In the Beginning

It was late 2007. Mad Men was the hottest show on TV. The BlackBerry was still the most popular smartphone. Senator Barack Obama was securing his party’s nomination for the next presidential election. And a young clinical data exchange specialist named Max Kanevsky was contemplating the future of the biopharmaceutical industry.

During his tenure at Merck, Max had been responsible for integrating the company with many external partners (e.g., laboratories, CROs, joint ventures, technology providers), working with many non-standardized sources of data. Though the norm, gathering all that disparate data and mapping it into Merck’s internal standard was a huge challenge. When the Clinical Data Interchange Standards Consortium (CDISC) started to make headway in its mission to develop a global set of standards, it marked a new beginning. CDISC would eventually define the standards for the entire industry.

But Max wondered how sponsors would possibly manage such a sea-change. At the time, software options to help ensure a submission’s compliance with FDA business rules were limited. WebSDM offered limited performance and capabilities, at a price point that was prohibitive to many. Meanwhile, Max was helping Merck with its early manual implementations of CDISC standards, including LAB, ODM and SDTM, which were difficult and time consuming. And each new challenge provided an obstacle that could threaten FDA approval of any given drug. There had to be a better way. But what?

On March 24, 2015, CDISC published Version 1.3 of its ADaM Validation Rules.

So, what’s changed?

In the simplest terms: the release’s biggest enhancement is the ability to recognize and validate ADAE (Adverse Event Analysis) and BDS-TTE (Time-to-Event Analysis) datasets. CDISC has added 75 new rules in total, and, at the same time, cleaned up some of the checks from the prior release to ensure that their failure criteria is machine-testable.

So, what should concern you?

These published business rules conform to the definition of CDISC’s intention that each rule requirement be broken down into its constituent parts and should be machine-testable. For example, a simple rule which states “C BETWEEN A and B” will be stated as C >= A and C<=B. This normalized model works for business requirement capture … but it can make implementation, testing and human understanding more complicated than they need to be.

Beyond that, these newly enhanced ADaM validation rules still don’t provide a complete solution. Since ADaM IG v1.0, CDISC has been providing mere specifications documents. ADaM validation requires more than that. You need the ability to supplement the ADaM rules with sponsor-specific checks, especially for sponsor defined controlled terminology and value level metadata. And you need to be able to test those checks with the same software used by the FDA.

It was a long time coming. But, finally, on December 17, 2014, the FDA announced that applications must be submitted electronically, and that submissions will be required to contain study data in conformance with CDISC standards.

The industry has been given 24 months from the publication of the final guidance documents to comply. Not wanting to waste any precious time, Pinnacle 21 hosted two webinars — on January 7th and 8th, 2015 — to help guide you through the new processes.

Registration is now open for the next NJ CDISC User Group meeting, scheduled for Wednesday, January 28, 2015 from 1-5pm. The meeting will be held at TAKE Solutions in Princeton, NJ. Please register by January 20, via the link below:

Register for the NJ CDISC User Group

Meeting Agenda:

• Kevin Lee (Accenture):  Standards Metadata Management: Version Control and its Governance
• Fred Hofstetter and Ian Fleming (d-Wise):  Leveraging R and Shiny for point and click ADaM Analysis
• Archana Bhaskaran and Kannan Subramanian (Novartis):  Metadata Management – Our Journey Thus Far
• Sangeeta Bhattacharya:  Trial Design Domains
• Max Kanevsky and Sergiy Sirichenko (Pinnacle 21):  FDA Finalizes Requirements for Standardized Data
• Andrew Ndikom (Novartis Vaccines):  ADaM Compliant Table Creation Macros

November was an important month for people who deal with clinical research data and metadata. First, the FDA published new, official validation rules for SDTM. Second, Pinnacle 21 released the next generation of its renowned open source toolkit: OpenCDISC Community 2.0.

In the webinars that took place on December 11 and 16, we covered how the latter can provide enormous help in dealing with the former. Community 2.0 comes with a wealth of game-changing new tools — including an upgraded version of Validator, a Define.xml Generator, a Data Converter, and a Clinicaltrials.gov Miner — to help you address these new FDA rules, as well as issues around CDISC compliance and submission readiness.

On December 17th, the FDA made its long-awaited announcement: future submissions will be required in standardized format.

“ The Agency may Refuse To File (RTF) for NDAs and BLAs, or Refuse To Receive (RTR) for ANDAs an electronic submission that does not have study data in conformance to the required standards… ”  – FDA Guidance for Industry

This represents a seismic shift for the industry. However, adapting to this new paradigm can be relatively painless — if you have the right guidance.

Through this webinar, we’ll cover the details of the new mandate, what it all means, and the steps you’ll need to take. Our speakers are Dhananjay (DJ) Chhatre (former FDA operations research analyst) and Sergiy Sirichenko (co-founder of OpenCDISC): two industry experts who currently support the FDA’s eDATA team.

For your convenience, we’ll be providing this webinar at two different times.

In this webinar, we will cover:

• Descriptions of the final guidance documents and their contents
• How these new regulations will impact you
• FDA’s timeline for implementation
• How to communicate with the FDA during the process
• Technical implementation of CDISC standards
• Questions & Answers

Best regards.
OpenCDISC Team

On November 19, 2014, the FDA’s Center for Drug Evaluation and Research (CDER) released its new “Validation Rules for Study Data Tabulation Model (SDTM) Formatted Studies.’’ According to CDER, the organization is doing this “to improve the standardization and quality of [submitted] clinical data … as well as to improve the predictability of data quality and usefulness.”

But what does this mean for you? Fortunately, Pinnacle 21 recently hosted a webinar to answer this very question.

We are proud to announce the release of our next generation open source toolkit. Community 2.0 was created just for the CDISC professional and provides a wealth of game-changing new tools, including an upgraded version of Validator, a Define.xml Generator, and more. Download OpenCDISC Community 2.0 here

OpenCDISC Community 2.0 includes the following new features:

• Validator – upgraded with FDA validation rules and ability to validate against study specific value level metadata
• Define.xml Generator – creates fully compliant Define.xml 2.0 for SDTM, SEND, and ADaM datasets
• Data Converter – quickly converts data between SAS XPORT, Dataset-XML, Excel, and CSV formats
• ClinicalTrials.gov​ Miner – aggregates clinical outcome measures/endpoints across trials and therapeutic areas

This morning, November 18th, the Food and Drug Administration (FDA) published its first official list of validation rules for CDISC SDTM. These long awaited rules cover both conformance and quality requirements, as described in the FDA Study Data Technical Conformance Guide. Conformance validation rules help ensure that the data conform to the standards, while quality checks help ensure the data support meaningful analysis.

The FDA is asking sponsors to validate their study data before submission using these published validation rules and either correct any validation issues or explain, why they could not be corrected, in the Study Data Reviewer's Guide. This recommended pre-submission validation step is intended to minimize the presence of validation issues at the time of submission.

Rest assured: we have implemented the new FDA validation rules in the upcoming OpenCDISC Community 2.0 — keeping you ahead of the curve. Please join Sergiy Sirichenko — co-founder of OpenCDISC and an FDA Data Fitness Analyst — to learn about the new FDA validation rules and how you can get compliant in time for your next submission.

On October 9, 2014, the Pinnacle 21 tour bus rolled over the Golden Gate Bridge and into Foster City, where we held our third OpenCDISC Live event. And what an event it was.

We kicked off with a brief history of OpenCDISC, where Max Kanevsky, Pinnacle 21 president and CEO, talked about the origins of the project and how it has evolved over years. Attendees then received tutorials on two FDA programs — JumpStart and DataFit — and learned why both are so critical to the modern FDA review process.