Biotech companies developing new drugs carry out phase 1 clinical trials to test the safety and preliminary efficacy of their compounds.
Phase 1 studies are designed to assess how well patients tolerate the new drug under investigation and to determine the maximum tolerated dose (MTD) recommended for phase 2 trials.
What is the cost of a phase 1 clinical trial conducted in the U.S.? This article provides a detailed explanation of the expenses involved in these studies.
What are the factors involved in the cost of a phase 1 trial?
The cost of a phase 1 clinical trial depends on several aspects, such as trial dimension (number of subjects to be treated), number of countries, number of clinical sites, type of disease and drug, and the specific assessments needed per clinical protocol, among other factors.
Early-phase (phase 1) trials require few patients (12-20 in average). The typical design of a phase 1 study consists of testing a number of increasing dose levels, in sequential patient cohorts.
Dose-limiting toxicities (DLTs) are defined in the protocol and dose levels are increased to test how well patients tolerate the therapy. Depending on the dose levels needed, the exact total number of patients may change (normally in the 12-20 range).
Moreover, academic (not for profit) and commercial trials should be differentiated. Non-commercial sponsors may run trials without financial interest and with more limited resources, while biotech and pharma will need higher budgets to develop their research programs.
This article describes the typical costs included in a Contract Research Organization (CRO) budget.
A phase 1 cancer clinical trial budget
This article provides a budget example for a phase 1 commercial clinical trial in oncology to be conducted in the United States.
A total of 18 subjects would be enrolled in 3 U.S. sites, with the following timelines:
Approvals and activation: 4 months
- Enrollment period: 10 months
- Treatment: 6 months
- Follow-up: 3 months for last subject enrolled
- Close-out: 3 months
- Total: 26 months
Regulatory affairs include the issuance of an insurance policy, Institutional Review Board (IRB) and regulatory (FDA) initial submissions for trial authorization, protocol amendments, regulatory reporting, as well as the writing and distribution of annual progress reports to involved parties.
This section comprises the setup, gathering and assessment of feasibility questionnaires, as well as onsite selection visits, in order to evaluate the facilities and capabilities of each clinical site.
Each selection visit implies effort dedicated to scheduling, preparation, traveling, the onsite visit itself, the post-visit report, and follow-up activities with the hospital.
Site Contracting and Payment Management
These tasks involve a written agreement negotiation and execution with each hospital and the management of payments to the sites per recruited participant (fees paid by the Sponsor to the hospitals for each subject enrolled).
The activation of participating sites includes onsite initiation visits in which the Clinical Research Associates (CRAs) and Clinical Project Managers of the CRO explain the objectives and assessments of the study to the site’s Principal Investigator and his/her team (Study Coordinator, nurses, etc.).
Each visit requires time dedicated to visit arrangement, travel time, the visit itself, the post-visit report, and follow-up.
After the site initiation visit, the activation process may involve essential document review/signatures, and giving access to the study systems (electronic Case Report Form, etc.).
The CRAs of the CRO are in charge of providing complete support to clinical sites during the enrollment and follow-up phases of the trial.
This work consists of constant contact with site staff via e-mail and telephone calls, responding to research team questions, protocol doubts, reviewing site performance, and escalating problems or difficulties to the Clinical Project Manager or Sponsor managers.
CRAs will also send to sites updated documentation during the development of the trial, making sure the researchers have the most recent approved versions of the study documents (e.g. Study protocol, Investigator’s Brochure, Patient Information Sheet / Informed Consent Form).
Onsite monitoring activities firstly involve the writing of a detailed monitoring plan, which must be ready before study initiation.
Once the trial recruitment has begun, onsite monitoring visits are performed by CRAs during the enrollment period and follow-up stage, in order to verify source data and site documents, according to the monitoring plan.
Each onsite monitoring visit includes time devoted to scheduling, preparation, traveling, the visit itself, post-visit report, and follow-up. A suitable monitoring schedule for a phase 1 trial can be one onsite monitoring visit per site every month, since patients should be followed very closely.
From the CRO’s perspective, pharmacovigilance tasks involve the receipt, review, listing, reporting, and follow-up of serious adverse events (SAEs), with particular attention to safety events related to the study drugs under investigation.
Moreover, suspected unexpected serious adverse reactions (SUSARs) have to be reported to regulatory authorities and other parties involved in the trial according to local laws.
The CRO is also in charge of developing and circulating annual safety reports.
Medical Monitors play a very important role in patient safety supervision. The CRO can provide a Medical Monitor for the study, but this is not always the case as this role may also be played by medical experts of the biotech company.
Total: $9,945.00 (Medical Monitor cost not included)
The activities linked to drug logistics may vary a lot depending on each clinical trial.
The CRO may be involved in drug manufacturing and importation tasks as well.
Signing a contract with a drug depot in charge of receiving, labelling, storing, and shipping the drugs to the site pharmacies is a common need.
The CRO personnel can also oversee drug stocks (at depot and site pharmacies) and control drug shipments from depot to sites.
The drug depot expenses are included as a pass-through cost.
Total: $9,100.00 (CRO cost only, depot not included)
Handling of Tumor and Blood Samples
Clinical trials, and especially phase 1 studies, require the handling of biological samples.
Cancer trials require the extraction and shipment of tumor and blood samples to central laboratories for translational or pharmacokinetics (PK) studies.
CROs may coordinate the shipment of these biological samples from sites to central labs.
Total: $4,550.00 (shipping costs not included, since they are listed as pass-through expenses)
Different studies may require different types of clinical supplies.
In phase 1 cancer trials, laboratory kits are needed for hospitals to collect and ship blood and biopsy samples (i.e. blood tubes, containers, boxes).
CRO personnel can prepare and send clinical supplies for sites as needed, checking supplies and sending additional kits during the course of the study.
The clinical supplies are listed as pass-through costs.
Trial sponsors may ask the CRO to write and/or review the clinical study protocol, the Patient Information Sheet / Informed Consent Form, interim/final study reports, and scientific publications (such as abstracts, posters, and manuscripts), among other documents.
At the end of the clinical trial, onsite close-out visits (one per site) are performed. These visits are done to review study documents and materials to be archived (or returned) and preserved according to local legislation.
Close-out visits include time for scheduling, preparation, traveling, visit, post-visit report, and follow-up.
Project Managers are well experienced professionals who develop the global project plan (including trial timelines and milestones), the central filing, and the communication plan.
Clinical Project Managers lead teams and have periodic meetings with other CRO staff (CRAs, CTAs, Data Managers), the Sponsor, and external vendors.
They coordinate and oversee the whole project, including financial, technical, and administrative aspects.
Furthermore, Clinical Project Managers check site initiation, routine monitoring, and close-out visit reports to ensure their correctness and quality.
In CROs, Clinical Trial Assistants (CTAs) are focused on file/document management.
They take care of initial Investigator Site File (ISF) preparation and shipments, electronic Trial Master File (eTMF) maintenance during the entire study, and final eTMF reconciliation.
Clinical Data Managers write the data management plan and work on the electronic Case Report Form (eCRF) specifications, setup, development, testing, and validation.
Data Managers also provide eCRF technical support to end users, review data coding (adverse events, concomitant medications, and medical history of the patient), and review/clean eCRF data.
Furthermore, data management includes SAE reconciliation with clinical database, as well as database locks and exports for analyses.
Statistics & Statistical Programming
Statisticians and statistical programmers are dedicated to the development of the randomization code (if the trial is randomized) and the writing of the statistical analysis plan.
They are also in charge of the sample size calculation, protocol review (statistical design sections), SAS programming, and statistical analyses and reports.
If needed, statistical programmers will work on SDTM/ADaM dataset specifications, mapping, programming, and validation.
Ensuring the good quality of a clinical trial is critical, and the following activities are conducted by Quality Managers: eTMF/document reviews, major/minor protocol deviation management, and hosting/attending Sponsor’s audits and regulatory inspections at the CRO or hospital facilities.
Pass-through expenses are those costs related to other parties or vendors involved in the trial.
In phase 1 clinical trials, typical pass-through costs include:
- Trial insurance policy
- Shipping: physical files to sites, site contracts, and tumor/blood samples
- Blood tubes and shipping packages
- Office supplies: files, paper, and printing
- Payments to sites per recruited patient (to cover clinical procedures and laboratory tests)
- Publication fees
- Ethics committee evaluation fees
- Site contract fees
- Regulatory authority evaluation fees
- Travel costs for selection, initiation, routine monitoring, and close-out visits
- Central pathology and radiology reviews
- Coordinating investigators
- Drug distribution services
- eCRF license fees
- Web tools (imaging platforms, eTMF)
- Document translations
Pass-through total: $1,163,448.00
The phase 1 clinical trial quote discussed in this article adds up to $1,947,946.50 ($784,498.50 in CRO services and $1,163,448.00 in pass-through).
Clinical trial costs depend on many factors. Sponsors should plan their budgets well and CROs can help with that task.
Send an email to firstname.lastname@example.org to get a quote for your specific trial.