EJP RD Internal Call for Proposals 2019 – Clinical Trials Methodology Demonstration Projects


The call is now closed 

The content and procedures of the call described in this announcement may be subject to change and are not legally binding.

Please note that this call is open only for teams from institutions that are beneficiaries of the EJP RD project (more information below).

There are at least 7000 distinct Rare Diseases (RD), the great majority being of genetic origin. Although individually rare, taken together rare diseases affect at least 26-30 million people in Europe. Moreover, they represent a major issue in health care: a large number of these diseases have an early or very early onset and/or lead to a significant decrease of life expectancy. Furthermore, most of them cause chronic illnesses with a large impact on quality of life and the health care system.

The specificities of RD – limited number of patients per disease, scarcity of relevant knowledge and expertise, and fragmentation of research – single them out as a distinctive domain of very high European need.

Recent developments suggest that traditional statistical methodologies to design and analyse efficient trials could not be applied in general to RD treatment evaluations as required. Thus, there is a greater need to apply innovative statistical methodologies for clinical trials for therapy evaluation to RDs.

In this context, the EJP RD implements the present internal call for demonstration projects to evaluate existing innovative statistical methodologies to improve RD clinical trials.

During the last 5 years, three unique EU funded projects asterix, IDeAl, and InSPiRe, developed innovative statistical methodologies to improve the design and analysis of small population clinical trials aimed at efficient evaluation of novel therapies useful in rare diseases research. Most of the developed methods are evaluated from the methodological point of view, but not applied to specific RD problems yet. Thus, the scientific RD community including stakeholders such as patient advocacy groups, regulators and clinicians have difficulties to understand the value of these innovative methodologies for their research.


The call for demonstration projects aims to show the usability and capability of the innovative statistical methodologies for clinical trials in rare diseases, which have not been demonstrated on existing data for specific rare disease clinical trials yet. Necessary for a successful demonstration project is the collection of sufficient data from a rare disease clinical trial and related information to enable demonstration of the practicability, performance and opportunities of the innovative methodologies applied to these already acquired data. Trials are often performed with standard classical methodologies not specific for rare diseases resulting in a loss of power to show positive effects.

The aim of this demonstration call is not to reanalyse or question the original analysis of data from randomized controlled clinical trials, where efficacy was established, but rather to re-evaluate data that lacked efficiency because it was analysed with classical statistical methodology, which might be not feasible for trials in the rare disease context.


Projects may concern a group of rare diseases or a single rare disease following the European definition of a rare disease i.e. a disease affecting not more than five in 10.000 persons in either the European Community, EC associated states or Canada.

The demonstration projects should use one of the following nine innovative statistical methodologies

  1. Uncertainty evaluation (bias assessment)
  2. Primary outcome variable (surrogate)
  3. Primary outcome variable (co-primary)
  4. Use of external information (historical control)
  5. Use of external information (extrapolation)
  6. Use of external information (dose response profiles)
  7. Use of external information (single arm trials – threshold crossing)
  8. n-of-1 trials
  9. Rigorous use of longitudinal information, linked to an existing clinical trials dataset for a specific rare disease.

Projects shall involve data from rare diseases (a group of rare diseases or a single rare disease following the European definition) related clinical trials. There is no limitation with respect to type of treatment (molecule, device, intervention…).

Only existing data from clinical trials that were complete, i.e. completed enrolment, lock of database, and published final study report should be used. Consequently, projects based on data of trials currently recruiting patients or ongoing are NOT eligible. External data e.g. control groups from other trials or registries can be annotated to the clinical trial data for evaluation of some specific methods. Data from pre-terminated trials, e.g. after final decision based on interim analysis or terminated for other reasons, not reaching their study goal are eligible, as long as the trial is completed with respect to patient enrolment, database lock, and final study report.

Please see all details in the Call Text


Submission of demonstration projects is limited to partners from institutions beneficiaries of the EJP RD. This includes Linked Third Parties or, parties bound by the Network Agreement with the beneficiary institution (and thus being able to integrate EJP RD project as Linked Third Party at later stage). In addition, each proposal must include one of the methodological experts matching the expertise for methodologies identified under section 4.3 Table 1 of the Call Text.

To verify if your institutions is partner in the EJP RD click HERE and check “Members Country” tab. For the specific case of ERNs and their Affiliated Partners please see below.

IMPORTANT: The applicants are asked to NOT to engage with any statistical experts and elaborate statistics plan until the preparation of full proposal.

The list of eligible methodology experts that will accompany the projects (and were identified in advance by the Task Force Group as the best experts to fulfil the objectives of this call) will be provided only on the 31 of March 2020 to avoid any potential Conflict of Interest and privilege any proposal over the other (please see further instructions below). A partnership with one of these experts is mandatory to efficiently prepare the full proposal.

Each full proposal must nominate a project consortium coordinator among the project partner principal investigators. In the case that one PI participates in more than one proposal, he/she should not be coordinating more than 2 projects. Each consortium partner will be represented by a single principal investigator. Each consortium partner will be represented by a single principal investigator. Each proposal is limited to 10 partners including a maximum of two participants from the same country.

Specific case of European Reference Networks (ERNs):

At present, all 24 ERNs are involved in the EJP RD through their coordinating institution or (in exceptional cases) through one of the ERN member institutions. In order to accommodate the participation of specific members of each ERN it was agreed that they should be attached to the main ERN beneficiary as Linked Third Parties (LTP). Each identified LTP must be enumerated in the EJP RD Grant Agreement and their tasks and budget should be described. The legal connection between the main ERN beneficiary and its LTP(s) is ensured by the Network Agreement signed within each ERN and independent on their participation in the EJP RD. Similarly the bilater agreement signed between ERN coordinating institution and the Affiliated Partners of an ERN counts as legal document.

In case new (not yet identified as main beneficiary or its LTP in the GA of the EJP RD) ERN entities (including Affiliated Partners) that will participate and will be granted in the demonstration projects, it will be mandatory to amend the EJP RD Grant Agreement and identify them as LTPs with respective budget. Thus, it is mandatory that the Network Agreement or bilater agreement (for Affiliated Partners) is signed within each participating ERN.

In case of doubts related to the current status of your ERN and your institution please contact the Call Secretariat at: demonstration.callsec(at)ejprarediseases.org

Specific case of Partners from institutes of the Slovak Academy of Sciences (SAS):

SAS partners are obliged to consult their application with the SAS Department of International Cooperation before submission, please contact Zuzana Cernakova at:
Tel: +421 (0) 2 5751 0 118

The duration of the demonstration projects can be up to 24 months.

Key facts:

  • Official call opening: 1 February 2020
  • Deadline for submission of 1-pager: 31 March 2020
  • Feedback and recommendations on matching methodology expertise: 15 April 2020
  • Deadline for submission of full proposals: 8 June 2020
  • Foreseen announcement of results: end of July 2020
  • Maximum number of funded projects: 6
  • Maximum amount of funding for each project: 220,000€
  • Maximum duration: 24 months
  • Foreseen start of funded projects: October 2020

The submission of proposal will follow two-phase process.

Phase 1.
After the official opening of the call on the 1 February 2020, the proposers possessing suitable data sets will be asked to submit only 1-pager (template will be provided) by 5 PM Central European Time (CET) on 31 March 2020 to the Call Secretariat at:

This stage will serve ONLY to review available data and ideas, and subsequently propose matching experts in methodology. It is not necessary to identify your methodologists in advance of this stage!

All 1-page applications will be gathered by the Call Secretariat and submitted to the group of methodologists that will accompany the projects (and were identified in advance by the Task Force Group as the best experts to fulfil the objectives of this call).

The methodology experts will review all applications and issue recommendations including the most suitable methodology and matching expert to develop the project. The recommendations and contact details of respective methodologists will be communicated to the applicants on the 15 April 2020.

IMPORTANT: Phase 1 is not an evaluation process! It will serve only to provide the best recommendations on the methodologies that can be explored with proposed data sets and relevant expertise from methodology experts to be included in the full proposal.

Phase 2.
The applicants with matching methodologists will be asked to submit full proposals.

Please note that only proposals using the Full Proposal template that will be provided on the EJP RD webpage at the opening of the call (1 February 2020) will be accepted. The proposal document must respect the format and the length indicated.
Proposals exceeding these limitations will be rejected without further review.


Further information and the official publication of the call will soon be available on the website of the EJP RD

For questions regarding the joint call please contact the Call Secretariat at:


The content and procedures of the call described in this announcement may be subject to change and are not legally binding. Please refer to the latest version of the Call Text and provided templates.