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How can we ensure proper documentation of eligibility criteria?
Dr Pratibha Mehendle
The common practice is to document the eligibility criteria in the CRF by ticking the question: Did the subject satisfy all study entry criteria? with 'yes'. However, this is not adequate for regulatory inspection purpose. A system with an overall statement in the CRF regarding a subject's eligibility does not ensure the safety of the subjects, the quality of the data and sponsor oversight.
The GCP inspectors expect that adherence to all individual inclusion and exclusion criteria are documented in the source data. Adherence to the criteria of the protocol can originate from different sources like blood samples, physical examination, medical history, information from the subject etc. When designing the protocol and the related CRF, the sponsor should carefully consider where each source data originates from, with reference to a specific visit. This is important since some data originate from screening visits, others from the randomisation visit and some data could be historical.
It is the expectation that a qualified physician who is an investigator for the trial has assessed each individual eligibility criteria and has taken the final decision to include the subject in the trial (ICH GCP 4.3.1). This decision should be documented prior to the subject receiving the first dose of the IMP.
What are the regulatory expectations regarding investigator’s copy of CRF using a web-based application?
Dr Indira Subrahmanyam
ICH GCP 8.3.14 mandates that the investigators should keep a copy of the CRF. The CRF copy kept by the investigator is a contemporaneous and independent copy of the CRF, i.e. that it is not held by the sponsor. This requirement is valid irrespective of the media used; however, the introduction of electronic CRFs in clinical trials presents an additional challenge in achieving this requirement - especially if data are being submitted directly via a web-based application. The GCP inspectors do not consider the requirement above to be met if data are captured in an electronic system and the data are stored on a central server under the sole control of the sponsor. This is because the investigator does not hold a contemporaneous and independent copy of the data. Selecting an electronic solution for CRF should not jeopardise the credibility of data and should not result in lower quality as compared to a paper CRF. The sponsor should provide the investigator with support in keeping a copy of the CRF e.g. a third-party vendor, printed data prior to transferring to the database or saving a contemporaneous copy at the investigator's local computer hard drive.
What considerations are important when the sponsor provides Site Management Organization (SMO) support to the investigator?
Sandeep Gupta
It is important for the sponsor and the investigator to ensure that the division of roles of the responsible parties is maintained in accordance with ICH GCP guidelines.
The investigator should retain the final decision on whether the SMO intended to support the investigator, is appropriate. The investigator also retains the ultimate responsibility for any tasks involving trial-related medical decisions e.g. participant eligibility and enrolment, protocol specified medical procedures, assessment of efficacy/safety, evaluation of test results, decision to dispense or make changes to the trial medication and, the appropriate supervision of the persons or parties undertaking the activities delegated. Any trial related procedure that is delegated to an SMO should be specified in a written agreement. Where the agreement is between the sponsor and the SMO and involves tasks under investigator responsibility, it should be clear in the agreement between the sponsor and the SMO as well as in the agreement between the sponsor and the investigator that the investigator maintains adequate control and oversight over the contracted tasks.
Dr Arun Bhatt is a Consultant - Clinical Research & Development,
Mumbai. Readers can send their queries at:arun_dbhatt@hotmail.com
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