The Necessity of Clinical Research Documentation Training Programs and the Value of Learning from Mistakes

Paula Smailes, DNP, RN, CCRP, CCRC

Clinical Researcher—November 2018 (Volume 32, Issue 9)

PEER REVIEWED

Paula Smailes, DNP, RN, CCRP, CCRC

 

Source documentation lies at the heart of clinical research workflows for investigative sites. Adequate documentation of protocol-related visits ensures that required information on study conduct and results has been captured for sponsors and other stakeholders.{1}

In the clinical research milieu, the focus is on capturing visit information as source data. According to the International Council for Harmonization (ICH),{2} source data include all information in original records and certified copies of original records, which may include clinical findings, observations, or other elements in a clinical trial that can be used to recreate or evaluate the trial. These data elements are collected in source documents, which the ICH further describes as original documents, data, and records.{3}

Bargaje{4} states that source documentation in clinical research:

  • Documents the progress of the subject from consenting until the subject completes the study;
  • Records the accountability of the investigational product dispensed, consumed, and returned by the subject;
  • Serves as the complete record of the subject as the reference for the treating physician at any point in time.

Clinical research documentation is heavily scrutinized to ensure compliance with federal regulations. Because of this, it is imperative that investigative sites have a structured program for training new hires and ensuring annual competency for existing staff. Good documentation practices are essential for site success; instruction in proper documentation techniques for staff helps improve data quality and can lead to fewer queries and audit findings. This can establish a positive reputation for study placement at a site, and perhaps most importantly, increase patient safety.

Essential Components of Good Documentation

Key attributes for good documentation were first described by the U.S. Food and Drug Administration (FDA) using the acronym ALCOA, which stands for Attributable, Legible, Contemporaneous, Original, and Accurate (see Table 1).{5} Additional attributes that documentation should possess are that they be enduring, available, accessible, consistent, credible, and corroborated (see Table 2).{4} These traits are essential qualities that clinical research staff should be taught as new hires to incorporate into their practice.

 

Table 1: Breaking Down the Parts of ALCOA{4,5}

ALCOA
Attributable Who documented the data is clear.
Legible The document is readable and any signatures on it are identifiable.
Contemporaneous Documented in the correct time frame along with the flow of events. If a clinical observation cannot be entered when made, chronology should be recorded. Acceptable amount of delay should be defined and justified.
Original The first record made by the appropriate person.
Accurate Consistent and real representation of facts.

 

Table 2: Attributes of Good Clinical Research Documentation{4}

Documentation Attributes
Enduring Long-lasting.
Available and Accessible Easily available for review by treating physicians and during audits/inspections. The documents should be retrievable within a reasonable time.
Consistent Unchanging over time.
Credible Based on real and reliable information.
Corroborated Evidence should support the data.

 

Source Documentation Guidance

The value of source documentation was further noted by the Joint Task Force (JTF) for Clinical Research Competency, which included it as part of the Core Competency Framework within a domain labeled Data Management and Informatics.{6} Within this domain, the JTF addresses the close relationship between clinical research data management and informatics. In treating documentation as a recognized competency for clinical research staff, sites have a responsibility to ensure that a focused training program exists for ensuring team success with its related tasks.

 

Table 3: Excerpt of Section 6 of the Core Competency Framework Identified by the Joint Task Force for Clinical Research Competency{6}

 

The use of an electronic means of documentation has become the norm, moving away from paper-based sources. For clinical researchers, if an electronic health record (EHR) is used, considerations may be with both documentation and extraction (data mining) of information from the system. This has important considerations for the care of research participants, such as study eligibility, continuity of treatment longitudinally, and ongoing subject follow up.

In July 2018, the FDA announced its finalized guidance on “Use of Electronic Health Record Data in Clinical Investigations,”{7} giving directions to sponsors, clinical investigators, contract research organizations (CROs), institutional review boards, and other interested parties on the  use of electronic health record data in FDA regulated clinical investigations. Some of the key concepts from the guidance are that:

  • EHR data improve patient safety, data accuracy, and clinical trial efficiency;
  • Study staff can more easily combine, aggregate, and analyze data from multiple sources (orders, notes, etc.);
  • EHR systems provide access to real-time and longitudinal healthcare data, and can facilitate post-trial follow up on patients to assess long-term safety and efficacy.

From this FDA guidance, use of electronic systems for clinical trial documentation and management is encouraged. The efficiency that electronic documentation allows can significantly save documentation time for sites, while promoting continuity of care. Once again, site documentation programs should cover considerations with electronic systems and their features specific to clinical research. It also is important that the elements of ALCOA should be present whether the documentation is paper or electronic.

Source Errors

In clinical research training programs that teach research documentation, the ultimate goal is to have sustainability of correct documentation workflows in practice. Unfortunately, the role of human error comes into play. As the old saying goes, to err is human, and well-intentioned people can make very costly mistakes in clinical research. Even with proper training, guidance, and regulations, we know that source documentation errors will still exist.

Experience is always a good teacher, but in the absence of experience, one can learn from the mistakes of others. One approach can be to expose research staff to examples of real-world mistakes made in clinical research and the inevitable consequences. This can be done by sharing details from auditing or interim monitoring visit reports. Sites can learn from these mistakes and become proactive concerning source documentation errors by finding root causes and patterns, then creating adequate solutions.

Site Challenges

Rapid enrollment periods and short timelines can cause staff to hurry through documentation and not give it the attention it requires. Heavy workloads and low staffing can contribute to errors. During these times, staff may start documentation but not complete it until weeks later, forgetting what should have been documented at the time of the event. Important details may be missed or misunderstood, and staff may not be as thorough as desired, leading to errors in records that are not caught until the time of a routine monitoring visit. The discovery of ineligible research participants in this fashion is a study coordinator’s nightmare.

When multiple protocols are being conducted by a site for the same disease state, it is also easy to confuse protocols. Similar studies can create confusion, but so can multiple staff assisting with and documenting data on an individual study. This can also lead to inconsistencies in documentation. Protocols may be amended and staff may be in the habit of documenting under a previous version, or revert back. Lastly, while research staff can be excellent at their jobs, investigator oversight and documentation that reflects it are critical.

FDA Warning Letters

When training staff how to document research visits, also consider providing exposure to what not to do. The best way to do that is to review Warning Letters publicly shared by the FDA. The FDA is quite transparent about findings from its audits. Researchers can subscribe to e-mail updates about FDA Warning Letters on the agency’s website.{8}

The posted letters can be reviewed by company, issuing office, subject, response letters, or closeout letters. Further, throughout their website, Warning Letters can easily be shared using Facebook. Twitter, LinkedIn, Pinterest, or sent with e-mail.

  

Figure 1: FDA Warning Letters Online{8}

 

Documentation Findings

The most common inspection findings related to source documentation are that it is not reliable, not adequate, or not accurate.{4} Staff  should be trained to recognize that, when findings are made by the FDA, they are reported in relation to specific expectations stated in the Code of Federal Regulations (CFR). When the FDA gives a site a citation, it does so with examples of how the site is in violation of the expectations.

Using Warning Letters as examples can be useful to show new hires the consequences of failing to follow regulations on proper documentation as dictated in the CFR. Reviewing violation examples and considering ways that site workflows can prevent such violations can be useful for new hire training and ongoing staff competency review (see Table 4).

 

Table 4: FDA Citations Using the Code of Federal Regulations and Examples

FDA Citation Violation Examples Prevention Strategies
21 CFR 312.60: Failure to ensure that the investigation was conducted according to the investigational plan. 1. Enrolling ineligible subjects not meeting study entry criteria.

2. Missing study procedures indicated in the protocol, such as chest X-rays or electrocardiograms.

3.  Disqualifications during study run-in period, yet patient enrolled.

1. Have a colleague double-check study entry criteria before a patient is enrolled.

2. If using an EMR, capitalize on tools to help you find information quickly.

3. Cross reference protocol with Schedule of Events to make sure procedure milestones are met.

21 CFR 312.62(a): Failure to maintain adequate records of the disposition of the drug, including dates, quantity, and use by subjects. 1. Drug dispensed does not match the amount taken by the research participant.

2. The amount of drug returned does not match what should have been returned.

1. Count and document drug return with the subject present, not after the person has left.

2. Count medication before dispensing.

3. Discrepancies should be explained in source or note to file.

21 CFR 312.62(b): Failure to maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation. 1. Absence of accurate histories documented.

2. Failure to complete forms required.

1. Keep medical history section updated.

2. Use source documents that have been verified by sponsor or CRO.

21 CFR 312.62 (c ): Failure to retain records required to be maintained under 21 CFR Part 312 for a period of two years following the date a marketing application is approved for the drug for the indication for which the drug is being  investigated; or, if no application is filed or if the application is not approved for such indication, until two years after the investigation is discontinued. 1. Not maintaining records related to drug disposition, including dates, quantities, and usage.

2. Not retaining consent forms and case report forms.

1.  Keep a drug dispensation log with study drug accountability.

2. Check with sponsor prior to shredding documents.

3. If possible, scan informed consents into the electronic medical record.

 

Proactive Approach

A study of FDA violations can lead to focusing on the prevention of documentation errors. Learning from the mistakes of others can be a powerful tool in training. The most impactful, proactive approach is staff education. Each member of the study team should undergo training on the study and that training should be documented. Principal investigators should delegate responsibilities to staff adequately trained on the protocol and the tenets of Good Clinical Practice. Particular training should be provided on ALCOA and other good documentation practice requirements.{5}

Use of an eligibility checklist can help prevent wrongful enrollment. A checklist can be created if a sponsor does not provide one. When utilized, having a second person review the checklist for completion and tie the results to successful enrollments is key. Rushing and distraction can both easily contribute to errors related to subject eligibility, so remember to take time to focus on each and every individual who is being enrolled.

Staff workload also needs to be considered by management. If the enrollment period is extremely fast or if staff are responsible for too many studies, errors are likely to occur. Sites should determine if it is feasible to take on additional studies. Keeping realistic workloads can go a long way in error prevention for both staff and investigators.

Sponsors and CROs, meanwhile, need to determine if investigators are committed to full participation throughout the duration of studies.{5} While study staff may be doing the bulk of documentation, that does not preclude the investigator from responsibilities detailed in the Form FDA 1572.

If a site does not already have one, its leaders should consider the importance of having a standard operating procedure (SOP) on source documentation. The SOP should provide an overview of the essentials of documentation, while not being so rigid that the site staff cannot comply with it. New staff should be trained in this SOP, which should be evaluated annually. Existing staff should review any updates and document the review.

Having an internal quality assurance (QA) program can also lead to enhanced site data and documentation quality. These programs should be run by a point person who can perform internal QA audits to make sure that staff are in compliance with the protocol. Ideally, this should begin to occur around the time of first randomization in a new study.

Once new hires are out of an orientation period, consider including them on an internal QA committee. They can be given a QA checklist to review source documentation from experienced peers who can help them know the essential requirements for review. By learning from their team, they can contribute to site quality, and in turn, improve their own documentation.

Conclusion

Staff who are true novices to clinical research will need an experienced preceptor to show them proper documentation techniques within the limits of the protocol and federal regulation. Value lies in having site staff learn from the mistakes of others as a means of preventing similar mistakes. As time becomes the teacher and staff become confident and skilled in their documentation, it is important to also consider ongoing refresher training and annual competencies.

Documentation could be thought of as creating a story of patient activity over the duration of the protocol. Site staff should look at their documentation and ask if it will make sense four years from now when someone inspects the records. Training with the rationale for how the regulations shape how one documents the data that are documented, along with FDA Warning Letters to learn from the mistakes of others, can solidify proper technique and further ensure site success.

References

  1. Source Documents for Clinical Trial Visits. J Clin Res Best Pract 8:2. firstclinical.com/journal/2012/1202_Source_Docs.pdf
  2. International Council for Harmonization (formerly known as International Conference on Harmonization). 1996. ICH E6(R1) 1.51 Source Data. https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf
  3. International Council for Harmonization (formerly known as International Conference on Harmonization). 1996. ICH E6(R1) 1.52 Source Documents. https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_Guideline.pdf
  4. Bargaje C. 2011. Good documentation practice in clinical research. Perspectives in Clinical Research 2(2):59–63. http://org/10.4103/2229-3485.80368
  5. Woolen, S. (2010). Data Quality and the Origin of ALCOA. southernsqa.org/newsletters/Summer10.DataQuality.pdf
  6. Joint Task Force for Clinical Trial Competency. 2017. Version 2.0 of Framework Released. https://www.clinicaltrialcompetency.org/news-updates/
  7. S. Food and Drug Administration. 2018. Use of Electronic Health Record Data in Clinical Investigations-Guidance for industry. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM501068.pdf
  8. https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm

Paula Smailes, DNP, RN, CCRP, CCRC, (paula.smailes@osumc.edu) is a senior systems consultant at The Ohio State University Wexner Medical Center and Visiting Professor with Chamberlain College of Nursing. She also serves as vice chair of the ACRP Editorial Advisory Board.