Study title:

Randomized controlled phase 1 trial of hyaluronic acid injection in

patients with moderate osteoarthritis.
 
Factors impacting clinical trial costs:

The cost of a clinical trial depends on several factors, such as study size
(number of patients), locations (number of countries), number of clinical
sites, therapeutic area, drug type, and the specific tests and procedures
needed per protocol, among other aspects.

The study size (number of patients to be recruited) is closely related to

the study phase.

Furthermore, academic (non-commercial) and industry-led (commercial)

trials should be distinguished. Academic, not-for-profit sponsors may
conduct trials without commercial interest, counting on less financial
resources to cover trial activities. On the other hand, commercial sponsors
have higher budgets to execute their drug development programs.

A typical clinical trial budget includes

 Regulatory affairs
 Site identification and selection
 Site contracting and payments
 Site initiation and activation
 Site management
 On site monitoring
 Drug safety management
 Drug logistics
 Biological sample logistics
 Clinical supplies logistics
 Medical writing
 Site close-out
 Project management
 Study files/document management
 Data management
 Statistics
 Quality control
 Communication with central CRO/sponsor
 Pass-through costs
In the following paragraphs these cost items are further explained and
valued.

Study example assumptions: A phase 1 trial in pain and

anesthesia

A total of 32 patients would be recruited in 1 government Hospital sites

located in Addis Ababa Ethiopia

Assumed trial stages and timelines are: 

 Start-up/Recruitment: 2 months
 Per-patient treatment and follow up : 3 months
 Close-out: 2 weeks
 Total study duration: 4 months

The proposed CRO management strategy consists of central management

services provided from the CRO temporary control center located at
AHRI/ALERT compound site.

Regulatory affairs

Clinical trial regulatory affairs include the issuance of insurance policies

in each country where the trial is conducted, ethicscommittee (EC) and
regulatory authority (RA) initial submissions, study amendments, EC/RA
reporting/communication, as well as the development and distribution of
annual progress reports.

Total: $3250

Site identification and selection

This section comprises the preparation, collection and analysis of

feasibility questionnaires, as well as on site selection visits, in order to
verify the capabilities of each hospital.

Each selection visit includes time dedicated to scheduling, preparation,

travel, the visit itself, post-visit report, and follow-up tasks.

Total: $2200

Site contracting and payments

These tasks involve contract negotiation and execution with each hospital
and site payment management (amounts paid by the Sponsor to the
hospitals for each patient enrolled).

Total: $2350 (the amounts paid per patient are listed as pass-through
costs)

Site initiation and activation

The activation of clinical sites requires onsite initiation visits in which the
CRAs and Clinical Project Managers of the CRO explain the goals and
procedures of the trial to the site’s research team (Principal Investigator,
Study Coordinator, nurses, etc.).

Each visit involves time dedicated to scheduling, preparation, travel, the

visit itself, the post-visit report, and follow-up.

After the initiation visit, the activation process involves local document
verification/signatures and providing sites with access to the different
trial systems (EDC, etc.).

Total: $2,700

Site management

The CRAs of the CRO provide comprehensive support to sites during the
recruitment and follow-up stages of the study.

This support consists of daily communication with sites via e-mail and
telephone, responding to site inquiries, reviewing site performance, and
escalating any issues to the Clinical Project Manager or Sponsor.

CRAs must also notify sites about any updated documents during the
course of the study, ensuring that research teams have the latest versions
of the study documents (e.g. Protocol, Patient Information Sheet /
Informed Consent Form).

Total: $4400

On site monitoring

Monitoring activities firstly require the development of a monitoring

plan.
Then, on site monitoring visits are conducted by CRA s during
recruitment and follow-up, in order to verify source clinical data and
other aspects, according to plan.

Each onsite monitoring visit includes time devoted to scheduling,

preparation, travel, the visit itself, post-visit report, and follow-up.A
reasonable monitoring strategy can be one onsite monitoring visit per site
every month.

Total: $15,000

Drug safety management

From the CRO’s side, drug safety requires the receipt, review, listing,
reporting, and follow-up of serious adverse events (SAEs).

In addition, suspected unexpected serious adverse reactions (SUSARs)

must be reported to regulatory authorities and other parties according to
legislation.

The CRO can also take care of writing and distributing annual safety
reports.

Another relevant role in drug safety is that of the Medical Monitor.

Total: $1500 (not including Medical Monitor)

Drug logistics

The tasks related to drug logistics may greatly vary depending on each
trial.

For instance, the CRO may or may not be involved in helping with drug
manufacturing and importation aspects.

The selection and contracting of a drug depot in charge of receiving,

labelling, storing, and distributing the drugs to the sites is a commonly
required task (subcontracted vendor).

The drug depot service cost is listed as a miscellaneous expense.

The CRO can also supervise drug stock availability (at depot and sites)
and coordinate drug shipments from depot to sites.

Total: $1,990
Biological sample logistics

Clinical trials commonly require the handling of biological samples.

For example, oncology trials involve the collection and shipment of

tumor and blood samples for translational/biomarker or pharmacokinetics
(PK) studies.

CROs coordinate the shipment of biological samples from sites to central

laboratories.

Total: $74,620 (not including shipping costs, which are listed as pass-
through costs)

Clinical supplies logistics

Different trials may require different types of clinical supplies such as

laboratory kits, biological samples.

CRO prepare and ship clinical supplies for sites as needed, tracking and
sending additional supplies during the course of the study.

The supplies as such are listed apart, as pass-through costs.

Total: $22,575

Medical writing

Medical writing activities may include the writing and/or review of the
study protocol, the Patient Information Sheet / Informed Consent Form,
interim/final clinical study reports, and scientific publications (abstracts,
posters, and manuscripts), among other documents.

Total: $1990

Site close-out

The closure of the clinical trial requires onsite close-out visits (one per
site), used to review study documentation and materials to be archived,
once the trial has ended.

An onsite close-out visit includes time for scheduling, preparation, travel,

visit, post-visit report, and follow-up.
Total: $1800

Project management

Clinical Project Managers are senior staff who develop the global project
plan (including timelines and milestones), the central filing, and the
communication plan.

Project Managers lead teams and have periodic meetings with other CRO
staff, the Sponsor, and vendors.

They manage and supervise the project, including financial, clinical,

technical, and administrative aspects.

In addition, Clinical Project Managers supervise, review, and follow up

site initiation, monitoring, and close-out visit reports.

Total: $10.000

Study files/document management

CROs have Clinical Trial Assistants (CTAs) in charge of study

file/document management.

These tasks encompass Investigator Site File (ISF) preparation and

shipments, electronic Trial Master File (eTMF) maintenance, and final
eTMF reconciliation.

Total: $2988

Data management

The CRO’s Data Managers develop the data management plan and take
care of the electronic Case Report Form (eCRF) or Electronic Data
Capture (EDC) system specification, configuration, development, testing,
and validation.

Moreover, Data Managers provide EDC technical support to sites,

perform data coding (adverse events, concomitant medications, and
medical history), and review/clean EDC data (through data queries).

In addition, data management activities include SAE reconciliation with

clinical database, as well as database locks and exports.

Total: $14,528
Statistics

Biostatisticians and statistical programmers will work on the

development of the randomization code (if the trial is randomized) and
the statistical analysis plan.

They will also work on the sample size calculation, protocol review, SAS
programming, and statistical analyses and reports.

If required, statistical programmers will be in charge of SDTM/ADaM

dataset specifications, mapping, programming, and validation.

Total: $4788

Quality control

In order to ensure the quality of the study, the following activities will be
conducted by the CRO’s Quality Managers: eTMF/document reviews,
protocol deviation management, and hosting/attending Sponsor’s audits
and regulatory inspections at the CRO/site.

Total: $2348

Communication with central CRO/sponsor

CRAs need to dedicate time to communicate with the CRO’s central

office as well as with the Sponsor. This may include on site meetings and
teleconferences.

Total: 970

Pass through / Miscellaneous costs

Are those expenses and services related to other parties or vendors.

In clinical trials, typical pass-through costs include:

 Trial insurance policies for each country

 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 enrolled 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
 Translational/biomarker studies
 Coordinating investigators
 Drug manufacturing and testing
 Drug distribution services
 Web tools (imaging platforms, eTMF)
 Document translations
 Data and Safety Monitoring Board (DSMB)

Total: $32,672

CLINICAL TRIAL BUDGET TOTAL: $128,096