Sponsor responsibilities under good clinical practice (GCP) guidelines are extensive. While many of these tasks may be — and often are — transferred to a contract research organization (CRO), the sponsor is ultimately responsible for study quality. But just what do sponsors need to make sure their clinical trial meets GCP standards? Read on to find out.
1. Ensure that good quality management and monitoring systems are in place
Monitoring is defined by the International Council for Harmonisation (ICH) GCP standards as overseeing a clinical trial to ensure that it is conducted, recorded and reported in accordance with the protocol, its amendments, GCP guidelines and any applicable regulatory requirements. While the sponsor is responsible for ensuring this task is completed, monitoring is often contracted to an outside vendor.
In some countries, for example the U.K., a sponsor must notify the appropriate licensing authority in writing of any serious breach in GCP standards — one that is likely to significantly affect the safety or physical or mental integrity of a study participant or the scientific value of the trial — within seven days of becoming aware of the event. The sponsor must also ensure that essential documentation and materials are stored in accordance with the local country’s requirements, appointing named individuals responsible for archiving these documents. While translation responsibilities are largely left undescribed by ICH GCP, back translations of key documents to verify accuracy are required.
2. Appoint appropriately qualified personnel
This includes medical personnel available to advise on medically related trial questions or problems as well as study investigators themselves. Sponsors must ensure that these individuals meet the education and training requirements necessary to perform these tasks under local law and international GCP guidelines.
3. Select reliable vendors
Remember to include all vendors to which study-related activities have been contracted, such as site management organizations and data handling/processing companies. The sponsor must ensure that these vendors themselves also have a good quality management system in place, which is often accomplished via auditing. Quality agreements for vendors are also becoming increasingly common. These documents help to clearly define expectations, standards, metrics, risk management strategies, governance, meeting schedules, roles, responsibilities, training, escalation processes and more. Vendor quality agreements promote consistency and communication and also ensure audit and inspection readiness.
4. Ensure protocol compliance
Sponsors are responsible for making sure the protocol and any amendments are being followed as well as informing authorities of any serious breaches. All significant protocol deviations/non-compliance events should be listed in the clinical study report and in any publications. The sponsor must have a process in place that defines how non-conformances are captured, escalated and reviewed for significance, along with how corrective or preventive measures are implemented.
5. Submit regulatory documents to both Research Ethics Committees / Institutional Review Boards (REC/IRBs) and regulatory / competent authorities
This must be done before trial commencement, at other defined points in the trial’s timeline and upon addition of substantial amendments. (Non-substantial amendments are defined by the ISO as logistical changes not affecting the rights, safety or well-being of study patients and not related to clinical objectives or endpoints. An example would be corrections to typos. While it is usually the investigator who obtains REC/IRB approval, the sponsor normally assists in this process.
6. Oversee regulation of the investigational medicinal product (IMP)
At the most basic, sponsors need to ensure that the IMP is characterized, manufactured and packaged to good manufacturing practice specifications. The sponsor must provide information on labeling, storage, and handling of the IMP, which is a two-step release process covering both technical and regulatory release. Sponsors must certify import requirements and ensure that the IMP is adequately labeled. Sponsor oversight of IMP at the site level is controlled through site monitoring or remotely through interactive response technologies. Non-investigational medicinal products (nIMPs) may also be given during the trial, including rescue medications, concomitant medications, challenge agents and others. Sponsors must also ensure that any appropriate regulatory requirements for nIMPs are met.
A method of unblinding in a blinded study must also be put in place for emergency situations. This can be done through physical code break envelopes or interactive response technology services. A full reconciliation of code breaks should be performed at the end of the trial. Limiting the number of team members who can access code breaks is necessary to minimize the chance of accidental unblinding.
Finally, sponsors are responsible for drug accountability, ensuring the right subjects have received the right medication. This includes oversight of the whole supply chain from when the IMP was shipped from the sponsor to its use, return or destruction. This process needs full documentation, with any discrepancies noted and reported. Data loggers are used to ensure that the correct temperature, light, and humidity protections are maintained throughout shipment and storage. Study participants must be trained on proper storage and be provided with the necessary equipment for IMPs that are self-administered.
7. Adequately train all study personnel, participants, and vendors
While training is not well defined by GCP guidelines and regulations, it is nonetheless extremely important that all staff are trained appropriately for their roles. This includes training investigators on the protocol and investigator’s brochure. Likewise, these brochures should be reviewed annually and updated if required. Training needs to be structured, systematic and documented. In the case of investigators, training involves not only the study protocol but also the basic principles of clinical research and GCP.