Stakeholders in clinical research

Motivation to involve in clinical research:

Learn about new diseases. Work with the cutting edge of technology New career opportunities. Improve patient care $$$

Careers in Clinical Research

Clinical Research Associate

Clinical trial project manager

Clinical Research Investigator

Study Coordinator Data manager Biostatistician Regulatory affairs manager

Clinical research Manager

Business development manager Clinical IT Clinical Business Analyst Drug safety specialist

Clinical trial auditor

Clinical Trials Players

Regulatory Authority

Overseas Local
CRO Central Lab Ethics Committee
IDMC

SMO/ARO

Sponsor

Investigator

Subjects
4

There are four major clinical trial players

Regulatory authority local & overseas
Sponsor + CRO, Central Lab

Investigator + team members & patients +ARO/SMO

Ethics committee + IDMC

Clinical trial are performed under the supervision of a doctor and/or researcher
Maybe located at:
Hospitals Private specialist clinics

General Practices
Research institutes

Academic institutions
Other health providers
6

Financing of Clinical Trails

Patient foundations or medical institutions Government agencies eg: NIH, NIC Commercial sponsor Private companies

Public listed companies

Venture Capitalists/ Business Angels Licensing partners Private monies
7

Sponsor

Sponsor: Can be an individual, a company, (pharmaceutical, device or biotech) or a academic organization that initiates a clinical trial.

A recent trend has been for industry sponsors to partner with agencies such as the National Institutes of Health and manage trials

In investigator-initiated trials, the investigator takes on all responsibilities of sponsor and investigator.
8

Sponsor responsibilities may include:

Protocol development and IND submission Select qualified principal investigators, monitors and sites. 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)

CRO is an organization that performs any or all of the duties of
a sponsor.

For FDA regulated trials, the sponsor is required to describe in

writing exact responsibilities and obligations transferring to

CRO.
10

Project Manager
The project manager is responsible for monitoring the overall progress of the trial. He/She is in changer of all the reporting to FDA, budgets, cost control and global

trial communications

Medical Monitor
He is individual with therapeutic expertise Involved in protocol development, safety reporting, interpretation of data and clinical findings.
11

Data Manager

He overlooks all the data collected from the trials. Generate data queries to ensure quality of data Maintain ongoing data entry, monitor data analysis and provide reports.

Statistician

He analyzes the data from the trial and provides reports for data safety monitoring board (DSMB) or Endpoint committee
12

Clinical Research Associate

Definition:

Clinical Research Associates are research professionals carrying out activities that may include investigational site selection, set up, initiation, monitoring and close-out, and can be involved in all operational aspects of

the clinical phases of drug development

13

CRA -Role & Functions

Selection of Principal investigator Liaison between the trial site and the regulatory bodies i.e. IRB, FDA Setting up and designing documentation. Investigator meetings Trial site initiation, monitoring, close-out Training of site staff Financial management and negotiations with sites. Check for adherence to protocol, verify data, adverse events
14

Routes to becoming a CRA

Administrative Clinical trials administrator (CTA) Project assistant Clinical data co-coordinator

Laboratory work QA (GMP/GLP)

Trainee program Nursing Clinical trials co-coordinator Research nurse
15

Typical work activities can include:

Developing, writing and presenting the clinical trial protocols. Setting up the study centers -ensuring each center has the trial materials

Monitoring the trial throughout its duration

visiting the study centers on a regular basis to check the patient data in the case report forms (CRFs) and to sort out any problems which may arise

Validating and collecting completed CRFs from hospitals and general practices
Discussing results with the statistician.

The specific duties a CRA performs can vary tremendously from company to company.
16

Working conditions
CRAs spend a limited amount of time in the office
Most of the CRA job includes travelling to the trial sites. Most of the CRAs work independently CRAs can be home based, part time or free lance

17

Investigational Site Team

Principal Investigator
CRC

18

Investigator (PI)
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 compliance in trial conduct. The PI will be directly involved in: 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 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
19

Sub-Investigator
Clinicians 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.

20

CRC Clinical research coordinator

The definition of clinical research coordinators: A Clinical Research Coordinator, Study Site Research Nurse or Study Site Coordinator, works at a clinical research site under the immediate direction of a Principal Investigator, whose research activities are conducted under GCP regulations. The CRC is a vital link between the research subjects, the Investigators and other site members. Association of Clinical Research Professionals
21

Roles and responsibilities of CRC

The ICH GCP has not defined the roles and responsibility of the CRC due to which the CRC responsibilities are not well defined. CRC responsibility defers from institution to institution and what the Principal Investigator delegates.

22

Typical CRC job responsibilities include:

Ensure adherence to the protocol and document breaches or violations with sponsor and IRB

Liaison with sponsor/CRO in site selection, study initiation, conduct and completion.
Collaborate with PI and facility Complete all regulatory and IRB submissions Develop study source documents, visit schedules, pre-screening questionnaires, logs, forms, letters and regulatory files Determine storage and supply needs Screen, enroll subjects and schedule study visits.
23

Typical CRC job responsibilities include continued

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) 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 Ensure proper study product storage and accountability
24

The Safety Squad

IRB

Data Safety Monitoring Boards (DSMB)

Food and Drug Administration (FDA)

25

IRB
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) A specially constituted board established to protect rights, safety and well being of human subjects participating in clinical trials.

May be a part of an institution or independent/private IRB

26

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

27

Responsibilities of the Data Monitoring Committee

The DMC may perform a variety of tasks in meeting its overall responsibilities for safeguarding trail participants and trial integrity.
These tasks may address primarily scientific issues, such as an advisory review of the study protocol, as well as primarily practical issues such as quality assurance.

Trials may be considered for early termination based on proven efficacy, unfavorable results ruling out benefit, safety concerns, or low probability of achieving the trial objectives.
All trials monitored by a DMC should function under a charter, agreed to by the trial sponsor and the committee members, that describes the structure and operation of the committee.
28

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

29

Potential employers
Pharmaceutical companies CRO ( contract research organizations)

Research organizations
Academic organizations

Biotechnology companies
Research laboratories

Hospitals
Government organizations
30

Clinical Collaborations:
Contract Research Organizations Site Management Organizations Academic Medical Centers Physician Practice Management Organizations Physician Networks National Organizations
31

Services offered by Contract Research Organizations (CROs)

Full service clinical research enterprises Protocol development: Phases I, II, III, IV Statistical and data management support Monitoring Analysis and manuscript writing Regulatory Submissions/ filing Outsourced research from sponsors Data belongs to the sponsors
32

SMO
Site Management Organizations (SMOs) Site service clinical research enterprises Site selection Entry into trials Training, enrollment, communication Evaluation

Maintenance
Human Resources
33

Academic Medical Centers (AMCs)

Hybrids of CROs and SMOs Site Management personnel Safety Desk Training Consortia Development

Protocol Development
Data management, statistical analysis Manuscript FDA filing Data is owned jointly between sponsor and AMC
34

Physician Networks
Physician affiliations of interest

Generally are specialty specific

Offer greatest freedom

35

Physician Networks
May be organized as a cooperative group that is clinically oriented towards a common goal.
Examples:

American College of Surgeons Oncology Group

Cooperative Outcomes Group in ENT

36