eSolutions to Meet FDA Requirements to Maintain Adequate Records (Part 6 of 6)

This post is the final of a 6 part series. Visit weekly or enter your email to subscribe.

FDA “… recommends that clinical data be entered electronically by study site personnel at the time of the subject visit to avoid transcription from unnecessary paper records1. The acronym “ALCOA” is frequently used in reference to best practices related to source documentation. When eSource solutions are selected and developed appropriately, data is attributable to a unique user with a secure password and role-specific privileges; legible in a clean and easy to read standardized format; and contemporaneous with a date and time stamp for every entry/edit/modification. Original records initially captured electronically can include direct entry of clinical data into a study database, data transmitted from an electronic health record, and electronic diary data entered by a subject or transmitted from an automated instrument that captures a biological result. eSource provides the opportunity to engineer accurate data with boundary and edit checks for missing and/or out of range data devoid of contradicting information often represented by subjective reporting in an unstructured format.

To minimize risks related to FDA requirements to keep accurate records and protect human subjects, sponsors using electronic source solutions should keep records of:

  • system validation and maintenance,
  • system specifications showing customization to fit the eSource for the purpose of the study,
  • 21 CFR § 11 compliance and
  • data integrity practices.

Ultimately, the same system development collaboration and documentation intended to manage risk, will have the added benefits of quality design, validated performance and accurate data capture with electronic efficiencies that reduce data noise, facilitate analysis and expedite time to data lock…and that’s what is best for patients.

eSource Best Practices
1Guidance for Industry Electronic Source Documentation in Clinical Investigations Draft Guidance. U. S. Department of Health and Human Services, Food and Drug Administration, Office of the Commissioner. December 2010. Retrieved October 23, 2012 at…/Guidances/UCM239052.pdf


eSolutions to Meet FDA Requirements to Maintain Adequate Records (Part 5 of 6)

This post is Part 5 of a 6 part series. Visit weekly or enter your email to subscribe.

FDA guidance suggests sponsors should include information about the intended use of computerized systems in their data management plan. Compliant with 21 CFR part 11, this data management plan should also describe the “security measures employed to protect the data and a description of the flow of electronic data”1. In the workflow demonstrated in the Figure below, note that a unique user name and password is required to access the system. Each user is associated with a user group and each user group is limited to specific roles/functions within the eSource. The user activity is date and time stamped in real time and an audit trail serves as the automated documentation of who did what, to whom and when.

Figure 3 

eSource systems/vendors should:

  • support controlled and secure access typically by
    • a username/ ID and password,
    • user roles,
    • role-specific privileges,
    • data encryption, and
    • workflow
  • create and maintain an audit trail of data entry and data revisions including
    • the “old” value,
    • the “new” value,
    • date and time stamp,
    • and the user who entered/changed the data
    • reason for the data edit
  • have a provision for data transfer and storage for the time required by the regulations

to be continued…

1 Guidance for Industry Electronic Source Documentation in Clinical Investigations Draft Guidance. U. S. Department of Health and Human Services, Food and Drug Administration, Office of the Commissioner. November 2012. Retrieved December 18, 2012 at






eSolutions to Meet FDA Requirements to Maintain Adequate Records (Part 4 of 6)

This post is Part 4 of a 6 part series. Visit weekly or enter your email to subscribe.

Electronic diary solutions are typically customized software programs built with rules and edit checks that can track compliance, facilitate efficiencies and significantly reduce queries. Electronic boundary and edit checks should be used to minimize errors and omissions at the time of data entry. Additionally, an eDiary solution can include a subject dosing screen to capture required investigational product administration as well as software customization to prompt the subjects to complete missing data before allowing them to move from one question or screen to the next. Electronic diaries can include fields to “record storage temperatures of study medication that was stored in subjects’ refrigerators”1 in compliance with storage condition requirements specified by the protocol. Likewise, drug administration screens can be linked to drug inventory management systems to meet the FDA requirement to maintain adequate records of the disposition of the investigational drug (21 CFR §312.62(a)).

When implementing electronic edit checks, user acceptance testing should be a priority to ensure business logic and protocol driven rules fit the purpose, prevent duplicate entry, make sense to the user and do not conflict. For example, it would be confusing for a patient who identifies himself in the eDiary as male to be asked about his pregnancy status. Data elements that are captured more than once should auto populate when the data is static (i.e. date of birth), but require a new entry for data expected to change (i.e. weight). Electronic triggers should be tested to avoid conflict and verify missing or out of range data. Device logic that requires the patient to answer a question about climbing stairs before moving on to the next question should have an option to indicate a reason for leaving the question blank. In this example, the patient may be in a wheelchair, or may not have climbed any stairs in the applicable timeframe for the interval questionnaire. In another example, an electronic rule that requires the patient to complete a “visit 2” diary before allowing access to “visit 3” diary data entry could be problematic when the patient may have missed or skipped their second visit or the allowable time window to enter the visit 2 information. Sponsors should include information on electronic prompts, flags, and data quality checks that are designed to address data inconsistencies, missing data, and entries out of range in their data management plan so that it is available for FDA inspection.2

to be continued…

1 FDA Warning Letter Ref. No. 06-HFD-45-11. Retrieved October 25, 2012 at

2 Guidance for Industry Electronic Source Documentation in Clinical Investigations Draft Guidance. U. S. Department of Health and Human Services, Food and Drug Administration, Office of the Commissioner. November 2012. Retrieved December 18, 2012 at



eSource in Clinical Trials: A brief overview

Many clinical trial teams are tiptoeing into the world of eSource, anxious to reap the benefits, yet uneasy about the impact.  To many, the unknowns seem daunting and overwhelming, and maybe not worth the effort.  To those who have taken the plunge, the value to the study team has far outweighed the initial investments.  This blog is geared to address the typical concerns: What is Source? Why eSource?  What problems are solved with eSource?  What are the potential gotchas?  What is the impact on the study team? and What does the FDA say about all this?

According to the FDA, “initial documentation of data in a clinical study is considered Source documentation or Source data”.1  This is a fairly straight-forward concept.  The source data and documentation is the original record of a data element, and integrity is maintained by using an audit trail to track any changes and modifications.

Now, introduce electronic source “eSource”.  For all intents and purposes, the definition is the same, except the original record is captured electronically.  This excludes source data that was captured on paper and transcribed into an electronic database.  eSource is true to its name and the source data element itself must be electronic; and must be followed with a detailed audit trail as well.

On the face, the benefits are obvious.   The FDA promotes eSource in clinical studies because it will help to:

  • “eliminate unnecessary duplication of data,
  • reduce the opportunity for transcription errors,
  • promote the real-time entry of electronic source data during subject visits, and
  • ensure the accuracy and completeness of data (e.g., through the use of electronic prompts for missing or inconsistent data).” 1

The advantages can go further than even those stated above.  Let’s take a few examples:

Example 1:  A patient receives an infusion treatment for a study drug.  During her visit, all data (vital signs, concomitant medications, infusion data, etc) is captured electronically.  That night the patient has a serious adverse event which results in a trip to the emergency room, and the study investigator is contacted.  The beauty of having the patient’s most recent visit captured electronically is that the investigator has immediate access to the day’s treatment details (along with previous treatments) directly at his fingertips.  If data relating to the infusion treatment was captured on paper, the investigator, at best, might have access to a chart at the infusion clinic.   When time is critical, paper is not the answer, and can potentially jeopardize the patient’s safety.  Using eSource allows the data to be accessed and assessed in real time.  Any subsequent events relating to the emergency room visit can too be captured electronically and automatically disseminated to key team members.

Example 2:  A patient reports symptoms on an electronic diary that are undesirable.  The study staff is automatically notified via email.  If this were collected on paper, the patient would report the symptom, and would likely not get any resolution until a site visit sometime in the future.  Their recollection of the undesirable symptom or event will not be as clear as it was when originally reported.  Using eSource allows the study staff to determine the severity in real-time and follow-up as needed.  Any subsequent contact with the patient regarding the undesirable symptom can too be captured electronically and automatically shared with key team members.

From a data manager’s point of view, eSource can solve a multitude of problems, most notably consistency of data (pre-defined medication lists for example) and access to data as described above. The key is to avoid any potential gotchas relating to the integration of data with an existing study database (or EDC system).  Every study team desires consistency and is not necessarily gung-ho about introducing another system/website/database into a study.  This is one area where things can get complicated.  If it is the study teams’ wish to use eSource, there must be a backend designed to integrate the eSource data into the existing database or EDC system.  Audit trails must remain intact, and query processes must be clearly defined.  What good is an eSource system if team members cannot use it seamlessly with study data reported into other system(s)?

The obvious benefit to any study using eSource is quality and access to data.  The access to ongoing, real-time data can speed the overall process an average of 6 months.  Since drug approval is what sponsors are after, this cannot be ignored.   Equally as interesting is the substantial cost savings.  If a true eSource solution is used, all transcription and source data verification costs are eliminated.  This can cost upwards of $15 per page (CRF and non-CRF data).  You do the math; the savings are significant.  Just as noteworthy is the fact that data can be monitored remotely and queries fall, on average, by 70% (headaches and frustration decrease at the same rate!).

Although the FDA’s guidance on eSource is still in its “draft” stage, the implication is clear.  The FDA appears to support the collection of source data electronically as a means to promote accuracy, integrity, traceability, and completeness of data.  If your team is still tiptoeing around this powerful movement in clinical trials, consider starting with an eSource solution that collects primary endpoints electronically and integrates directly with a database that your team is confident using.  Work out the kinks and transition to using eSource to capture all data elements once you’ve gotten your feet wet.

  1.  U.S. Department of Health and Human Services, Food and Drug Administration (December 2010).  Guidance for Industry:  Electronic Source Documentation in Clinical Investigations.  Available at