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Are you a biotech company planning to run a global phase 3 clinical trial?
Phase 3 trials are large projects with many operational and financial complexities that can get very challenging.
I would like to show you a cost breakdown for a phase 3 pivotal clinical trial with drugs in oncology, to be run globally.
- $Ethics and Regulatory Services
- $Site Contracting and Payment Services
- $Site Selection Services
- $Site Initiation and Activation Services
- $Site Management Services
- $Monitoring Services
- $Close-Out Services
- $Safety Services
- $Drug Logistics Services
- $Clinical Supplies Logistics Services
- $Files and Document Management Services
- $Medical Writing Services
- $Project Management Services
- $Quality Control Services
- $Administration Services
- $Data Management Services
- $Statistical Programming Services
- $Pass-Through Costs
- $Total Clinical Trial Cost
My intention is that this explanation can help you when planning the funding and resources needed for your upcoming phase 3 trial.
The actual budget grid discussed in this article can be viewed here:
Our trial has the following characteristics:
- Oncology pivotal trial with drugs (registration study)
- 15 sites in Spain, 15 in France, 10 in Germany, 10 in Poland, 10 in the United Kingdom, and 20 in the United States (80 selected sites total)
- Total recruitment is 300 patients
- The timelines are 12 months for start-up (to open all countries), 24 months of recruitment, 6 months of treatment per patient (as average), 12 months of survival follow-up for the last patient in, and then 6 months for closing all the sites
Then, the entire duration of this phase 3 cancer study is 60 months.
Before analyzing 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 parts. On one hand we have the direct CRO services and, secondly, the pass-through costs, which include any expenses coming from third party vendors.
To simplify the structure of our budget grid, we did not generate separate grids for each country, but included all sites on the same general table.
Even though there are cost differences from country to country, particularly between the staff rates of North America vs. United Kingdom vs. Europe, we have used average hourly rates that represent a realistic cost in the global calculation.
In this budget, the direct CRO services are classified into the following 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
Please note that all the costs reflected in this article are expressed in US dollars.
Ethics and Regulatory Services
So, let’s begin 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 policies, the ethics committee initial application submissions, and the regulatory authority initial application submissions.
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 reports (which are required by regulatory authorities and the ethics committees).
The ethics and regulatory tasks are very similar for all of the European sites. These processes are quite unified within the EU. The United States and the United Kingdom have particular aspects to be considered.
The total amount for this first cost section is 214,200 dollars.
Site Contracting and Payment Services
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 trial to pay the visit costs.
The CRO personnel can help with the negotiation of agreements and budgets between the sites and the sponsor.
The total cost per patient will vary from site to site, and it will be higher in some countries when compared to others.
Then, this section 2 adds up to 196,800 dollars.
Site Selection Services
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.
Ensuring that your trial will recruit the required subjects on time is very critical in phase 3 pivotal studies.
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 90 onsite qualification visits.
Please note that not all the sites that have a site qualification visit done will end up being selected to participate in the trial. In fact, we would have 90 qualification visits to finally select 80 sites for participation.
Thus, the site selection block will have a cost of 193,160 dollars.
Site Initiation and Activation Services
Once the sites have been qualified, we will continue with “Site Initiation and Activation” (section 4).
In this quote we propose one onsite site initiation visit (SIV) per hospital.
SIVs can also be performed remotely, and this modality has become very popular during and after the COVID-19 pandemic. However, if possible, an onsite SIV is recommended.
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 167,200 dollars.
Site Management Services
After trial enrollment has started, CROs provide site management services (this is our block number 5).
Site management involves communication with hospital staff to offer support and solve protocol questions, reviewing site performance, and escalating breaches. This task seeks to ensure that the trial is conducted according to good clinical practice (GCP) principles.
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 global study is 3.8 million dollars.
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.
The monitoring visits that are performed during the trial are called “interim” or “routine” monitoring visits.
In this trial a total of 1,040 onsite monitoring visits are proposed (using nearly 12 CRAs in total; around 2 CRAs per country).
The CRAs will also work on remote reviews of EDC data and query management.
In our study, monitoring costs add up to 2.6 million dollars.
Once the trial is finished, clinical sites need to be closed. Then, we have budgeted 80 close-out visits (COVs) for a total of 202,400 dollars.
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 reports.
The Medical Monitor cost is not included in this quote. CROs can provide Medical Monitors if needed, but the trial sponsors (biotech and pharma companies) may also have these specialists in their teams already.
The total for these basic safety services is 138,160 dollars.
Drug Logistics Services
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.
In a global clinical trial with so many hospitals and countries, drug logistics can become a real challenge. In the example we are discussing the use of two depots (one in Europe and one in the United States) would be advised.
Please note that the cost described in this section has to do with the support provided by the CRO staff only. The actual depot service cost has been included as a pass-through expense below.
Drug logistics total is 271,780 dollars.
Clinical Supplies Logistics Services
In oncology trials there is a frequent need to collect and ship biological samples.
For instance, a pre-treatment central diagnosis confirmation may be a protocol requirement (which involves shipping a tumor sample -biopsy- from each site to a central lab), or maybe there is a biomarker/translational study to be conducted.
CROs can help with the clinical supplies logistics, which includes the purchasing of kit components (bags, boxes, etc.) and the preparation of the lab kits (including their shipment to sites).
The CRO personnel will also track the availability of clinical supplies at hospitals during the course of the trial.
Clinical supplies logistics total: 105,700 dollars.
Files and Document Management Services
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).
In Europe ISFs usually take the form of physical folders/binders containing the key documents of the study, which are sent to sites at the beginning of the trial. However, depending on each country, a physical ISF is not always a requirement.
With the advent of new technologies, ISF management is becoming electronic too (eISF).
The total amount for files and document management is 560,000 dollars.
Medical Writing Services
When it comes to “Medical Writing”, clinical trial sponsors may need help depending on their own available resources.
The following medical writing services may be outsourced to the CRO:
- Protocol writing
- Protocol synopsis translation (into local language)
- Informed consent form writing
- Study publications (abstract, poster, and scientific manuscript)
- Final clinical study report (CSR)
Medical writing total: 51,920 dollars.
Project Management Services
Section 13 (“Project Management”).
Clinical project managers coordinate and supervise all the tasks and processes of a clinical trial. They ensure that everything runs smoothly.
In fact, project managers are crucial roles in global clinical trials since a strong leadership is needed to coordinate so many teams, sites, and countries.
A phase 3 pivotal cancer study requires well experienced clinical project managers with international expertise in oncology.
The CRO budget will at least include:
- the project manager trainings
- the development of study plans and manuals
- internal and sponsor meeting costs
- study management work (financial management, vendor management, escalation and resolution of study issues and deviations, and communication with the sponsor)
In addition, project managers will 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 in a trial budget, 3.7 million dollars in this example.
Quality Control Services
Section 14 is “Quality Control”.
In this case, the budget includes the support of quality managers to handle protocol deviations and to help with sponsor audits and regulatory inspections.
Quality control total: 88,000 dollars.
A large pivotal clinical trial will require administrative support to manage travel logistics and invoice control in each country.
Then, administrative personnel is proposed with a budget of 151,200 dollars.
Data Management Services
Full-service CROs have specialized 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
- medical coding
Data management total for this phase 3 trial is 446,040 dollars and would include the participation of a central data management team provided by the CRO.
Statistical Programming Services
Finally, another key CRO service needed in a phase 3 trial is statistical programming.
In this quote we are offering:
- the development of the statistical analysis plan (SAP)
- 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 109,600 dollars has been quoted for statistical programming.
Therefore, the global amount for the direct CRO services is 13.1 million dollars.
The second general part in a clinical trial quotation involves the pass-through costs.
These are services and resources provided by third-party vendors, not directly given by the CRO itself.
The study CRO will normally subcontract these services and then these expenses will be billed to the sponsor.
So, let’s look at the typical pass-through costs required in a phase 3 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
- Biological sample 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 40,000 dollars per subject.
- Research team and pharmacy start-up fees
- Screen failures fees
- The trial insurance policies for all countries in which they are needed
- Site contract management fees (3,000 dollars per site)
- Ethics committee evaluation fees (3,000 dollars for initial submissions and then 600 dollars for each amendment)
- Regulatory authority evaluation fee (5,000 dollars per regulatory authority)
- Traveling costs for onsite qualification, initiation, monitoring, and close-out visits
- Drug distribution services (500,000 dollars)
- License and hosting fees for the EDC system, the electronic TMF, the drug safety platform, the randomization and trial supply management system, and the radiological imaging platform
In summary, the pass-through costs of this phase 3 oncology trial are 14.7 million dollars.
The cost per patient to be paid to the hospitals will depend on the budget negotiation carried out with each site. This price will mainly depend on the complexity and duration of the trial treatment and the required medical tests and procedures.
Please note that the management of some cancer therapies can be very costly, involving a large number of treatment cycles (some treatment schemes last until tumor progression or unacceptable toxicity, and this can be several months depending on the cancer type and the efficacy and tolerability of the drug).
Total Clinical Trial Cost
Let’s finish with the cost summary: the grand total for this phase 3 clinical trial is 27.8 million dollars (including CRO services and pass-through costs).
I hope this article has been useful for biotech companies planning a global phase 3 trial in oncology.
Sofpromed is a cancer-focused CRO with international clinical trial management expertise. We provide full support for phase 3 multinational oncology studies.
If you need clarifications about the budget presented in this article, or if you want to get a personalized quote for your phase 3 trial, please send us an email to email@example.com.