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26 Jan / Clinical Trials in Horizon 2020 – The many flavours of consortia

The need for flexibility in patient recruitment

Generally speaking, patient recruitment plans must be flexible enough to accommodate the potentially-changing availability of the patients, and enable the recruitment of the full patient quota needed for the trial. It is not always possible to predict how many patients each medical centre (site) will be able to recruit, and in turn how many medical centres (sites) will be needed to reach the trial’s recruitment quota. Naturally, this issue is more prevalent in rare diseases or when having highly stringent inclusion/exclusion criteria, but it is not limited to these cases.

In sponsor-funded clinical trials, recruitment plans are ‘per-patient’ payment-based. Although these plans usually have an initial set of medical centres (sites) to recruit patients for the trial, they are also flexible enough to recruit patients from other medical centres (sites), as needed during the actual execution of the trial. The ‘per-patient’ payment-based structure enables this flexibility and allows the clinical trial managers to meet the full recruitment quota on time.

The limitations

In contrast to this industry-wide conduct, the Horizon 2020 programme has two inherent limitations which affect the desired flexibility needed in clinical trials.

  • Relatively low flexibility in amending the structure of the consortium. By definition, Horizon 2020 forces applicants to secure the consortium structure (including linked third parties) at the time of proposal submission, and assume that this structure will stay intact during the full duration of the project. Technically speaking, it is possible to amend the structure of a Horizon 2020 consortium during the execution of the project, but the process involved is cumbersome and not encouraged by the EC, unless there is no other alternative.
  • No flexibility in the EC payment cycles. Funds are transferred to Horizon 2020 consortium members at fixed payment cycles dictated by the EC. Normally the EC will pay the consortium (via the Project Coordinator) once every 12 or 18 months. This means a rigid cash flow, which does not accommodate the typical dynamics of patient recruitment.

Although it is highly motivated to support clinical trial projects, Horizon 2020 lacks the level of flexibility needed for the execution of clinical trials.

The good news

The EC has acknowledged the flexibility challenge needed for clinical trial projects, when compared to all other projects under the Horizon 2020. In order to tackle this challenge, the Horizon 2020 has introduced two complementary options to allow more flexibility in these projects:

  • “Unit Cost” – an instrument that mimics, to some extent, the ‘per-patient’ payments used in clinical trials, which makes it easier to adapt clinical trials to the Horizon 2020 project structure.  Although this instrument is a great improvement, its application is still limited (Learn about Unit Cost in Horizon 2020). It can enable more flexibility in patient recruitment in a specific site, but it does not solve the flexibility required in recruiting medical centres (sites) as an extension to the existing consortium. In addition it does not fully solve the issue of dynamic payments according to recruitment.
  • Sub-contracting – Unique privileges were added to clinical trials when using sub-contracting. Learn about the sub-contracting privileges in Horizon 2020 clinical trials.

Let’s examine the various options of consortium building for clinical trials, with or without utilizing the “Unit Cost” and/or sub-contracting.

The traditional way

Horizon 2020 projects are always consortium-based: at least 3 partners from 3 different countries (member states or associated countries).  Clinical trials can use the traditional consortium structure, mainly when it is targeting a patient population that is easy to recruit, or when the medical centres (sites) involved are large enough to allow the recruitment of the full patient quota.

Figure 1 illustrates a simple consortium structure: A consortium of 9 beneficiaries, including the Project Coordinator (which serves also as a clinical site), a CRO and additional 7 sites.

 

Figure 1 – Simple Clinical Trial structure

An elaborated consortium structure is presented in Figure 2. This consortium has 8 beneficiaries, including the Project Coordinator, a Product Development partner (responsible for the provision of the product to be tested), a CRO, a patient group and 4 sites.

Figure 2 – A more elaborated clinical trial structure

In both cases, the consortia have the ability to fully execute the project and recruit all patients. As such they do not rely on sub-contracting.  They can, however, utilize the “Unit Cost” to structure the budget of the clinical sites.

Advantages: The consortium structure is classic and simple. It is easy to manage and in line with the normal EU expectations. The flexibility of patient recruitment can be achieved by utilizing the “Unit Cost” in the budget of the medical centres (sites).

Disadvantages: They have to fully rely on the existing beneficiaries for recruiting the patient quota. In case the existing beneficiaries fail to recruit the full patient quota, they will have very limited flexibility in adding more medical centres (sites) to the grant, and they may even face a risk of project termination. In addition, the medical centres (sites) will be paid only via the rigid Horizon 2020 payment cycles, which do not accommodate the actual dynamics of ‘per-patient’ payment recruitment.

The enhanced-flexibility way

We will look into two options of employing for maximizing the recruitment flexibility (of patients as well as medical centres).

Figure 3 presents an elaborated clinical trial project which includes 3 sites as direct beneficiaries, while one of those is also responsible for any additional recruitment that may be needed in the scope of the project. The flexibility here is two-fold: a) the 3 sites, which are beneficiaries to the grant, can use the Unit Cost for the inner-consortium patient recruitment, and then, if needed, b) a designated consortium partner (beneficiary) can utilize the sub-contracting option for adding medical centres (sites) ad-hoc. The ad-hoc medical centres will be paid on a ‘per-patient’ on-going basis, as the sub-contracting payments do not conform to the EC payment cycles.

Figure 3 – Sub-contracting as means for flexibility

Figure 4 presents an even more ‘radical’ option of Horizon 2020 clinical trial consortium, which in fact resembles a common structure of many sponsor-funded clinical trials in the industry. According to this structure, a large segment of the grant to cover patient recruitment costs is secured within the CRO’s budget under ‘sub-contracting’ cost category. The CRO (a direct beneficiary), responsible for monitoring the trial conduct, will sub-contract patient recruitment to a selection of medical centres (sites), and will pay them on a ‘per-patient’ basis, while maintaining ‘best value for money’ practice. This will be done in parallel to recruitment done by an additional medical centre (site), which is a direct beneficiary.

Figure 4 – Recruitment is monitored by the CRO using sub-contracting

In both options (Figure 3 and 4), the flexibility of recruiting patients via medical centres is enhanced by the option of sub-contracting. However, in that context, it is imperative to recall the limitations of this option when building the consortium structure.

Advantages: You gain more flexibility in both patient and medical centres (sites) recruitment. As a result the project will resemble the traditional sponsor-funded clinical trial structure. It means easier management and fewer adjustments when adapting your clinical trial into the Horizon 2020 programme.

Disadvantages: Extensive use of sub-contracting is not encouraged. This requires strict understanding and planning of this tool.

 

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By Yoram Bar-Zeev in Pre-award