At last year’s PharmaSUG 2018 annual meeting in Seattle, Washington, DataCeutics Lead Consultant, Clinical SAS Programmer Analyst, Luke Reinbolt and Liz MacDonald of Nuventra Pharma Sciences, presented an exciting and important paper they co-wrote: Paper DSO2 titled, “Coming Soon: ADNCA and the PK Submission.” Their presentation gave a preview of the soon to come non-compartmental Pharmacokinetic (PK) analysis CDISC ADaM standard (ADNCA). ADNCA promises to be the submission dataset of the future…the dataset that will be sent to PK scientists for the calculation of non-compartmental PK parameters. The presentation covered an overview of the steps involved in developing this new standard for analysis and submission to the FDA, and outlined the need for and importance of these changes.
The industry is in full agreement that currently, there is a critical gap in the landscape of the Study Data Tabulation Model (SDTM) and Analysis Data Model (ADaM) standards for handling and formatting data to allow for non-compartmental PK parameter calculations. The data that is required for PK parameter software is a combination of several datasets, so an SDTM convention (like PC) does not meet the requirements necessary for this analysis, and requires more variables than the currently defined ADaM Basic Data Structure (BDS). This is why the ADaM leadership team formed a sub-team to develop a new set of specifications to deal with this problem and fill the gap. The sub-team was tasked with creating a standard that closely follows current ADaM guidance, but also allows for flexibility in working with all the different types of software packages that may be used to analyze PK data and calculate parameters…quite a challenge!
We’ve been curious how the process is coming along, and interviewed Luke Reinbolt to get an update.
DC: Luke, thank you so much for making time in your busy schedule to meet with us. To start, would you please provide some background about CDISC and your group?
LR: CDISC is the organization behind submission standards for clinical trials. It is made up of many teams, like SDTM (collected data) and ADaM (analysis data). It is also supported by various pharmaceutical, biotech, and contract research organizations. At DataCeutics, we are Platinum CDISC members. My group is an ADaM SubTeam comprised of many SMEs, software vendors, PK Scientists, and Programmers.
DC: What’s the latest on ADNCA?
LR: The process is moving along well. There are a lot of steps and requirements when working with an ADaM/CDISC proposed standard. ADNCA is still in the ADaM review process, and will hopefully be going to CDISC review soon.
DC: Can you give us a breakdown of the process?
LR: Here’s a very simple overview of the process: The Leader gets a team together to talk about the assigned idea.The team comes up with a draft, and agrees upon an endpoint for the ADaM team to submit to the leadership team. The leadership team either approves the draft, or sends it back for further updates. This can take several go-arounds. Once the leadership approves the document, it goes to the next level of review by the full ADaM team. Again, this is an iterative process and there may be several rounds of comments/updates. After the full ADaM team gives the okay, the document is sent to the final process in CDISC, the Global Governance Group (GGG). The GGG team is made up of a lot of CDISC members, and goes through three phases: Phase 1 involves a lot of discussion to make sure that it’s a good document/endpoint. In Phase 2, the document is sent out for public review (this takes a while, as you can imagine). Then in Phase 3, public issues are combined and examined, and the GGG looks at it again, to decide if it can go on.
DC: Wow, that certainly involves a lot of steps. I can see why these things take so much time to develop.
LR: Yes, and it’s been going on for quite a while. We’ve just been given the okay to submit this to the ADaM team as a whole, which is exciting. We have been working on this very diligently, and have spent a lot of time on the comments we received to this point. We want all the people on this sub team to voice their opinions, which leads to many good discussions, and to a strong document.
DC: What exactly is the greatest benefit of ADNCA?
LR: Currently, there’s not a lot of documentation out there from the conformance group that indicates how PK noncompartmental analysis data should be written when submitted. Right now, it is up to the agency’s discretion. Because they don’t yet have the ADNCA model, they generally rely heavily on the PC and PP SDTM domains for Pharmacokinetics. The problem with using just SDTM is that it is source data, and this requires some analysis. We need to combine multiple domains to develop the variables needed for noncompartmental analysis. We are creating timing variables and flags, which by definition, indicates it’s an analysis dataset. This will be the dataset standard that everyone will be using in the future to make PK parameters consistent. ADNCA will define how the data should be when it is submitted to the FDA…exciting stuff!
DC: What’s next?
LR: It’s going to the full ADaM team next for review. They will review and comment on it. After that review, It will go to GGG.
DC: How long before these new standards are fully accepted?
LR: I anticipate that it will be done with public review by January of 2020. It is a process and it will take time. GGG review might happen towards the middle of this year. Optimistically, public review might happen this fall. I am not expecting too many delays or hurdles, but reviews can take a while, so we’ll just have to be patient and allow the process the time it needs.
DC: Luke, thank you so much for this exciting update! It must be so rewarding to be making such an impact on the industry and doing your part in getting life-saving drugs to the people who need them. Thank you for all your hard work, and we look forward to your next update, and of course, to ADNCA’s final approval.
If you’d like to read more about this topic, visit: Coming Soon: ADNCA and the PK Submission on our blog.