Pharmaceutical Submission

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Pharmaceuticals:

If your company is interested in proposing a compound for a EUnetHTA rapid REA on a pharmaceutical technology, please contact the Pharmaceutical Joint Production team via:

WP4_Pharmaceuticals@zinl.nl

After an initial discussion on the Joint Assessment process, the next step is to complete a Letter of Intent, in which further details about the suggested compound are described: population, intervention, comparator and outcomes. The letter can be accessed at this link:

Letter of Intent

Finally, the Letter of Intent is submitted to the team at the same WP4_Pharmaceuticals@zinl.nl team address.

Please note that a Joint Assessment on your suggested compound will only be performed if sufficient EUnetHTA partners are interested in working on this topic, since one of the aims of EUnetHTA is to ensure high uptake of EUnetHTA assessments in European Member States.

Once the Joint Assessment is started, you are requested to submit a dossier. To do so, please see the following links in which you can download and consult the submission requirements and templates required for the process:

Submission Requirements – Pharmaceuticals

Evidence Submission Template – Pharmaceuticals

We are happy to explain the Pharmaceutical Joint Assessment process in further detail. As such, we have provided an extensive FAQ list for Pharmaceuticals that we strongly recommend first checking. For any further queries, the WP4 Team will be pleased to be of assistance.

 

FAQs:

What is a Health Technology Assessment (HTA)?

Why a European collaboration on HTA?

Why do we strive for European collaboration on HTA?

What is the scope of EUnetHTA Assessments?

Compounds eligible for a EUnetHTA Assessment (TISP and EPL).

How do products end up in an EPL?

How and where are EUnetHTA Assessments used (uptake)?

How does EUnetHTA facilitate the uptake of EUnetHTA Assessment reports?

How can the company help to facilitate the uptake of EUnetHTA Assessment reports?

How does EUnetHTA select an assessment team?

What methodologies are used in the EUnetHTA Assessment production?

How and where are EUnetHTA Assessments being used?

Interested in participating with EUnetHTA?

How can a pharmaceutical company suggest a compound for a EUnetHTA Assessment?

What does the participation of a company in a EUnetHTA Assessment of a pharmaceutical compound look like?

A company has a possible compound to suggest – when should EUnetHTA be contacted? What are the timelines?

Is there a fee for suggesting a topic or for participating in a EUnetHTA Assessment?

What does a company need to invest?

Which documents/data are required from the manufacturer?

What information and/or documents are made public?

What are the key procedural milestones in a EUnetHTA Assessment?

HTA AT THE EUROPEAN LEVEL

 

What is a Health Technology Assessment (HTA)?

HTA is a multidisciplinary process that summarises information about the medical, social, economic and ethical issues related to the use of a health technology in a systematic, transparent, unbiased, and robust manner. HTA answers clinical questions of new, potentially innovative healthcare technologies such as: How well does a new technology work compared with existing alternative health technologies? For which population group does it work best?

EUnetHTA Assessments use the common reporting framework, namely the HTA Core Model®, to systematically search for, analyse, and integrate clinical evidence, while assessing the quality of the body of evidence. It gives national HTA bodies essential content for national appraisal procedures. Since member states have an individual legal framework for decision making, EUnetHTA Assessments refrain from providing recommendations or conclusions on the added therapeutic and/or clinical benefit. Cost-effectiveness analyses (CEA) and ethical, organisational, patient/social and legal aspects are also beyond the scope of a EUnetHTA Assessment.

The EUnetHTA Rapid Relative Effectiveness Assessments (REAs) include the following four domains:

 

  1. Health Problem and Current Use of the Technology.
  2. Description and Technical Characteristics of the Technology.
  3. Safety.
  4. Clinical Effectiveness.

 

For complete information about EUnetHTA’s definition on HTA and Rapid Relative Effectiveness Assessments, please follow this link.

 

Why a European collaboration on HTA?

The Directive 2011/24/EU on the application of patients’ rights in cross-border healthcare was adopted in 2011 and stipulates (Article 15) that the Union shall support and facilitate cooperation between national authorities or bodies responsible for health technology assessment designated by the Member States. According to the Implementing Decision, the HTA network is to be supported by a scientific and technical cooperation to meet the objectives of the European cooperation on HTA as per Article 15 of the Directive.

EUnetHTA performs the function of the scientific and technical cooperation of the HTA network. Read more about the network here:

Health Technology Assessment Network

Health Technology Assessment Network Stakeholder Pool

For complete information about the history of EUnetHTA, please follow this link.

 

Why do we strive for European collaboration on HTA?

 A European collaboration on HTA benefits pharmaceutical companies national HTA agencies and ultimately patients. By participating in EUnetHTA Assessments, companies have the opportunity to collaborate with EUnetHTA and shape the future of European HTA.

Benefits for a pharmaceutical company are:

 

  • Potentially faster and less intensive national assessment on clinical effectiveness.
    • Head start on national work because of the availability of the EUnetHTA Submission Dossier.
    • European scope of the EUnetHTA Assessment.
    • Timely availability of the EUnetHTA Assessment around two weeks after publication of the European Public Assessment Report (EPAR).
  • Pooling of expertise and experience in the assessment team.
  • Predictable and consistent process to secure transferability of the results across Europe.
    • Quality Assurance via tools, templates and Standard Operating Procedures (SOP).
    • Stakeholder engagement.
  • Professional guidance before and during the assessment by central project management.

 

What is the scope of EUnetHTA Assessments?

 EUnetHTA Assessments are HTA reports jointly produced by at least four EUnetHTA partners from different European countries. EUnetHTA processes, guidelines, and the HTA Core Model® are used for the production of Assessments. The HTA Core Model® is a common reporting framework to systematically search for, analyse, and integrate clinical evidence and assess the quality of the body of evidence. It gives national HTA bodies all the essential content required for national appraisal procedures.

Since Member States have an individual legal framework for decision making, EUnetHTA Assessments refrain from providing recommendations or conclusions on the added therapeutic and/or clinical benefit. Cost-effectiveness analyses (CEA) and ethical, organisational, patient/social and legal aspects are also beyond the scope of a EUnetHTA Assessment. EUnetHTA Assessments are also subject to extensive review procedures in order to ensure high quality.

Pharmaceutical EUnetHTA Assessments are centrally coordinated by the WP4 Co-Lead Partner Zorginstituut Nederland (ZIN).

 

Compounds eligible for a EUnetHTA Assessment (TISP and EPL).

All new medicines and extensions of indication that enter the market via the central procedure (i.e. via the European Medicines Agency [EMA]) are eligible for EUnetHTA Assessments. In order to actively identify compounds of specific interest for EUnetHTA partner organisations, EUnetHTA is developing a process called ‘topic identification, selection and prioritisation’ (TISP), which will result in a prioritisation list. Where the first EUnetHTA Prioritisation List (EPL) was launched as a pilot, its findings will feed into the structural and systematic approach of TISP. In addition, voluntary compound submissions by companies are much welcomed.

 

How do products end up in an EPL?

The EPL was based on the Innovation Observatory. The list was cross-checked with the open access Dutch Horizon Scan and the publicly available EMA list of medicines under evaluation to estimate regulatory timelines. In compiling the list, EUnetHTA partners were asked to indicate their interest, including using the Assessment at the national level. The final prioritisation was based on this feedback and combined with the anticipated feasibility of the compatibility of timelines of the EUnetHTA Assessment and estimated regulatory timelines. Therefore, prioritisation does not discriminate between pharmaceutical companies, compounds or indication. Of note, the EPL is an ad-hoc approach. In the future, this process will be replaced using the aforementioned systematic approach called ‘topic identification, selection and prioritisation’ (TISP).

 

How and where are EUnetHTA Assessments used (uptake)?

As part of the implementation network, EUnetHTA collects use and uptake information by EUnetHTA partners (HTA agencies) of its jointly produced HTA information. The information is collected through surveys and interviews carried out with implementation network participants.

 

How does EUnetHTA facilitate the uptake of EUnetHTA Assessment reports?

 EUnetHTA has several processes in place to facilitate the national uptake of the EUnetHTA Assessments:

  • Selection of the assessment team: Experienced HTA agencies with commitment to use the EUnetHTA Assessment report in their national appraisal process are eligible as part of the assessment team.
  • Population, Intervention, Comparator and Outcome (PICO) survey: EUnetHTA partners that assess pharmaceuticals are asked to indicate whether the proposed PICO is of national relevance.
  • Implementation Network: EUnetHTA has established this network in order to gather information on national uptake of the Assessment reports.
  • EUnetHTA actively approaches national HTA bodies before and during the process in order to let the HTA bodies prepare for the upcoming EUnetHTA Assessment and enhance uptake.
  • The Heads of HTA Agencies of the countries represented in the EUnetHTA Executive Board (ExB) have agreed to take a more proactive approach in performing Joint Assessments. There is a strong consensus within EUnetHTA that this approach will strengthen the methods and procedures of the pharmaceutical Joint Assessments to increase the benefits of EU cooperation on HTA and to shape the future model of collaboration. This facilitates national implementation and uptake of the Joint Assessments.

 

How can the company help to facilitate the uptake of EUnetHTA Assessment reports?

EUnetHTA also identified some steps and activities in which the company can help facilitate the national uptake of the Assessment. One of the recommendations for the company is to share information on the EUnetHTA Assessment and its processes with national affiliates who prepare the national submission dossiers. In addition, EUnetHTA recommends having each national/regional affiliate communicate to the local decision maker that they are participating in a EUnetHTA Assessment and that they should explore the options for the use of the EUnetHTA submission dossier in the national appraisal.

 

 

PROCEDURES

 

How does EUnetHTA select an assessment team?

EUnetHTA defined a set of selection criteria that are followed when an assessment team is created (see below). EUnetHTA focusses on including relevant expertise, the commitment to use the Assessment nationally and available resources within the EUnetHTA Joint Action 3. In addition to this, EUnetHTA also seeks to build capacity by employing the following selection criteria:

  • Commitment to use the EUnetHTA Assessment in the national setting. Deviations from this criterion might occur if specific skills (for example for dedicated reviewers) are required.
  • Expertise/knowledge of the disease area and the drug/medical device should be available within the authoring team.
  • Experience with and understanding of EUnetHTA procedures, tools, and methodology should be available to the authoring team.
  • Available skills and experience from previous Joint or Collaborative Assessments within the authoring team. Ideally, at least one agency within the authoring team should have experience with previous EUnetHTA Assessments.
  • Availability during suggested timelines.
  • No conflict of interest of participating persons (following JA3 DOI procedure)/
  • Sufficient amount of person months in budget / willingness of agency to use local budget for production.
  • A geographical spread of the authoring team throughout Europe.

A Declaration of Interest and Confidentiality Agreement (DOI) is signed by all participating individuals from the HTA agencies and external stakeholders (e.g. individual patients, healthcare providers, medical editor).

 

What methodologies are used in the EUnetHTA Assessment production?

EUnetHTA Assessments are conducted following the EUnetHTA Guidelines. The primary aim of the EUnetHTA Guidelines is to guarantee consistency between Assessments and to guide the assessors in all steps of EUnetHTA Assessment production, e.g. how available evidence/data is analysed and interpreted. Existing guidelines are being revised regularly and new guidelines are being developed.

 

How and where are EUnetHTA Assessments being used?

Detailed information on the use of EUnetHTA Assessments can be found here.

 

 

INDUSTRY – HOW TO PARTICIPATE/RELEVANT INFO

 

Interested in participating with EUnetHTA?

  • Get in contact (prior to submitting to EMA) with EUnetHTA via WP4_pharmaceuticals@zinl.nl
    • EUnetHTA can present the assessment procedures and answer questions in an informal meeting or call.
  • Submit a Letter of Intent.

 

How can a pharmaceutical company suggest a compound for a EUnetHTA Assessment?

If your company is interested in suggesting a pharmaceutical compound for a EUnetHTA Assessment, you should submit a Letter of Intent to Zorginstituut Nederland – the Pharmaceutical Co-Lead Partner of WP4. This can be sent to WP4_Pharmaceuticals@zinl.nl. In the Letter of Intent, further details about the suggested compound are described: population, intervention, comparator and outcomes (PICO). The template for this letter can be found here.

As soon as a completed and signed Letter of Intent is received, the project manager(s) will reach out to all relevant EUnetHTA WP4 partners to identify assessment team members. Please note that, since EUnetHTA aims to ensure high national uptake of an Assessment, a EUnetHTA Assessment on a suggested compound can only be performed if there is sufficient interest from WP4 partners in (working on) this topic.

 

What does the participation of a company in a EUnetHTA Assessment of a pharmaceutical compound look like?

 The participation of a company starts by submitting a completed and signed Letter of Intent. After a team is formed, the manufacturer is invited to submit a Scoping Document, focussing on the manufacturers’ view of the PICO (+ justification), prior to attending a scoping face-to-face meeting with the authoring team and the project manager(s). The scoping face-to-face meeting provides the possibility to discuss the PICO and the information the authoring team (author and co-author) requires in the Submission Dossier.

One month prior to CHMP opinion, the company delivers the Submission Dossier to EUnetHTA, which forms the basis for the Assessment (

Approximately three weeks prior to publication of the EUnetHTA Assessment, there is a possibility for the company to do a factual accuracy check of the draft EUnetHTA Assessment, i.e. they can make sure that the factual information in the EUnetHTA Assessment regarding their product is correct. The authoring team will formally answer fact-check related comments which are published on the EUnetHTA website in order to allow transparency.

 

A company has a possible compound to suggest – when should EUnetHTA be contacted? What are the timelines?

The best time to contact Zorginstituut Nederland (WP4 pharma Co-Lead Partner) depends on the EMA submission date and the regulatory pathway (i.e. initial marked application, Type II variation or accelerated access). CHMP opinion and publication of the EPAR always form the basis of the EUnetHTA Assessment timelines. In order to publish the EUnetHTA Assessment report close after EPAR to facilitate a high national uptake, the assessment has to start immediately after CHMP opinion. This results in strict deadlines and the need for everyone to comply with the timelines set in the Project Plan.

To allow for a proper scoping phase (i.e. assembling the team, scoping face-to-face meeting) a Letter of Intent should be submitted around day 0 of EMA submission. Informal dialogue between the company and EUnetHTA on, for example, procedures, can be initiated well before EMA submission.

 

Is there a fee for suggesting a topic or for participating in a EUnetHTA Assessment

There is no fee for suggesting compounds or for participating in a EUnetHTA Assessment.

 

What does a company need to invest?

The main investment of companies is the time spent by their employees to prepare the EUnetHTA Submission Dossier. It is expected that the company will be able to use parts of, or the entire EUnetHTA Submission Dossier/report, for national submissions. We strongly encourage companies to get in touch with their national affiliates to make them aware of the (upcoming) EUnetHTA Submission Dossier and Assessment report to enhance the use of the EUnetHTA documents in national submissions.

The company is also invited to a face-to-face scoping meeting (see the question on “How does the participation of a company in a EUnetHTA Assessment of a pharmaceutical compound look like?”). Travel/accommodation costs of company employees cannot be reimbursed by EUnetHTA. Scoping meetings are held in Amsterdam (Netherlands) at the office of the WP4 Pharma Co-Lead Partner, Zorginstituut Nederland.

 

Which documents/data are required from the manufacturer?

 In order to proceed with a EUnetHTA Assessment the following documents are required:

 

Letter of Intent (LOI)

The LOI is submitted by the company will be shared with all WP4 partners that assess pharmaceuticals, in order to form an assessment team.

In the Letter of Intent, details about the suggested compound should be outlined: Population, Intervention, Comparator and Outcomes (PICO) and statistical methods available to analyse the data. The template for this letter can be found here.

 

Scoping Document

In order to have an efficient and informed scoping face-to-face meeting, the manufacturer is requested to submit a Scoping Document. This document should be concise and focus on the manufacturers’ perspective (and justification) of the PICO and any statistical methods for presenting the data (e.g. Network Meta-Analysis).

 

Submission Dossier

The Submission Dossier, provided by the company of the compound under assessment, forms the basis for the EUnetHTA Assessment. This dossier consists of:

  • The Core Submission Dossier.
  • Appendices to the Core Submission Dossier: all Clinical Study Reports (CSRs) and other relevant background information, such as the statistical analysis plan and raw data of Network Meta-Analyses when relevant.

The EUnetHTA Submission Dossier was created based on the most common submission requirements from around Europe; therefore, parts of it can be used in national processes.

In short, the Submission Dossier consists of a description of the technology and disease, provides an overview of current treatments/guidelines, proposes a scope for the assessment consisting of Population, Intervention, Comparator(s) and Outcomes (PICO), systematic literature search, and all relevant publications together with the evidence synthesis. The Submission Dossier is used as a basis in the EUnetHTA Assessment.

The Submission Dossier typically follows the rapid Relative Effectiveness Assessment (REA) model of the HTA Core Model which consists of four domains, themselves consisting of generic research questions, the so-called ‘assessment elements’:

  • The description of the technology and its comparators (TEC).
  • The health problem and the current use of the technology (CUR).
  • Clinical effectiveness (EFF).
  • Safety (SAF).

The EUnetHTA Submission Dossier is shared with the project manager, who then shares it with the assessment team (authors, co-authors, dedicated reviewers and observers). Authors are free to cite from the Submission Dossier.

Only after publication of the EUnetHTA Assessment will the Core Submission Dossier be made public. Appendices to the Core Submission Dossier, e.g. CSRs are not published by EUnetHTA. For further information, please read EUnetHTA’s Submission Requirements Fact Sheet available here.

 

What information and/or documents are made public?

The following items will be made publicly available:

  • Once an assessment team is formed, the topic of the assessment and the assessment team (institutional level only) will be published on the EUnetHTA’s webpage. The Letter of Intent itself will not be made public.
  • After positive CHMP opinion, the finalized project plan will be published together with the comments from external experts and the answers of the authors/co-authors to these comments.
  • Around two weeks after publication of the EPAR, the EUnetHTA Assessment will be published together with the Core Submission Dossier, the comments from external experts, the factual accuracy check by the company, and the answers of the authors/co-authors to these comments.

 

What are the key procedural milestones in a EUnetHTA Assessment?

 The exact timelines are dependent on the regulatory pathway. To give a general understanding of the timelines, please see the list below. For a thorough understanding of what the timelines may look like for a specific compound, please contact us at WP4_pharmaceuticals@zinl.nl

 

Key Activity & Time Expectation

Letter of Intent – Around Day 0 of EMA submission.

Scoping Document – 1 month prior to scoping face-to-face meeting.

Scoping face-to-face meeting – 2-3 months prior to CHMP opinion.

Submission Dossier – 1 month prior to CHMP opinion.

Start Assessment Phase – CHMP opinion.

Factual Accuracy Check – 3 weeks prior to publication of the Assessment Report.

Publication of the Assessment Report – 2 weeks after EPAR publication.