there is no registration for it.”

A2

32) “Sometimes off-label use is already in the guidelines…then it is clear that everyone agrees with it.”

33) “I think the NIHDI plays a big role in off-label use. Sometimes it is not reimbursed and sometimes it is. If it is not reimbursed, it is often financially difficult to establish off-label use.”

34) “It will always be difficult to report the negative effects, but we actually need that.”

D1

35) “But not the off-label use and that is the problem…evaluations of all systems have to be made and again about GDPR…who should collect which data, who is allowed to…who is entitled to that data and who owns it and so on.”

36) “…what we are reflecting about are those centers of expertise, reference centers, after the European example…for those kinds of very rare diseases off-label use could be permitted in only one or two centers in Belgium. This could be done with other people, so that there is peer control. There must be, so to say, a joint database. Or at least have some sort of yearly reporting in an expertise center.”

I2

37) “I think that there should be partial responsibility between authorities and companies…And, of course, you could also think about a shared responsibility for financing. Now, the doctor is completely dependent on the goodwill of the company and we are aware that some companies are more willing to participate than others.”

38) “…evidence should also be collected, which could perhaps be part of the answer…So that, in case of off-label use, data is also produced by those doctors and that progress can be made, that evidence is created.”

C2

39) “This may be possible through the FAMHP. A legal framework can be drafted by the FAMHP in which, based on an evaluation, is determined which (off-label use) we now think is justified.”

I2

40) “But that's why it might not be a bad idea what C2 proposes, that is possibly one option. That the limited evidence that there may be of off-label use, because I think we agree that it is limited compared to when there is a market authorization, that you let an independent body judge it. When you talk about the FAMHP, I have my reservations since the FAMHP currently works on a fee for service basis…a fee of 11 000 euros should be paid for an evaluation, which is not free, I would say. Another option could be…similar to the Netherlands, that scientific associations would do that evaluation. For example, that doctors who prescribe off-label are evaluated for impertinence by scientific association…so basically, the peers. Then one would have to deal less with that financial element and perhaps be even closer to practice and the people who are really aware of the latest good practices, than when you would involve FAMHP.”

41) “What is the representativeness if you have two patients in Belgium? It would be better to have an international registry.”

C2

42) “But then again, we have to be careful to do it in controlled circumstances, because that's the problem right now. Certain companies acquire those (smaller businesses), then re-exploit the monopoly position making it to become extremely expensive, whereas before, it could be used unnoticeably at a reasonable price.”