This is Patricio Ledesma, Head of Clinical Operations at Sofpromed CRO. I would like to explain the details of a full-service CRO clinical trial quotation.
My goal is to help biotech companies that are planning their budget to execute a clinical trial.
More specifically, I will show you a cost breakdown for a phase 1 clinical trial with drugs in oncology, to be run in Europe (Spain).
- $General Structure of a Clinical Trial Quote
- $Ethics and Regulatory
- $Site Contracting and Payments
- $Site Selection
- $Site Initiation and Activation
- $Site Management
- $Drug Logistics
- $Clinical Supplies Logistics
- $Files and Document Management
- $Medical Writing
- $Project Management
- $Quality Control
- $Data Management
- $Statistical Programming
- $Pass-Through Costs
- $Cost Summary
Our trial has the following characteristics: four sites in Spain, total recruitment of 15 patients, 4 months for start-up, 9 months of recruitment, 6 months of treatment per patient (as average), 12 months of survival follow-up for the last patient in, and then 3 months for closing the sites.
Then, the total duration of the study is 34 months.
General Structure of a Clinical Trial Quote
Before going deep into each of the cost sections, I would like to provide an overview of the general structure of our quotation.
We are going to divide our budget into two general sections.
On one hand we have the direct CRO services and, secondly, the pass-through costs, which include any expenses coming from third party vendors (these are services not directly provided by the CRO).
In this budget, and this can be different depending on each CRO, the direct CRO services are broken down into the following 17 blocks:
- Ethics and regulatory
- Site contracting and payments
- Site selection
- Site initiation and activation
- Site management
- Drug logistics
- Clinical supplies logistics
- Files and document management
- Medical writing
- Project management
- Quality control
- Data management
- Statistical programming
Ethics and Regulatory
So, let’s start with cost section number 1, “Ethics and Regulatory”.
This includes the collection and preparation of site documents required for initial ethics and regulatory submissions, the issuance of the initial insurance policy (with its subsequent updates if needed), the ethics committee initial application submission (including preparation, submission, and response to clarification requests), and the regulatory authority initial application submission via the CTIS system (also including preparation, submission, and response to questions).
Additionally, the CRO can take care of ethics and regulatory reporting (including the communication of study initiation, first patient in, the annual progress report, the annual safety report, and the close-out). These same communications are to be sent to the clinical sites as well.
Finally, the CRO can also write and review the annual progress report (which is required by the Spanish regulatory authority and the ethics committee).
The total amount for this first cost section is 16,740 euros.
Site Contracting and Payments
Secondly, we have “Site Contracting and Payments”.
This section has to do with the negotiation and execution of site contracts (including budgets) and the payment of start-up fees required by clinical sites.
Site payments are also needed during the course of the trial to pay the visit costs.
Then, this section 2 adds up to 5,340 euros.
Number 3 (“Site Selection”).
Site feasibility is a very important task to determine whether the clinical sites will be able to recruit the expected number of patients.
Then, it may be necessary to prepare a feasibility questionnaire, which will be sent to sites, and then returned to the CRO for review and discussion with the sponsor (to select the most convenient sites).
We will also need to perform site qualification visits that may be either onsite or remote. In this case we would conduct two onsite and two remote visits.
Thus, the site selection block will have a cost of 5,600 euros.
Site Initiation and Activation
Once the sites have been qualified, we will continue with “Site Initiation and Activation” (section 4).
In this quote we propose two onsite and two remote site initiation visits.
After the SIVs have been completed, sites need to be activated by signing some documents and having their EDC system access enabled.
Site initiation and activation total is 4,800 euros.
After trial enrollment has started, CROs provide site management services (this is our block number 5).
Site management involves communication with hospital staff to provide support and solve doubts, reviewing site performance, and escalating infringements.
This task seeks to ensure that the trial is conducted according to good clinical practice.
Site management is typically quoted by proposing a number of hours per site per month (during recruitment and treatment, and then during follow-up).
Site management total for this study is 67,200 euros.
Section number 6 (“Monitoring”).
Firstly, before onsite monitoring begins, the CRAs (also called monitors) have to review the study documents and get trained in the trial systems.
Then, during the study, they will perform onsite monitoring visits, which include preparation, traveling, the visit itself, the report and visit follow-up.
In this trial a total of 40 onsite monitoring visits are proposed (ten per site).
The CRAs will also work on remote reviews of EDC data and query management.
In our study, monitoring costs add up to 75,840 euros.
Once the trial is finished, clinical sites need to be closed.
Then, we have budgeted 4 close-out visits for a total of 7,360 euros.
CROs also take care of drug safety management, depending on their internal capabilities.
This “Safety” section includes the initial configuration and setup of the safety database, serious adverse event and SUSAR management, and also the writing and review of the annual safety report.
The total for safety services is 12,160 euros.
Section 9 is “Drug logistics”.
In a clinical trial normally the sponsor or CRO will subcontract a drug depot, which will receive, label, store, and distribute the study drug.
In this example the CRO gives support for depot contracting, shipping the drug from the manufacturer to the depot, and then coordinating drug shipments from the depot to the pharmacies of the clinical sites.
Drug logistics total is 5,320 euros.
Clinical Supplies Logistics
In phase 1 oncology trials there is a frequent need to collect and ship blood samples (for PK/PD studies).
CROs can help with the clinical supplies logistics, which includes the purchasing of kit components (tubes, bags, etc.) and the preparation of lab kits (including their shipment to sites).
The CRO personnel will also track the availability of clinical supplies at hospitals.
Clinical supplies logistics total: 2,585 euros.
Files and Document Management
Section 11 (“Files and Document Management”).
Clinical trials generate a lot of documents, which are stored in a Trial Master File (or TMF).
The CRO personnel will be in charge of TMF setup, maintenance, and reconciliation.
Each clinical center will also require an investigator site file (ISF).
Additional documents will be managed by the CRO team as needed.
The total amount for files and document management is 35,200 euros.
When it comes to “Medical Writing”, clinical trial sponsors may need more or less support depending on their own internal resources.
The following medical writing tasks may be outsourced to the CRO: Protocol writing, protocol synopsis translation (into local language), informed consent form writing, and the study publications (abstract, poster, and scientific manuscript), as well as the final clinical study report.
Medical writing total: 28,080 euros.
Section 13 (“Project Management”).
Clinical project managers coordinate and supervise all the tasks and processes of a clinical trial. They ensure that everything goes well.
The CRO budget will include the project manager trainings, the development of study plans and manuals, internal and sponsor meeting costs, and study management work (financial management, vendor management, escalation and resolution of study issues and deviations, and communication with the sponsor).
In addition, project managers review SIV, monitoring, and close-out visit reports, and they will organize and participate in kick-off meetings.
Project management is commonly one of the highest cost items, 229,270 euros in this example.
Section 14 is “Quality Control”.
In this case, the budget includes the support of a quality manager to handle protocol deviations and to help with sponsor audits and regulatory inspections.
Quality control total: 12,600 euros.
A clinical trial may require administrative support to manage travel logistics and invoice control. Then, an administrative person is proposed with a budget of 7,425 euros.
Some CROs have data management capabilities, to manage the collection, cleaning, and reporting of clinical trial data.
Here you can see the main elements required in clinical data management: the development of a data management plan and a data validation plan, the writing of the EDC specifications, the creation of the EDC completion guideline, the implementation of the EDC forms (including automatic queries and edit checks), the EDC testing and validation, EDC trainings for sites, EDC modifications during the study (if needed), data cleaning (through manual queries), EDC system technical support, and medical coding.
Data management total for this phase 1 trial is 39,060 euros.
Finally, another key CRO service is statistical programming.
In this quote we are offering the development of the statistical analysis plan, the SAS programming work (to produce tables, figures, and listings), SDTM tasks (annotated CRF, mapping specifications, programming, data transfers, data validation, the study data review guide, and the Define.xml), and the same set of tasks for the ADaM standard.
A total of 75,320 euros has been quoted for statistical programming.
Therefore, the global amount for the direct CRO services is 629,900 euros.
But we are not done yet.
The second general section in a clinical trial quotation involves the pass-through costs. These are services and resources provided by third-party vendors.
The study CRO will normally subcontract these services and then these expenses will be invoiced to the sponsor (but not necessarily all of them).
So, let’s look at the typical pass-through costs required in a phase 1 cancer trial:
- The shipment of physical files to sites
- The costs of electronic signature systems (for contracts and other documents)
- The shipment of tumor samples for central diagnosis and translational study
- The shipment of blood samples for a translational study at ambient temperature
- The shipment of frozen blood samples to central labs (for PK or PD studies)
- Blood tubes and shipping packages
- Office supplies and communication costs
- Payments to clinical sites for each patient enrolled (to cover staff, tests, and procedure costs). In this case 11,000 euros per patient.
- The trial insurance policy (6,000 euros for 15 patients)
- Site contract management fees (3,000 euros per site)
- Ethics committee evaluation fees (2,500 euros for initial submission and then 500 euros for each amendment)
- Regulatory authority evaluation fee (4,500 euros) in the case of Spain
- Traveling costs for onsite qualification, initiation, monitoring, and close-out visits
- Drug distribution services (this is the central depot) (40,000 euros)
- And finally, the license and hosting fees for the EDC system, the electronic TMF, and the drug safety platform
In summary, the pass-through costs of this phase 1 oncology trial are 343,180 euros.
Let’s finish with the cost summary: the grand total is 973,080 euros (including CRO services and pass-through costs).
I hope this article has been useful for biotech companies planning phase 1 clinical studies in Europe.
If you want to get a personalized quote for your clinical trial in Europe, please send us an email to email@example.com or give us a call at +34 607 939 266.
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