Overview

Project Management activities are essentially required to start-up, execute, and complete a particular Clinical Trial (Study) project in compliance with study protocol, other Sponsor’s requirements and GxP guidelines (e.g., Good Clinical Practice, Good Manufacturing Practice, Good Laboratory Practice etc.).

Aim

This article aims to briefly describe Carpathian Research Group (CRG) Project Management activities in Clinical Trials.

Process

Below are relevant definitions for better understanding:

• Project – is a temporary and unique endeavor designed to produce a product, service, or result
• Project Management – the use of specific knowledge, skills, tools, and techniques to deliver the value and achieve goals within the given constraints (of which primary are scope, time, and budget)
• Subject Matter Experts (SMEs) – individuals with specific expertise and responsibility in a particular professional area or field

Project Management Team (Project Director, Clinical Project Manager, and Clinical Project Leader) has full control of a given Clinical Study to ensure participating Subjects’ safety, optimize its resourcing, accelerate its delivery, reduce cost, preserve, and enhance its scientific/medical merit, and ensure highest data quality.

To achieve the above Project Management Team is always uniformly delivering the Clinical Studies within the agreed time, budget, and quality, with support from other Project Team members and other SMEs as per business need.

As Project Management is evidence based and data driven, every decision is made based on scientifically supported facts. The Project Management Team uses all available internal and external systems to collect and analyze all necessary data and performance indicators in order to support and improve project delivery to the highest.

Below are key elements with regards to Project Management:

1. Project Team and Communications

It is main responsibility of Clinical Project Manager to ensure that adequate Resources are available to the Clinical Study project.

Clinical Project Manager is a key contact person for External Parties (Sponsor and applicable Third Party Vendors) and internal Project Team.

Internal Project Team apart from Clinical Project Manager itself, consists of such roles (non-exhaustive list):

• Project Director – usually involved in more complex Clinical Study projects as a support to Clinical Project Manager
• Clinical Project Leader(s) – leading the teams of Clinical Research Associate(s) and Clinical Trial Assistant(s). In Clinical Studies involving blinding of Study Drug there could be blinded and unblinded Clinical Project Leaders leading respective Clinical Research Associate(s) and Clinical Trial Assistant(s)
• Clinical Research Associate(s) and Clinical Trial Assistant(s) – main roles responsible for management of Clinical Study Sites
• Regulatory Manager – as part of Regulatory Affairs supporting all necessary related activities
• Project Coordinator(s) – providing administrative and other support to Clinical Project Manager
• TMF Coordinator(s) – managing the Trial Master File and ensuring its inspection readiness at all times
• Logistic Coordinator(s) – providing logistical support to Clinical Project Manager and the rest of the Project Team as applicable.

Clinical Project Manager develops and maintains a separate standalone list of the Project Team members, their assigned roles and contact details and provides the list upon request.

In addition, Clinical Project Manager develops and maintains a separate standalone Project Communication Plan in order to ensure that Clinical Study project’s communications (including escalations pathways, if applicable) between all involved Parties are effective and consistent.

Careful consideration for Project Team composition and communications should be exercised in the clinical study projects having blinded and unblinded components. In such cases both Project Management and Communication Plans should clearly describe separation of tasks/communication lines between blinded and unblinded clinical study Project Teams and an additional Project Blinding Plan and Site Blinding Plan may need to be created for these purposes.

2. Project Scope of Work and Milestones

After project award a scope of work (responsibility matrix) is being agreed between CRG and Sponsor and is clearly documented in a corresponding Project Management Plan. The above scope of work also includes responsibilities of any project-specific Third Party Vendors.

Every Clinical Study project has project milestones. A milestone anticipates what the Clinical Study project is supposed to achieve at a pre-set date. It should describe a desired future situation.

Clinical Study projects milestones are linked with each other and follow a chronological pattern; therefor careful milestone planning should be considered in order to reach all project deliverables within the scope, budget, and time.

Typical project milestones include, but are not limited to:

• Project start – usually Sponsor defined date
• Dates for First and Last Pre-Study Site Selection Visit
• Site list approved – date at which Sponsor provides initial written list of Clinical Study Sites approved for study participation
• Database Go-Live – date at which Clinical Study database (e.g., Electronic Data Capture system) is live and Subjects’ data can be entered into it
• First Site Initiation Visit – date at which first Clinical Study Site is initiated (opened)
• Recruitment related milestones, such as: First Subject In (date at which first subject in the Clinical Study signs Informed Consent Form), First Subject Randomized (Dosed), Last Subject In (this is an end of study recruitment period), Last Subject Last Visit (date at which last subject in the Clinical Study performs last study visit as per study protocol)
• Database locked – date at which Clinical Study database is locked (“frozen”) and no more information can be entered into it
• Last Close-out Visit – date when the last Clinical Study Site had Close-out Visit
• Project end – date when all project deliverables have been achieved and the project can be considered as closed.

3. Project Documentation

A list of Controlled Documents (SOPs, Policies, Work Instructions, Manuals, Guidelines etc.) applicable to Clinical Study project is agreed between CRG, Sponsor and applicable Third Party Vendor(s) during project start-up phase and is clearly documented in corresponding Project Management Plan.

Clinical study Project Plans are developed to document the process of how the contracted project deliverables will be provided, and who has responsibilities for completing each related activity.

For more information refer to InfoCRG article on Study Materials Development:

https://www.linkedin.com/pulse/infocrgarticle-1study-materials-development-

4. Project Status Reports

Regular updates on the Clinical Project conduct should be reflected in the corresponding Project Status Reports.

The aim of these Reports is to provide (non-exhaustive list):

• Milestones’ achievement status
• Site related information (feasibility, study equipment/materials, initiation, monitoring, recruitment status etc.)
• Regulatory submissions/approval status
• Protocol deviations status
• Third Party Vendor Management status and updates (if any)
• Fulfilment of Key Performance Indicators (if implemented in the Clinical Study project)
• Clinical Study Site payments status
• Project issues, risks, and action items.

Frequency and delivery methods for Project Status Reports submission to Sponsor are documented in the corresponding Project Management Plan.

5. Project Training

Clinical Study project-specific training is provided to the Project Team to improve their level of understanding of the therapeutical (clinical), technical and/or operational aspects of the Clinical Study project. It is the ultimate responsibility of the CRG Clinical Project Manager or designee to ensure that the appropriate Clinical Study project-specific training is timely provided to the Project Team throughout the Clinical Study.

Clinical Study project-specific training may include, but is not limited to Clinical Study Protocol, therapeutic indication (area) of Clinical Study, study Project Plans, various Clinical Study project tools and guidelines, – all of the above is provided to the individual Project Team member according to defined role in Clinical Study project and should be completed prior to starting the associated Clinical Study project tasks.

6. Project Change

All project changes will be logged and evaluated for impact to the Clinical Study project scope, schedule, and cost. The Clinical PM in cooperation with the Project Director (if applicable) will recommend whether to incorporate the changes into a change order request immediately or hold the changes for a future change order release. All suggested changes to the Clinical Study project scope of work, tasks or defined deliverables will be sent to the Sponsor for review. The Clinical PM in cooperation with the Project Director (if applicable) should provide a detailed report of out-of-scope budgetary impact of any changes prior to implementation of the changes. The Sponsor should review and approve any changes prior to their implementation.

7. Project Risk Management

The objectives of the Clinical Study Project Risk Management are to decrease the probability and impact of the negative events in the Clinical Study project.

The evaluation of risks is being performed according to the corresponding severity/likelihood and detectability scales.

Clinical Study Project Risk Management (including risk identification, assessment, and review) should be documented in the corresponding Project Risk Management Plan (or any other Clinical Study Project Plan as per agreement with the Sponsor).

8. Project Quality

Maintaining consistent Clinical Study project quality is a key factor to a successful Clinical Study project delivery.

Depending on the agreed Clinical Study project scope of work the Quality Assurance for a particular Clinical Study could be CRG’s or Sponsor’s responsibility. All quality related responsibilities and activities should be clearly documented in the corresponding Clinical Study Project Plans.

In any case CRG QA is responsible for Quality Assurance of all CRG internal processes (e.g., Controlled Documents management, training, internal audit program and corrective and preventive action implementation, archiving etc.).

All inspections and audits of Clinical Study Sites should be handled as per applicable CRG’s and/or Sponsor’s Controlled Documentation.

9. Project Governance

Project governance is an “oversight function that is aligned with the organization’s governance model and encompasses the project life cycle” (according to Project Management Institute definition).

As per particular Sponsor’s requirement some Clinical Study projects may have an established project governance procedure and CRG should follow it as much as practically possible.

Typically, a project governance charter is being created and agreed between CRG and Sponsor. The aim of this charter is to specify the responsibilities of each participating Party with respect to the objectives of the Clinical Study, the achievement of Clinical Study project milestones, any financial issues, escalation of issues, key performance indicators, risk review etc.

Carpathian Research Group capabilities

CRG as a CRO has a high Project Management expertise tailored to specific participating Country requirements. With CRG support Sponsors can be sure that their projects will be delivered on time, within scope and agreed budget.

Information on all other Clinical Trial services that we provide could be found at www.crg.global