How Many Places?

We recently received a question about maintaining information in two places in case a digital protocol solution would have to coexist with a traditional Word authoring solution, in particular when amendments have to be incorporated. It’s a really good question and like with all good questions, the answer to it is “it depends”, and let me explain some of the dependencies.

First off, the study designer and protocol development apps on the Nurocor Clinical Platform (NCP) have a versioning mechanism to manage protocol amendments. Initiating an amendment can only be done if the latest protocol version is in an approved state. Approval and amendment cycles can be tied into a workflow process, so that you can associate a review opportunity before committing to approval or starting an amendment. A new amendment will start as a copy from the last approved version and any earlier versions can only be accessed in read-only mode.

As part of the Nurocor Lean Protocol (TM) process, we also have the opportunity to formally define quality gates during protocol development, including gated review cycles tied into workflow, so that important trial planning related processes can be started once certain quality gates are met, but before final protocol approval. This means that a lot more work and clarifications can be done before final protocol approval, which will lead to less amendments in the first place. This may require a restructuring of existing processes but will generally result in leaner processes – the core idea of the lean approach being to maximize value and minimize waste.

The question as to “in how many places do we have to make changes” may not be what it seems. If you just think about current processes and leave the Nurocor study designer on the side, it should be clear that if you make an amendment today, changes will not be limited to one place (the protocol), but will have ripple effects in many other places as well, and may manifest themselves in having to update other protocol related documents, trial execution specifications, functional plans, and information in other systems. Now, the whole idea to have a digital protocol is to have one central place to manage and control change, and to avoid or automate these ripple effects in the first place. In the ideal solution, there would be only one place if a true single source of digital protocol development can be adopted. Having to do changes in only two places is still significantly better compared to changes in many places.

In the scenario where the Nurocor study designer / digital protocol has to coexist with traditional protocol authoring, there are factors that depend on the type of changes and the actual app components of the Nurocor digital protocol that would be in play. For the sake of argument, I will break down the Nurocor digital protocol solution into 4 logical application areas: authoring, study and protocol elements (SPE), disclosure, and Schedule of Activities (SOA).

As an example, if you have SPE and SOA, then I would expect that amendments that are only related to clarifying language in the protocol document may not have any impact on SPE and SOA. To have an impact on SOA, it would mean amendments that relate to changes in the schedule (events, activities) or the actual data collection. I would not consider that just to be just a clarification. In this case, it would have a ripple effect on the EDC specification and EDC build, possibly also on data standards compliance. This would already be reason enough to control that change through the SOA app rather than a series of manual and more costly changes. To have an impact on SPE, that may be contingent on the specific SPE configuration, depending if we include only essential study design elements or a more fully Common Data Model as envisioned by TransCelerate DDF. Finally, the disclosure elements support the publication of information to different targets such as the population of the CDISC Trial Summary domain or submissions to CT.gov and EMA. Again, if an amendment impacts information related to that, then it is still better to do those centrally in the disclosure app rather than manually chasing these manually for the different disclosure targets.

Finally, if the Nurocor authoring app is included, then all the information of the common data model across SOA, SPE, and disclosure is integrated, not just with the protocol authoring, but across all authoring apps (CDP, SAP, CSR, functional plans), something that a Word based authoring app cannot achieve. If “one place” means in a specific Word document, then that may be a correct view from the perspective of that protocol author, but it is certainly not true from a holistic clinical lifecycle perspective.

To sum up. Having things in many places is really the result of not having one source of truth for a digital protocol solution. Having it in two places is the next best thing that can be achieved if the Nurocor digital protocol apps must coexist with a traditional Word based authoring solution, but it would still be major progress compared to manually chasing these changes in many other documents and systems across the clinical lifecycle.

Finally, it would be interesting to catalog in more detail what kind of changes usually lead to amendments. I would as a first stake in the ground argue that some amendments could be avoided in the first place with a gated protocol approach, which is another major goal of a combined digital protocol / lean protocol process. We should not take amendments as given, but as something that proper solutions should be designed for to avoid.