Sponsor-CRO

Study monitors or clinical research associates (CRAs) can be employed by the study sponsor, CRO, or independently contracted for a specific study and, according to the International Committee on Harmonisation (ICH) and formalized by FDA in the Guidance for Industry Good Clinical Practice (GCP), the purpose of a CRA is to ... 

Signature sheets for all staff involved in the study (including sponsor/CRO )... 

Supply of the investigator brochure, updates, product and documentation by the sponsor. (CRO may produce study documents such as... 

The sponsor/CRO has a duty to place a study safely. That is, the sponsor (or the delegated CRO) must assess and choose a site where study subjects... 

Well-designed study All studies must have a valid study design, documented in a protocol, so that it can be fully reviewed by all interested parties. The data collection plans, as described in the CRF, are part of the protocol Qualified personnel All personnel (sponsor/CRO and study site) must be experienced and qualified to undertake assigned tasks. Documentation of qualifications and training must be evident... 

Ethics committee review and approval All studies must be independently reviewed by ethics committees/IRBs, to assess the risk for study subjects, before clinical studies begin. Review must continue throughout the study Informed consent All study subjects must be given the opportunity to personally assess the risk of study participation by being provided with certain information. Their assent to participate must be documented Monitoring A primary means of quality control of clinical studies involves frequent and thorough monitoring by sponsor/CRO personnel... 

The following items should be assessed at study sites by sponsor/CRO monitors before studies begin ... 

The sponsor/CRO must go through a formal assessment procedure before placement of a study. Some of the most important areas requiring assessment are described in Table 12.2. All studies involving research of investigational medications and devices require qualified investigators, and the internationally accepted standard for qualified usually encompasses three main criteria medically qualified, that is legally licensed to practise medicine as a physician experienced in the relevant therapeutic specialty and experienced in clinical research. 

Part of the selection process for a study site involves confirming that ethics committee/IRB review will be safe and that all study subjects will be properly informed prior to consent to study participation. If the sponsor/CRO cannot obtain documented evidence of compliance with these two fundamental requirements, it is not safe to work with that site. 

Adhere to the protocol exactly. No changes to the protocol may be undertaken without following a formal protocol amendment procedure and without agreement by the sponsor/CRO... 

Maintain a confidential list identifying the number/code and names of all subjects entered into the study Allow authorized representatives of the sponsor/CRO and regulatory authorities direct access to study subject clinical notes (source documents) in order to verify the data recorded on CRFs Ensure CRFs are complete and accurate... 

Prior to selection of a clinical study site, the sponsor/CRO must confirm and document, in the pre-study assessment visit report, that the investigator has access to a local ethics committee/IRB. Local committees cannot be bypassed the only... 

Normally, the sponsor/CRO will prepare all necessary documentation for submission by the investigator to the ethics committee/IRB (it is not usual procedure for the sponsor/CRO to directly submit items to the committee, unless requested to do so by the committee). Whatever the local variations, the sponsor/CRO is usually responsible for ensuring the submission of the items in Table 12.4. Some committees require other additional items. 

The membership of an ethics committee/IRB will vary nationally and regionally. However, the sponsor/CRO is only permitted to conduct studies that are approved by ethics committees/IRBs that have a sufficient number of qualified members to enable a medical and scientific review of the proposed study and a review of all other ethical aspects of the study. Generally, ethics committees also have to be diverse in composition. Details of the membership of the ethics committee/IRB should be obtained and reviewed by the sponsor/CRO, prior to initiating the study, to ascertain the above and to determine that there is no serious conflict of interest (e.g. investigator voting on her/his study). 

The sponsor/CRO should also request a written copy of the working procedures of the ethics committees/IRBs. These procedures should provide sufficient information to assure sponsors/ CROs, investigators, auditors and inspectors of the integrity and independence of the ethics committee/IRB. Unfortunately, today, it is still difficult to obtain working procedures from many committees. 

Potential study subjects may enter a clinical study conducted by the sponsor/CRO only after being properly informed and consenting to participate. The researchers must consider who does what,... 

The conduct of clinical studies is a cooperative undertaking between the sponsor/CRO and the investigator each is responsible for ensuring that the study is in conformity with the protocol and in accordance with all applicable laws and regulations, and, of course, that study subjects are protected at all times. This responsibility involves regular and conscientious review of the progress of the study by the sponsor/CRO and by the investigator and study site personnel. 

One of the most important means of quality control of a clinical study is managed by frequent and thorough monitoring. A monitor s aim is first to protect the agenda of the sponsor/CRO who employs him/her. Monitors (often referred to as CRAs or Clinical Research Associates or Assistants in the pharmaceutical industry) must ensure maintenance of proper standards, compliance with the protocol, accurate and complete data capture and standardization across sites in a multicenter study. Basically, monitors will undertake the review noted in Table 12.8. 

Indemnity/insurance provisions for the sponsor/CRO, investigator, institution and so on (as relevant to the study and if required by local regulations)... 

Instructions on use and storage of study medication/device, if relevant Name of sponsor/CRO... 

Explanation that participation is confidential, but records (which divulge study subject names) may be reviewed by authorized sponsor/CRO representatives and may be disclosed to a regulatory authority... 

The following tasks should be undertaken by the sponsor/CRO monitor at each study site visit ... 

Source data verification is the process of verifying CRF entries against data in the source documents. Source data verification is only carried out at the study site, usually by the sponsor/CRO monitor (auditors will also conduct source data verification on a sample of CRFs inspectors may conduct source data verification on a sample or all CRFs). 

Direct access to source documents is required for all studies - direct access means monitors, auditors, other authorized representatives of the sponsor/CRO and inspectors are permitted to view all relevant source documents needed to verify the CRF data entries. Other restricted methods of access to source documents (e.g. across-the-table , back-to-back , interview method ) are not acceptable, as they do not allow proper verification of the data in CRFs. To ensure direct access, the study subject consent form must clearly indicate that permission for access has been granted by the study subject. 

Systems must be in place to ensure that documents will be securely retained for a long period of time. The purpose of archiving is to safeguard all documentation that provides evidence that a clinical study has been conducted in accordance with the principles of GCP. Archives at both the sponsor/ CRO and investigator sites must be reasonably secure with regard to indexing, controlled access, fire-resistance, flood-resistance and so on. 

The investigator must be held responsible for ensuring that all source documents, especially records acquired in the normal practice of care and treatment of a study subject, are safely archived and available for inspection by authorized company personnel or regulatory authorities. Further, the investigator must archive all necessary documents for a minimum of 15 years - the usual industry standard. All appropriate clinical study documents should be archived by the sponsor/ CRO, essentially for the lifetime of the product. The specific documents to be retained are described in the ICH GCP document. 

Generally, destruction of returned study medications/devices by the sponsor/CRO may not take place until the final report has been prepared and until there is no further reason to question the accountability of the study medication/device. The actual destruction process must be documented in a manner which clearly details the final disposition of the unused medications/devices and the method of destruction. The information is particularly necessary in case of any query regarding environmental impact. In exceptional circumstances, unused study medications (e.g. cytotoxics, radio-labeled products) may be destroyed at the study site, with appropriate documentation. 

---