Вы находитесь на странице: 1из 5

Jules T.

Mitchel, MBA, PhD | Eva Jurewicz, BA | Katie Flynn-Fuchs, MS


PEER REVIEWED

R E S E A R C H
Erin Sharpe, BS | Glen D. Park, PharmD

NEW CAREER OPPORTUNITIES

The Role of CRAs in the

C L I N I C A L
Development and Implementation
of Internet-based Clinical

I N
Trial Applications

C A R E E R S
I nternet-based clinical trials (IBCTs) are radically changing the clinical research
environment. Kelly and Oldham (1997) addressed the barriers to entry for imple-
menting IBCTs, as well as their obvious advantages and potential impact on drug
The goal of this paper is to development. Kuchenbecker, et al. (2001) emphasized the emerging role Internet
technologies for data acquisition in clinical trials and reinforced the concept that
describe…what new career IBCTs can and should be effective in collecting clinical data. The article predicted
the eventual common use of IBCTs in the pharmaceutical industry. Richardson
opportunities are now available (2003) provided specific details on how to plan and execute an IBCT.
When properly designed, IBCT solutions offer a convenient, cost-effective
to CRAs with the advent of approach for clinical sites to enter data, for CRAs to monitor a study, for data man-
agers to more effectively assure data quality, and for project managers to evaluate
Internet-based clinical trials. the study status in “real time” (Mitchel, et al. 2000, 2003a, 2003b). While there are
some intrinsic differences between electronic case report forms (eCRFs) and paper
case report forms (CRFs), visually they should basically look the same. The main
difference is that the eCRF interacts with the user at the time of data entry. For
example, if a value is out of range, the system informs the user to either explain the
value or go back and enter the correct value. There is also no longer a need to ask
the question at each visit, “Was there an adverse event: yes/no?” Instead, there is
usually a single location to report adverse events where the question is asked only
once. If there is more than one adverse event, all the coordinator has to do
is click on the icon that says “Add Another.” There is no need to print pages that
will never be used. The use of radio buttons and drop-down boxes help to mini-
mize spelling errors, and these types of features can standardize the way cer-
tain questions must be answered (e.g., gender is either male or female, with no
abbreviations).
The changing roles of clinical research, data management, and project manage-
ment in the world of IBCTs has recently been described (Mitchel, et al. 2004a;
2004b). The goal of this paper is to describe how the role of the CRA is changing
and what new career opportunities are now available to CRAs with the advent of
IBCTs.

PEER REVIEWED ❘ 17
CRFs in Paper Trials forms associated with the study. With the Currently,when site monitors
advent of IBCTs and Clinical Data
In paper-based clinical trials, CRFs are
Interchange Standards Consortium†,
usually generated by CRAs based on the
companies have begun to enforce com- visit a study site,it is not
protocol, printed on 3-part no-carbon-
pany-wide standards for CRFs. As a
required paper, and then mechanically uncommon to discover that
result, CRAs should now be able to more
bound or placed in binders. A sufficient
quickly put together draft CRFs for the
number of CRFs are shipped to the sites
and the rest are stored for future ship-
development of the eCRF application. the site is not fully prepared
After the draft paper CRF forms are
ments. When the CRFs are received by created, the CRA provides application
the sites, they are filed until used. If there development with: 1) the overall CRF
for the visit ...
are amendments during the study which navigation scheme (the visits and
require a new or revised CRF, new pages the forms associated with each visit);
need to be provided to the study sites. 2) which forms appear only once (e.g. range; if correct, please provide the rea-
This can be a labor intensive and costly medical history); 3) which forms repeat son. If not correct, please go back and
process and can have a large impact on (e.g., adverse events); 4) which forms correct the data).
quality assurance. occur at more than one visit; 5) unique Once application development re-
During the course of a study, as calculations; and 6) any study specific ceives the information from the CRA,
source document verification is com- instructions. Simple edit check specifica- the programmers can begin to generate
pleted for individual CRF forms, the tions can also be generated by the CRA the data entry screens based on the
study monitor removes the original CRF (e.g., if age is less than 18, generate the design of the paper CRF. A sample eCRF
pages and ships them to the home office following message: Patient’s age is out of form is found in Figure 1.
for double-key data entry. Paper-based After application development posts
queries generated during the course of the draft data entry screens on the Web,
the study must be attached to the site’s †
CDISC is an open, multidisciplinary, non-profit the CRA can review them for accuracy.
copy of the CRF, to the original copy at organization committed to the development of All errors and/or modifications are com-
worldwide standards to support the electronic
the sponsor’s home office, and to the municated to the application develop-
acquisition, exchange, submission and archiving of
copy provided to the data entry group. clinical trials data and metadata for medical and ment department, in writing, using
biopharmaceutical product development. For more change management procedures. During
CRF Development in IBCTs information, go online to http://www.cdisc.org. this review period, application develop-
With the advent of IBCTs, CRF develop-
ment is somewhat modified and allows Figure 1. eCRF Form
for new opportunities for the CRAs.
Interestingly, there is now potential over-
lap of CRA functions and traditional
data management. The CRAs now have
an opportunity to be retrained to be part
of the application development and data
management teams. This is especially
attractive for those knowledgeable and
experienced CRAs who, for whatever
reason, prefer not to have the extensive
travel schedules normally imposed on
field monitors.
In an IBCT, there is no need for a for-
mal signoff of a paper CRF, as it is now
the responsibility of the application
development department to finalize the
CRFs. The CRA only has to create a draft
paper CRF, which becomes part of the
application master book. If a company
has a library of CRF forms, it may be as
simple as retrieving the appropriate

18 ❘ MONITOR OCTOBER 2005


Figure 2. Monitoring an IBCT In an IBCT, at the time of source doc-
ument verification and resolution of
outstanding queries, instead of pulling
the original white copy of the CRF, the
field monitor can also have the autho-
rization to electronically review/lock the
form to prevent the site, without autho-
rization, from modifying data after com-
pletion of source document verification.
(Figure 4)
In the event of a query, perhaps gen-
erated by data management or medical
after source document verification, the
form can be unreviewed/unlocked as
many times as necessary until final
database lock at the end of the study.
Each change to the database generates an
automatic audit trail (view only) which
is also displayed on the form level.

Study Management

ment begins programming the online areas which might require additional site Some of the most challenging tasks in
edit checks. Prior to release, the CRA training, or perhaps even modification the management of a clinical trial are the
approves the overall eCRF navigation of the eCRF. Now, when the field moni- determination of the status of enroll-
layout, form content, and edit checks for tor visit the clinical study site, missing or ment, the status of data entry, and what
both accuracy and completeness. If there out-of-range data have already been rec- CRFs have been monitored. When using
are protocol amendments during the onciled in electronic format prior to the a paper CRF, the site is instructed, on a
study, the CRA submits a change request visit. There is no need for the CRA to weekly basis, to send to the CRA, either
to the programming group, the applica- make inquiries at the time of the moni- electronically or via fax, a study enroll-
tion is reprogrammed, and once the toring visit as to why data are missing, ment status. The CRA then transfers
change is accepted by the sponsor, the out-of-range, or inconsistent, since most these data into a functional spreadsheet
change can automatically be displayed at of these issues would have had already for review by the project team. This task
each study site. been resolved prior to the visit via online is labor intensive for both the site and
query management. (Figure 3) sponsor, and the data are often not com-
Monitoring an IBCT
Currently, when site monitors visit a Figure 3. CRAs Can Now Electronically Generate a Query
study site, it is not uncommon to dis-
cover that the site is not fully prepared
for the visit (e.g., the CRFs have not been
updated or even filled out). In paper-
based clinical trials, when the CRA visits
a clinical study site, it is often the first
time the CRA sees the data. In contrast,
in IBCTs there is a record of all forms for
which data have been entered. (Figure 2)
CRAs can now do the initial data
review out of the home office. In fact, a
new job may be created to perform an
online initial data review, including
review of out-of-range data and genera-
tion of queries. The reviewer will also be
able to identify, early in the clinical trial,

PEER REVIEWED ❘ 19
Figure 4. CRAs Can Now Electronically Review a Form there is a clear indication of how many
forms and pages were entered, as well as
the number of pages reviewed by both
the in-field and in-house CRAs.

Training

An experienced CRA with good inter-


personal skills should have the necessary
background to be a IBCT trainer. There
are many users of an IBCT and each user
needs to be trained. Users include, but
are not limited to: 1) clinical site coordi-
nators (data entry and answer queries);
2) investigators (CRF review and elec-
tronic signature); 3) CRAs (source docu-
ment verification and query generation);

plete and accurate. In IBCTs, online man- Both project managers and CRAs can An experienced CRA with
agement reports can include, but are not now assess when to visit the site based on
limited to, enrollment, data entry, moni- the number of CRF pages that have been
toring status, and adverse events. Enroll- entered into the system, but not reviewed
good interpersonal skills
ment data are current, are based on in the field. In fact, based on predeter-
actual patient data and need not be re- mined rules programmed into the eCRF, should have the necessary
entered into a project management soft- electronic alerts can be generated, for
ware. There is no longer a need to request example, that a monitoring visit is due. background to be a IBCT
information from the sites or to reformat Importantly, the entire study team can
faxed information. Of course, if the site have access to real-time status reports. A trainer.
has not entered any data, a phone call will sample status report from an IBCT is
most likely be in order to find out why. illustrated in Figure 5. In the report, 4) data management (data review and
edit check designation); 5) medical
experts (drug safety review); 6) central
Figure 5. Sample Status Report of Data Entry and Data Review
laboratories (data upload); 7) central
readers (blind evaluation of study out-
comes); and 8) project management
(study status and planning).
General and study-specific training
manuals need to be created, including
CRF completion guidelines for each
study. Initial training of the clinical sites
takes place either at the qualification
visit or at the investigator meeting. Fol-
low-up training occurs at the initiation
visit and retraining can occur via Web-
based applications such as WEBEX®.
Demo sites can also be made available
for practice. Training of CRAs can be
done on the day before the investigator
meeting and can also be done using
WEBEX®-like systems. Once a CRA
has experience using an IBCT system,
only study-specific training should be

20 ❘ MONITOR OCTOBER 2005


required. CRAs should be able to fully end up being stuck in the ancient world of 7. Mitchel J, Ernst C, Cappi S, Beasley W, Lau A,
paper CRF-based clinical trials. Kim YJ, and You J. 2004a Implementing Inter-
train the study sites at the initiation
net-based Clinical Trials. DIA Forum. 40:22-23.
visits. 8. Mitchel J, Ernst C, Cappi S, Beasley W, Lau A,
References Kim YJ, and You J. 2004b Meeting the Chal-
lenges of Internet-based Clinical Trials. Applied
Discussion and Conclusion 1. Kelly MA and Oldham J. 1997. The Internet and Clinical Trials. 14:44-53.
Randomised Controlled Trials. International
IBCTs are here to stay with more rapid Journal of Medical Informatics. 47: 91-99.
acceptance due to the introduction of 2. Kuchenbecker J, Dick HB, Schmitz K, Behrens- Jules T. Mitchel, MBA, PhD, is President of Target
user-friendly software which is replacing Baumann W. 2001 Use of Internet Technologies Health Inc., a NYC-based full-service CRO. Previ-
some of the early cumbersome systems. for Data Acquisition in Large Clinical Trials. ous positions include Ayerst Laboratories (now
Telemedicine Journal and e-Health. 2001:73-76. Wyeth), Pfizer Laboratories, Pfizer Consumer
While there will be those who will prefer 3. Richardson A. 2003. Planning and Running the Health Care, and academic positions at NY Medical
using paper CRFs, at least in the short run, e-Clinical Trial.” Applied Clinical Trials. January College, Cornell University School of Medicine and
it will be a losing battle. Job descriptions 2003; 28-34. NYU School of Medicine. He can be reached at
will be changing and already the role of 4. Mitchel J, You J, Lau A, and Kim YJ. 2000. Paper julesmitchel@targethealth.com
double-key data entry has been eliminated Versus Web; A Tale of Three Trials. Applied
Clinical Trials. August 2000, 34-35. Eva Jurewicz, BA, is a CRA at Target Health Inc.
in many companies. CRAs are in a unique
5. Mitchel J, You J, Lau A, Kim YJ, Cheng L, Fein S,
position to be retrained both in the way and Nardi R. 2003a Clinical Trial Data Integrity. Katie Flynn-Fuchs, MS, is a CRA at Target Health
clinical trials are monitored as well as in Using Internet-Based Remote Data Entry to Inc.
the development and implementation of Collect Reliable Data. Applied Clinical Trials. Erin Sharpe, BS, is a CRA at Target Health Inc.
IBCTs. There are ongoing radical shifts in March 2003 (Supplement, 6-8).
6. Mitchel J, You J, Kim YJ, Lau A, Levinson B, Glen D. Park, PharmD, is Sr. Director and Clinical
roles and responsibilities in the clinical
Lynch S, O’Connor P. 2003b. Internet-Based and Regulatory Affairs at Target Health Inc. Dr. Park
trial arena. Those individuals and compa- Clinical Trials—Practical Considerations. Phar- has 17 years of experience in the pharmaceutical
nies who can clearly see what is happening maceutical Development and Regulations. industry and 9 years of experience in clinical phar-
will quickly outpace the laggards who will 1:29-39. macy academia/practice.

PEER REVIEWED ❘ 21

Вам также может понравиться