SponsorWho is Sponsor?

An individual, company, institution, or organisation

which takes responsibility for the

Initiation

Management

Financing of a clinical trial.ICH E6, 1.53

A clinical research coordinator (CRC) is responsible for conducting clinical trials at

clinical trial sites according to the protocol, ICH-GCP and other regulatory requirements.
The role of a study coordinator in clinical trials is very important. Every clinical trial site
may have one or more study coordinators depending on the workload at the trial site.
Clinical trials at site level can be roughly divided into 3 stages. Let us discuss about the
role of the study coordinator in these three stages. The three stages are:

1) Before the start of the clinical trial

2) During the conduct of the clinical trial
3) After close out of the clinical trial

1) Before the start of the Clinical Trial:

During this stage the study coordinator has to collect and complete feasibility
questionnaires received form different CRO’s and Sponsor’s. CRC’s also have to collect
required information from the principal investigator, and send it back to the respective
people who contacted the site regarding the study. Sponsors select sites based on the
responses filled in the feasibility questionnaire and conduct Pre-site selection visits to
confirm the sites participating in the study.
The sponsors or CRO’s after selecting clinical trial sites conduct Investigator meetings,
which have to be attended by the study coordinator along with the principal or co-
investigator. Investigator meetings are conducted either at national level or international
level. Before start of the trial CRC’s are usually busy with submitting all study
documents to the ethics committee. Documents to be submitted to the ethics committee
normally include the study protocol, investigator brochure and informed consent forms
(vernacular languages at site) with translation certificates. If any amendments are
available those also need to be submitted to the ethics committee. In addition to these
documents, investigator’s CV with MRC, FDA-1572, Financial disclosure forms,
Insurance statement, subject diaries if applicable, clinical trial agreement,
indemnification letter, protocol signature page and different study logs, eCRF or CRF
entry guidelines, blank CRF’s etc also need to be submitted.
In all these processes a clinical study coordinator plays a vital role. After obtaining
approval from the ethics committee the clinical trial can be initiated at the site level.
2) During the conduct of clinical trial:
By the time a clinical trial is initiated at a site the CRC must have a good understanding
of the study protocol and must know well about inclusion and exclusion criteria. During
the screening time, the study coordinator has to obtain informed consent from the
subject in if delegated to do so by the Principal Investigator. Study coordinators have to
collect subjects previous medical records and according to study protocol he/she has to
conduct subjects scheduled visits. Before randomization visit of the subject the CRC
must check inclusion and exclusion criteria thoroughly, and only then eligible subjects
must be enrolled into the study.

After completion of all visit procedures coordinators have to enter data in case report
forms (CRF). CRF’s are two types, one is paper CRF and another one is eCRF. eCRF’s
are usually of 5 types namely , Phase forward – Inform, oracle clinical remote data
capture, medi data rave, novartis EDC (or) Pasco and Data track. All the visit details like
demographics, vital signs, subject past medical history, any SAE or AE details have to
be entered in these online data collection tools based on source documentation
available. During monitoring, sponsor representatives (CRA’s) cross verify both the
source documents & the data filled by the CRC in the case report forms. During the
monitoring visit the CRA’s also verify EC notifications and Investigator Site Files (ISF).
To keep all these documents up to date is the responsibility of the clinical study
coordinator. Study coordinator also has to maintain site SOP’s, EC sops and EC
members list.

Whenever study subjects come for next schedule visit, study drug accountability has to
be calculated by the CRC. Along with that subject diaries have to be reviewed if
applicable. IVRS (Interactive voice response system) and IWRS (Interactive web
response system) to record the subject visit have to be performed as per the study
requirement. IVRS reports have to be maintained in the ISF’s. IP (Investigational
product) is the major part in clinical trial and study coordinators have to store the same
in proper condition and maintain required temperature logs.

In case of any adverse events (AE’s) or serious adverse events (SAE’s) that occurred at
the trial site, coordinators have to collect all applicable details such as start date, stop
date, severity (Mild, Moderate or Severe), concomitant medications consumed by the
subject and the route of administration. Also information related to any dechallenge and
rechallenge, therapy provided to the subject during the SAE, recovery details and
whether it is related to study drug or not have to be collected. Study Coordinators have
to notify SAE’s to the Ethics committee within 7 working days and details of SAE have
to sent to the sponsor within 24 hours.

Throughout the clinical trial the study coordinators have to check all Central lab reports
as well as local lab reports and take PI signatures on them to document that the PI
reviewed the lab reports. CRC is also responsible for telephonic reminders to the
subjects regarding the visits. If the CRC is involved in data entry then it is the study
coordinators responsibility to resolve all queries within 48 hours or as per timeline
specified by the sponsor. Queries are of three types i.e. 1) system generated queries 2)
data management generated queries and 3) CRA generated queries.

3) After Close out of clinical trial:

Before a clinical trial is closed at the site, study coordinators have to check all
documents and all the documents have to be updated. On the day of close out CRA will
verify all documents. After verification of all documents by the CRA, CRC will assist in
archiving the documents at site. Site has to maintain all study related records for 15 to
20 years.

As you can see a CRC plays a vital role in managing a clinical trial at the site level and
acts as a link between the sponsor, EC and the Investigator Site.

Clinical trials: Study investigator

responsibilities
In a clinical trial, the responsibilities of an investigator generally include:

 Protecting the rights, safety and welfare of subjects in the clinical

study
 Ensuring that informed consent is properly obtained from clinical
trial subjects
 Conducting the clinical study (that is, directly overseeing the
administration of the test products to the subject). In situations
where there is a team of researchers, the investigator will act as
the team leader
 Ensuring that the clinical trial is conducted in accordance with the
signed agreement and the investigational plan
 Controlling the products under investigation (for example,
supervising medical-device use and disposal)
 Ensuring proper record-keeping and reporting requirements are
met (for example, mandatory safety reporting)3,4

https://www.slideshare.net/sekhar101/clinical-trials-an-introduction?next_slideshow=1

The specific regional requirements for a clinical study sponsor can vary.
Generally, a sponsor is responsible for:3,4

Sponsors Responsibilities: 4 Broad Areas

 Preclinical / non-clinical
 Manufacturing
 Clinical
 Post-approval
 May use a CRO (Contract Research Organization)
Information on Investigational Product(s)<br />When planning trials, the sponsor
should ensure that sufficient safety and efficacy data from nonclinical studies
and/or clinical trials are available to support human exposure by the route, at the
dosages, for the duration, and in the trial population to be studied.<br />The
sponsor should update the Investigator's Brochure as significant new information
becomes available.

Manufacturing, Packaging, Labeling, and Coding Investigational Product(s)<br

/>The sponsor should ensure that the investigational product(s) (including active
comparator(s) and placebo, if applicable) is characterized as appropriate to the
stage of development of the product(s), is <br />manufactured in accordance
with any applicable GMP, and <br />is coded and labelled in a manner that
protects the blinding, if applicable. <br />In addition, the labelling should comply
with applicable regulatory requirement(s).<br />The sponsor should determine,
for the investigational product(s), <br />acceptable storage temperatures,<br
/>storage conditions (e.g. protection from light), <br />storage times, <br />

Multi-centre studies<br /><ul><li>The CRFs are designed to capture the required

data at all multicentre trial sites. For those investigators who are collecting
additional data, supplemental CRFs should also be provided that are designed to
capture the additional data.</li></li></ul><li>Clinical trial/Study reports<br
/>Whether the trial is completed or prematurely terminated, the sponsor should
ensure that the clinical trial reports are prepared and provided to the regulatory
agency(ies) as required by the applicable regulatory requirement(s). The sponsor
should also ensure that the clinical trial reports in marketing applications meet
the standards of the ICH Guideline & Schedule Y (appendix II) for Structure and
Content of Clinical Study Reports. <

 Selecting the investigator(s)

 Providing investigator(s) with the necessary information to conduct the
clinical trial
 Ensuring proper monitoring of the clinical study
 Ensuring all the necessary ethic review(s) and approval(s) are obtained
 Preparing and submitting clinical trial application(s)
and amendment(s) to the appropriate regulatory agencies
 Ensuring that any reviewing ethics board and regulatory agencies are
promptly informed of any significant new information (for example,
important findings that affect product safety) in a clinical study
 Ensuring compliance with labelling, reporting and record-keeping
requirements
 Refraining from engaging in promotional activities and other prohibited
activities such as commercializing an investigational medical device
  Ensuring that the clinical study is conducted in accordance with Good
Clinical Practice (GCP)

Funding for clinical research comes from the federal government or the private sector. In addition to
providing financial resources, some funding groups also provide the investigational agent. They are
referred to as the Sponsor and are responsible for the initiation and management of a new agent under
the FDA’s Investigation New Drug (IND) Application (Title 21 Part 312). This module will review the role
of the IND sponsor.

At the conclusion of this module, you will be able to: • Define what is meant by a “sponsor” • List the 4
broad areas of sponsor responsibilities • Describe the purpose of FDA Form 1571 • List 5 items that are
submitted with an initial IND application

Following are the key responsibilities of the sponsor in in clinical trial according to ICH GCP.
Data Management and Record Keeping:
The sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial, to handle the
data, to verify the data, to conduct the statistical analyses, and to prepare the trial reports.
When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should:
a. Ensure and document that the electronic data processing system(s) conforms to the sponsor’s established
requirements for completeness, accuracy, reliability, and consistent intended performance (i.e., validation).
b. Maintains SOPs for using these systems.
c. Ensure that the systems are designed to permit data changes in such a way that the data changes are
documented and that there is no deletion of entered data (i.e., maintain an audit trail, data trail, edit trail).
d. Maintain a security system that prevents unauthorized access to the data.
e. Maintain a list of the individuals who are authorized to make data changes.
f. Maintain adequate backup of the data.
g. Safeguard the blinding, if any (e.g., maintain the blinding during data entry and processing).
The sponsor-specific essential documents should be retained until at least 2 years after the last approval of a
marketing application in an ICH region and until there are no pending or contemplated marketing applications in an
ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the
investigational product. These documents should be retained for a longer period however if required by the applicable
regulatory requirement(s) or if needed by the sponsor.
The sponsor should inform the investigator(s)/institution(s) in writing of the need for record retention and should notify
the investigator(s)/institution(s) in writing when the trial related records are no longer needed.
Investigator Selection:
The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by
training and experience and should have adequate resources to properly conduct the trial for which the investigator is
selected. If organization of a coordinating committee and/or selection of coordinating investigator(s) are to be utilized
in multicentre trials, their organization and/or selection are the sponsor’s responsibility.
Before entering an agreement with an investigator/institution to conduct a trial, the sponsor should provide the
investigator(s)/institution(s) with the protocol and an up-to-date Investigator’s Brochure, and should provide sufficient
time for the investigator/institution to review the protocol and the information provided.
The sponsor should obtain the investigator’s/institution’s agreement:
a. to conduct the trial in compliance with GCP, with the applicable regulatory requirement(s) , and with the
protocol agreed to by the sponsor and given approval/favourable opinion by the institutional review
board/independent ethics committee (IRB/IEC);
b. to comply with procedures for data recording/reporting;
c. to permit monitoring, auditing and inspection and
d. to retain the trial related essential documents until the sponsor informs the investigator/institution these
documents are no longer needed .
Allocation of Duties and Functions
Prior to initiating a trial, the sponsor should define, establish, and allocate all trial-related duties and functions.
Compensation to Subjects and Investigators
If required by the applicable regulatory requirement(s), the sponsor should provide insurance or should indemnify
(legal and financial coverage) the investigator/the institution against claims arising from the trial, except for claims that
arise from malpractice and/or negligence.
The sponsor’s policies and procedures should address the costs of treatment of trial subjects in the event of trial-
related injuries in accordance with the applicable regulatory requirement(s).
When trial subjects receive compensation, the method and manner of compensation should comply with applicable
regulatory requirement(s).
Financing:
The financial aspects of the trial should be documented in an agreement between the sponsor and the
investigator/institution.
Notification/ Authority(ies)Submission to Regulatory

Before initiating the clinical trial(s), the sponsor (or the sponsor and the investigator, if required by the applicable
regulatory requirement(s)) should submit any required application(s) to the appropriate authority(ies) for review,
acceptance, and/or permission (as required by the applicable regulatory requirement(s))to begin the trial(s). Any
notification/submission should be dated and contain sufficient information to identify the protocol.
Confirmation of Review by IRB/IEC
The sponsor should obtain from the investigator/institution:
a. The name and address of the investigator’s/institution’s IRB/IEC.
b. A statement obtained from the IRB/IEC that it is organized and operates according to GCP and the
applicable laws and regulations.
c. Documented IRB/IEC approval/favourable opinion and, if requested by the sponsor, a current copy of
protocol, written informed consent form(s) and any other written information to be provided to subjects, subject
recruiting procedures, and documents related to payments and compensation available to the subjects, and any other
documents that the IRB/IEC may have requested.
Information on Investigational Product(s)
When planning trials, the sponsor should ensure that sufficient safety and efficacy data from nonclinical studies
and/or clinical trials are available to support human exposure by the route, at the dosages, for the duration, and in the
trial population to be studied.
Manufacturing, Packaging, Labelling, and Coding Investigational Product(s)
The sponsor should ensure that the investigational product(s) (including active comparator(s) and placebo, if
applicable) is characterized as appropriate to the stage of development of the product(s), is manufactured in
accordance with any applicable
GMP, and is coded and labelled in a manner that protects the blinding, if applicable. In addition, the labelling should
comply with applicable regulatory requirement(s).
The sponsor should determine, for the investigational product(s), acceptable storage temperatures, storage
conditions (e.g., protection from light), storage times, reconstitution fluids and procedures, and devices for product
infusion, if any. The sponsor should inform all involved parties (e.g., monitors, investigators, pharmacists, storage
managers) of these determinations.
The investigational product(s) should be packaged to prevent contamination and unacceptable deterioration during
transport and storage.
In blinded trials, the coding system for the investigational product(s) should include a mechanism that permits rapid
identification of the product(s) in case of a medical emergency, but does not permit undetectable breaks of the
blinding.
If significant formulation changes are made in the investigational or comparator product(s) during the course of
clinical development, the results of any additional studies of the formulated product(s) (e.g., stability, dissolution rate,
bioavailability) needed to assess whether these changes would significantly alter the pharmacokinetic profile of the
product should be available prior to the use of the new formulation in clinical trials.
Supplying and Handling Investigational Product(s)
The sponsor is responsible for supplying the investigator(s)/institution(s) with the investigational product(s).
The sponsor should not supply an investigator/institution with the investigational product(s) until the sponsor obtains
all required documentation (e.g., approval/favourable opinion from IRB/IEC and regulatory authority(ies)).
The sponsor should:
a. Ensure timely delivery of investigational product(s) to the investigator(s).
b. Maintain records that document shipment, receipt, disposition, return, and destruction of the investigational
product(s).
c. Maintain a system for retrieving investigational products and documenting this retrieval (e.g., for deficient
product recall, reclaim after trial completion, expired product reclaim).
d. Maintain a system for the position of unused investigational product(s) and for the documentation of this
disposition.
The sponsor should:
a. Take steps to ensure that the investigational product(s) are stable over the period of use.
b. Maintain sufficient quantities of the investigational product(s) used in the trials to reconfirm specifications,
should this become necessary, and maintain records of batch sample analyses and characteristics. To the extent
stability permits, samples should be retained either until the analyses of the trial data are complete or as required by
the applicable regulatory requirement(s), whichever represents the longer retention period.
Record Access
The sponsor should ensure that it is specified in the protocol or other written agreement that the
investigator(s)/institution(s) provide direct access to source data/documents for trial-related monitoring, audits,
IRB/IEC review, and regulatory inspection.
Safety Information
The sponsor should promptly notify all concerned investigator(s)/institution(s) and the regulatory authority(ies) of
findings that could affect adversely the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC’s
approval/favourable opinion to continue the trial.
Selection and Qualifications of Monitors
a. Monitors should be appointed by the sponsor.
b. Monitors should be appropriately trained, and should have the scientific and/or clinical knowledge needed to
monitor the trial adequately. A monitor’s qualifications should be documented.
c. Monitors should be thoroughly familiar with the investigational product(s), the protocol, written informed
consent form and any other written information to be provided to subjects, the sponsor’s SOPs, GCP, and the
applicable regulatory requirement(s).
Extent and Nature of Monitoring
The sponsor should ensure that the trials are adequately monitored. The sponsor should determine the appropriate
extent and nature of monitoring. The determination of the extent and nature of monitoring should be based on
considerations such as the objective, purpose, design, complexity, blinding, size, and endpoints of the trial. In general
there is a need for on-site monitoring, before, during, and after the trial; however in exceptional circumstances the
sponsor may determine that central monitoring in conjunction with procedures such as investigators’ training and
meetings, and extensive written guidance can assure appropriate conduct of the trial in accordance with GCP
Audits:Sponsor should perform regular audit duringClinical trial.

Auditing Procedures
a. The sponsor should ensure that the auditing of clinical trials/systems is conducted in accordance with the
sponsor’s written procedures on what to audit, how to audit, the frequency of audits, and the form and content of
audit reports.
b. The sponsor’s audit plan and procedures for a trial audit should be guided by the importance of the trial to
submissions to regulatory authorities, the number of subjects in the trial, the type and complexity of the trial, the level
of risks to the trial subjects, and any identified problem(s).
c. The observations and findings of the auditor(s) should be documented.
d. To preserve the independence and value of the audit function, the regulatory authority(ies) should not
routinely request the audit reports. Regulatory authority(ies) may seek access to an audit report on a case by case
basis when evidence of serious GCP non-compliance exists, or in the course of legal proceedings.
e. When required by applicable law or regulation, the sponsor should provide an audit certificate.
Noncompliance
Noncompliance with the protocol, SOPs, GCP, and/or applicable regulatory requirement(s) by an
investigator/institution, or by member(s) of the sponsor’s staff should lead to prompt action by the sponsor to secure
compliance.
If the monitoring and/or auditing identifies serious and/or persistent noncompliance on the part of an
investigator/institution, the sponsor should terminate the investigator’s/institution’s participation in the trial. When an
investigator’s/institution’s participation is terminated because of noncompliance, the sponsor should notify promptly
the regulatory authority(ies).

 Project management

 Database design & build

 Data entry & validation

 Clinical trial data management

 Medicine and disease coding

 Quality and metric reporting

 Statistical analysis plans and reports

 Validation programming

 Safety and efficacy summaries

 Final study report

 Contract

 Submission for Institutional Review Board or Independent Ethics Committee (IRB/IEC)

approval. In Europe, submission to Ethics Committee is often done by sponsor or by CRO,
i.e. not by SMO

 Patient Counseling

 Patient Recruitment

 Patient Follow-up

 Informed consent form (ICF) translation into vernacular languages[dubious – discuss] . In Europe, this
is often done by the Sponsor or CRO

 Site initiation and trial close-out operations

 Trial-related documents archival and maintenance

 Reporting serious adverse events to the Sponsor or CRO and the IRB/IEC

 Ensuring protocol compliance

 Advising & alerting investigators of potential protocol violations

 Advising & alerting investigators of potential ICH-GCP violations