Potential endpoints are predefined by protocol, and generally declared by the investigator by prespecified events, or by site interpretation of images, but may also be triggered by entries on the case report form or laboratory results. These triggers and potential endpoints can be developed by ICON Medical Imaging if required by the sponsor, in consultation with the Physician Panel. These endpoints and triggers need to be discussed and coordinated with the Data Managers for the study. This facilitates the creation of the “Adjudication Package” by the Data Management group. Alternatively the “Adjudication Package” can be created in house at ICON Medical Imaging. The data in the “Package” is cleaned, queries resolved, masked of identifiers and therapy received before being uploaded into MIRA™ where it can be accessed by the committee. The MIRA™ fields relevant to an event include a patient summary, appropriate source documents and an eCRF. Translation of source documents, if required, documents and a CEC review form. For International studies, some translation may be required.
It is critical to define the data fields that need to be transferred for each triggered event, so that the appropriate fields can be created in MIRA™. Either the Data Management organization can do the programming/validation to create PDF pages that describe the adverse events experienced (or not experienced by the patient), as well as relevant ancillary data, or SAS datasets can be transferred to ICON Medical Imaging and the programming, validation and QA can be performed in house, to yield the data fields or PDF pages that are viewed by the Adjudicators.
Although this process covers the majority of data required for adjudication, in some cases out of protocol data may be required by the committee. For example, the patient may be hospitalized for an off protocol event, and that admission incorporates relevant data not covered in the standard CRF and therefore not in the master clinical trial database.
In that situation, an unblinded CRA is required to obtain relevant data from the site, ensure adequate translation as required, and ensure that the data is transferred back to the Data Management organization for addition to the master clinical trial database, query resolution and subsequent transfer to ICON Medical Imaging.
Generally the unblinded CRA will be part of the Medical Affairs Group at the Clinical CRO but can also be provided by the sponsor or by ICON Medical Imaging. For example, obtaining out of protocol images such as angiographic images in a trial involving a cardiovascular drug may be easier for the ICON Medical Imaging CRA to obtain.
Example
A typical Cardiology endpoint Adjudication committee consists in the initial step of two independent physicians. Each independently completes an eCRF. The 2 eCRF are programmatically compared. If there is concordance, the outcome of the event is considered final and ready for transfer. If there is discordance, there is a second step in which the event is reviewed by an additional group comprising one to three Cardiologists who adjudicate in further review. The complexity of this process and the amount of data reviewed provides a clear rationale for the ICON Medical Imaging Adjudication Solution.