Protect Study Blinding and Improve Transparency by Numbering Trial IP
Ian Davison, Ph.D. Neuroscience, Medrio’s RTSM Subject Matter Expert
Does your CRO or sponsor have a policy around IP numbering in clinical trials? If not, they could be putting your clinical trial at risk. Not numbering your IP may not seem like a problem, but that lack of identification and traceability could be critical in a safety situation or during reconciliation; it may even risk study blinding. Protect your clinical trial using Treatment Numbers as a standard practice.
Engaging randomization and trial supply management (RTSM) services early in study startup can help protect clinical trials and expose substantial efficiencies, effectively baking in practices that help streamline supply chains.
In a previous blog, Winning the Race to FPI with Early Randomization and Trial Supply Management – Medrio, we discussed the importance of your investigational product (IP) packaging on study success. However, how the product kits are labeled and whether they are numbered is just as critical to study efficiency. Deciding between labeling distinct units or shipping un-numbered units of investigational products can have significant implications for study outcomes.
Breaking study blinding
To streamline production, some studies choose not to number individual units and instead ship IP in bulk labeled with batch details only. While taking this course may seem like the more efficient solution, it can put the blinding of your IP at risk.
When bulk-labeled packs of investigational products are outwardly labeled with their unblinded identity for use in the trial, individual kits are not labeled with a unique treatment number. Instead, a designated and unblinded pharmacist at the site reviews which group a particular participant is in and selects the appropriate kit for them to match the treatment arm. Then, the pharmacist or an investigator will manually write the subject’s number on the side of a vial or dosing pack.
The problem is now, at least one individual is aware of each participant’s treatment arm, putting the study’s blinding in jeopardy. Despite best intentions and safeguards, there is a significant risk when you have unblinded material that could be found by study participants and members of the clinical staff.
If a study blind is accidentally broken, the participant may continue to be a part of the study, but the protocol violation compromises the data quality, and the burden of additional reporting and extra work is introduced. Additionally, sponsors may need to exclude and replace the participant to bring balance back to the trial. This can impact both the study budget (due to the high costs of patient recruitment and the cost of IP dispensed to the participant before the accidental unblinding) and timeline.
Limited transparency in safety events
This approach also limits a study team’s visibility into the status of each kit, preventing them from knowing who received which kit and when. For example, what happens if a kit is accidentally dropped or damaged during the study? Likely, the site will just pick another out of the box. But what if this happens more than once, or if an entire package is somehow destroyed? This can quickly lead to a site running out of kits – either active or placebo – and the study team won’t know until the site calls asking for more, forcing them to scramble to produce and ship more kits and delaying study progress.
What if there is an issue with misdispensations or other patient safety concerns? Without direct numbering of the product for randomization, the ability to identify and quickly resolve these issues is hindered and may not be discovered until a post hoc reconciliation exercise.
With proper advanced planning and integration into the protocol design, there can be a full line of sight into the inventory of the sites and how it was utilized. In the case of a misdispensation, the clinicians will be able to say, “the patient has had this vial, with this serial number on it; we know where it was produced, we can review the temperature track for every truck that it’s been on, and see which site received it.”
That level of traceability is increasingly expected, but it can only be delivered if you have a unique identifier on every kit.
Compromised returns and reconciliation
A limited or insufficiently granular labeling strategy can also create risk at the end of the study linked to the IP returns and reconciliation process. Without adequate labeling, it is impossible to accurately account for everything that’s come in and gone out. Without the ability to track and trace your IP, you can find yourself in a situation where, for example, you expect to have six kits left, but you only have four and you have no information regarding what happened to the other two.
This blind spot introduces regulatory, financial and patient safety risks because your team lacks visibility into the trial supply. The ability to accurately record every single item, including their return and disposal, is critical. Without it, study closeout goals can be missed while additional time and money are spent on drug reconciliation.
Reducing Study Risk with RTSM Best Practices
Early clinical trial decisions on packaging and labeling can have serious implications. Involving your RTSM vendor early in the feasibility and study startup stages helps sponsors and CROs alike reduce risk. The most effective way to avoid an unblinding incident and successfully manage trial returns and reconciliations is to partner with an experienced RTSM provider. The right RTSM vendor can help you design a labeling strategy that includes the appropriate safeguards based on your study design. Don’t risk the loss of valuable participant data by managing a blinded trial in a spreadsheet, with unblinded site staff, or through another more manual, error-prone solution.
With Medrio RTSM, you can feel confident that participant data, participant safety, and study operations are protected. Learn more about how Medrio RTSM can help reduce your study risk by clicking here.