During 2002, the Clinical Data Interchange Standards Consortium (CDISC) and CenterWatch, the Clinical Trials Listing Service,
undertook a survey on the adoption of, and attitudes to, electronic data capture (EDC) within the biopharmaceutical industry.
The survey revealed that one of the biggest factors slowing the uptake of EDC was the concern over how to interpret the various
regulations and guidelines.
One particular area of uncertainty is the use of electronic patient diaries (ePDs) and how such systems meet the regulations
regarding source data and source documents. While ePDs are in their relative infancy compared with electronic case report
forms (eCRFs), their use within clinical trials is on the increase, and there has been some concern expressed about their
compliance with the regulations.
The aim of this article is to examine the issue of ePDs and source data by reviewing the regulations and proposing a practical
solution. The solution proposed is not an end in itself; it is there for illustrative purposes and to show that there are
practical ways of solving the problem. This solution is not proposed as the best, nor is it the only possible solution. It
is presented to provide a starting point for constructive discussion and debate on an issue that, in the opinion of the author,
is slowing the acceptance of a technology that can aid and speed the drug development process.
Regulatory background The requirements relating to source data are to be found within two Food and Drug Administration (FDA) documents, 21 CFR Parts
11 and 312,1,2 and also in the International Committee on Harmonization's (ICH) Good Clinical Practice (GCP) guidelines.3
In addition to the regulations, the FDA has issued the Guidance for Industry, Computerized Systems Used in Clinical Trials
(CSUCT).4
Two important definitions are found within the ICH GCP document for source data and source documents:
Source Data-All information in original records and certified copies of original records of clinical findings, observations,
or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained
in source documents (either original records or certified copies).
Figure 1. Local server with a disconnected ePD. This option relies on the device being "docked" at intervals to allow connection
to the investigator's local PC or server and Figure 2. Central or trusted server with a disconnected ePD. This option, too,
relies on the device being "docked" at some point to allow connection to the server.
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Source Documents-Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes,
memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments,
copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm
or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments
involved in the clinical trial).
When subjects use ePDs, they enter data directly into an electronic system; no paper is employed. It is here that we encounter
eSource. eSource is defined in eClinical Trial's Planning and Implementation8 as:
"Source data (per ICH) captured initially into a permanent electronic record."
It is this initial storage in electronic form, rather than paper, that sits as the center of the eSource debate.
Practical considerations Three storage locations for data entered by an investigator into an eCRF have been noted previously.5 These repositories are
equally applicable to subject-reported data:
- the data is stored locally on the investigator's own PC or a server on his or her own network-the local model;
- the data is stored on servers operated by the sponsor or an Application Service Provider (ASP) acting on behalf of the sponsor-the
central model; or
- the data is stored on servers held by a Trusted Third Party (TTP)-the trusted model.
When considering the three scenarios from a practical rather than a regulatory perspective, the central model and the trusted
model are essentially the same in that the servers are remote from both the investigator and the subject. It is worth noting
that the two models were distinguished over concerns regarding the attributability of the data and over the ability to modify
the data without the knowledge of the investigator.5
The combination of these scenarios and the myriad of technologies offered by the ePD vendors can result in a complex picture.
To aid the discussion within this article, the ePD technologies have been placed into three categories:
Connected, where the subject has to be connected to the server for the entire session while data is entered. Examples of connected
systems are a Web site that captures subject data or a telephone using an interactive voice response system (IVRS).
Semiconnected, where the data is stored on a device before being sent to the server at frequent intervals (daily or overnight).
An example is a personal digital assistant (PDA) equipped with mobile data communications capability or a dial-up modem connecting
over a telephone line.
Figure 3. Central or trusted system with semiconnected or connected ePD. Connection is via fixed line, mobile or wireless
communications links (possibly utilizing the Internet) to the server and Figure 4. Logical data flow model.
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Disconnected, where data is stored on a device with the device having no communication ability of its own. Data is only passed
from the device to a server when a connection is made, generally at infrequent intervals (for example, on a visit to the investigator
or at the end of the study). An example is a PDA that can only communicate when it is docked in a cradle connected directly
to a PC.
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