Sponsor is responsible for validation of clinical trial processes

What level of validation to be performed by sponsor on electronic systems qualified by a vendor?
Indrani Kulkarni
In clinical trial settings, the use of electronic systems, e.g. for data collection, data management, safety data collection and evaluation, treatment allocation and trial management is quite common.

According to ich e6(r2), sections 5.2.1 and 5.5.3.a, respectively, “the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor” and “the sponsor should ensure and document that the electronic data processing system(s) conforms to the sponsors established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e. validation).”

According to ich e6(r2), section 1.65, validation of computerised systems is “a process of establishing and documenting that the specified requirements of a computerised system can be consistently fulfilled from design until decommissioning of the system or transition to a new system.”

The approach to validation should be based on a risk assessment that takes into consideration the intended use of the system and the potential of the system to affect human subject protection and reliability of trial results.

The sponsor is ultimately responsible for the validation of the clinical trial processes, which is supported by electronic systems and for providing sufficiently documented evidence to regulatory inspectors on the validation process and the qualification of the electronic systems. The sponsor may rely on qualification documentation provided by the vendor if the qualification activities performed by the vendor have been assessed as adequate. However, the sponsor may also have to perform additional qualification/validation activities based on a documented risk assessment.

Sponsors and vendors should be aware that if the electronic systems used for generating/handling relevant clinical trial data or to maintain control and oversight of clinical trial processes, documentation regarding the qualification process and any other relevant documentation on the electronic system maintained at the sponsor level, as well as on the vendor level.

What would be regulatory expectations if we wish to conduct some clinical trial procedures at the participant’s home?
Dr. Santosh Diwakar  
The regulatory authorities would consider performing any practice at the participant’s home and not at the clinical trial site should be avoided as much as possible and applied only if in compliance with regulation and when duly justified. Some situations which would be acceptable are:
    • The clinical condition of the patient and/or the disease treated should clearly justify that certain activities are conducted at participant’s home with the scope of minimizing the discomfort for the patient e.g. the patient is obliged to stay in the bed, motor difficulties, procedures that could be hard for the subject to be performed by themselves or by their caregiver.
    • The participant should not be exposed to higher risks than those foreseen for the same procedure applied in a health care facility. Therefore, a documented risk assessment is expected before the implementation of the procedure and the lack of availability of equipment and facilities (i.e. Emergency Department or Intensive Care Unit) should be carefully considered.
    • The procedure should be clearly described in the clinical trial protocol and related informed consent form and approved by the regulatory authority and Ethics Committee.
    • A written agreement should be in place between the Institution/Hospital/Investigator and the single individual(s) or the organization which will provide the service/personnel.
    • The personnel appointed for the procedure should be educated and qualified for the activities according to applicable law and specifically trained.
    • The personnel appointed for the procedure should be identified and their tasks should be documented on the contract/delegation log; the principal investigator (PI) remains ultimately responsible for the conduct of the trial.
    • Tasks related to medical decisions (i.e. protocol specified medical procedures, AE/SAE assessment, changes in medication, etc.) should remain the responsibility of a qualified physician.
    • Effective lines of communication between the principal investigator and the personnel who manage the patients at home should be established in advance and described in the clinical trial protocol (or related specific document) to guarantee that the principal investigator is constantly kept informed; in this context there should be specific consideration in relation to the protection of patient safety.
    • The activities conducted at subjects’ homes should be adequately documented; source documentation should be part of the investigators source documents and could be retained at the subjects’ home just for the time required by the procedure, providing that any source documentation will be transferred to the site according to trial management procedures.

What should be considerations whilst transferring copies of medical records from investigator sites to the sponsor?
Dr. Deepal Waghmare
Failure to implement adequate technical and organizational measures for the protection of data could result in undermining the dignity of clinical trial participants.

There should be procedures in place at the investigator site to redact copies of medical records in an appropriate way, to protect patients' identity, before transferring them outside the clinical environment to a sponsor, or a third party working on behalf of the sponsor.

Adequate security measures by the data controller, which are relevant to the process, including pseudonymisation and redaction, should be applied when transferring personal data e.g. redacted copies of medical records, SAE forms, CRFs, etc. from investigator sites to a sponsor, or a third party working on behalf of the sponsor. The sponsors need to take appropriate security measures and provide organizational and technical measures that fulfil the requirements of the data protection regulation.

Due to the sensitive type of information recorded in medical records, the extent to which sponsors request these data should be ethically and scientifically justified and limited to specific critical information. Any planned collection of redacted copies of medical records by the sponsor should be described in the protocol, or related documents, and should be explicit in the patient information.

Overall, it is expected that during and after the conduct of clinical trials patients' integrity, involving handling of personal data, is respected, and that regulations governing both clinical trials and data protection are fulfilled.