Clinical trial protocols are largely written as documents aimed at the communication of the trial to the local Ethics Committees, Institutional Review Boards and investigators. Furthermore, they also serve as the foundation for study planning, conduct and reporting internally within pharma organizations. Trying to cover these two scopes, they typically vary greatly in content and quality. Nevertheless, clinical trial protocols must meet a standard that adheres to the principles of Good Clinical Practice.
An area where clinical trial protocols today can be greatly improved is in the area of standardization in terms of:
- Information presentation (TransCelerate Common Protocol Template)
- Content standardization (Structured Study Definition)
- Data integration (Meta Data Repository)
- Knowledge management (Proactive Amendment Avoidance)
In this paper, I would like to focus on the ‘Data integration’ topic affecting clinical trial protocols, as that is the main culprit behind our inability to properly address E2E clinical data standardization.
Why is that so?
Simply put it, we do not have an industry-wide alignment on the integration of the Protocol Standards into the Clinical Data Standards.
Yes, we do have CDISC PRM model which is representing clinical trial protocol. However, I am not aware of any implementation where the PRM is integrated into the clinical trial protocol development process. The abstract protocol representation model does not integrate itself very naturally into the process of writing the protocol document or extracting protocol information into such model.
On the other hand, Clinical Data Standards, as defined by CDISC, or any company’s extension of that, are usually well defined and managed within an MDR (Meta Data Repository) system. Such system, is typically presented as a system for managing E2E Clinical Data Standards, but for the most part it does not contain any Protocol Standards beyond a simplified version of the visit schedule.
What is required?
To bring the Protocol Standards and Clinical Data Standards together, an integration layer is required. One way to implement such an integration layer is to use what we call ‘Medical Concepts and Medical Items’. They can be thought of as a more granular representation of an annotated CRF. By bringing such Medical Concepts together in a different formation, we are able to model any protocol assessment/activity/procedure as required.
In order to implement the true E2E standards within our MDR systems, we need to re-think our protocol authoring process. One approach in that direction is the SSD (Structured Study Definition). In essence, within this approach the protocol is built from the standard protocol elements, aligned within the compound under study or the clinical project. The protocol document is then created based on that structured protocol information. The standard protocol elements for assessment/activity/procedure are then naturally integrated, via the medical concepts, into the data collection, management and analysis standards – a true E2E or rather B2E (Beginning to End) standardization.
Using this approach, supported by SSD and MDR technology, the required CRFs, Edit Checks, Tabulations and Analysis sets are defined and automatically created once the assessment/activity/procedure in the protocol are specified.
Not only does this approach yields:
- Better clinical standards integration
- Study setup automation
- Bi-directional line of sight of every data point and it’s protocol origin
It also presents studies in the structured form for:
- Effective protocol content sharing
- Better transparency and project alignment
- Study comparison
- Compound knowledge management
- Protocol amendments avoidance
intilaris specializes in introducing pharma and biotechnology companies to Structured Study Definition and protocol authoring processes, effective E2E standards implementation with leading industry tools as well as managing the processes with simple tools (e.g. Office 365).