sponsor support for the quality of site management - Drug ...

Drug Information Journal, Vol. 34, pp. 1303–1308, 2000 0092-8615/2000
Printed in the USA. All rights reserved. Copyright © 2000 Drug Information Association Inc.
CLINICAL STUDY PREPARATION:
SPONSOR SUPPORT FOR THE QUALITY
OF SITE MANAGEMENT
C. I. CORDARO
Bracco S.p.A., Milan, Italy
G. TABUSSO
Regulatory Consultant, Milan, Italy
This paper provides an overview of the role of the sponsor in supporting and improving
quality in the conduct of a trial through improved performance at the site. Critical issues
reside in ensuring standardization of performance at all sites, hence homogeneous and
unbiased results. Sponsor responsibilities in this process mainly include preparation of
a feasible protocol, care in ensuring that personnel are qualified and trained, providing
a communication and information network, and definition and enforcement of standards.
A leading function is played by study monitors whose role is evolving into processmanagers
who are no longer confined to data verification. In such a context, the monitor’s
careful analysis of microactivities at the site substantially facilitates implementation of
a system aimed at preventing performance deficiencies and delays.
A key to success is commitment to the project by all involved parties, not only
the company and the investigator, but also hospital staff, monitors, clinical research
organization (CRO) personnel, and patients. The sponsor’s support in organizing and
coordinating teams with different levels of responsibility, either managerial or operational,
facilitates harmonized behavior, integrated communications, recognition of each member’s
role, and ultimately improved global performance and quality.
Key Words: Quality; Clinical trial; Sponsor
INTRODUCTION of quality management which are relevant
IN A WORLD OF INCREASING demands,
quantitative aspects of a clinical trial, such
as the mass of data to be collected, the redun-
dance of investigational centers, and the need
to meet predetermined deadlines and objec-
tives, often overwhelm qualitative features.
Nevertheless, quality is the leading concept
in clinical research, and it is mandatory to
reconcile quantity with quality. It is, there-
fore, essential to define the basic attributes
for building quality into a trial (1). It is
known that the outcome of a study derives
from a multidisciplinary and multifaceted effort
involving many players, all of whom
contribute to quality in an interactive manner:
the sponsor, the CRO, the hospital staff,
and the patient (Figure 1).
In multicenter studies, the overall quality
of the trial depends on the average quality
of the performance at each of the study sites.
Therefore, the focus should be on the quality
of the study conduct at each single site. Yet at
Reprint address: C. I. Cordaro, Bracco SpA, Medical & the site, there are numerous parties involved,
Regulatory Affairs, Via Folli 50, Milan 20134, Italy. where responsibility is segmented according
1303

1304 C. I. Cordaro and G. Tabusso
FIGURE 1. A high-quality study relies on an interactive multidisciplinary effort of all
the involved parties.
to the specific function: principal investiga- sponsor during the design, preparatory activi-
tor, coinvestigators, nurses, administrative ties and implementation of a clinical study.
staff, laboratories (if not centralized), phar- Ensuring that the investigator, hospital staff
macist or drug dispensing person, the institu- and IRBs pursue strict observance of Good
tional review board (IRB), and the monitor Clinical Practice (GCP) requirements must
of the sponsor company or of the clinical
research organization. The global responsi-
be a primary sponsor concern (2).
bility, however, rests with the sponsor which
must support and coordinate the activities
of the various parties to a successful global
performance (2). Stemming from models
rooted in past experience, innovative techni-
cal and managerial approaches may be de-
vised to improve study conduct. This paper
is not aimed at presenting a complete manual
for clinical research, but rather at highlight-
ing a number of points critical to the quality
of the study.
The Protocol and the Case Record Form
One of the most effective means of prevent-
ing potential complications is to identify the
most adequate study design to verify the test
hypothesis (3,4). The protocol should define
clear and measurable objectives and should
not try to prove too many hypotheses.
Involvement of actual investigators through
an early investigators’ meeting may provide
a valuable contribution in verifying the target
population, and confirming the study design,
POINTS TO CONSIDER WHEN
PLANNING A MULTICENTER
CLINICAL STUDY
the clinical parameters to be measured, and
the assessment methodology.
A complex and not straightforward protocol
may introduce interpretative uncertain-
The quality of the site management depends ties. Furthermore, all the parts of the protocol
on planning activities in the framework of not directly related to the study conduct, such
specific processes, as well as on implementa- as administrative parts and general information
of a system aimed at preventing deficien- tion, may be assembled in a separate section.
cies. A number of critical issues contributing In any case, flow charts showing the se-
to the quality of the site management (Figure quence of activities will be of help to the
2) should be taken into consideration by the
involved staff in understanding the protocol

Sponsor Support for Quality Clinical Site Management 1305
FIGURE 2. Critical elements requiring coordination and support by the sponsor.
requisites. Paying a visit to the ward and quence of events to answer the study ques-
understanding responsibilities, activities, and tions is pivotal for improving study quality
roles within the department will facilitate and protocol compliance. The CRF should
generation of a feasible protocol.
be structured in such a way as to avoid over-
For a study to become successful, two load of information and to optimize real time
main objectives must be pursued: 1. assess- data collection and unbiased data processing.
ment of feasibility at all sites, and 2. homoge- To facilitate documentation and processing
neity of data collected (Table 1). The latter of data, the site’s customary source documen-
is closely related to homogeneity of study tation should be checked and verified versus
conduct, and leads to reduced deviations, vi- the CRF data to be collected. If no source
olations, and errors. To prevent misunder- document contains the requested informastandings
and inconsistencies, a true agreetion, appropriate notes that will become offiment
on the protocol scope and structure of cial hospital notes and source documents for
the study design, as well as on trial methodology,
should be reached between sponsor,
the study should be prepared.
CRO, and staff at the site.
A user-friendly case record form (CRF) Personnel and Communication
focused on essential information and the se-
It is a sponsor’s responsibility to guarantee
adequate and qualified resources, therefore,
TABLE 1
Factors Relevant to a
Feasible Protocol and CRF
trained and experienced investigators and
monitors should be selected (5). Where necessary,
specific and effective training should
be provided. Training tools, including video-
Study Planning
Selection of an adequate study design
Involvement of investigators in the design of
the protocol/CRF
recorded instructions and coaching by senior
officers, would be desirable for qualifying
junior coinvestigators or monitors.
Feasibility of the schedule of events A team approach is useful to improve effi-
Optimization of data to be collected by a
user-friendly CRF
Identification of recruitment possibilities
ciency, to foster harmonized behavior, and
ultimately, to improve quality. These teams
should include key persons at different levels

1306 C. I. Cordaro and G. Tabusso
and from different structures, such as a spon- of quality standards to be followed. Once the
sor/CRO team with managerial tasks, or a protocol and the basic concepts have been
CRO/sponsor/hospital staff team with opera- defined, the application phase, aimed at
tional objectives (6,7,8). The sponsor’s ef- achieving standardization of trial methodolforts
should be devoted to creating a con- ogy, begins. This phase principally covers
structive, motivated environment leading to materials, instruments, methods, and instruc-
integrated communications (Table 2) (8,9). tions. At this point, among the critical issues
Realization of these conditions ensures to be considered the following can be countthat
each person involved feels like an active ed: availability of Good Manufacturing
and respected player in the project; this also Practice (GMP) clinical material; labels in
contributes to consistent and accurate perfor- compliance with the relevant regulatory remance
in terms of quality and timing. Supquirements; organization of specimen collecportive
participation of the sponsor’s manag- tion and handling, labeling, and shipment
ers in team activities substantiates the interest where necessary; homogeneity of methods;
of the company in the project and fosters a instrumentation and standards; equipment
collaborative attitude (10).
calibration; and adverse events reporting.
Appropriate communication should be Comprehensive instructions prepared by
valued and the exchange of information the company should be carefully reviewed
should be facilitated, taking advantage of in conjunction with each investigator and rel-
electronic technology and networking, such evant hospital staff to identify site-specific
as online data transfer among team members, adjustments which facilitate compliance,
centralized safety data mapping, and infor- without jeopardizing homogeneity of data
mation technology support for project coor- generation and handling. It is, therefore, fun-
dination and status tracking, and so forth damental that the monitor understand the
(7,8,9). specific hospital system, and ensure that the
instructions are adapted to the processes and
The Processes
the organization of the site. He/she must understand
the roles and responsibilities of the
Before any study starts, critical paths need hospital staff and identify who could perform
to be identified both inside and outside the the relevant task to avoid out-of-scope per-
company. Internal and external activities are formance or nonperformance. He/she should
usually identified by a sequential and interac- become familiar with individual site organi-
tive sets of tasks which can be classified as zation, documentation, and procedures. He/
conceptual and applied. The conceptual as- she should also become acquainted with the
pects cover protocol outline, feasibility as- structure and format of hospital patient recsessment,
protocol discussion, and definition ords to easily identify medical history, concomitant
medication, adverse events, and so
TABLE 2
Key Elements for a Collaborative
and Integrated Environment
forth. Later on during the study, this will
allow for a correct source data verification
and scrutiny of adverse events. A flow chart
of specified processes, that is, patient man-
A Team Approach
Empowerment: Project leader and team are
responsible for management and outcome
Commitment on the project
Shared responsibility
Integrated communications
agement, handling of clinical trial material,
record keeping, drug dispensing, blood col-
lection and shipment, and lab data medical
evaluation, should be prepared, and written
directions left with the site staff.
Recognition of each member’s role
Value of intense goal and action-oriented
activities
At the site, a dedicated full-time study
coordinator is the backbone of a clinical trial.
This is particularly true for Europe where

Sponsor Support for Quality Clinical Site Management 1307
most trials are conducted in state-run venues to the follow-up visits, will increase global
and investigators and hospital staff are state
employees and part-time researchers. Briefing
the hospital staff and rehearsing each sin-
protocol compliance.
gle process in the development of a clinical
trial facilitates procedural compliance. Re-
CONCLUSION
hearsal should be performed with all of the All of the conceptual and operational aspects
involved personnel, that is, nurse, coinvesti- that contribute to building quality into a study
gator, referring department physician, and must be predisposed by the sponsor in such
principal investigator. a way that quality becomes an intrinsic value.
The “hidden” hospital staff, that is, those A well-thought out, feasible protocol and an
involved in activities not immediately visible easy-to-use CRF, availability of communicaat
the department, are to be taken into consid- tion technology, and care for those coneration.
The nurse or the person who collects ducting the trial are basic elements of the
blood, the administrative person who for- sponsor’s support. Optimization of the involvewards
the specimen via courier to the central ment of all of the personnel participating in
lab, the pharmacist and drug dispensing per- the study through a team approach with the
son, and the administrative person in charge company, CRO, and investigational sites, will
of the document tracking and archiving contribute to achievement of a quality and sucshould
all be briefed. The relevant flow chart cessful study. In this framework, the study
of activities could be of help for the various monitors’ role is prospectively evolving from
segments of the processes. checkers of documents and data into process
What are generally thought to be trivial managers acting as coordinators of all pertinent
operation details, such as collection of blood,
centrifugation and handling of samples for
shipment, archiving results into the appropriate
activities at the site.
file, and collecting safety lab results should not
be disregarded. Negligence in these operations
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