"Conducting Clinical Trials A-Z"

Who are the players and what are their roles and responsibilities?

The Research Sponsor Lineup 

Sponsor – An individual, organization or company, (pharmaceutical, device or biotech), that initiates a clinical investigation.  A recent trend has been for industry sponsors to partner with agencies such as the National Institutes of Health and Academic Health Centers to co-sponsor and manage trials in specific therapeutic areas.  National efforts such as the FDA Critical Pathways to new medical products, have encouraged these collaborations.  In investigator-initiated trials, the investigator takes on all responsibilities of sponsor and investigator.  See Part II for guidance in investigator-initiated trials.

Sponsor responsibilities may include:
Protocol development and IND submission
Select qualified investigators, sites and monitors
Provide all information needed to conduct investigation
Monitor and ensure study conducted according to protocol and good clinical practice
Ensure compliance with regulations
Inform FDA and PIs regarding adverse events and safety reporting
Monitor data for safety and efficacy
Provide study supplies and/or investigational product
Perform data analysis and report findings

Contract Research Organization (CRO) – Organization that is contracted by a sponsor to perform any or all of the activities normally done by the sponsor. For FDA regulated trials, the sponsor is required to describe in writing exact responsibilities and obligations transferring to CRO.

Sponsor Monitor or Clinical Research Associate (CRA) – Interface with investigative site on behalf of sponsor or CRO. May be involved in any or all of the following:
site evaluation and initiation
assure regulatory requirements met
assure site personnel are trained and informed
assure site is provided with all materials required to conduct trial
assure site personnel are qualified and aware of obligations
monitor data and verify source records
oversee the progress of the study at site level
May be an employee of sponsor, CRO or a private contract monitor

Project Manager – responsible for overall implementation of trial; oversee progress of trial; global trial communications; reporting to FDA, budget and cost control.

Medical Monitor – individual with therapeutic expertise; involved in protocol development, safety reporting, interpretation of data and clinical findings.

Data Manager  - generate data querries to ensure quality of data; maintain ongoing data entry; monitor data analysis and provide reports.

Statistician – analysis of data – provide reports for data safety monitoring board (DSMB) or Endpoint committee

The Safety Squad

Institutional Review Board (IRB)or Independent Ethics Committee (IEC) – a specially constituted board established to protect rights, safety and well being of human subjects by providing review (initial and continuing) and oversight.  May be a part of an institution or independent/private IRB (sometimes referred to as a central IRB).  The University of Kentucky maintains 3 medical IRB boards and is administered by the Office of Research Integrity (ORI).

Data Safety Monitoring Boards (DSMB) – An independent committee, composed of community representatives and clinical research experts, that reviews data while a clinical trial is in progress to ensure that participants are not exposed to undue risk. A DSMB may recommend that a trial be stopped if there are safety concerns or if the trial objectives have been achieved.

Food and Drug Administration (FDA) – the US regulatory authority in charge of review and approval of drug applications (IND/NDA), dissemination of safety information and conducting audits or inspections of any sector of clinical research including sites, sponsors, or IRBs.

Investigational Site Team

Research Subject (Volunteer/Participant) – individual participating in a clinical trial.  Research subjects may be a healthy individual (don’t refer to as “normal volunteers”) or patient with a disease state or condition. They may be the recipient of an investigational intervention or a control subject.  It is important to remember that research subjects are people and their private information that doesn’t belong to the Investigator.   UKCRO maintains a Clinical Trials Volunteer web site where the public can learn about clinical trials and browse open trials at UK.

Principal Investigator (PI)–
FDA regulations require that investigators be “qualified by training and experience to be appropriate to serve as PI for a trial”.  International guidelines specify that the medical care and decisions made for trial subjects should be the responsibility of a qualified physician or dentist where applicable.  While technically a non-physician can be listed as PI, a physician is typically included as a sub-investigator (sub-I) to perform study functions requiring medical care. Example: PharmD as PI for pharmacokinetic study or clinical psychologist for psychiatric study with MD as sub-I.

The PI is the individual who conducts, supervises and is responsible for all aspects of a clinical trial.  They are responsible for ensuring regulatory, GCP, and fiscal compliance in trial conduct. The PI will be directly involved in determining a recruitment plan, evaluation and treatment of research subjects; supervising the medical staff participating in the study; timely review of all clinical and laboratory data; reading and interpreting clinical procedures (ECGs, x-rays); ensuring proper adverse event reporting and assessing causality of all adverse events; ensuring proper study product management; performing physical exams and any other required physician procedures; meeting with study monitor when needed, verifying subject data; and ensuring proper retention of study documents.

The PI may delegate many tasks to study staff provided that they are qualified to perform the task and it is within their scope of practice.  It is recommended to have written task delegations that both parties’ sign (SEE Sample: Investigator Delegation of Task Authorization).  Exception: Medical decisions (decisions regarding cause, treatment and response to adverse events, abnormal lab values, drug dosing, dropping a subject, breaking blind, etc), must be made by the physician investigator. Tasks may be delegated, but responsibility can not.

The trial is conducted under the PIs immediate direction and supervision. FDA is concerned about phantom PIs who do not provide adequate oversight. PI’s must document oversight, particularly if conducting trial at remote or off-site locations.

Sub-Investigator – other clinicians and members of the study team who assist the PI in conducting the trial. As a practical matter, NPs and PAs who make clinical decisions regarding study subjects should be listed as sub-investigators as well.

Clinical Research Coordinator – Responsible for coordinating all aspects of the clinical trial and day to day operations of the research program. This is a pivotal role in the efficient progress of the study.   Therapeutic expertise and credentials should be appropriate for the specific trial.  Multidisciplinary teams provide a wide-base of abilities and expertise.   Responsibilities typically include:

• Learn protocol and coordinate how study will be conducted at the site
• Ensure adherence to the protocol and document breaches or violations with sponsor and IRB
• Perform protocol assessment and feasibility
• Liaison with sponsor/CRO in site selection, study initiation, conduct and completion.
• Collaborate with PI and facility
• Complete all regulatory and IRB submissions
• Ensure initial and continued IRB review and approval
• Develop study source documents, visit schedules, pre-screening questionnaires, logs, forms, letters and regulatory files
• Determine storage and supply needs
• Define and implement recruitment plan
• Screen, enroll subjects and schedule study visits.
• Document all written and phone correspondence with sponsor, labs, IRB, other regulatory organizations
• Maintain organized, accurate, and complete subject study records including source documents, correspondence, and case report forms (CRFs)
• Promote fiscal compliance and proper billing
• Conduct study in manner to ensure integrity of data and safety of subjects
• Perform study related procedures and collect data
• Accurately report and track adverse events
• Provide paramount customer service for clinical research subjects
• Ensure proper study product storage and accountability
• Close study with sponsor and IRB and store records appropriately

Others: Investigational pharmacist, clinical research manager, technicians, phlebotomist, research assistants, regulatory specialist, recruiters, data coordinators, writers & presenters.