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Frequently Asked Questions (FAQ) - Clinical Trials

Answer: 

You cannot start any project activity without ethics approval. Ethics approval is not required by the time you submit your proposal (even though you should add any relevant documentation that you already have in place), but is indispensable for the start of activities. If your project is selected for funding and your ethics approvals are not in place yet, you should start the procedure immediately. Once you obtain your ethics approvals, they have to be submitted to the EC.

Answer: 

If possible, try to address the issues that were raised and led to the rejection, so that you fully comply with the requirements of the Ethics Committee and file again. If it is clear that you cannot get approval for that center, you have to adjust your workplan and recruit from different centers. In any case you cannot start any project activity without ethics approval.

Answer: 

It is sufficient to describe how you are planning to deal with ethical concerns and what the status of your ethical approval process is. To emphasize the likeliness and to increase the credibility that the ethical approval will be granted for this trial, it is helpful to mention your experience with any similar Clinical Trials (e.g. on national level) and explaining that you received ethical approval for those.

Answer: 

Yes it is necessary. The ethical approval will only be granted if the CT will be performed according to GCP.

Answer: 

According to the European Commission’s website on Medicinal products for human use http://ec.europa.eu/health/human-use/clinical-trials/index_en.htm and the respective document, http://ec.europa.eu/health/files/eudralex/vol-1/reg_2014_536/reg_2014_53..., the directive has been effective since April 2014.

Question details: 
Regarding ethical issues: at the time of the writing of the proposal, you might not have all required documentation (e.g. ethics approval). Is it sufficient to mention you will obtain all the documents you listed?
Answer: 

Yes.

Answer: 

You should mention the national Ethic regulations of the respective countries and state that you will perform your trials in accordance to those.

Question details: 
No. What might be helpful for your application: show that you have ethic committees at (some of) your partner institutions, show that you have experience with similar CTs in the past, or that you are already in discussions with ethic committee, and sometime an ethical board (with supervisory function) may be a good idea, if e.g. with transplanting organs, you have VERY sensible aspects.
Answer: 

Approval needs to granted by EMA, but they offer a lot of assistance - contact them EARLY enough! The FDA approval might help as enabler/ door opener so you might receive Orphan drug designation earlier.

Question details: 
Our company has succesfully passed the 1st stage evaluation of the "H2020-PHC-2015-two-stage" call. Coordinator of the project is a new entity, subsidiary of a big dermatological company, but with no financial data at the moment. We wonder if this financial situation will penalize our stage 2 proposal. Will it be better that the parent company coordinates the project? Explaining that the parent company fully supports the new entity is it enough? Thank you for your help,
Answer: 

Regarding the very limited information given here, we strongly recommend to contact your local National Contact Point for "Legal and Finance" which you can find here: http://ec.europa.eu/research/participants/portal/desktop/en/support/nati... and Financial/1/1/0&+person.last_name/desc

If you are in doubt of the financial situation of your company, you can find information on the financial viability self-check here:
http://ec.europa.eu/research/participants/docs/h2020-funding-guide/grant...

In principle, a change of coordinator is possible, but needs to be very well justified.

Answer: 

Beneficiaries must award the subcontracts ensuring best value for money or, if appropriate, the lowest price. The best value-for-money principle does not require competitive selection procedures in all cases. However, if a beneficiary did not request several offers, it must demonstrate how best value-for-money was ensured. For the best price-quality ratio, price is an essential aspect (together with quality criteria, such as technical quality, etc.), but it is not automatically necessary to select the offer with the lowest price. In order to provide a good analysis of the price-quality ratio, the criteria defining ‘quality’ must be clear and coherent with the purposes of the action task that is subcontracted (AMGA, §13, S. 130-135).

Question details: 
I would be more than grateful if you could bring more clarity on subcontractors participation in a clinical trial. Is it fine to have a certain number of sub-contractors providing clinical recruitment and sample collection?
Answer: 

It is OK to subcontract in general. But it depends on the nature of the tasks. Core tasks cannot be subcontracted, they have to be done by partners. Minor tasks can be subcontracted. If subcontracting, you have to do so via procurement according to your organization's rules. So you cannot name the organization which will be subcontracted in the application.

Question details: 
Can you add a study site at a later stage, i.e. while the CT is running as subcontractor although centers with the same tasks i.e. conducting the trial, are listed as "partners" in the initial proposal? I guess the question is what are the options to add study site to a running CT, due to recruitment difficulties in the existing sites.
Answer: 

In this case you will have to make an amendment to your grant agreement. I understand that it is getting more difficult to add amendments. I would recommend to plan as conservative as possible and try to include "enough" study sites. We are not sure how high drop-out rates will be handled.

Question details: 
How should the hospitals recruiting patients be included in the project? As subcontractors, partners, service providers? Sometimes at the beginning of the project the list of the hospitals is not available or it is not possible to quantify how much budget they will need to manage the patients. In some case it is necessary to add additional hospitals during the project.
Answer: 

The EC prefers to include study sites as partners. Other options are to subcontract the task (Attention: Only minor tasks can be subcontracted), to include them as In-kind contributions provided by Third Parties against payment or affiliated entitities and third parties with a legal link to a beneficiary. Please refer to slide 29 and 30 of the first presentation (webinar on 18.3.2015) for details. If you need to add study centers during the running project, it depends on how you have included them in your project. If you need additional partners, you have to file an amendment.

Answer: 

Including them as a beneficiary is always the preferred option. However, subcontracting is also possible. This has to be decided individually for each project. The document “Frequently Asked Questions” concerning the Horizon 2020 societal challenge “Health, demographic change and wellbeing” says: Every clinical center can be a beneficiary, and the Commission will not oppose or discourage a large number of beneficiaries for this purpose. Alternative ways to include and reimburse such clinical centers are:

(i) As third parties providing in-kind contributions against payment (Art. 11 of the grant agreement). A requirement for this is a written agreement between the beneficiary and the third party prior to the start of the work. These third parties need to document their costs in the same way as beneficiaries (actual costs or unit costs). Wherever possible, third parties should be listed in section B4.2 of the full proposal.

(ii) As subcontractors (Art. 13 of the grant agreement). In this case, the beneficiary needs to ensure that it complies with the obligation to ensure the best value for money and institutional rules for subcontracting and if the beneficiary is a public body, with national and EU legislation on public procurement. Subcontractors would not usually be named in a proposal given the necessity to undertake the processes required to ensure compliance with the conditions described above. If however such processes have been undertaken in advance, subcontractors may be named in a proposal.

(iii) Another option, to participate as ‘linked beneficiary’, is limited to entities that fulfil the specific conditions of Art. 14 of the grant agreement on ‘affiliated entities and third parties with a legal link to a beneficiary’. As these conditions are rather specific, the use of this option is likely to be limited.

Question details: 
We are a SME in Barcelona. We have experience in several FP7 projects, developing the recruitment database for patient’s data collection. I don't know where to find Institutions and other partners that can be interested in such a partnership.
Answer: 
Question details: 
Does the rule of not subcontracting of core tasks also apply to PHC12, which is SME Instrument? A small biotech or IVD company might not have the capabilities to conduct the CT, so it must be obliged to subcontract them entirely.
Answer: 

The clinical study partners should be partners= beneficiaries whenever possible, this is right; but in PHC12 only SME are eligible for funding. So you either can identify a for-profit CRO that is willing to act as beneficiary (as it is 100% funding rate this is not too bad), or they act as subcontractor. If you are or prefer working with non-profit CROs or with academic partners (university hospitals), they must be subcontracted for this topic. The commission is aware of the dilemma, but confident that the amount of subcontracting will not be a major hurdle for the applicants respectively the evaluation result. Note that in PHC12 like in any other SME instrument topic, the “impact” is even more important than in research & innovation actions, compared to “excellence”. This is: plan and write your project proposal in the best way for your company so that you will be able to become a champion in your market.

Answer: 

"Too much" is not budget-wise. It is referring to amount and scope of tasks: how central/ crucial is the task you are going to subcontract, compared to the rest of you project?

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No and yes, the task to be subcontracted must be named in the application, but not the name of the subcontractor. For any subcontracting, respect the guidelines on procurement (European, national and of your institution).

Answer: 

Your suggested project has to fully respond to the call text, i.e. reach the objectives and bring about the expected impacts listed in the work programme by the end of the project duration. If the project you are suggesting builds on results that are funded otherwise, that is a good thing. It has to be ensured though that the other periods are either already completed, or that funding is already secured – otherwise, reviewers may see this as too high a risk.

Answer: 

In all types of Clinical Studies or even in EU funded Projects in general, only those costs incurring during the running project will be reimbursed by the Commission. So all costs that incurred before the start of the project will not be reimbursed.

Answer: 

Fees for ethical committees will be other direct costs. Insurance costs can be part of the unit costs or other direct costs (when choosing actual costs).

Answer: 

Funding of Phase 3 or Phase 4 Trials depends on the topic. Some topics might even require later phases of trials as well. Generally, it is possible to claim partial costs. Just make sure to explain how you will cover the remaining costs that won’t be requested from the EC, so it will be clear to the reviewers that you will be able to conduct the CT properly. If you will apply only for partial costs of the study in the scope of the EU project, e.g. for certain study sites but will cover other sites by yourself, you will have to convince the reviewers that data of those sites not included in your project will still be obtained to ensure the feasibility of your project.

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Yes, costs of insurance can be part of the unit costs.

Answer: 

Yes, please see page 5 of the template. It states: Costs incurred in another currency shall be converted into Euro at the average of the daily exchange rates published in the C series of the Official Journal of the European Union, determined over the corresponding year N-1. If no daily Euro exchange rate is published in the Official Journal of the European Union for the currency in question, conversion shall be made at the average of the monthly accounting rates established by the Commisson and published on their website.

Answer: 

Inclusion of ‘regular’ CROs as beneficiaries is also possible (in that case: full partners, i.e. involved from the planning phase on and active partners in study design). But some CROs that work on a 'for profit' basis might not be willing to become a beneficiary, in these cases, subcontracting could be an option. BUT only limited part of the action can be subcontracted.

Answer: 

Depends on the topic. They also fund observational studies, if there is a respective topic for that.

Answer: 

Yes that is correct. Each beneficiary can decide to be reimbursed on basis of unit costs or actual costs for a given clinical study.

Question details: 
In a clinical study involving different countries with very different actual cost levels, (personnel costs of doctors, other medical personnel and technical personnel) e.g. one very high, one very low, how can the unit costs be calculated to "be the same for all members of the consortium” as stated in 1.9 in the template for clinical trials?
Answer: 

For unit costs, the EC foresees different cost levels for different beneficiaries (see table in the template you are referring to column 3 & 4 + example provided in the table). While the total amount per unit can vary between beneficiaries of a consortium, the estimated effort (e.g. time of a doctor spent per unit & amount of resources used per unit) must be the same for one trial, study investigation.

Answer: 

Costs for hospital care that are paid through the national healthcare system/covered by health insurance cannot be charge to the project. Any costs for managing the patient that incur only due to the implementation of your project can be listed in the project budget.

Answer: 

You would have to estimate as good as you can, based on information that is available and that has been recorded in the past. For example, even if that specific clinical trial has not been implemented at your site yet, you should be able to estimate the amount of time that your staff will spend per patient, and use the personnel costs from the last recorded year to calculate the personnel cost per patient included in this new study. All other components, such as consumables etc., should be calculated similarly.

Answer: 

As this system is completely new, we have no information as to how the evaluators are briefed. Nevertheless, the calculation of unit costs must be based on recorded & certified figures and the methodology of calculation can be audited in the CFS / by the EC.

Question details: 
How are the unit costs audited and on what extent the details must be identifiable in the accounts of the beneficiary? In other words, can we include in the unit costs that are usually used by hospitals, based on a national tariff system?
Answer: 

Unit costs that are usually used by hospitals may be a very good option for estimates on some components of your unit costs per patient, yes. Please note that costs which are paid for by the national health system cannot be charged to the project though. The calculation of the unit costs (see table in template for clinical studies) will become part of the Grant Agreement (Annex II). The methodology applied in order to calculate unit costs will thus be auditable in the frame of a CFS or an official audit by the EC. The number of actual units claimed during the action must comply with the following conditions:
- the units must be actually used during the project
- they must be necessary for implementing the action & identifiable and verifiable, in particular supported by records and documentation.

Question details: 
In the scope of PHC14: as the clinical development is depending on the data that will be obtained in preclinical studies, it will be difficult to have a precise budget to submit. How detailed should be the submitted budget in such a case? How detailed must be the study information that we will submit to H2020?
Answer: 

For PHC 14 (rare diseases) you are advised to contact EMA very early in the process. This is: before submitting stage 2 you MUST HAVE received orphan drug designation, so start contacting EMA today! http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/gen... http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/gen...

Answer: 

Study medication I personally would put under "other direct costs", but NOT to use in the "unit costs per patient". With the study medication, you have some more steps to get funded: packaging, blinding/ coding, maybe even (GMP) manufacturing. Overall, I would put it as bigger tasks than just as "consumables".

Question details: 
For the Certificate on Financial Statement and an audit by the EC, I assume that the beneficiary should be able to specify the unit costs with actual and auditable costs (which origin from the year in which the application was written)? In other words, it cannot be a ballpark figure?
Answer: 

No ballpark figure, no. Numbers must be based on actual costs recorded in last closed accounts of beneficiary, described in detail in the full proposal, and will be assessed by the evaluators.

Answer: 

Any costs that will be reimbursed by health care providers/ insurance are NOT eligible for funding via the EU project.

Answer: 

Unit costs are partner specific - i.e. you will most likely have different unit costs for each partner.

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Yes - they would have to be defined for that linked third party specifically in any case.

Question details: 
Unit costs "for all patients at this institution": If one institution participates in several proposals: Must unit costs be used for ALL proposal or is this just "all patients within this project"?
Answer: 

The use of unit costs is a decision that can be made project by project, i.e. one institution can use unit costs in one project and actual costs in another project.

Answer: 

Yes, this is true. Unit costs per patients have to be used for ALL patients of a beneficiary, for ONE CT. For a second CT, a second template will be filled-in (make sure to upload in ONE document).

Question details: 
Is the discussion ongoing or does it give a clear written statement on that?
Answer: 

It is possible to include study centres as 3rd parties providing in-kind contributions against payment. These third parties need to document their costs in the same way as beneficiaries (actual costs or unit costs). Please also see question 8 under “Consortium / Partners / Third Parties”.

Answer: 

Regarding the description of CT in PHC 12 (SME instrument) the same "instructions" apply as to the description of CT in projects addressing other SC1 topics where the template is not mandatory.
That means: The template should be used as a checklist or guidance document and all information about the trials that is requested in the template should be provided in the Concept and Approach section of part B of the proposal application.
Since projects funded under the SME Instrument should focus on the exploitation of the results (closer to market) this should be considered as well. Since funding of projects with only one SME as partner is possible under the SME-Instrument, it is possible to subcontract the CT (but again: subcontracting rules apply), so in this case the expertise for the CT does not have to lie within the consortium (and this is even not possible in case of only one SME).

Answer: 

Yes it is correct that for PHC 12, the clinical trial template is NOT mandatory. Info regarding the trial needs to be included in the main template (= Part B).

Answer: 

Yes, but not in a separate template.

Answer: 

Yes, and as topic says: you should have granted the orphan drug designation at the time of stage 2 submission.

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The topic says “based on clinical trials and/ or real world data”. Duration depends fully on your concept and approach.

Question details: 
I raise the question because I now for a fact that a proposal for the development of an IVD without a biomarker involved has been funded, when a NCP told me that the diagnostic devices must always have to have a biomarker involved.
Answer: 

I understand the topic PHC 12 in a way that it can be and/ or medical device, so I would say, the evaluators have decided accordingly.

Answer: 

No, not compulsory (mandatory), but EC sees good chances that applicants will present "Concept & approach" where CT is a part of. If you will not conduct a CT in such a topic (*), please reflect on the budget. Of course the budget has been drafted to fund CT as part of the project.

Answer: 

Reviewers may have different backgrounds. Therefore the proposal should be written in such a way that it can also be understood and assessed by an evaluator who is not an expert in exactly that scientific field.

Answer: 

Any documentation that you have at the time of submission should be added to the proposal. If you do not have the final informed consent form, you could for example add a draft version. Ethics approval is definitely required before starting related project activities, and need to be submitted to the EC as soon as they are obtained during the project.

Answer: 

As much as necessary to understand why the study needs to be done. The template does not specifically ask for scientific background. But you need to describe the background under Concept & Approach in Part B of your proposal.

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You should use the template as a "checklist" to make sure you cover all relevant aspects. All relevant information needs to be mentioned in the proposal body (Concept & Approach; Part B) in those cases.

Answer: 

You should use the template as a guidance document. Although there is only limited space in stage 1 proposals, you should include all info that is important for the reviewers to understand what you are planning to do and that you have considered all important issues (according to the template).

Answer: 

Yes, you give as many details as you are able to give at that moment. The later the CT will happen, the less details you will know at the time of application. Evaluators need to be convinced, nevertheless, so at least give a vision of your idea.

Answer: 

Evaluation criteria are applied for chapters 1-3 only. As I mentioned, I would put as much info as possible into the chapters which are not page limited, but you should of course MENTION them in chapter 3 as well (and make reference to the extended versions).

Project (10)

Question details: 
Can you explain how the different Phases (I to IV) of clinical trials correlate with the TRL scale (1 to 9)? Which Phases of clinical trials can be funded under SME Instrument or Fast Track to Innovation, which both require a minimum TRL of 6?
Answer: 

That depends on the topic.

Answer: 

No, project funded in 2019 for example will definitely continue after 2020.

Answer: 

There are no rules on the duration of H2020 projects. It depends on the nature of your project. The average project duration is between 3-5 years.

Answer: 

No, there are no guidelines on that. You should include as many participants as needed to successfully conduct the CT / project. So it totally depends on your project.

Answer: 

Any work related to the observation of, data collection from or diagnostic or therapeutic intervention on patients is defined for the purpose of using the template and thereby is a CT.

Answer: 

There is no EC definition of ‘major change’. It is up to the evaluators to decide whether a change is significant or not. In some calls (e.g. LEIT-BIO; SFS ), consortia were asked to list any substantial differences between the 1st stage & 2nd stage proposal (i.e. changes with regards to partnership, budget, approach, workplan) and indicate the reasons in the proposal submission forms.

Question details: 
At the stage of the application, documents like informed consent form, information sheets, ethics approvals etc. are not available yet. These will often be established during the project. How should one deal with that?
Answer: 

Say as it is – we have this, we are here, but xyz is not yet precisely projectable.

Question details: 
Based on the points made about time planning would you expect the duration of a project including clinical trials to be longer than those under FP7, for example, 6 years instead of 5? Do you think this will be accepted by the Commission?
Answer: 

With regards to “realistic” 6 years might be better than 5 years – so you need to argue accordingly. With regards to credibility and manageability – I would not recommend to prolongate the projects too much. The longer a project is, the more may happen meanwhile which affects results etc. You might rather consider to leave out 1 or 2 Work steps and make the project more tiny and focused.

Answer: 

EC told us that a cost-neutral prolongation of EU projects will be more difficult now, compared to FP7. I would say that in worst case, you will not be able to deliver all deliverables that you are committed to (Grant agreement), so that you might lose some of the final funding portion.

Answer: 

Please refer to the following presentation explaining that usability study is no clinical study: http://de.slideshare.net/Banderlin/usability-testing-medical-devices.

Answer: 

Please see here for non-pharmaceutical products: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/gen.... In general, we advise you to contact your national competent authority very early - and you might get great support from ethic committees located at your local/ regional university hospitals etc.

Answer: 

EC does not make big differences here. They clearly say (in the additional template) that they have a very broad definition of CTs - as long as you COLLECT human data (patients/ volunteers). Sure all we are presenting today is applicable for psychological therapy. Whenever a question in the template is not to answer, just write "not applicable".

Template (13)

Answer: 

For the purpose of the Template, a clinical study is defined as any clinical research involving a substantial amount of work related to the observation of, data collection from or diagnostic or therapeutic intervention on multiple or individual patients. It includes but is not limited to the clinical trials in the sense of the EU Clinical Trials Directive (2001/20/EC). So according to this definition would be regarded as a clinical trial.

Answer: 

Collecting data from or diagnostic or therapeutic intervention on multiple or individual patients is considered a clinical trial and the template needs to be submitted. If you are not sure, if your work would be considered a CT, we recommend to fill in the template to be on the safe side.

Answer: 

You should use the template as a guidance document. Although there is only limited space in stage 1 proposals, you should include all info that is important for the reviewers to understand what you are planning to do and that you have considered all important issues (according to the template).

Answer: 

For these topics you cannot upload the clinical trial template as a separate document, but you should use the template as a guiding document include this information in your proposal.

Answer: 

The template for essential information on clinical trials is mandatory at stage 2 (full proposal) for projects addressing all topics marked with an asterisk in the slides (slides are available on the FFH2.0 website) or indicated on the template.

Answer: 

You are supposed to fill in the template for each study, no matter how many study centers will be invlvoved in one study. If you have 3 Studies included in your project, you'll have sections 1-9 filled in for each of those (1.1, ...1.9; 2.1,...2.9 ....), please remember to upload everything as one single document.

Answer: 

There is one template consisting of 9 sections. All sections have to be completed for each study of your project. So there will be one single document to be uploaded containing information (section 1-9) for each study.

Question details: 
Can you please clarify whether the clinical trial approach is mandatory?
Answer: 

In the version of August 2014 it is mentioned: " Single-stage- and stage-2 proposals: The use of this template is mandatory for all clinical studies included in a single-stage- or stage-2 proposal submitted to topics PHC-2, PHC-3, PHC-11, PHC-14, PHC-15, PHC-16, PHC-18, PHC-22, PHC-24, PHC-33 and HCO-62. For these topics, you will have the possibility to upload the completed template as a separate part of your application in the submission system."

Answer: 

The template can only be uploaded for those topics that are marked accordingly. For all other topics, you can use it as a 'checklist' to make sure you cover all relevant aspects, but cannot upload it. All info needs to be mentioned in the proposal body in those cases.

Answer: 

Annexes are to be uploaded with the full proposal, and yes, accessible for the evaluators. You do not have to repeat everything in the proposal body, but can be more concise there and make cross references to the annexes. In stage 1, you must be very brief, as the overall page limit is the same for all proposals, including those that entail clinical study elements.

Answer: 

Some of the information that is part of the protocol will also appear in the proposal body at places where you describe your study. The protocol as such can be included in a draft version as part of the extra documents that are to be uploaded. The final protocol does not have to be part of the proposal.

Other (4)

Answer: 

Recruitment should be very closely monitored. There are different software or web-based solutions available that can indicate recruitment progress at the different sites and on project level. As a coordinator, it is advisable to have access to this information in real time throughout the implementation period of the study.

Answer: 

There are certainly other funding opportunities as well. Fit for Health is specialized in providing support for Horizon2020 participation though.

Answer: 

Societal Challenge.

Answer: 

The sponsor should not have significant say in the study protocol so that it will still be seen as “investigator initiated”; also, sponsor shall not have access to raw data/ uncoded data.