Conditional inclusion of orphan drugs, conditionals and exceptionals

The new policy focusses specifically on:

• medicinal products that are designated orphan medicinal products;
• medicinal products that are given a conditional authorisation (the so-called conditionals); and
• medicinal products that are given an exceptional authorisation (the so-called exceptionals).

Letter to the Lower House

On 22 October 2019, the Minister for Medical Care and Sport, sent a letter to the Lower House (in Dutch), informing its members of the new conditional inclusion. The new policy came into effect on the same date. Conditional inclusion is implemented by the National Health Care Institute.

Marketing authorisation holders with an orphan drug, conditional or exceptional that wants to be considered eligible for conditional inclusion in the basic healthcare package and which meets the criteria, can submit an application to the National Health Care Institute. They are also required to submit a file with a research proposal in collaboration with medical professionals, patients’ associations and an (independent) research institute.

Medicinal products for an unmet medical need

Medicinal products can only be eligible for conditional inclusion in the basic healthcare package if they have been granted marketing authorisation by the European Medicines Agency (EMA). Almost all these medicinal products are automatically included in the basic healthcare package in the Netherlands. Only some of these are first assessed by the National Health Care Institute. In a few cases, the National Health Care Institute is expected to assess a medicinal product that is promising, but for which insufficient evidence has been collected to be able to fulfil the package criterion ‘effectiveness’. As these are often medicinal products for the treatment of severe - often less prevalent - diseases for which no proper treatment exists, from the perspective of society, it is right that, under certain conditions, patients are nevertheless allowed access to this type of products. This is the reason for the new conditional inclusion policy.

During the conditional registration trajectory, marketing authorisation holders of a medicinal product carry out research - at their own expense - into its effectiveness and also into possibilities for using it appropriately (‘gepast gebruik’). This should take place in collaboration with medical professionals, patients’ associations and an independent research institution. At the end of the period of conditional inclusion, the National Health Care Institute issues a statement, based on all available scientific evidence, about the value of including the product concerned in the basic healthcare package.

Motives for the new policy

Whether a form of treatment or a medicinal product is worth including in the basic healthcare package depends on the availability of clinically relevant evidence of its effectiveness. Such information is generally not available (in sufficient quantities) at the moment of registration of medicinal products for severe - often less prevalent - diseases. This may be, for instance, because the group of patients is too small or its composition too heterogeneous. Or it may involve a new medicinal product for a (chronic) slow and progressive disease. In such cases, researchers have to follow a group of patients for years in order to be able to determine the effectiveness. In such cases, it is difficult to prove that, for a given treatment, a medicinal product should be included in the basic healthcare package as insured care. This requires more time. The consequence being that, in practice, patients who still have an unmet medical need do not have access to a medicinal product for which, based on the registered indication, they are eligible.

Research set-up will need to be customised

Conditional inclusion in the package will allow marketing authorisation holders an opportunity to carry out further research into the effectiveness and appropriate use in the Netherlands of their new medicinal products for what are frequently less prevalent diseases. Randomisation and blinding will not always be possible because the medicinal products that are targeted by the new policy often have special characteristics. In that case, in consultation with the National Health Care Institute, other methods will be used. Based on the research outcomes, the National Health Care Institute will eventually be able to issue advice on whether a medicinal product complies with ‘established medical science and medical practice’, i.e., that its effectiveness has been scientifically proven. Pharmaceutical companies will have to set up and carry out their research in collaboration with medical professionals, patients’ associations and an independent research institute.

Opting in advance for a 7-year or a 14-year period

When submitting an application form, and later when submitting the dossier with a research proposal, parties will have to stipulate a specific research period. The point of departure is that research (including assessment by the National Health Care Institute) provides the results needed to be able to assess the effectiveness of (treatment with) a medicinal product as rapidly as possible (at most within 7 years). In specific cases, a longer period may be necessary, though it may never be longer than 14 years. During the period of conditional inclusion, the medicinal product will be available, via the basic health insurance, for all patients who are eligible for it. Such patients will be obliged to participate in the research in order to be eligible for reimbursement. The National Health Care Institute will start the assessment by no longer than six months prior to the end of the period of conditional inclusion. The Minister for Medical Care and Sport decides, based on the National Health Care Institute’s assessment, whether a medicinal product is allowed into the basic healthcare package.

Procedures and criteria for applications

There are two moments at which marketing authorisation holders of orphan drugs, conditionals and exceptionals can apply for conditional inclusion in the basic healthcare package:

1. Prior to an assessment of a medicinal product by the National Health Care Institute.
2. After receiving negative advice or a negative assessment from the National Health Care Institute due to insufficient evidence to be able to settle a package-related question.

The following conditions must have been fulfilled when submitting a file:

1. The medicinal product has been registered by the European Medicines Agency (EMA), and is a designated orphan medicinal product, conditional or exceptional for the indication concerned, on the basis of which conditional inclusion in the basic healthcare package is being requested.
2.  There is an unmet medical need for the indication concerned, according to the definition of the EMA.
3. The main entity submitting the dossier is the marketing authorisation holder. Co-submitting parties are professionals’ associations, patients’ associations, and a(n) (independent) research institute.
4. It must be deemed plausible that, based on the data collected, it will be possible to answer the question regarding inclusion in the package at the end of the research period. The full research trajectory up to and including (renewed) assessment by the National Health Care Institute  can be completed within the period of conditional inclusion. This period will last no longer than 7 or 14 years. The marketing authorisation holder must determine the length of the trajectory when submitting the file. 

All requirements that an application must fulfil can be found in the (Dutch) document 'Dossiereisen aanvraag voor voorwaardelijke toelating weesgeneesmiddelen, conditionals en exceptionals'.

Applications for conditional inclusion

Applying for conditional inclusion
When applying for conditional inclusion, use must be made of the application form (in Dutch): 'Aanvraagformulier voorwaardelijke toelating weesgeneesmiddelen, conditionals en exceptionals'.
The application form, fully completed, can be sent by e-mail to: VTgeneesmiddelen@zinl.nl.
Has the medical product been designated by the Minister as a potential candidate for conditional inclusion? Then use this format to draw up the convenant (in Dutch): ‘Modelconvenvant voorwaardelijke toelating weesgeneesmiddelen, conditionals en exceptionals’.

The full set of procedures is described in the document Conditional inclusion procedure for medicinal products.

Price agreement and covenant

Once the National Health Care Institute has selected a medicinal product for conditional inclusion in the basic healthcare package, the Ministry of Health, Welfare and Sport (VWS) starts negotiations with the marketing authorisation holder in order to arrive at an agreed price for the duration of the conditional inclusion. The price paid per individual medicinal product must be made public. Furthermore, all parties involved (the marketing authorisation holder, medical professionals, patients’ organisations and independent research institution) are obliged to draw up a joint covenant. This contains agreements on the (minimum) outcome parameters of the research, on informing patients and on the criteria for starting, discontinuing and gradually withdrawing treatment. Furthermore, all parties must promise to cooperate if the National Health Care Institute nevertheless issues a negative assessment of the medicinal product after the end of the period of conditional inclusion. This will mean that the medicinal product cannot be included in the basic healthcare package.

Available budget for the conditional inclusion of medicinal products

In the first 4 years (between October 2019 and October 2023), a conditional inclusion procedure was started for 4 medicinal products. The available budget for the conditional inclusion of orphan drugs, conditionals and exceptionals was € 24.2 million in 2019, € 25.5 million in 2020, € 26.8 million in 2021 and € 34.2 million in 2022. As of 2023, that budget will be € 36.8 million. Part of the budget for 2023 and the following years has already been allocated. That is why a further € 11.3 million will be available in 2023 and a further € 14.1 million in 2024. If the budget has been exhausted for a certain year, a queue will be formed. So far, this has not happened.

The National Health Care Institute has advised the Minister for Medical Care and Sport, to evaluate the procedure for conditional inclusion every 2 years.