Essential Regulatory Documents in Clinical Trials

The term ‘’essential documents’’ refers to the documents which, according to the ICH-GCP Guidelines, serve to evaluate the trial conducted, data quality and integrity. These documents are contained in the Trial Master File and are otherwise known as Regulatory Documents. Such documents are usually the important agreements, contracts, delegation logs, training logs, etc.
Maintaining and storing these essential regulatory documents is an important practice in clinical research. The proper filing and organization of these documents can greatly improve a clinical trial management. Usually, Regulatory Documents will be stored in a binder (or binders) that’s provided to the site for that specific study.
Filling out these documents and filing them properly is the site’s and especially the PI’s responsibility. Storing them properly is also the site’s responsibility, not the CRA’s. In any case, after the study is over, the sponsor or the CRO will inform the site if they should keep the originals or make copies of the Regulatory Documents for storage. Similarly, the sponsor or the CRO will also tell the site how long they need the documents to be kept and stored on-site.

1. Essential Regulatory Documents in Clinical Trials ‹#›

2. Introduction Maintaining and storing the essential regulatory documents is an important practice in clinical research. The proper filing and organization of these documents can greatly improve a clinical trial management. Usually, Regulatory Documents will be stored in a binder (or binders) that’s provided to the site for that specific study. Filling out these documents and filing them properly is the site’s and especially the PI’s responsibility. Storing them properly is also the site’s responsibility, not the CRA’s. In any case, after the study is over, the sponsor or the CRO will inform the site if they should keep the originals or make copies of the Regulatory Documents for storage. Similarly, the sponsor or the CRO will also tell the site how long they need the documents to be kept and stored on-site. ‹#›

3. Defining Essential Regulatory Documents The term ‘’essential documents’’ refers to the documents which, according to the ICH-GCP Guidelines, serve to evaluate the trial conducted, data quality and integrity. These documents are contained in the Trial Master File and are otherwise known as Regulatory Documents. Such documents are usually the important agreements, contracts, delegation logs, training logs, etc. ‹#›

4. Most Important Regulatory Documents There are many essential Regulatory Documents in a clinical trial. In the next few slides, we’ll give examples and explain some of the most important documents for a clinical research site. ‹#›

5. Most Important Regulatory Documents previous protocols current protocol protocol amendments Form FDA 1572 IRB approvals IRB correspondence site visit (monitoring) log subject visit log CDAs ‹#›

6. Most Important Regulatory Documents list of subjects ID codes screening and enrollment log HIPPA forms IP-related documents protocol deviations training logs informed consent forms ads and marketing materials IND safety reports CFRs ‹#›

7. Form FDA 1572 (Statement of Investigator) According to 21 CFR 312.53(c): The Form FDA 1572, otherwise known as the Statement of Investigator, is one of the most important documents in a clinical trial because it shows the sponsor that the PI (principal investigator) will comply with all FDA regulations. The Statement of Investigator also provides the sponsor with all necessary information and data of the investigator such as education, past experience, training, site addresses, IRB forms, facility locations, etc. “No investigator may participate in an investigation until he/ she provides the sponsor with a completed, signed Statement of Investigator, Form FDA 1572.” ‹#›

8. Confidentiality Disclosure Agreement (CDA) The second important Regulatory Document is the CDA which has to be completed and filled out by the site or PI. The purpose of this agreement is to ensure that all trial-related information and data is protected and secured. The CDA represents a legal document which binds everyone working at that site to secrecy and privacy. Anything connected to the trial should stay private. An example of this is the Investigator Brochure, protocol synopsis, the full protocol, etc. These things and all other intellectual property of the Sponsor/CRO should stay confidential, thus the need for a CDA. ‹#›

9. Financial Disclosure Forms (FDFs) All investigators listed on the Form FDA 1572 are obliged to fill out an FDF. The purpose of the FDF is to check if any of the investigators have a financial interest or expectation from the study. When such an interest exists, the investigators are obliged to state the amounts, arrangements, and payment schedules and timelines as well as ways in which the investigator and the site will avoid or minimize the potential for bias. And finally, the FDF should contain the maximum number of monetary or equity amounts that the investigator is allowed to receive for the trial. ‹#› $ Investigator’s financial interests

10. Training Logs & Protocol Signature Pages Anyone who attends protocol training and all other amendment trainings should sign these documents. Afterwards, the PI should also sign these documents as a confirmation that he/she managed to properly train other site staff. As we all know by now, the PI is responsible for conducting a study that will adhere to the given protocol as well as comply with all FDA and GCP guidelines and regulations. This means that it’s the PI’s job to train and educate site employees on the protocol. For this reason, Training Logs and Protocol Signature Pages exist. ‹#›

11. Delegation of Duties Log As you can imagine by the name, the Delegation of Duties Log serves exactly that purpose – states which duties the PI delegated to whom. At a site, it’s important that everyone knows their own tasks. In order to achieve this and make the job more efficient, the PI will delegate duties and roles to each person according to their experience and education. Each study-specific task that an individual performs should be noted in this log, and at the end, the PI signs off as an approval of the delegated roles. The Delegation of Duties Log usually includes the first name and last name of the person performing a task, the role or the task itself, the signature of the individual, the start and end date, and other similar details. ‹#› nurses/ other staff sub-Is coordinator PI Delegation of Duties

12. The E-signature is just as valid as a handwritten signature. For this reason, all investigators should respect the concept of password confidentiality and e-signatures. Understanding the importance of E-signatures is important for many reasons, the most important being that it’s still a legally binding signature. Password Confidentiality & E-signatures There are many tasks throughout a trial that will require an E-signature, such as signing off on e-CRFs (electronic case report forms). These forms belong in the EDC (electronic data capture) system and signing off on them shows that the data entered there fits the original source documentation.

13. IRB Correspondence Central IRB Deals with independent clinical research sites. Local IRB Deals with University or Hospital clinical research sites. As we all know, IRB stands for Institutional Review Board. All documents related to the IRB and all correspondence should be considered important and essential. IRB correspondence is usually closely connected to subjects’ safety and well-being and conducting the trial according to FDA and GCP rules and regulations. Having into consideration that the subjects’ safety is the most important thing in a trial, it’s understandable why these IRB documents are crucial. The job of the IRB is to make sure that the site has the appropriate PI, staff, and capabilities to be able to safely conduct the trial. They are concerned with the PI’s oversight, his/her experience, qualifications, number of studies he’s conducting at that given time, etc. All of these things are monitored in order to ensure maximum protection and safety of the participants. The IRB that’s responsible for a site can be Central or Local. Usually, local IRBs take only University or Hospital sites. So, if your site is an independent one, you’ll probably be dealing with central IRB. All in all, the IRB is there to decide whether or not the site is capable and equipped to conduct an ethical trial.

14. Note-To-Files (NTFs) ‹#› No site can conduct a trial without any errors or mishaps. So, whenever something happens that needs a further explanation or clarification, Note-To-Files are the perfect tool for that. Sometimes, there are unpredictable problems, deviations, or discrepancies that cannot be explained and noted anywhere else in official documents. Anything that happens on site that needs further clarification can be noted though Note-To-Files. www.trialjoin.com Although this might seem as additional and unnecessary documentation to take care of, sometimes it’s the only legal and correct way to justify an action that happened on site. For example, a protocol deviation might have occurred by mistake or it might have been necessary because it was connected to a patient wellbeing and safety. This is where NTFs can help you explain yourself.

15. www. trialjoin.com CONCLUSION The above-mentioned documents are only a portion of all essential regulatory documents that everyone involved in clinical research should be familiar with. Being aware of the importance of these documents will help you conduct a better and more organized clinical trial. Properly managing and storing these documents in a timely and accurate manner is crucial for every sponsor and FDA audit. And finally, doing this will ensure that the final results and data of the trial are produced with quality and integrity. ‹#›