This call closed on 15th June 2021
Background
At the request of LUSS (Ligue des Usagers des Services de Santé), the French-speaking umbrella organisation of patient organisations, KCE started a scientific report in December 2020 on the needs and follow-up of people with long COVID. The full report is expected to be published in October 2021, but intermediate chapters are regularly published in order to inform policy makers and other stakeholders as soon as possible.
In response to the need for clinical research into the treatment of long COVID (1) identified during the process of writing this KCE report, KCE Trials is opening a call for proposals on treatment modalities for long COVID patients. Because sufficient data to perform large confirmatory trials of possible interventions is currently often lacking, single-centre proof of concept studies are also accepted. The existing KCE Trials selection process is adapted and simplified to select, fund and follow-up long COVID studies using a fast-track selection process which aims to select proposals in 2-4 months and have studies started before the autumn. The procedure is outlined below.
This call for proposals for trials on long COVID treatment focuses on non-commercial randomised interventional trials, where there is some rationale to test the intervention in a proof of concept study but where good quality evidence on the intervention in this indication is currently lacking. Larger confirmatory studies are also accepted. Studies focusing exclusively on PICS are out of scope. Research proposals should be designed to deliver rapid relevant outcomes. Projects can be up to 24 months in duration, but shorter proposals are encouraged. The call will use a 2-step selection process where applicants first submit a research outline and in a second step prioritised proposals are invited to submit a full proposal.
This call for proposals is organized in collaboration with researchers and the expert group of the ongoing KCE report.
The funding of trials selected in this call will not originate from the usual KCE Trials Programme budget, but will be decided on a case by case basis and will require specific approval from the Federal Minister of Budget.
[1] In the literature different terms are used such as long COVID, long-haulers, long-term effects of COVID-19, post-COVID syndrome, chronic COVID syndrome, etc. Due to absence of an international consensus about the terminology, we have arbitrarily chosen to use long COVID in the current call to refer to patients with symptoms that persist or develop after the acute phase of a confirmed or suspected COVID-19. Long COVID is reported after both a mild or severe acute phase of COVID-19.
Scope
Inclusion criteria
The primary aim of the study is non-commercial (see Belgian law on experiment on human of May 7, 2004).
- The candidate sponsor (and the BCC, if applicable) qualifies as a non-commercial sponsor under the applicable laws, including the law of May 7, 2004 related to experiments on human person, or equivalent if the sponsor is not located in Belgium.
- The holder of the intellectual property rights on the studied intervention or comparator to which the experiment relates is neither directly nor indirectly the sponsor of the experiment.
- The sponsor exercises the intellectual property rights to the concept of the experiment, its implementation and the scientific data resulting from it.
- The funding granted under the research agreement complies with the European state aid regulations.
Design
- The trial is randomised, single or multi-centric.
- Proof-of-concept studies are allowed in which case sample sizes are pragmatically determined and a formal sample size calculation is not required.
Patients
- Proposals must focus on treating and/or supporting individuals (adults and/or children) with Long COVID. Long COVID patients hospitalised and/or not hospitalized during the acute phase are in scope of the current call.
Setting
Patients can be treated in hospital, primary care, outpatient care or rehabilitation centre.
Therapies and Interventions
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The trial aims at improving outcomes for individuals with long COVID, for an intervention for which there is still a need to generate new evidence. This could include a range of pharmaceutical and non-pharmaceutical therapies addressing physical and/or psychological aspects, including how they interact. Specific examples could include:
- Assessments of interventions and therapies particularly those which are currently being used in practice or which could be repurposed.
- Assessment of rehabilitation programmes including both physical and psychological support. This could include multidisciplinary team rehabilitation interventions.
- Use of medication still on patent is in scope, provided the Sponsor has a strong justification why the study would/could not be performed by the marketing authorisation holder.
- A rationale for the selected intervention/therapy is required. Both proof of concept or confirmatory trials are eligible.
Outcome
- Proposals should include appropriate outcomes which focus on individuals and could include quality of life, daily activities, return to work, etc and should also include some objective measures of the disease.
Duration
Research proposals should be designed to deliver rapid tangible outcomes. Projects can be up to 24 months in duration, but shorter proposals are encouraged. Projects are expected to be able to start in the autumn 2021.
Exclusion criteria for the 2021 call
Started studies
- Studies for which recruitment has already started in Belgium, or which have already been submitted to a Belgian ethics committee or to the FAMHP (Federal Agency for Medicines and Health products) are out of scope. International studies that have already started abroad (but not in Belgium) are eligible if all other criteria are met.
PICS Post Intensive Care Syndrome
- Studies focusing exclusively on PICS are out of scope.
Development and innovation studies of drugs or devices
- Drugs without marketing authorisation in Belgium are out of scope, except if they are used already in daily practice. Medical devices without a CE label are out of scope.
Mobile health studies (apps)
- Software and apps used as part of the intervention that are not fully developed and that do not meet all regulatory requirements on data protection are out of scope. Study proposals where the main objective is to test the effect of a software or an app are also out of scope.
Deadline
15th June 2021 13h
Who can submit to the Long COVID Call?
This call is investigator-led, meaning that investigators who submit a research outline should have the support of a non-commercial sponsor to perform the trial. It is strongly recommended that trials are developed and conducted with the assistance of a clinical trial unit or equivalent. Single or multi-centre studies are eligible, in a primary care, hospital or outpatient setting.
Participation of Belgian centres to an international non-commercial trial within the scope of this call, is also eligible for funding.
The aim of the study cannot be commercial, and the sponsor should be qualified as a non-commercial sponsor under the applicable laws (including law of May 7, 2004 related to experiments on human person), in Belgium or abroad. In this case, KCE Trials will provide funding for the participation of Belgian centres through a Belgian coordinating centre (BCC) which should also qualify as a non-commercial sponsor.
A letter of support, using the template provided by KCE Trials, signed by the candidate sponsor confirming acceptance of the trial sponsor obligations and acceptance of the terms and conditions included in the template KCE-sponsor research agreement should be included in the submission. Potential co-funders should also accept terms and conditions of the research agreement by signing the appropriate letter (see downloads section below). If the sponsor is located abroad, a signed commitment letter by the international sponsor confirming acceptance of the KCE Trials terms and conditions regarding the non-commercial nature of the trial and data sharing conditions (see below) and a signed letter of support by the Belgian Coordinating Centre, both using the KCE Trials templates, should be included.
For international trials with a Belgian sponsor and with more than 10% of patients recruited abroad, participation of other funders in the sponsor and site costs will be required.
Budget and duration of proposed trial
The duration of the study should be realistic and be able to generate results rapidly. The maximum duration of the study is 2 years, but shorter proposals are encouraged.
For the budget of the proposed trials, no maximum amount is defined in this call, but the “budget tool” from KCE Trials (with guidance, see section Downloads) has to be used to calculate the trial budget. A thorough evaluation of the proposed budget is part of the assessment procedure.
How to submit ?
- The call will be open to submissions from 18th May 2021 until 13h on 15th June 2021.
- As a first step, candidates are asked to submit a research outline (if the protocol is already available at the time of submission, it can also be submitted as an appendix). Shortlisted candidates will be invited early July to submit a full research proposal (FRP) (with the study protocol)
- All submissions must be done using the KCE Trials online submission platform. To be able to submit, you have to create an account, if you have not yet done so. Please create an account as soon as possible and at least 1 week before the submission deadline to enable us to correct possible problems with the online submission platform. Once you have created the account, you can find information to start your submission under the “funding opportunities” tab.
- You may prefer to prepare your application using the application form in Word format, which is available below (section downloads) for your convenience (no application submitted in the word template will be accepted). This document also contains guidance on how to complete your application.
- Only the chief investigator can start an application and complete the submission. However, other members of the research team can help completing the application form if added to the contacts list. You are encouraged to contact your legal advisor, clinical trial unit or equivalent early in the process and give them also access to your application.
- A detailed budget should be submitted using the dedicated budget tool, for which guidance notes are also available. It is advisable to complete the budget tool in collaboration with the clinical trial unit.
- All documents for the submission are detailed below in the “Links & downloads” section and can be found on our website.
- To be deemed valid and to enter the selection process, a submission must:
- Be written in English.
- Be submitted through the online submission platform before the deadline.
- Include details of chief investigator and candidate sponsor.
- Include a sponsor support letter using the KCE Trials template or, for international trials with a non-Belgian sponsor, a support letter from the Belgian coordinating centre and a commitment letter signed by the international sponsor, using the applicable KCE Trials templates.
- Include a clearly defined research question in the PICO format (Patients, Intervention, Comparator, Outcome).
- If there is any collaboration with a commercial partner (e.g. delivery of free/discounted medication, apps, medical devices etc.), a signed commitment letter from the commercial partner accepting the KCE Trials terms and conditions using the applicable KCE template or the contract should be included in the initial submission in order to assess the non-commercial nature of the trial. Simple purchasing on normal market condition does not require this signed commitment letter.
