Clinical data management plans aren’t mentioned in FDA regulations, but don’t be fooled – they’re a key ingredient in winning product approval. So don’t just shrug them off, says a top agency official.
“Please don’t say ‘It’s not in the regulations, I don’t need to do it,’ because at the end of the day, if you don’t have that good data, your product is not going to be approved,” Cynthia Kleppinger, CDER’s senior medical officer, cautioned last week at a joint FDA-MHRA workshop on data integrity in global clinical trials.
Data management plans – strategies for more effectively and efficiently achieving high-quality, statistically sound, reliable data – aren’t just set aside after they’re drawn up; they’re considered “living documents” throughout the lifespan of clinical trials, she noted.
Sponsors should assign responsibilities, with data management plans detailing who will be writing, reviewing, approving and finalizing them, and how they will be modified, if necessary, during projects.
Kleppinger emphasized that data management plans aren’t isolated documents—and should “never stand alone.” They should link to numerous SOPs – and tie together many elements, including the design plan for case report forms (CRFs) and a CRF tracking system to ensure that the required CRFs are gathered.
Data security measures in clinical trials, such as data backup and access restrictions, should be mentioned, as well as a list of what sponsors need to do before database lock . Conditions for database unlocking – which should only be for critical issues – should also be described in the plan.
Plans should include data extraction tools, such as electronic health records and recording devices, too. While the devices are “more and more being pulled into… clinical trials,” sponsors should understand they weren’t intended for clinical research, Kleppinger noted.
Sponsors should also tie in external data (such as off-site lab and imaging data), quality assurance and quality control (auditing and monitoring activities), how they deal with discrepancies and how they will generate both standard and custom reports.
“You’re looking at a quality system, so you should hopefully be generating reports that are also looking at how the trial’s going, and if there are any issues that are developing,” Kleppinger explained.
Sponsors should be especially wary of certain potential pitfalls such as poor case report form design, not addressing missing data before it goes missing, site and monitoring issues, and not involving appropriate staff members.
Kleppinger urged sponsors to “have some prompts, some flags and quality checks to address any sort of data inconsistencies, missing data, etc.” in their plans – and to refrain from having sites do calculations to enter their data. “There are a lot of errors noted,” she warned, adding they should craft separate validation plans, which are frequently requested during FDA inspections, as a backstop.
