ICH GCP states that Essential Documents are those documents which individually and collectively are necessary for the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator and sponsor to Good Clinical Practice standards, and to ensure that they comply with all applicable regulatory requirements.

ICH-GCP lists 56 essential documents, and therefore this is a good example of where the clear statement in ICH-GCP about applying these guidelines in proportion to the risk and complexity of the trial is an important and pragmatic consideration.

For all trials, investigators are encourage to think about what is essential in terms of the following:

1. Ensuring the trial is designed (i.e. the protocol is written) in order that the question set can be answered
2. That the answer obtained via the trial is accurate and valid
3. That, where possible, bias is considered and removed
4. The rights and privacy of the participants are protected
5. The safety and well-being of the participants are protected

A risk and complexity assessment of a trial can help determine what is needed in terms of essential documents that provide evidence or guide the above steps to ensure the quality and safety of the trials.

In many trials, but not all, here are a number of files that are helpful if set up pragmatically to document and guide the conduct of the study.

For a typical regulatory drug trial these would include:

1. Sponsor File: This is where key documents that are central in nature are filed. They include the clinical trial dossier, regulatory and EC approval letters, original contracts, documents related to the study drug, insurance etc. These documents will be filed in the sponsor or CRO files (where applicable).

2. Investigator Site file: This file will mainly contain documents that are site specific but will also include the protocol, the investigator brochure, insurance certificate and other documents that are useful and are a requirement as part of fulfilling the ICH GCP guidelines.

3. In-House Site File - This is a replica of the investigator’s site file maintained at the sponsor or CRO file. It is not compulsory to maintain this file, however for large multi-centre studies, it is often a good idea to have this file in-house to ensure that all sites have the same set of documents. It also helps the sponsor verify at any time what documents are held at each site. Maintaining this file however means that a strict process will need to be in place to ensure that each time a document is generated or updated at a site, a copy is forwarded to the sponsor files.

Fulfilling these objectives ensures that the necessary documents were retrieved prior to commencing the study. Essential Documents also serve a number of other important purposes such as assisting in the successful management of a trial by the sponsor, and (in the case of registration trials) regulatory authorities, as well as being used by the sponsor’s independent auditors as part of the process to confirm the validity of the trial and the integrity of the data collected.

The documents to be maintained before, during and after the trial are clearly stated in the ICH GCP guidelines (See Appendix 1), which also specifies which documents should be filed in the investigator and sponsor files.

Whilst all these documents are likely to be needed and relevant for a new drug or vaccine registration trial, they will not all need to be applied in pragmatic trials of other types of intervention (such as a trial assigning staff members to one of two types of training, then monitoring the results). Here common sense should be applied and from the following table only the relevant documents need be applied.

References
European Medicines Agency - ICH Topic E 6 (R1) Guideline for Good Clinical Practice
http://www.emea.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002874.pdf

For an additional resource please see the Regulatory Database http://regulatory.ghtcoalition.org/