Study medications/devices

The aim of this chapter is to describe the general framework for conducting good clinical practices (GCP)-compliant clinical research. As it is difficult to cover this broad topic in such a short chapter, the authors will focus on those areas that are most discussed, most problematic and most critical to achieving a GCP-compliant clinical study. Thus, there is particular emphasis on ethical issues, source data verification and data integrity, monitoring and safety review, and study medication/device management. 

Control of study medications/devices The product being studied must be managed so that study subjects ultimately receive a safe product and full accountability can be documented Archives Documentation of research activities must be securely retained to provide evidence of activities... 

Setting up clinical studies is a lengthy process, as there are many documents to prepare [e.g. protocols and case report forms (CRFs)], study facilities to be assessed (e.g. study sites, CROs, clinical laboratories, phase I units), regulatory review to be considered and negotiations and agreements with study sites (e.g. contracts, finances, confidentiality, indemnity, insurance) to be undertaken. In addition, as will be dealt with in subsequent sections, ethical aspects of the study must be considered (e.g. ethics committee and IRB review and informed consent requirements), and study medications/devices must be organized. 

Facilities, for example offices, wards, archives, pharmacy, clinical laboratory study medication/device storage areas clinical laboratories access to source documents ethics committee/IRB requirements... 

Be thoroughly familiar with the properties of the clinical study medications/devices as described in the investigator brochure... 

Have sufficient time to personally conduct and complete the study. If more than one investigator is involved at a specific study site, the specific responsibilities must be described for each investigator. The investigator must ensure that no other studies divert study subjects, facilities or personnel from the study under consideration Maintain the confidentiality of all information received with regard to the study and the investigational study medication/device... 

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

Explanation that the study is a research procedure Description of study type and research aims Description of study medications/devices Description of procedures to be followed... 

Conduct an inventory and account for study medications/devices and arrange for extra supplies, including other items, such as CRFs, blank forms and so on, if necessary. Resolve discrepancies between inventory and accountability records, and medication/device use, as recorded in the CRFs. If a pharmacy is involved in the study, the pharmacy and pharmacist must be visited. Check that the medication/device is being dispensed in accordance with the protocol. Check that the medication/device is being stored under appropriate environmental conditions and that the expiry dates are still valid. Check that the medication/device is securely stored in a separate area that is not accessible to individuals not involved in the study. Check that any supplies shipped to the site since the last visit were received in good condition and are properly stored. 

Record of exposure to study medication/device. The medical file should clearly indicate when treatment began, when treatment finished, and all intervening treatment dates... 

Requisition of study medication/device (including placebo and comparator products, if relevant) must be initiated at an early stage to allow sufficient time to procure the study medications/devices and to prepare the final labeling and packaging, taking into account any special circumstances for blind studies and for import requirements. 

Control of study medications/devices at study sites... 

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. 

Maintain the security and accountability of clinical study supplies, ensure that medications/devices are labeled properly, maintain records of clinical study medication/device dispensing, including dates, quantity and use by study subjects and return or disposition (as instructed by the sponsor/CRO) after completion or termination of the study Archive all CRFs and documents associated with the study for a minimum of 15 years. Notify the sponsor/CRO of any problems with archiving in potential unusual circumstances, e.g. investigator retires, relocates, dies study subject dies, relocates, etc. 

Control of Study Medications/Devices at Study Sites... 

Compliance with medication/device use (by the study subject) should be assessed in all studies. If supplies are dispensed to subjects for self-administration, methods to assure compliance (e.g., diary cards, instructions on labeling, supervised administration) and methods to check compliance (e.g. tablet counts, plasma/urine assays, diary card review) must be in place. At each study visit, the study subjects should be asked to return all unused supplies and empty containers to the investigator, who will check the supplies for assessment of compliance and store them for return to the sponsor/ CRO. The monitor will review all relevant documents (e.g. source documents, CRTs, medication/ device inventory, dispensing forms) to ensure that the data in the CRFs reflect the subjects compliance with the study medications/devices. 

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