Study Documentation FAQs
General study documentation
Reference our Good Documentation Practices page for more information.
Reference our Source Documents and Source Data page for more information.
A certified copy is “a copy (irrespective of the type of media used) of the original record that has been verified (i.e., by a dated signature or by generation through a validated process) to have the same information, including data that describe the context, content and structure, as the original” [1]. In other words, a certified copy is a copy of an original document that has been validated as an exact copy (with identical information and attributes).
Recall that Good Clinical Practice (GCP) and Good Documentation Practices call for the maintenance of original source documentation.
Certified copies of originals are generally accepted as source documentation, but only when they are certified. Certification minimally involves reviewing the integrity of a paper or scanned copy to verify the document’s integrity, ensuring that no information has been deleted or altered, and documenting that verification has occurred via signature and date. All other applicable site-specific standard operating procedures and/or study-specific operation manuals that further define the verification and certification process should also be followed. [2,3].
References:
- International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) – Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2). (2016, November 9). Retrieved March 30, 2020 from the ICH
- Mathieu, M (ed.). (2009, May). Good Clinical Practice: A Question & Answer Reference Guide. Needham, MA: Barnett International.
- WCG CenterWatch. Ask the Experts: Certifying and Maintaining Copies of Original Source Documents. Retrieved May 24, 2022 from CenterWatch
The certification process is required when copies of source documentation are maintained in lieu of originals for research regulated by the Food & Drug Administration (FDA). For all other research, this process is considered good practice.
Documentation of errors, deviations, and non-compliance
We’re human so mistake happens but when it comes to study documentation, it’s important to correct mistakes appropriately in order to maintain the integrity of the data maintained within the document. The key to correcting a mistake appropriately is maintaining an audit trail of edits–it should be clear what the original entry was, who made the edit, when the edit was made and why.
OHSP Policy 901: Investigator Responsibilities states: “Changes to study records should be traceable, should not obscure the originally entry, and should be explained if necessary (e.g., written revisions to study records should be made with a single-line through the original entry and the correction should be dated and initialed)”.
Therefore, in accordance in OHSP Policy 901, as well as in accordance with Good Clinical Practice (GCP) guidance and Good Documentation Practices:
- Written errors should be corrected by drawing a single line through the error, noting the correction, signing (or initialing) and dating the revision (see the example in below).
- An explanation of the revision should be provided when the reason for the revision is not obvious (e.g., something that cannot be verified against other source documentation) and/or if the revision involves removing (deleting) information.
- Do not use white-out, redact or otherwise obliterate information that requires correction.
- Do not destroy original documents that require correction.
- Do not back-date corrections; the date identified as the date of correction should reflect ‘real time’.
A note to file (NTF) or memo to file is a type of study documentation used to explain discrepancies or provide additional information about issues that arise during the lifecycle of a study. These issues typically involve deviating from the study protocol or other standard practices, or missing, delayed or incomplete data. When used appropriately, NTFs can be useful in reconstructing how a study was conducted. [1,3]
Unfortunately, NTFs have become a ‘go to’ solution for addressing errors. Simply identifying an error in a NTF alone does not equate to adequately addressing the issue. Nor does a NTF change or erase the issue or error that occurred. Once written, a NTF becomes part of the study record; it cannot be withdrawn or omitted. Misuse and overuse of NTFs accomplishes little more than demonstrating a site’s poor performance. It effectively provides a road map of a site’s faults for any monitor, auditor or inspector to review. [1, 2, 3]
A first step in preventing the need for NTFs is to build quality practices into a study from the start. This could include:
- Training on protocol adherence and good documentation practices;
- Thoroughly planning and evaluating study documentation prior to study initiation; and
- Conducting routine internal monitoring to identify/prevent issues proactively.
When and if an error occurs during a study, it is best practice to determine the most appropriate method of documenting the error, based on the nature of the incident, prior to committing to a NTF. In some cases, it may be more appropriate to document the error and subsequent correction directly in the source documentation (e.g., below the signature blocks of a consent form or in the ‘Notes’ section of a data collection form). In other cases, it may be worthwhile to keep a protocol deviation log for documenting minor deviations that don’t impact subject safety or data integrity. This is especially useful when conducting complicated, procedure-intensive or longitudinal research.
If it is determined that a NTF is necessary:
- Include the protocol number, subject ID, a description of the incident (including why it occurred), and any corrective action and preventative action taken to address the root cause of the incident, signature of individual writing the NTF, and date. [1]
- Review and discuss the NTF with the study team to prevent similar incidents in the future.
- Ensure the NTF is clear, accurate, relevant, provides appropriate detail and timely. Ensure that the information provided in the NTF does not contradict other study documentation.
- File the NTF with applicable study documentation, in either the subject or regulatory file.
- Monitor all NTFs generated to ensure preventative action measures are appropriately implemented and to assess for larger patterns or trends that may require protocol and/or procedural modifications.
An editable NTF template can be found on our Templates page.
References:
- Mathieu, M (ed.). (2009, May). Good Clinical Practice: A Question & Answer Reference Guide. Needham, MA: Barnett International.
- Anderson, C. (2008, March 1). Note to Self: No More Notes to Self. Applied Clinical Trials. Retrieved May 24, 2022 from: Applied Clinical Trials
- Hazra, A. (2011, January-March). Use, Abuse and Misuse of Notes to File. Perspectives in Clinical Research, 38-40. Retrieved May 24, 2022 from: National Library of Medicine
Federal regulations require investigators to carry out research in compliance with the protocol approved by the Institutional Review Board (IRB), but research occurs in the real world, deviations from what is stated in the approved protocol happen.
These deviations (also referred to as protocol non-compliance, protocol non-adherence and protocol violations), however, can lead to issues regarding subject safety, data integrity and the outcome of the research. Therefore, it is important to document all deviations from the approved protocol.
Best practice is to use a protocol deviation log to document non-compliance from the protocol that occurs throughout the study.
Examples of protocol deviations (or non-compliance) include:
- Investigational product dosing errors
- Consenting errors
- Out of window visits
- Missed study assessments
- Incomplete or missing data collection forms
The following information should be noted on a protocol deviation log:
- Description of the deviation
- Date the deviation occurred
- The reason the deviation occurred
- Date the IRB was notified (as applicable) – Each protocol deviation should be evaluated to determine who needs to be notified (e.g. IRB, sponsor, funding agency)
- The Principal Investigator’s acknowledgement with their signature and date reviewed
Study teams should routinely review protocol deviations to consider whether events are a single occurrence or a systemic problem. While a single occurrence may be explained by the reason the deviation occurred, systemic problems may require an analysis of the problem and implementation of a corrective and preventative action plan (CAPA) to alleviate the likelihood of the deviation being repeated.
Ensure your CAPA is EXACT: Examine root cause, eXecute specific plan, Adequately document action, Carry out for current and future protocols, and Timely follow up to ensure plan is still effective. This is a long-term solution that prevents reoccurrence, should be measurable, and documented.
An editable protocol deviation log can be found on our Templates page.
Note: A protocol deviation log should not be confused with a Report of New Information (RNI) or any other research event that is reported to the IRB. All adverse/research events should be reported to the Reviewing IRB per their policies and procedures.
For additional information, reference:
- OHSP Policy 801: Reporting Research Events
- OHSP Guideline for Reporting Research Events
- OHSP Policy 802: Non-Compliance in Human Subjects Research
Miscellaneous documentation FAQs
‘Tracked changes’ is a tool available within Microsoft Word that, when turned on, shows all revisions and additions made to an existing document. Utilizing the tool facilitates review of revised documents by research colleagues, study team members, project managers, and Institutional Review Board (IRB) staff/members by pinpointing the exact changes made to the document. Instructions on how to turn tracking on/off and other functionalities related to the tool are readily available through Microsoft Office and internet searches.
A curriculum vitae (CV) is your professional biography; it is a document used to showcase your professional activities, experience, skills, and accomplishments. Traditionally, CVs are used to apply for academic, scientific or research positions or when applying for grants and fellowships. In the conduct of human subject research, CVs are also used to as a method for demonstrating Investigator and study staff qualifications.
Recall that Food & Drug Administration (FDA) regulations specifically require Sponsors to “select only investigators qualified by training and experience…” and to collect each participating Investigator’s CV (21 CFR 312; 21 CFR 812). Similarly, Investigators conducting FDA-regulated research are required commit to supervising the conduct of the research, which includes, as per FDA Guidance on Investigator Responsibilities, appropriately delegating study-related tasks based on education, training, experience, and potentially licensure. CVs are then used as means to demonstrate compliance with these requirements.
So, who needs to maintain a CV?
For FDA-regulated research (research involving drugs, devices and biologics), all members of the study team designated to perform study-related procedures (i.e., individuals directly involved in performing study procedures, collecting data, making study-related decisions, or are otherwise identified on a Delegation of Authority Log) need to maintain a CV as part of their regulatory file.
For all other research, maintaining team members CV is good practice. Of note, OHSP Policy 901: Investigator Responsibilities also requires all Investigators to delegate research activities appropriately as described above; this responsibility is not limited to FDA-regulated research only.
How do I write a CV?
Templates and guides for writing a CV are readily available on the internet. E.g., the Office of Faculty Academic Affairs.
Do I need to sign and date my CV?
Neither FDA regulation, nor FDA guidance specify that a CV must be signed and dated. Some Sponsors however, will require that the CV be signed and dated (with a wet signature) to confirm the date and ownership of the document.
Although not new to research, the onset of the COVID-19 pandemic forced many sponsors and coordinating centers to re-think their monitoring approaches, specifically their level of and ability to perform remote monitoring. As a result of this, study teams may now find themselves with the time-intensive task of providing monitors with redacted source documentation for the purpose of source data verification. When/if you are asked to do so, attention must be paid to the redaction process as it is prone to error.
To minimize errors, export (or print) applicable files to PDF and use Adobe Pro to redact identifiable content (instructions are available from Adobe). As part of this process:
- Use the ‘search and remove text’ function to ensure all identifiers are found and redacted. Search multiple iterations of names, nicknames and other applicable identifiers (e.g., search Michael, Mike, and Smith for a patient named Michael Smith).
- Beware of scanned documents. The text in scanned documents may not be accurately ‘read’ by search functions; manual review and redaction may be necessary.
- Once content has been marked for redaction, as part of the process Adobe will asked if you want to ‘sanitize and remove hidden information’; answer yes. This will remove hidden text, comments, file attachments, metadata, etc. Document metadata is data about the document, such as the document title (separate from the file name), author, description, key words, and tags. Review instructions for viewing/editing metadata (e.g., the document title, author, description, and key words).
Finally, be reminded that:
- Taking the time to adequately and comprehensively redact and review records is a worthwhile endeavor. The nature of source documentation is such that information that might require redacting can easily be missed or overlooked. Committing the time up front to do the process justice is far less time consuming then dealing with potential breaches in confidentiality, if identifiable information is inappropriately disclosed.
- Your ability to share study materials (redacted or not) is limited by the data protection measures and data sharing entities identified in your study protocol, consent form, and, if applicable, any clinical trial agreement and sub-contracting agreements.