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There is an old saying that “if it wasn’t documented, it didn’t happen.” This saying applies to clinical research as well because accurate documentation in clinical trials plays a critical role in generating valid results. It ensures the accuracy of the research data. The effectiveness of clinical trials depends on collecting accurate data, which assures that the outcomes are credible and can be applied to make informed decisions for patient care. However, investigators often fail to provide credible, accurate, and appropriate source documentation, which is one of the most common audit findings during site inspections. This issue is also prevalent in sponsor audits. To ensure that research results are supported by reliable and accurate data, investigators need to understand the importance of accurate documentation and adhere to Good Clinical Practices (GCP).

All clinical trial activities and clinical processes must conform to relevant state and federal regulations, as well as follow the standards set by GCP and International Committee on Harmonization (ICH) guidelines.

Data Integrity and Credibility in Clinical Trial Documentation

Maintaining data integrity and credibility in clinical trial documentation is crucial. Assessors place less importance on ambiguous or imprecise data, and in some cases, they may intentionally omit uncertain data from the clinical trial dataset. This practice can have broader implications since excluding data from a single site may weaken the overall trial’s statistical significance, reducing or eliminating the study’s ability to identify drug impacts.

To avoid such issues, researchers should document clinical trials according to ICH E6(R2) guidelines. ICH E6 1.51 defines source data as ‘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 (original records or certified copies).’

In addition, source documents are defined as original documents, data, or records such as ‘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.’1

The United States Food and Drug Administration (USFDA) outlined a set of guiding principles named ALCOA or ALCOA+ in 2018 to help people stay compliant with 21 CFR Part 11 in the manufacturing industry.2 However, these principles are also done in clinical trial practices to collect data while maintaining its quality as it is also a part of Good Documentation Practices (GDP).

As per the FDA’s Questions and Answers Guidance for Industry and MHRA’s ‘GXP’ Data Integrity Guidance and Definitions, ALCOA is an acronym that stands for Attributable, Legible, Contemporaneous, Original, and Accurate.3,4 This approved set of principles now includes the words Complete, Consistent, Enduring, and Available. These good documentation principles are described together as ALCOA+.

Regulatory Compliance for Accurate Documentation

During a clinical trial, researchers must submit several documents to the regulatory authorities. These documents include clinical study protocols, financial disclosures and contracts, regulatory approvals, subject records, drug accountability logs, and any relevant correspondence regarding the trial. The list below represents the FDA’s GCP guidance documents for the submission of accurate regulatory documentation for clinical trials.5

Each document, should comply with the above-mentioned relevant guidance document.

Additionally, the US FDA demands that each Principal Investigator (PI) operating a clinical trial under an IND submit an FDA Form 1572. This form is ‘an agreement signed by the investigator to provide certain information to the sponsor and assure that he/she will comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic.6 This form is considered a contract between the investigator and the FDA since it consists of a consolidated listing of PI’s regulatory obligations.

Accurate Documentation leading to Patient Safety

Every clinical trial goes through an intense review process from start to finish. Although the main objective of clinical research is to enhance medical practice, managing clinical trials and supervising them to ensure patient safety and minimize risk is a very difficult task. Accurate documentation is crucial in tracking a patient’s progress during a clinical trial, which can help detect any adverse event or safety concern promptly. Additionally, this information is to modify or adjust treatment plans as well as to take the required precautions to ensure the patient’s safety.

In addition, clear documentation also helps the researchers to be aware of the patient’s medical history and relevant treatment patterns. Regulatory authorities like FDA require accurate documentation of all clinical trial activities, including patient information, informed consent, and adverse event reporting.

For instance, the ICFs should include detailed information about the clinical trial and the patient’s role in it, explaining how they are involved in the trial and what adverse events they may face during its conduct. Researchers should write or document the ICF according to FDA 21 CFR Part 50, Protection of Human Subjects, which consists of several factors related to patient safety. This guideline states that ‘the information given to the subject or the representative shall be in language understandable to the subject or the representative.’No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.7

Replication, Verification, Accountability, and Transparency of Documents

Accurate documentation enables other researchers to replicate the trial precisely, following the same methods and procedures. This replication helps validate the initial findings and strengthens the overall scientific evidence. Internal replication, or the replication of a study’s conclusions using the same data, can assist enhance the quality and dependability of research used in policymaking. It does this by assuring the reliability of study results as well as encouraging the application of best practices and transparent research. It increases dependability not just by ensuring errors that do not impact the results (e.g., coding or data cleaning issues, typographical errors). But also by determining if the results are affected by alternative analytical choices.

Additionally, verification is essential in demonstrating the credibility of the research and its potential usefulness in improving patient care. Accurate documentation helps ensure that the study’s results are valid and can be verified through subsequent research.

Moreover, reliable and correct records ensure that researchers are responsible for their actions, follow ethical guidelines, and accurately report all relevant data. It helps maintain the integrity of the study and builds trust among stakeholders. Similarly, recorded data should be transparent as it allows for scrutiny and evaluation by the scientific community, regulators, and the public. It promotes reproducibility, enables verification of results, and helps identify any potential biases or errors. Accountability and transparency in documentation are crucial for ensuring the reliability and credibility of clinical trial findings.

Decision-Making and Future Research and Development

Accurate documentation of clinical data is also pivotal in decision-making during or after a clinical trial. It provides a comprehensive record of all procedures, interventions, and outcomes, allowing researchers and clinicians to make informed decisions based on reliable data. Besides, it supports trial monitoring, identifies protocol violations, and evaluates the safety and effectiveness of the intervention. It also enables the analysis of trends and patterns, facilitating evidence-based decision-making for the trial’s success and the well-being of the participants.

As already mentioned above, accurate documentation facilitates:

Hence, reliable and correct documentation leads to shaping the future of clinical research and development.

Accurate Documentation for Litigation and Legal Considerations

During clinical research, accurate documentation is critical for litigation and legal issues. Why? The following points explain why is it so important during a legal dispute or regulatory audit: 

  1. If there’s any legal disagreement before or after the trial, the proper documentation of each step. That serves as concrete evidence to support the defense’s side rather than solely relying on hearsay or personal recollection.
  2. Documentation in clinical trials is for FDA and GCP as per set standards. If not followed properly, it can lead to legal issues and fines, which can gravely affect the trial’s results.
  3. During regulatory inspections, audits, and inquiries of clinical trials, accurate documentation helps demonstrate compliance with regulations. Incomplete and inconsistent documentation is more likely to prolong the investigation and leave room for legal action.

Therefore, accurate documentation is crucial in litigation and legal considerations during clinical trials. It improves regulatory compliance, creates an informed consent process, develops responsibility, and makes regulatory inspections easier. It also acts as a proof of any legal issue. As a result, accurate documentation is a crucial component of managing clinical trials.

Conclusion

The accurate documentation is of utmost importance in clinical trials. It makes sure that all information is accurately and consistently documented and allows for the replication and verification of the study by other researchers, which increases the validity of the results. In summary, it facilitates regulatory compliance, ethical review, and transparency in the research process. As well as it helps sustain clinical trials’ integrity and credibility, improving medical knowledge, and ensuring research participants’ safety.

References

  1. International Council for Harmonization. Integrated Addendum To ICH E6(R1): Guideline For Good Clinical Practice: E6(R2). database.ich.org. Accessed August 12, 2023. Published November 9, 2016. https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf
  2. United States Food and Drug Administration. Data Integrity And Compliance With CGMP; Guidance For Industry. fda.gov. Published April, 2016. Accessed August 12, 2023. https://www.fda.gov/files/drugs/published/Data-Integrity-and-Compliance-With-Current-Good-Manufacturing-Practice-Guidance-for-Industry.pdf
  3. United States Food and Drug Administration. Data Integrity and Compliance with Drug CGMP Questions and Answers Guidance for Industry. fda.gov. Published December, 2018.  Accessed August 12, 2023. https://www.fda.gov/media/119267/download
  4. Medicines & Healthcare products Regulatory Agency (MHRA). ‘GXP’ Data Integrity Guidance and Definitions. Published March, 2018 Accessed August 12, 2023. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/687246/MHRA_GxP_data_integrity_guide_March_edited_Final.pdf
  5. United States Food and Drug Administration. Regulations: Good Clinical Practice and Clinical Trials. fda.gov. Published January 01, 2021. Accessed August 12, 2023. https://www.fda.gov/science-research/clinical-trials-and-human-subject-protection/regulations-good-clinical-practice-and-clinical-trials
  6. United States Food and Drug Administration. Information Sheet Guidance for Sponsors, Clinical Investigators, and IRBs: Frequently Asked Questions – Statement of Investigator (Form FDA 1572). fda.gov. Published May, 2010. Accessed August 12, 2023. https://www.fda.gov/media/78830/download
  7. Code of federal regulation. Part 50—Protection of Human Subjects. ecfr.gov. Updated August 16, 2023. Accessed August 16, 2023. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50

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